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www.rsc.org/njc Volume 33 | Number 1 | January 2009 | Pages 1–212
ISSN 1144-0546
Volume 33 | N
umber 1 | 2009 N
JC Pages 1–212
1144-0546(2009)33:1;1-2
New Journal of Chemistry An international journal of the chemical sciences
PAPERT. Yong-Jin Han et al.The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene in a 3-ethyl-1-methylimidazolium acetate–DMSO co-solvent system
www.rsc.org/metallomicsRegistered Charity Number 207890
A new journal from RSC Publishinglaunching in 2009
MetallomicsIntegrated biometal science
This timely new journal will cover the research � elds related to metals in biological, environmental and clinical systems and is expected to be the core publication for the emerging metallomics community. The journal will be supported by an international Editorial Board, chaired by Professor Joseph A. Caruso of the University of Cincinnati/Agilent Technologies Metallomics Center of the Americas.
Metallomics will publish six issues in the � rst year, increasing to 12 issues in 2010. The journal will contain a full mix of research articles including Communications, Reviews, Full papers, and Editorials. From launch, the latest issue will be freely available online to all readers. Free institutional access to previous issues throughout 2009 and 2010 will be available following a simple registration process.
Contact the editor, Niamh O’Connor, at [email protected] for further information or visit the website.
Num
ber 1|
2008M
etallomics
Pages1–100 1754-5692(2008)1:1;1-6
www.rsc.org/metallomics Volume 1 | Number 1 | January 2009 | Pages 1–100
ISSN 1756-5901
MetallomicsIntegrated biometal science
1756-5901(2009) 1:1;l-m
060877
Submit your work now!Supporting the
ISSN 1144-0546
PAPERRudi van Eldik et al.Metal ion-catalyzed oxidative degradation of Orange II by H2O2. High catalytic activity of simple manganese salts
www.rsc.org/njc Volume 33 | Number 1 | January 2009 | Pages 1–212
New Journal of Chemistry An international journal of the chemical sciences
www.rsc.org/ibiologyRegistered Charity Number 207890
A new journal from RSC Publishinglaunching in 2009
Integrative BiologyQuantitative biosciences from nano to macro
Integrative Biology provides a unique venue for elucidating biological processes, mechanisms and phenomena through quantitative enabling technologies at the convergence of biology with physics, chemistry, engineering, imaging and informatics.
With 12 issues published annually, Integrative Biology will contain a mix of research articles including Full papers, Reviews (Tutorial & Critical), and Perspectives. It will be supported by an international Editorial Board, chaired by Distinguished Scientist Dr Mina J Bissell of Lawrence Berkeley National Laboratory.
The current issue of Integrative Biology will be freely available to all readers via the website. Free institutional online access to all 2009 and 2010 content of the journal will be available following registration at www.rsc.org/ibiology_registration
Volume
18|N
umber1
|2008Journal of M
aterials Chem
istryPages
1–140
www.rsc.org/ibiology Volume 1 | Number 1 | January 2009 | Pages 1–140 1–1401–140
ISSN 1757-9694
0959-9428(2008)18:1;1-J
Integrative Biology Quantitative biosciences from nano to macro
1757-9694(2009) 1:1;1
0608
58Contact the Editor, Harp Minhas, at [email protected] or visit the website for more details.
CHEMICAL SCIENCE
C1
Drawing together research highlights and news from all RSCpublications, Chemical Science provides a ‘snapshot’ of thelatest developments across the chemical sciences, showcasingnewsworthy articles and significant scientific advances.
EDITORIAL
17
Changes ahead for NJC in 2009
Denise Parent and Sarah Ruthven highlight the changesto NJC for the year ahead, together with the latest newsfrom the RSC.
N J CNew Journal of Chemistry. An international journal for the chemical sciences
www.rsc.org/njc
RSC Publishing is a not-for-profit publisher and a division of the Royal Society of Chemistry. Any surplus made is used to support charitableactivities aimed at advancing the chemical sciences. Full details are available from www.rsc.org
CoverSee T. Yong-Jin Han et al.,pp. 50–56.A very strong inter- and intra-molecular hydrogen bondingsolid, 1,3,5-triamino-2,4,6-trinitrobenzene, can be dissolvedand recrystallized in a 3-ethyl-1-methylimidazolium acetate–DMSOco-solvent system. Imagereproduced with the permission ofLawrence Livermore NationalLaboratory and T. Yong-Jin Han,Philip F. Pagoria, Alexander E. Gash,Amitesh Maiti, Christine A. Orme,Alexander R. Mitchell and LaurenceE. Fried from New J. Chem., 2009,33, 50.
Inside CoverSee Rudi van Eldik et al.,pp. 34–49.Organic dyes from industrialwaste water effluents can causelarge scale pollution of naturalrivers. Simple metal ions catalyzethe oxidative degradation of suchdyes and rapidly clean thepolluted water. Imagereproduced with permission ofErika Ember, Sabine Rothbart,Ralph Puchta and Rudi van Eldikfrom New J. Chem., 2009, 33, 34.
IN THIS ISSUE
ISSN 1144–0546 CODEN NJCHES 33(1) 1–212 (2009)
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 3
Associate editorsManuscripts should be directed to one of the Editors detailed below.
EDITORIAL STAFF
Editor (RSC)Sarah Ruthven
Editor (CNRS)Denise Parent
Assistant editorsMarie Cote (CNRS)Sarah Dixon (RSC)
Publishing assistantsJackie Cockrill (RSC)
Team leader, InformaticsCaroline Moore (RSC)
Technical editorsCelia Clarke (RSC), Nicola Convine (RSC), Bailey Fallon (RSC), Alan Holder (RSC), David Parker (RSC)
Administration coordinatorSonya Spring (RSC)
Administration assistantsAliya Anwar (RSC), Jane Orchard (RSC), Julie Thompson (RSC)
PublisherEmma Wilson (RSC)
Founding EditorLionel Salem
New Journal of Chemistry (Print: ISSN 1144-0546;electronic: ISSN 1369-9261) is published 12 times a year by the Centre National de la Recherche Scientifique (CNRS), 3 rue Michel-Ange, 75794 Paris cedex 16, France, and the Royal Society of Chemistry (RSC), Thomas Graham House, Science Park, Milton Road, Cambridge, UK CB4 0WF.
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NJC New Journal of Chemistry
An international journal for the chemical sciences
www.rsc.org/njcThe New Journal of Chemistry is a broad-based primary journal encompassing all branches of the chemical sciences. Published monthly, it contains full research articles, letters, opinions and perspectives.
INFORMATION FOR AUTHORS
Co-editor-in-chiefPascal Le Floch, Palaiseau, France
Co-editor-in-chiefJerry Atwood, Columbia, MO, USA
Consulting editorOdile Eisenstein, Montpellier, France
Board membersYasuhiro Aoyama, Kyoto, JapanKumar Biradha, Khargapur, IndiaLaurent Bonneviot, Lyon, FranceFabrizia Grepioni, Bologna, ItalyHelen Hailes, London, UKPeter Junk, Monash, AustraliaBarbara Nawrot, Lodz, Poland
Alan Rowan, Nijmegen, The NetherlandsMichael Scott, Gainesville, FL, USAMichael Veith, Saarbrücken, GermanyVivian Yam, Hong Kong, PR China
Full details of how to submit material for publication in the New Journal of Chemistry are given in the Instructions for Authors (available from http://www.rsc.org/authors). Submissions should be sent via ReSourCe: http://www.rsc.org/resource.Authors may reproduce/republish portions of their published contribution without seeking permission from the CNRS and the RSC, provided that any such republication is accompanied by an acknowledgement in the form: (Original Citation) – Reproduced by permission of the CNRS and the RSC.
©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009. Apart from fair dealing for the purposes of research or private study for non-commercial purposes, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988 and the Copyright and Related Rights Regulations 2003, this publication may
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EDITORIAL BOARD
Markus Antonietti, MPI, Potsdam, GermanyMatthias Bremer, Darmstadt, GermanyRobert Crabtree, New Haven, CT, USAFrançois Fajula, Montpellier, FranceJohn A. Gladysz, College Station, TX, USAGeorge Gokel, St Louis, MO, USA
Andrew B. Holmes, Melbourne, AustraliaMiguel Julve, Valencia, SpainHenryk Koslowski, Wroclaw, PolandJean-Pierre Majoral, Toulouse, FranceLuca Prodi, Bologna, ItalyJan Reedijk, Leiden, The Netherlands
David Reinhoudt, Enschede, The NetherlandsKari Rissanen, Jyväskylä, FinlandClément Sanchez, Paris, FranceJeremy K. M. Sanders, Cambridge, UKJean-Pierre Sauvage, Strasbourg, FranceJonathan W. Steed, Durham, UK
ADVISORY BOARD
LETTERS
19
Evidence of crystalline/glassy intermediates in bismuthphosphates
Marie Colmont,* Laurent Delevoye and Olivier Mentre
The wide NMR chemical shift range of 17O provides aprofitable source of information about partially orderedmaterials. In addition, original phosphorous/oxygenthrough-bond correlation experiments have allowed theunambiguous assignment of the 17O resonances.
23
A supramolecular sensing system for AgI at nanomolarlevels by the formation of a luminescentAgI– TbIII–thiacalix[4]arene ternary complex
Nobuhiko Iki,* Munehiro Ohta, Teppei Tanaka,Takayuki Horiuchi and Hitoshi Hoshino
The first example of the detection of AgI ions usingsupramolecular chemistry is demonstrated, in which twothiacalix[4]arene ligands are linked by analyte AgI ions andthen coordinate to TbIII ions to form a luminescent ternarycomplex, AgI2 �TbIII2 �TCAS2, enabling the detection of AgI atconcentrations as low as 3.2 � 10� 9 M.
PAPERS
26
Ionic liquids with dual biological function: sweetand anti-microbial, hydrophobic quaternaryammonium-based salts
Whitney L. Hough-Troutman, Marcin Smiglak,Scott Griffin, W. Matthew Reichert, Ilona Mirska,Jadwiga Jodynis-Liebert, Teresa Adamska, Jan Nawrot,Monika Stasiewicz, Robin D. Rogers* and Juliusz Pernak*
Newly synthesized dual function ionic liquids combine bothanti-microbial and sweetener properties into one compound.
34
Metal ion-catalyzed oxidative degradation of Orange IIby H2O2. High catalytic activity of simple manganesesalts
Erika Ember, Sabine Rothbart, Ralph Puchta andRudi van Eldik*
In an effort to develop new routes for the clean oxidationof non-biodegradable organic dyes, a detailed study of someenvironmentally friendly Mn(II) salts that form very efficientin situ catalysts for the activation of H2O2 in the oxidation ofsubstrates such as Orange II under mild reaction conditions,was performed.
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 5
RSC eBook CollectionAccess and download existing and new books from the RSC
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Registered Charity Number 207890
0408
98
PAPERS
50
The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene in a 3-ethyl-1-methylimidazoliumacetate–DMSO co-solvent system
T. Yong-Jin Han,* Philip F. Pagoria, Alexander E. Gash,Amitesh Maiti, Christine A. Orme, Alexander R. Mitchelland Laurence E. Fried
A highly hydrogen-bonded solid, 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), was dissolved and recrystallizedin various IL systems. Dissolution of TATB in EMImOAcoccurred by forming a very stable s-complex.
57
Supramolecular synthesis of some molecular adductsof 4,40-bipyridine N,N0-dioxide
Kapildev K. Arora, Mayura S. Talwelkar andV. R. Pedireddi*
4,4’-Bipyridine N,N0-dioxide has yielded different types ofsupramolecular assemblies from simple stacked sheet structuresto pseudorotaxane and stair-case type structures dependingupon its interaction with the co-crystallizing agents used in thesupramolecular synthesis.
64
Synthesis and characterisation of bulky guanidines andphosphaguanidines: precursors for low oxidation statemetallacycles
Guoxia Jin, Cameron Jones,* Peter C. Junk,Kai-Alexander Lippert, Richard P. Rose andAndreas Stasch
Reactions of alkali metal amides or phosphides with the bulkycarbodiimide, ArNQCQNAr (Ar = C6H3Pr
i2-2,6), followed
by aqueous work-ups, have yielded several guanidines, abifunctional guanidine and two phosphaguanidines (e.g. seepicture).
76
The hydrogen bond acidity and other descriptorsfor oximes
Michael H. Abraham,* Javier Gil-Lostes,J. Enrique Cometto-Muniz, William S. Cain,Colin F. Poole, Sanka N. Atapattu, Raymond J. Abrahamand Paul Leonard
The hydrogen bond acidity of cyclohexanone oxime andacetone oxime are 0.33 and 0.37, respectively; this placesoximes as about the same hydrogen bond acidity as alcohols.
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 7
www.rsc.org/chemcommRegistered Charity Number 207890
Introducing Professor Mike Doyle
Make an impact
Associate Editor for Organic ChemistryMichael P. (Mike) Doyle is Professor and Chair of the Department of Chemistry and Biochemistry at the University of Maryland, College Park. He has been the recipient of numerous awards, including the George C. Pimentel Award for Chemical Education in 2002 and the Arthur C. Cope Scholar Award in 2006. He has written or coauthored ten books, including Basic Organic Stereochemistry, 20 book chapters, and he is the co-author of more than 270 journal publications. The inventor of chiral dirhodium carboxamidate catalysts known as “Doyle catalysts,” his research is focused on applications with metal carbene transformations, Lewis acid catalyzed reactions, and selective catalytic oxidations.
Submit your work to ChemCommProfessor Doyle will be delighted to receive submissions from North America in the field of organic chemistry. Submissions to ChemComm are welcomed via ReSourCe, our homepage for authors and referees.
“ChemComm is an outstanding forum for the communication of significant research in the chemical sciences, and I am honoured to be a member of the editorial family. I continue to be amazed with the breadth of exciting chemistry that is being submitted to ChemComm and the high level of professionalism that is found at ChemComm.”
ISSN 1359-7345
1359-7345(2007)39;1-Y
www.rsc.org/chemcomm Number 39 | 21 October 2007 | Pages 3969 – 4060
Chemical Communications
COMMUNICATIONTakahiko Kojima et al.A discrete conglomerate of a distorted Mo(V)-porphyrin with a directly coordinated Keggin-type polyoxometalate
FEATURE ARTICLESYoshinori Yamanoi and Hiroshi NishiharaAssembly of nanosize metallic particles and molecular wires on electrode surfacesDonnaG.Blackmond and Martin KlussmannAssessing phase behavior models for the evolution of homochirality
0208
78
PAPERS
82
Electrochemical methodology for determinationof imidazolium ionic liquids (solids at room temperature)properties: influence of the temperature
M. P. Stracke, M. V. Migliorini, E. Lissner,H. S. Schrekker, D. Back, E. S. Lang, J. Dupont* andR. S. Goncalves*
Electrochemical impedance spectroscopy for determinationof imidazolium ionic liquid physicochemical properties: theinfluence of the temperature on the Nyquist diagrams.
88
A new family of biocompatible and stable magneticnanoparticles: silica cross-linked pluronic F127 micellesloaded with iron oxides
Zhaoyang Liu,* Jun Ding and Junmin Xue*
A new family of magnetic nanoparticles, silica cross-linkedpluronic F127 micelles loaded with iron oxides having theproperties of high biocompatibility, physical and chemicalstability, high magnetism, and low-cost production, have beensynthesized.
93
Novel thiophene-conjugated indoline dyes for zinc oxidesolar cells
Takuya Dentani, Yasuhiro Kubota, Kazumasa Funabiki,Jiye Jin, Tsukasa Yoshida, Hideki Minoura,Hidetoshi Miura and Masaki Matsui*
The introduction of thiophene ring(s) into D131-type indolinedyes improved cell performance due to their appropriateenergy levels and bathochromic shift in the UV-vis absorptionband on zinc oxide.
102
Gold imidazolium-based ionic liquids, efficient catalystsfor cycloisomerization of c-acetylenic carboxylic acids
Florentina Nea]u, Vasile I. Parvulescu,Veronique Michelet, Jean-Pierre Genet,Alexandre Goguet and Christopher Hardacre
Ionic liquid stabilized gold(III) chloride is shown to be a veryactive catalyst in the cyclization of sterically hindered andunhindered acetylenic carboxylic acid substrates even in theabsence of a base.
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 9
www.rsc.org/booksRegistered Charity Number 207890
Chemistry at Oxford:A History from 1600 to 2005A fascinating and unique history of the Oxford Chemistry School!
● Discover how individuals have shaped the school and made great achievements in teaching and research
● Read about the seminal works of Robert Boyle, Hinshelwood, Robinson and Hodgkin
● Discover how separate branches of chemistry (organic, physical, inorganic and biological) have evolved in Oxford
● Get to grips with the unusual character of Oxford University and learn more about its unique history.
This fantastic new book will appeal to all those interested in the history and present day style of science, especially chemistry, education and research at Oxford as contrasted with that to be found elsewhere.
Hardback | 300 pages | ISBN 9780854041398 | 2008 | £54.95
10070
PAPERS
107
Magnetically moveable bimetallic (nickel/silver)nanoparticle/carbon nanotube composites for methanoloxidation
Guan-Ping Jin,* Ronan Baron, Neil V. Rees, Lei Xiao andRichard G. Compton*
The functionalization of carbon nanotubes with both AgNPsand a minute fraction of NiNPs add to the electrocatalyticproperties of the AgNPs, the possibility to easily move them insolution using a magnet. The bi-functionalized carbonnanotubes are then easily recoverable after use.
112
Microwave-assisted facile synthesis of discotic liquidcrystalline symmetrical donor–acceptor–donor triads
Satyam Kumar Gupta, V. A. Raghunathan andSandeep Kumar*
The first examples of columnar phase formingtriphenylene-anthraquinone-based donor–acceptor–donortriads were prepared and characterized by polarizing opticalmicroscopy, differential scanning calorimetry andX-ray diffractometry.
119
Synthesis, crystal structures and luminescence propertiesof lanthanide oxalatophosphonates with athree-dimensional framework structure
Yanyu Zhu, Zhengang Sun,* Yan Zhao, Jing Zhang,Xin Lu, Na Zhang, Lei Liu and Fei Tong
Six new three-dimensional (3D) lanthanideoxalatophosphonates, [Ln(HL)(C2O4)0.5(H2O)2] �H2O(Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6);H3L = H2O3PCH(OH)CO2H), have been synthesized andstructurally characterized. Compound 6 shows strong redluminescence in the solid state at room temperature.
125
The annular tautomerism of the curcuminoidNH-pyrazoles
Pilar Cornago,* Pilar Cabildo, Rosa M. Claramunt,Latifa Bouissane, Elena Pinilla, M. Rosario Torres andJose Elguero
The structures of six NH-pyrazoles, derived from curcuminand related b-diketones, have been established byX-ray crystallography, and solid state 13C and 15N CPMASNMR spectroscopy.
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 11
www.rsc.org/njcRegistered Charity Number 207890
‘NJC book of choice’Why not take advantage of free book chapters from the RSC? Through our ‘NJC book of choice’ scheme NJC will regularly highlight a book from the RSC eBook Collection relevant to your research interests. Read the latest chapter today by visiting the NJC website. The RSC eBook Collection o� ers:
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Volum
e31
|Num
ber10|2007
NJC
Pages1693–1832
PERSPECTIVEZhaohua Dai and James W. CanaryTailoring tripodal ligands forzinc sensing
ISSN 1144-0546
New Journal of Chemistry
www.rsc.org/njc
An international journal of the chemical sciences
Volume 31 Number 10 | October 2007 | Pages 1693–1832
1144-0546(2007)31:10;1-8
www.rsc.org/analystRegistered Charity Number 207890
Not just an analyticalchemistry journal
detection
bio-analyticalanalytical
bio-analyticalbio-analytical
The Analyst
High pro� le and cited in MEDLINE, Impact factor: 3.198†
Immediacy index 0.925 - highest ranked general analytical
chemistry journal*
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Contains the i-section in every issue – a dynamic mix of reviews,
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The Analyst is the journal of choice for publishing urgent new work of the highest quality in analytical,
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0003-2654(2007)132:5;1-J
www.rsc.org/analyst Volume 132 | Number 5 | May 2007 | Pages 377–484
Interdisciplinary detection science
ISSN 0003-2654
CRITICAL REVIEWStepan Shipovskov and Curt T. ReimannElectrospray ionization mass spectrometry in enzymology
PAPERJoseph Wang et al.Discrete micro� uidics with electrochemical detection
†2006 Thompson Scienti� c (ISI) Journal Citation Reports*Based on the ISI JCR 2006 Science Edition for the Analytical Chemistry subject category
PAPERS
136
Neutral 5-nitrotetrazoles: easy initiation with low pollution
Thomas M. Klapotke,* Carles Miro Sabate andJorg Stierstorfer
New synthesis, crystal structures and characterization ofneutral 5-nitro-2H-tetrazole, 1-methyl-5-nitrotetrazole and2-methyl-5-nitrotetrazole are presented. These nitrogen-richcompounds were tested to be highly energetic with increasedsensitivities towards impact, friction and electrical discharge.
148
Probing multivalency for the inhibition of an enzyme:glycogen phosphorylase as a case study
Samy Cecioni, Oana-Andreea Argintaru, Tibor Docsa,Pal Gergely, Jean-Pierre Praly and Sebastien Vidal*
The concept of multivalency was applied to the inhibitionof an enzyme (glycogen phosporylase). Trivalent inhibitorswere synthesized and displayed improved activities incomparison to their monovalent counterparts.
157
The formation of silver nanofibres by liquid/liquidinterfacial reactions: mechanistic aspects
Kun Luo and Robert A. W. Dryfe*
Silver nano-fibres deposited by spontaneous reduction at thewater/organic interface.
164
The role of nucleophilic catalysis in chemistry andstereochemistry of ribonucleoside H-phosphonatecondensation
Michal Sobkowski,* Jacek Stawinski and Adam Kraszewski
Reactions of ribonucleoside 30-H-phosphonates with alcoholsproceed with high stereoselectivity towards the samediastereomer irrespective of the presence or absence ofnucleophilic catalysts.
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 13
PAPERS
171
Two polyaminophenolic fluorescent chemosensors forH+ and Zn(II). Spectroscopic behaviour of free ligandsand of their dinuclear Zn(II) complexes
Gianluca Ambrosi, Cristina Battelli, Mauro Formica,Vieri Fusi,* Luca Giorgi, Eleonora Macedi,Mauro Micheloni,* Roberto Pontellini and Luca Prodi
UV-Vis and fluorescence properties of two polyamino-phenolicligands; design of new efficient fluorescent chemosensors forH+ and Zn(II) ions.
181
Dynamic covalent self-assembled macrocycles preparedfrom 2-formyl-aryl-boronic acids and 1,2-amino alcohols
Ewan Galbraith, Andrew M. Kelly, John S. Fossey,Gabriele Kociok-Kohn, Matthew G. Davidson,Steven D. Bull* and Tony D. James*
Reaction of 2-formyl-aryl-boronic acids with1,2-amino alcohols results in dynamic covalent self assemblyto quantitatively afford tetracyclic macrocyclic Schiff baseboracycles containing bridging boron–oxygen–boronfunctionality.
186
N-Inversion in 2-azabicyclopentane derivatives: modelsimulations for a laser controlled molecular switch
Bastian Klaumunzer* and Dominik Kroner
Quantum model simulation of a N-inversion based lasercontrolled molecular switch by IR-ladder-climbing or UV.
196
How does non-covalent Se?SeQO interaction stabilizeselenoxides at naphthalene 1,8-positions: structural andtheoretical investigations
Satoko Hayashi, Waro Nakanishi,* Atsushi Furuta,Jozef Drabowicz, Takahiro Sasamori and Norihiro Tokitoh
Non-covalent G?SeQO 3c–4e interactions are demonstratedto determine the fine structures of 8-G-1-[MeSe(O)]C10H6 andoperate to protect from racemization of the selenoxides: G ofSeMe acts more effectively than G of halogens.
14 | New J. Chem., 2009, 33, 3–16 This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPERS
207
Mechanistic aspects of nitrate ion reduction on silverelectrode: estimation of O–NO2
� bond dissociationenergy using cyclic voltammetry
Mohsin Ahmad Bhat, Pravin Popinand Ingole,Vijay Raman Chaudhari and Santosh Krishna Haram*
Cyclic voltammetric investigations for nitrate ion reductionat silver electrode in alkaline medium, show that reactionfollows a concerted dissociative electron transfer mechanism,with bond dissociation energy of O–NO2
� bond ofca. 48.4 kcal mol� 1.
Call for abstractsThis is your chance to take part in IUPAC 2009. Contributions
are invited for oral presentation by 16 January 2009 and poster
abstracts are welcome until 5 June 2009.
ThemesAnalysis & Detection
Chemistry for Health
Communication & Education
Energy & Environment
Industry & Innovation
Materials
Synthesis & Mechanisms
Plenary speakersPeter G Bruce, University of St Andrews
Chris Dobson, University of Cambridge
Ben L Feringa, University of Groningen
Sir Harold Kroto, Florida State University
Klaus Müllen, Max-Planck Institute for Polymer Research
Sir J Fraser Stoddart, Northwestern University
Vivian W W Yam, The University of Hong Kong
Richard N Zare, Stanford University
For a detailed list of symposia, keynote speakers and to submitan abstract visit our website.
42nd IUPAC CONGRESS Chemistry Solutions2–7 August 2009 | SECC | Glasgow | Scotland | UK
Sponsored by
www.iupac2009.orgRegistered Charity Number 207890
This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 15
AUTHOR INDEX
Abraham, Michael H., 76Abraham, Raymond J., 76Adamska, Teresa, 26Ambrosi, Gianluca, 171Argintaru, Oana-Andreea, 148Arora, Kapildev K., 57Atapattu, Sanka N., 76Back, D., 82Baron, Ronan, 107Battelli, Cristina, 171Bhat, Mohsin Ahmad, 207Bouissane, Latifa, 125Bull, Steven D., 181Cabildo, Pilar, 125Cain, William S., 76Cecioni, Samy, 148Chaudhari, Vijay Raman, 207Claramunt, Rosa M., 125Colmont, Marie, 19Cometto-Muniz, J. Enrique, 76Compton, Richard G., 107Cornago, Pilar, 125Davidson, Matthew G., 181Delevoye, Laurent, 19Dentani, Takuya, 93Ding, Jun, 88Docsa, Tibor, 148Drabowicz, Jozef, 196Dryfe, Robert A. W., 157Dupont, J., 82Elguero, Jose, 125Ember, Erika, 34Formica, Mauro, 171Fossey, John S., 181Fried, Laurence E., 50
Funabiki, Kazumasa, 93Furuta, Atsushi, 196Fusi, Vieri, 171Galbraith, Ewan, 181Gash, Alexander E., 50Genet, Jean-Pierre, 102Gergely, Pal, 148Gil-Lostes, Javier, 76Giorgi, Luca, 171Goguet, Alexandre, 102Goncalves, R. S., 82Griffin, Scott, 26Gupta, Satyam Kumar, 112Han, T. Yong-Jin, 50Haram, Santosh Krishna, 207Hardacre, Christopher, 102Hayashi, Satoko, 196Horiuchi, Takayuki, 23Hoshino, Hitoshi, 23Hough-Troutman, Whitney
L., 26Iki, Nobuhiko, 23Ingole, Pravin Popinand, 207James, Tony D., 181Jin, Guan-Ping, 107Jin, Guoxia, 64Jin, Jiye, 93Jodynis-Liebert, Jadwiga, 26Jones, Cameron, 64Junk, Peter C., 64Kelly, Andrew M., 181Klapotke, Thomas M., 136Klaumunzer, Bastian, 186Kociok-Kohn, Gabriele, 181Kraszewski, Adam, 164
Kroner, Dominik, 186Kubota, Yasuhiro, 93Kumar, Sandeep, 112Lang, E. S., 82Leonard, Paul, 76Lippert, Kai-Alexander, 64Lissner, E., 82Liu, Lei, 119Liu, Zhaoyang, 88Lu, Xin, 119Luo, Kun, 157Macedi, Eleonora, 171Maiti, Amitesh, 50Matsui, Masaki, 93Mentre, Olivier, 19Michelet, Veronique, 102Micheloni, Mauro, 171Migliorini, M. V., 82Minoura, Hideki, 93Miro Sabate, Carles, 136Mirska, Ilona, 26Mitchell, Alexander R., 50Miura, Hidetoshi, 93Nakanishi, Waro, 196Nawrot, Jan, 26Nea]u, Florentina, 102Ohta, Munehiro, 23Orme, Christine A., 50Pagoria, Philip F., 50Parvulescu, Vasile I., 102Pedireddi, V. R., 57Pernak, Juliusz, 26Pinilla, Elena, 125Pontellini, Roberto, 171Poole, Colin F., 76
Praly, Jean-Pierre, 148Prodi, Luca, 171Puchta, Ralph, 34Raghunathan, V. A., 112Rees, Neil V., 107Reichert, W. Matthew, 26Rogers, Robin D., 26Rose, Richard P., 64Rothbart, Sabine, 34Sasamori, Takahiro, 196Schrekker, H. S., 82Smiglak, Marcin, 26Sobkowski, Michal, 164Stasch, Andreas, 64Stasiewicz, Monika, 26Stawinski, Jacek, 164Stierstorfer, Jorg, 136Stracke, M. P., 82Sun, Zhengang, 119Talwelkar, Mayura S., 57Tanaka, Teppei, 23Tokitoh, Norihiro, 196Tong, Fei, 119Torres, M. Rosario, 125van Eldik, Rudi, 34Vidal, Sebastien, 148Xiao, Lei, 107Xue, Junmin, 88Yoshida, Tsukasa, 93Zhang, Jing, 119Zhang, Na, 119Zhao, Yan, 119Zhu, Yanyu, 119
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16 | New J. Chem., 2009, 33, 3–16 This journal is �c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Light-responsive azobenzene groups have brought polymers to life
Polymers strut their stuff under the spotlight
Light can be used to make the polymer film move like a robotic arm
©The Royal Society of Chemistry 2009
Chemists in Japan have created light-driven polymer films that walk like inchworms and move like robotic arms.
The films, made by Tomiki Ikeda at the Tokyo Institute of Technology in Yokahama and collaborators, contain a polymer which contracts when visible light shines on it and expands again under UV light.
The polymers respond to light because they have azobenzene groups – which contain N=N double bonds – incorporated into them. Under visible light the N=N bonds have a cis conformation which means the polymer is bent. But when the light source is changed to UV the bonds become trans and the polymer flattens.
To make the polymer walk, the group incorporated it in a laminated film with one pointed end (at the back of the ‘worm’) and one flat end (at the front of the ‘worm’). As the polymer bends the pointed back end is dragged forward then, when the light source is changed to UV, the
January 2009 / Volume 6 / Issue 1 / ISSN 1478-6524 / CSHCBM / www.rsc.org/chemicalscience
Chemical Science
Glowing report for explosive detectionScientists are developing a new method to thwart terrorists
Crinkly tunnels aid gas storageTrifluorolactate crystals may offer an alternative route to hydrogen fuel cells
Porphyrins get energeticThis month’s Instant insight outlines recent advances in the construction of interlocked molecules
Lighting a billion livesNobel peace prize winner Rajendra K Pachauri talks about understanding climate change and giving light to humanity
In this issue
A snapshot of the latest developments from across the chemical sciences
ReferenceT Ikeda et al, J. Mater. Chem., 2009, 19, 60 (DOI: 10.01039/b815289f)
Chem. Sci., 2009, 6, C1–C8 C1
polymer flattens, pushing the front flat end forward. This continuous flattening–bending motion allows the film to move forward like an inchworm.
The robotic arm also requires clever lamination, but this time the polymer layer and laminated sections are alternated which
allows the film to act as a hinge joint and move flexibly. By controlling the intensity of the light and the position on the film where the light is concentrated, the researchers can make the film move as they chose.
‘The polymers function with a minimum of moving parts which minimises friction and surface contact problems,’ says Ikeda. ‘One can envisage applications such as direct light-to-mechanical energy conversion, storage systems and in microfluidic devices.’
Graeme George, an expert in polymer science at Queensland University of Technology, Brisbane, Australia, commends ‘the efficiency of the reversible photo-processes.’ He adds that the time is ripe for further detailed studies of such systems to see if these photo driven polymers offer any challenge to their electroactive counterparts.Ruth Doherty
CS.01.09.C1.indd 20 15/12/2008 15:00:16
French scientists have developed a photochemical method for patterning biomolecules inside glass capillary tubes. The technique could lead to lab-on-capillary devices as cheaper alternatives to lab-on-a-chip medical diagnostics, they claim.
Eric Defrancq, at Joseph Fourier University, Grenoble, and colleagues say their lab-on-capillary vision poses considerable challenges. ‘Retaining the functionality and patterning of biomolecules in the closed environment of a capillary tube is difficult because there is no easy access to the inside surface,’ explains Defrancq.
Defrancq overcame these challenges by grafting patterns of aminooxy groups masked with photocleavable protecting groups to the inside surface of the capillaries. By shining light on the tubes, he removed the protecting groups.
Capillary tubes offer cut price alternative to on-chip diagnostics
Cheaper than chips
Chemical Science
Austrian scientists unravel the secrets behind the dramatic colours of autumn.
Bernhard Kräutler and colleagues at the University of Innsbruck, have shown for the first time that a yellow breakdown product of chlorophyll contributes to the colours of autumn.
The change in autumn leaf colour is a phenomenon that affects the normally green leaves of many deciduous trees and shrubs. Every year, for a few weeks in autumn, a range of colours including intense yellows and reds shape the landscape. So far, these colours have been attributed to carotenoids and flavonoids, explains Simone Moser, a member of the research team. The colours are already present in the leaf, but are not visible due to the predominant green of chlorophyll. As autumn progresses chlorophyll disappears unmasking these hidden colours. But this is not the whole story, according to these researchers.
Why leaves turn red and orange during the autumn is not yet fully understood
Hints behind autumnal tints
Reference S Moser et al, Photochem. Photobiol. Sci., 2008, 7, 1577 (DOI: 10.1039/b813558d)
Biomolecules can be patterned to the inside of glass capillary tubes
Reference N Dendane et al, Lab Chip, 2008, 18, 2161 (DOI: 10.1039/b811786a)
Research highlights
C2 Chem. Sci. , 2009, 6, C1–C8 ©The Royal Society of Chemistry 2009
The exposed aminooxy groups then reacted with aldehyde groups in the peptide and carbohydrate biomolecules, fixing them to the side of the tubes. ‘This method of attaching molecules in patterns allows us to position not just one biomolecule but many,’ explains
The breakdown of chlorophyll is a process that was considered an enigma until about 20 years ago, when the first non-green chlorophyll breakdown product was discovered, says Moser. As these breakdown products were
colourless, they were thought not to contribute to the colours we see in autumn.
These compounds were considered to be the final products of chlorophyll breakdown, but now Kräutler has shown that they may be oxidised to give a yellow-coloured compound. Using leaves from the Katsura Tree, a deciduous tree known for its beautiful autumn leaves, they successfully detected this yellow chlorophyll breakdown product, thus proving its existence.
The similarity in structure between bilirubin, a natural compound reported to help protect cells from damage, and this oxidised breakdown product may suggest they too have important physiological properties. Moser says the team are interested in finding out just what roles, if any, these compounds play in the plant.Sarah Corcoran
Chlorophyll breakdown products may contribute to the colours of autumn
Defrancq.Once in place, the biomolecules
can bind cell proteins or antibodies present in biological fluids that are flushed through the tube. These protein and antibody biomarkers can be used to identify disease risk or progression or measure the effect of treatments. Different biomolecules can be attached in the one tube, which permits multi-analyses to be performed in one experiment.
‘The challenge now is to use these techniques to attach more complex carbohydrates and proteins without losing the recognition properties of the immobilised biomolecule for its target,’ says Defrancq. ‘It is only too easy to lose recognition during the immobilisation process through either the chemistry or the methods used.’ Janet Crombie
CS.01.09.C2.indd 20 15/12/2008 15:04:15
An European Union ban has reduced levels of the marine pollutant tributyltin
The tale of the snail
Reference E Sella and D Shabat, Chem. Commun., 2008, 5701 (DOI: 10.1039/b814855d)
Reference M Rato et al, J. Environ. Monit., 2009, DOI:10.1039/b810188d
Chemical Science
years, albeit at a slow rate,’ says Simon Apte, the leader of the centre of environmental contaminants research at the CSIRO in Sydney, Australia.
Although TBT levels are decreasing, they are still high, Rato comments. ‘Further monitoring surveys should be carried out in order to determine whether these EU measures are sufficient to reduce environmental TBT to a safe level,’ he adds.Rebecca Brodie
©The Royal Society of Chemistry 2009 Chem. Sci., 2009, 6, C1–C8 C3
Gender-switching in mud snails has decreased following a European Union ban on tributyltin (TBT) in ship hull paint.
TBT is an antifouling agent that was used in paint to prevent organisms from growing on the hulls of ships. Unfortunately, it was found that once it enters the water it has a toxic effect on other marine organisms. By 2003, the use of these paints was banned by the EU.
In the mud snails Nassarius reticulatus TBT was found to cause the imposex condition, where females develop male sexual characteristics such as a penis. Milene Rato from the University
of Aveiro, Portugal, and colleagues measured the penis lengths in the female snails to determine TBT pollution levels. ‘The main motivation to conduct this work was to find if the legislation implemented by the EU was effective,’ says Rato.
They found a decrease in the levels of imposex, and therefore a decrease in the levels of TBT, with hotspots being found within harbours that contain marinas and commercial fishing ports. From these results the group concluded that the regulation has had a favourable impact on pollution levels.
‘The data show that some recovery has occurred over the last five
Tributyltin causes imposex in female snails
a reporter group which fluoresces at 510 nanometres when released from the polymer structure. The trigger for the dendrimer breakdown is hydrogen peroxide, one of the natural decomposition products of the explosive.
Most colour-producing tests for TATP require the explosive to be pretreated with acid, say the scientists, so that it decomposes to produce large amounts of hydrogen peroxide. But this new method is sensitive enough to detect the tiny amounts of hydrogen peroxide generated by the small degree of natural decomposition of the
The dendrimer breaks down, and fluoresces, when exposed to hydrogen peroxide
Scientists are developing a new method to thwart terrorists
Glowing report for explosive detection
explosive and, because one molecule of hydrogen peroxide causes each dendrimer to release three fluorescent reporter molecules, a readable detection signal can be obtained for TATP present on the microgram scale.
Using more highly branched polymers each containing more fluorescently-tagged building blocks ‘will significantly increase the detection sensitivity’, says Shabat.
‘The main challenge’, he says, ‘will be to selectively identify TATP in the presence of other “powders” that contain oxidative species’.Freya Mearns
Israeli scientists have developed a sensitive method for detecting TATP – an explosive popular with terrorists.
Triacetone triperoxide, or TATP, is an explosive that has been used by suicide bombers in Israel since the 1980s. It was also employed by the thwarted British ‘shoe bomber’ Richard Reid in December 2001 and is alleged to have been used in the London bombings of July 2005.
The explosive’s ingredients are common chemicals and the material does not contain nitrogen so can pass through many scanners for nitrogenous explosives. Detection methods have been developed for TATP in the past, but now Eran Sella and Doron Shabat from Tel-Aviv University have designed a method that detects the explosive without any sample pretreatment, and also simply amplifies the resulting fluorescent signal. The scientists say that samples could be collected in the real-world using a swab or by vacuum.
Their method uses a type of dendrimer (a repeatedly branched tree-like polymer) that spontaneously breaks down into its separate building blocks following a single trigger event. The dendrimer was designed to consist of three building blocks that each contains
CS.01.09.C3.indd 30 15/12/2008 15:07:51
Japanese scientists have found a new way to store gases based on restraining gas molecules within narrow tunnels.
Gas storage in microporous materials generally relies on physisorption – involving weak Van der Waals interactions – to fill the micropores with gas, explains Toshimasa Katagiri, from Okayama University, who led the research team. Their new storage method involves physically restraining the gas within narrow tunnels (less than one nanometre diameter) running through nanoporous trifluorolactate crystals.
Katagiri and the team suggest that their new tunnel system may be useful for storing gaseous molecules with weak physisorption, such as hydrogen, and could have fuel cell applications.
The internal tunnel surface is serrated, thanks to the trifluoromethyl groups protruding into the tunnel cavity. These protrusions physically restrain the
Trifluorolactate crystals may offer an alternative route to hydrogen fuel cells
Crinkly tunnels aid gas storage
Chemical Science
European chemists have found that using fluorinated solvents in olefin metathesis reactions substantially improves the product yields obtained.
The metathesis reactions of alkenes (olefins) form a vital part of the armoury of transformations available to synthetic organic chemists. They provide a way of breaking and remaking carbon-carbon double bonds – allowing the substituent groups to be swapped – and are usually catalysed by transition metal complexes.
Commercially available catalysts, such as Grubbs’, remain popular among chemists but are often ineffective in more difficult reactions like the multi-step total synthesis of natural products and biologically active molecules.
Karol Grela, from the Polish Academy of Science, Warsaw,
A change of solvent found to dramatically improve important organic reactions
Fluorination gets a good reaction
Reference C Samojłowicz et al, Chem. Commun., 2008, 6282 (DOI: 10.1039/b816567j)
Reference T Katagiri et al, CrystEngComm, 2009, DOI: 10.1039/b814508c
C4 Chem. Sci. , 2009, 6, C1–C8 ©The Royal Society of Chemistry 2009
gas molecules within the tunnel. ‘The unique adsorption–desorption properties of these materials are very inspiring as they show the great potential of engineered hybrid systems where hydrocarbon and fluorocarbon domains alternate,’ comments Giuseppe Resnati, an expert in nanostructured materials at the Polytechnic of Milan, Italy.
The tunnel properties can be optimised to improve storage of a specific gas. Tunnel diameter, for
Poland, and colleagues have found that the yields of reactions using these catalysts can be dramatically improved by using fluorinated aromatic hydrocarbon solvents.
In particular, he reports that it is ‘possible to increase the metathesis reaction yield by up to 18 times by changing the solvent from 1,2-dichloroethane to perfluorotoluene.’
Jie Wu, professor of chemistry at Fudan University, Shanghai, China, adds: ‘This is an excellent improvement in metathesis reactions, which will find applications in the synthesis of advanced natural and biologically active compounds.’
Grela says that uncovering the nature of this effect and improving the recycling efficiency of the valuable catalysts – to satisfy the guidelines of green chemistry – are the next steps in his work.David ParkerFluorinated solvents
improve yields by up to 18 times
example, can be altered by changing the length of the organic chain in the trifluorolactates.
‘We are now trying to grow a perfect single crystal with tunnels. They could act as true molecular sieves for separating gaseous molecules by their size, at room temperature. Such a system would be a key technology for the realisation of a hydrogen fuel cell vehicle with a methanol reforming system,’ says Katagiri. Russell Johnson
Trifluorolactate crystals can be adapted to store different gases
CS.01.09.C4.indd 20 15/12/2008 15:15:33
Instant insightPorphyrins get energeticJonathan Faiz, Valérie Heitz and Jean-Pierre Sauvage, University of Strasbourg, France, outline recent advances in the construction of interlocked molecules inspired by photosynthesis
©The Royal Society of Chemistry 2009
Artificially recreating photosynthesis – in the quest to find environmentally friendly and renewable energy sources – is a hot topic across many scientific disciplines. It is now known that porphyrin-like units are key features of the reaction centre where photosynthesis occurs, and synthetically reproducing these molecules has become a very active research area.
Porphyrins are planar and highly conjugated cyclic molecules that can complex a variety of metals. They are found in many natural systems, including blood (as hemoglobin in their iron-complexed forms) and in the photosynthetic reaction centre (as magnesium-complexed chlorins, chlorophylls – which are structurally very similar to porphyrins).
The electrochemical and photoactive properties of porphyrins make them ideal for performing energy and electron transfer in a similar fashion to photosynthesis. Importantly their ability to form noncovalent interactions, with a metal centre, can be exploited to form mechanically interlocked systems – such as catenanes and rotaxanes – that incorporate porphyrins in their structure.
One of the most remarkable features of catenanes (two or several interlocked rings) and rotaxanes (two-component assemblies consisting of a central thread encapsulated by a ring and stoppered by two bulky units on each end of the thread to stop the ring slipping off ) is their high flexibility, meaning they can undergo a very large number of different motions. These movements are important in photosynthesis as they facilitate electron transfer. The motions occur both naturally due to the molecules inherent energy (when all the components are not or only very weakly interacting), and when the molecule’s most stable geometry is altered by an external stimulus.
Although seemingly simple when
sketched on paper, the construction of catenanes or rotaxanes is not trivial. This is because attractive forces are needed to hold the components together, to template the reaction, before either the rings are closed (in the case of catenanes) or the stoppers are attached (rotaxanes).
One construction method is the use of transition-metal templates, where the various components of the macrocycle contain 1,10-phenanthroline units that can coordinate to copper(i) ions – holding the components in place. The rotaxanes and catenanes then form around the metal ion, that is removed once the macrocycle is constructed. This method has been used to make a comprehensive range of rotaxanes, with porphyrin stoppers, and catenanes, containing porphyrins rings.
Other templating methods for rotaxanes include the use of hydrogen-bonding or π-stacking interactions to either form a macrocycle around a thread already bearing stoppers or to hold the macrocycle around the thread whilst the stoppers are grafted. The size and metal-binding properties of porphyrins make them ideal for stoppers for rotaxanes. This
route has given access to a wide variety of architectures in which electron transfer can occur between porphyrins and, for example, fullerenes and electron-deficient aromatic macrocycles.
Rotaxanes have also been made with a manganese porphyrin ring that has an olefin-containing backbone threaded through it. The ring can zip along the backbone and catalyse the oxidation of the olefins in the backbone to epoxides – demonstrating the sheer breadth of application of these porphyrin-containing systems.
Mechanically interlocked porphyrin-containing architectures are important synthetic analogues of natural systems as they contain subunits held at predetermined distances and geometries – but not through conventional covalent bonds. In this way, just like natural systems, any intercomponent process that occurs between subunits takes place through the shortest pathways, such as through hydrogen bonds or solvent.
Read Jean-Pierre Sauvage’s tutorial review ‘Design and Synthesis of Porphyrin-Containing Catenanes and Rotaxanes’ in issue 2, 2009 of Chemical Society Reviews
Chem. Sci., 2009, 6, C1–C8 C5
A transition metal ion can hold together the components needed to make a catenane
ReferenceJ Faiz et al., Chem. Soc. Rev., 2009, DOI: 10.1039/b710908n
Chemical Science
Instant Insight_SAUVAGE.indd 40 15/12/2008 15:16:54
What do you think have been the key achievements of the Intergovernmental Panel on Climate Change (IPCC) during your time as chairman?I think the IPCC as a whole has been an extremely significant success story. What I think we have done rather well with the Fourth Assessment Report [an IPCC report on climate change] is to have closed a number of gaps in knowledge. We’ve produced some very clear statements, largely because the scientific basis is now much more robust. This includes a firm statement saying that warming of the climate system is unequivocal and that there’s a high probability that during the last five decades or so, the warming that has taken place is a result of human actions. An extremely significant step that we have been able to take is with respect to disseminating the results of this particular report.
What key areas will the IPCC focus on in the future? We’re actually in the midst of a detailed dialogue within the IPCC in defining what our role and focus should be in the future. The IPCC has decided to continue with the five or six year cycles of comprehensive assessment reports and the fifth assessment report will come out by 2014. This will require some new efforts in terms of developing scenarios of what’s going to happen in the future and running climate models to come up with some of the answers that will form the basis of the next report. In addition, we will carry out work on special reports, which would be in response to a need for focussed and very specific information on subjects of relevance. We’re already working on the production of a special report on renewable energy. So I think essentially we are going to build on what we have achieved so far and try to address demands as they come from our audience from all over the world and ensure that the IPCC plays the role that the world expects it to.
You are also Director General for the Energy and Resources Institute. What research are they currently involved in?This is an institute that I have been with for over a quarter of a century. When I started, all I had was a part time secretary and one room. We are now a fairly large institution with over 750 people and a presence in different parts of the world including the UK, the US, Japan and more recently Africa, the Middle East and Malaysia. We have emerged not merely as an institution that focuses on India or
other developing countries in the region but globally. Apart from the work on energy, climate change and environmental issues, we are also involved in substantial scientific activities, for instance biotechnology research. We do a substantial amount of work at the grass roots level, too – the one thing that I’m now focusing on, and which I think will be my mission for the next 10 years, is what I call ‘lighting a billion lives’. What’s extremely tragic is the fact that 1.6 billion people in the world still don’t have access to electricity or modern forms of energy – that’s a quarter of humanity. If you wait for all these places to be connected to the grid and to get electricity, it will take a long, long time. We have developed a set of solar lanterns and torches, which are really attractive to people in villages in several parts of the world. If we can mobilise the resources for making these available, it can create market based solutions in these villages.
What are your thoughts on the new RSC journal Energy & Environmental Science?I think that any such medium by which knowledge can be created and provided to people is an excellent initiative. I think the focus that you [the journal] have, which embraces all aspects of chemistry, chemical engineering and so on, will be of great value as it will be a major contribution to the creation of knowledge and the production of an area of literature where we still need an enormous amount of expansion and improvement.
You have recently been awarded an honorary doctorate from the University of East Anglia. What advice would you give to young scientists graduating today?Well, I would only say that this is a period of great excitement. We really have to start thinking outside the box. When we have this privilege of getting higher education, we should ensure that we do so because I really believe the world needs to change on a massive scale. That has to be carried out by the people who have the benefit of higher education and the exuberance of youth. So I would tell students that are in the university system right now to just look at the horizons beyond and also look at the world in its entirety. As I said in the acceptance speech for the Nobel Peace Prize, we have a Hindu saying, which is Vasudhaiva kutumbakam, which means ‘the universe is a family’. We have to keep that in focus whatever we learn and whatever we do.
Lighting a billion lives Rajendra K Pachauri speaks to Leanne Marle about shedding light on climate change and giving light to humanity
Interview
Rajendra K Pachauri is the current chairman of the Intergovernmental Panel on Climate Change and the director general of the Energy and Resources Institute in New Delhi, India.
Rajendra K Pachauri
©The Royal Society of Chemistry 2009
Chemical Science
Chem. Sci., 2009, 6, C1–C8 C7
CT.interview pachauri.indd 15 15/12/2008 15:18:17
An InChI Resolver, a unique free service for scientists to share chemical structures and data, is to be developed via a collaboration between ChemZoo Inc., host of ChemSpider, and RSC Publishing.
Using the InChI – an IUPAC standard identifier for compounds – scientists can share, contribute and search molecular data from many web sources.
©The Royal Society of Chemistry 2009C8 Chem. Sci., 2009, 6, C1–C8
Essential elements
Double debut
InChI collaboration with ChemSpider
Chemical Science
And finally...Materials science researchers joined RSC Publishing last month at a celebration reception at the Fall MRS 2008 meeting. Authors and readers were thanked for their continued support, while RSC journal Soft Matter announced its increase in frequency for 2009 and five years of successful publication.
Delegates were invited to pre-order the latest edition of the bestselling textbook, Nanochemistry by Geoff Ozin, and take part in a prize draw to win a solar powered charger in celebration of the 2008 launch of Energy & Environmental Science.
Looking ahead, preparations are underway for the Third International ChemComm Symposium, which is to be held in China next month. The subject will be organic chemistry and keynote speakers include Professors Peter Kundig, Keiji Maruoka and Susan Gibson.
To find out more visit: www.rsc.org/chemcommsymposia
mice, cytotoxicity of chemical warfare degradation products, and identification and characterisation of metallodrug binding proteins. Visit www.rsc.org/metallomics
Authors from around the globe have submitted work of the highest quality, knowing that they can rely on RSC staff for overseeing a rigorous
peer-review process, efficient manuscript handling and rapid publication.
The current issues of both new journals are freely available to all readers via the website. Free institutional online access to all 2009/2010 content will be available following a simple registration process.
This month sees the debut of two highly interdisciplinary new journals from RSC Publishing: Integrative Biology: Quantitative biosciences from nano to macro and Metallomics: Integrated biometal science.
Integrative Biology is a unique journal focused on quantitative multiscale biology using enabling technologies and tools to exploit the convergence of biology with physics, chemistry, engineering, imaging and informatics. The first issue contains articles on human mammary progenitor cell fate decisions, the analysis of aptamer binding sequence–activity relationships using microarrays, and genome-wide transcriptome analysis of 150 cell
samples and much more. Visit www.rsc.org/ibiology
Metallomics covers the research fields related to metals in biological, environmental and clinical systems and is expected to be the core publication for the emerging metallomics community. First issue articles include a look at the effect of vanadium(IV) in diabetic
The InChI Resolver will give researchers the tools to create standard InChI data for their own compounds, create and use search engine-friendly InChIKeys to search for compounds, and deposit their data for others to use in the future.
‘The wider adoption and unambiguous use of the InChI standard will be an important development for the future of chemistry publishing, and further development of the semantic web,’ comments Robert Parker, managing director of RSC Publishing.
The InChI Resolver will be based on ChemSpider’s existing database of over 21 million chemical compounds and will provide the first stable environment to promote the use and sharing of compound data. ‘With the introduction of the InChI Resolver, we hope to expand the utility and value of both InChI and the ChemSpider service,’ adds Antony Williams of Chemspider.
This collaboration sees RSC Publishing remain at the forefront of chemical information technology.
Chemical Science (ISSN: 1478-6524) is published monthly by the Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge UK CB4 0WF. It is distributed free with Chemical Communications, Dalton Transactions, Organic & Biomolecular Chemistry, Journal of Materials Chemistry, Physical Chemistry Chemical Physics, Chemical Society Reviews, New Journal of Chemistry, and Journal of Environmental Monitoring. Chemical Science can also be purchased separately. 2009 annual subscription rate: £199; US $396. All orders accompanied by payment should be sent to Sales and Customer Services, RSC (address above). Tel +44 (0) 1223 432360, Fax +44 (0) 1223 426017. Email: [email protected]
Editor: Nina Notman
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Interviews editor: Elinor Richards
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Changes ahead for NJC in 2009DOI: 10.1039/b820900f
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18 | New J. Chem., 2009, 33, 17–18 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Evidence of crystalline/glassy intermediates in bismuth phosphates
Marie Colmont,* Laurent Delevoye and Olivier Mentre
Received (in Montpellier, France) 3rd September 2008, Accepted 27th October 2008
First published as an Advance Article on the web 14th November 2008
DOI: 10.1039/b815388b
31P and 17O NMR investigations have been achieved on bismuth
oxide phosphates by a comparison between ordered and semi-
ordered reference compounds; the wide chemical shift range for17O is revealed to be a profitable source of information about
partially ordered materials.
Bi2O3–MO–P2O5, (M = Co, Cu, Cd, Zn, Mn. . .) ternary
systems have been well investigated, leading to the charac-
terization of new bismuth oxide phosphates having particular
structural relationships.1–8 As intensively detailed,9 the
rigid frameworks of these materials can be considered as an
assembly by the edge sharing of O(Bi,M)4 polyhedra, leading
to infinite polycationic ribbons of variable width: one, two,
three, . . . tetrahedra wide, surrounded by isolated PO4 groups.
From XRD/ND crystal structure studies, we classified these
compounds as ‘‘disordered’’ or ‘‘ordered’’, depending on the
competition (or not) between several O4 configurations around
the central P sites. Indeed, in ordered compounds such as
BiM2PO6,3,4,10,11 the Bi3+ cations strictly sit in the middle of
ribbons, whereas the M2+ cations are located at their edges.
Similarly, in disordered compounds, e.g. Bi1.2M1.2PO5.5,7 Bi3+
cations still occupy the middle of the ribbons, whereas the
edges of the ribbons are filled by mixed site Bi3+/M2+. This
statistical distribution leads to a variable orientation of the
PO4 groups, depending on the local nature of its first (Bi, M)
cationic shell. The disorder is all the more important because it
also affects partially filled cationic channels (so-called tunnels
hereafter) surrounded by PO4 groups in between pairs of
ribbons. Of course, the notion of disorder is inexact because
of the existence at the microscopic scale of incommensurate
modulated phenomena (mainly along b*) in most of the
disordered compounds.12–14 This extra information does not
survive over long range scales, e.g., it is not observed in the
XRD of single crystals. Therefore, sometimes only ordered
fragments of the disordered PO4/tunnel interstitial areas can
be assumed from the average crystal structure, on the basis of
plausible interatomic distances.13 However, structural interac-
tions between the edges of the ribbons, PO4 groups and the
tunnel is far from being fully established, probably due to
various phenomena, including anti-phase boundary defects
within tunnels and the probable semi-ordered zones in these
materials. In view of a complementary approach to these
fascinating series and by an easy extension to different com-
pounds, 31P and 17O NMR spectroscopy have been used as
local probes. Indeed, recent technical advances in solid state
NMR has led to the emergence of this technique by adapting it
for use with low natural abundance nuclei having relatively
small gyromagnetic ratios, such as 17O. In addition, it is worth
mentioning that impedance spectroscopy measurements on all
of these materials (ordered and disordered) show low ionic
mobilities due to the strong P–O bonds involved for most of
the oxygen ions. Therefore, only the static aspect is considered
hereafter.
Thus, the present work focuses on a comparison between a
typical ordered and disordered compound, with the aim of
establishing the pertinence, complementarities, and limits of
both 31P and 17O nuclei as probes with regard to the structural
aspects of ordered vs. semi-ordered materials. With that aim in
mind, two compounds have been selected from among the
series:
(i) BiCd2PO6 was chosen as the archetype of ordered
compounds. Its structure is isostructural to BiZn2PO6,15,16
and it is interesting because it crystallizes in the Bbmm space
group, while many members of the BiM2PO6 class (including
the M = Zn term) adopt the less symmetrical Pnma space
group. The coordination around its unique phosphorus posi-
tion is constituted by two independent O2 (2�) and O3 (2�)atoms, while O1 is located in the two tetrahedra-wide ribbons
at the center of a OBi2Cd2 tetrahedron (Fig. 1(a)).
(ii) The simplest disordered compounds have the
BiB1.2MB1.2PO5.5 general formula (M = Mn, Co, Zn). Their
structure (space group Icma) is formed of triple ribbons with
Fig. 1 The structures of (a) BiCd2PO6 and (b) Bi1.2Zn1.2PO5.5. BiCd2PO6
consist of [Cd4Bi2O2]-ordered double ribbons surrounded by six
isolated ordered phosphates. Bi1.2Zn1.2PO5.5 is disordered because of
(1) the presence of mixed Bi3+/Zn2+ sites at the edges of triple
[(Bi0.15Zn0.85)4Bi4O6] ribbons, (2) disordered tunnels, partially occupied
by Zn2+, and (3) multiple PO4 configurations around the same
phosphorus.
UCCS, Unite de Catalyse et Chimie de Lille, UMR-CNRS 8181,Ecole Nationale Superieure de Chimie de Lille, Universite desSciences et Technologies de Lille, BP 90108, 59655 Villeneuve d’Ascq,France. E-mail: [email protected]
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 19–22 | 19
LETTER www.rsc.org/njc | New Journal of Chemistry
mixed Bi/M edges (for M = Zn: 15% Bi3+/85% Zn2+). The
partially M-filled tunnels and surrounding disordered PO4
groups are shown in Fig. 1(b). Only one phosphorus position
exists, even if it has finally been split into two close satellites,
P1 (B50%) and P2 (B50%), in the published model. To avoid
any paramagnetic perturbation, the M = Zn compound was
selected. It is noteworthy that the influence of Cd2+ for Zn2+
replacement in BiM2PO6 on the 31P NMR chemical shift has
already been fully quantified on the basis of the empirical z/a2
parameter,15 and no additional contribution is expected
between these two neighboring cations. The possibility of
quantifying the local cationic environment of the PO4 groups
in a Bi(M,M0)PO6 statistical solid solution compounds has
also been enhanced.31PMASNMR: Fig. 2(a) and (b) show the 31P NMR spectra
of BiCd2PO6 against Bi1.2Zn1.2PO5.5, which clearly reveals the
broadening of the signal for the latter due to the multitude of
individual resonances in the disordered compound. It is com-
parable to the IR spectra of ordered vs. disordered compounds
presented elsewhere.13 In that sense, the broad envelope does
not show discrete contributions but rather a continuum. Here,
in addition to the local distortion of each individual PO4
group, the influence of the nature of the neighboring Zn/Bi
cationic shell has to be considered.15 Furthermore, the 31P
double quantum MAS-NMR spectrum shows no particular
privileged out-of-diagonal correlations (Fig. 2(c)) reminiscent
of a glass-like state from the 31P NMR resolution.
Since oxygen occupies both the polycationic regular
sublattice and the disordered interstitial regions, 17O NMR
analysis would be expected to give relevant information about
disorder. Here, samples were enriched via the 17O enrichment
method developed by Flambard et al.17 Due to the presence of
water vapor, the sample was checked by 1H NMR to ensure
that all protons disappeared at the end of the enrichment.
Another difficulty in obtaining 17O NMR spectra is the
presence of the quadrupolar interactions of the nuclei (spin
I = 5/2) that largely broaden signals. This requires suitable
techniques, such as double rotation (DOR),18 multiple-
quantum magic angle spinning (MQ-MAS)19 or satellite
transition magic angle spinning (ST-MAS),20 in order to
remove the anisotropic broadenings that remain under magic
angle spinning conditions.17O MAS NMR: Fig. 3 shows the high resolution MQ-MAS
spectra of (a) BiCd2PO6 and (b) Bi1.2Zn1.2PO5.5. The horizontal
projections (top) correspond to MAS spectra still broadened by
the second order quadrupolar interaction. The vertical projec-
tions reveal 17O isotropic spectra of the two compounds, where
the quadrupolar broadening is removed, i.e., each maximum
peak corresponds to a given oxygen environment. The
resonance at 90 ppm, marked with an asterisk, corresponds
to a spinning sideband of site A on the isotropic dimension.
The two spectra show two groups of resonances, around
Fig. 2 31P MAS-NMR (9.4 T) spectra of (a) BiCd2PO6 and (b)
Bi1.2Zn1.2PO5.5. The spectra were acquired at an MAS speed of
10 kHz, with a short pulse excitation of 1.5 ms (201) and a recycling
delay of 20 s. (c) 31P double quantum MAS-NMR spectrum of
Bi1.2Zn1.2PO5.5. The spinning frequency was 10 kHz. The excitation
and reconversion period was composed of back-to-back 901 pulses21 of
4 ms, which gave a total excitation/reconversion time of 400 ms. Therepetition time was 30 s, preceded by a presaturation period. A total of
16 scans were used and 64 t1 increments were collected. The31P chemical shift was referenced externally to an 85%H3PO4 solution
at 0 ppm.
Fig. 317O MQ-MAS NMR (18.8 T) spectra of (a) BiCd2PO6 and (b)
Bi1.2Zn1.2PO5.5. The spectra were acquired at an MAS speed of
20 kHz, with a recycling delay of 1 s, using the SPAM sequence.24
The excitation and reconversion pulses were set to 3.75 ms and 1.20 ms,respectively, corresponding to an RF field strength of 80 kHz,
followed by a selective 901 pulse of 11 ms (RF field of 8 kHz). For
spectrum (a), each transient was accumulated with 72 scans, and 128 t1
data points were collected using the STATES method. For (b), a total
of 4500 scans were needed and 30 t1 increments were collected. The17O chemical shift was referenced externally to tap water.
20 | New J. Chem., 2009, 33, 19–22 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
180–250 ppm and around 50–130 ppm (see the MAS projec-
tions). The region around 200 ppm (resonance A) is assigned to
O(Bi,M)4 tetrahedral sites in the polycationic ribbons. The
value of the chemical shifts are close to those determined for
OBi4 tetrahedra in related compounds, 195 ppm in Bi2O322 and
265 ppm in a-Bi4V2O11.23 Our assignment was indirectly con-
firmed by a 17O T2 relaxation measurement (using a saturation
recovery pulse sequence) performed on the BiCd2PO6 com-
pound. The A site exhibited a short T2 relaxation time of about
200 ms, maybe due to the presence of Bi quadrupolar nuclei in
its first-neighbour cationic shell (111Cd and 113Cd are non-
quadrupolar). A similar measurement was not possible for the
disordered compound due to the low efficiency of the isotopic
enrichment (probably because the 17O-enriched water had
already been used in previous experiments).
Ordered compound: The second region around 100–160 ppm
is typically in the chemical shift range of oxygens involved in
PO4 groups.25 In BiCd2PO6, it is composed of two resonances,
B (120 ppm, T2 = 5 ms) and C (100 ppm, T2 = 500 ms),corresponding to O2 and O3. This assignment arises from their
proximity or otherwise to quadrupolar Bi nuclei in their
second cationic shell (Table 1). It was checked by a 31P–17O
heteronuclear multiple quantum correlation (HMQC)26
experiment that a correlation existed between the unique31P site and the 17O–B sites (Fig. 4). However, no correlation
signal was detected for the 17O–C sites due to the very short T2
relaxation time (500 ms). It is also noteworthy that both A and
C showed broad isotropic resonances compared to B. So far,
this is not understood in this ‘‘ordered’’ compound. Note the
presence of a broad signal of low intensity in the 17O dimen-
sion (Fig. 4), which is due to an impurity obtained after the
process of enrichment and was not detected by XRD.
Semi-ordered compound: Next, we analyzed a semi-ordered
compound, Bi1.2Zn1.2PO5.5. The17O MQ-MAS NMR spec-
trum is shown in Fig. 2(b). Two isolated regions are high-
lighted in the 2D spectrum. The broadness of the peaks seen in
the isotropic projection is a signature of the high disorder
present in this system, as discussed in the first part of this
work. The assignment of both regions was deduced by analogy
with the 17O spectrum obtained for BiCd2PO6. One region
corresponds to oxygen atoms linked to ribbons (resonance A)
between 160 and 240 ppm. Referring to the structure presented
in Fig. 1(b), two oxygen sites should be distinguishable in the
isotropic dimension, whether they are at the center (O1Bi4) or
at the edge (O2Bi2Zn2) of the ribbon. A close look at the two-
dimensional contours clearly suggests the presence of more
than two sites, probably due to the high sensitivity of the 17O
NMR chemical shift to the cationic environment, even at a
semi-local scale (second shell cationic neighbours). The
presence of additional oxygen sites is easily explained by
the existence of a mixed Bi/Zn cationic site at the edge of
the ribbon. The assignment of each individual resonance is not
yet possible due to the current absence of a large 17O NMR
chemical shift database for these systems. The development of
such a database would require a series of model compounds
to be isotopically enriched for further 17O MAS NMR
analysis. The second option available is to profit from the
recent development of first principles calculations of NMR
parameters using periodic boundary conditions.27 The latter
approach, which is beyond the scope of this Letter, is definitely
more realistic at present.
The chemical shift region centred on 50–150 ppm exhibits
two main resonances in the isotropic projection. These can be
assigned to the oxygen atoms in the PO4 groups. First, it
should be noted that the 17O resonances are spread over a
large chemical shift range, especially in the isotropic dimension
when the second order quadrupolar broadening is removed.
This large distribution of chemical shift values with respect to
the so-called ordered compound, BiCd2PO6, reveals the
important disorder associated with the PO4 groups in these
systems. Nevertheless, some discontinuities associated with
Table 1 The environment of the oxygen atoms (distances in A) inBiCd2PO6 and Bi1.2Zn1.2PO5.5. The first shell is given for the oxygen ofthe ribbons and the first two shells are presented for the oxygen of thePO4 groups.
15,16
BiCd2PO6 Bi1.2Zn1.2PO5.5a
1st shell 2nd shell 1st shell
O1–Bi1 2 � 2.27(2) O2–Bi1 2 � 2.243(1)Cd2 2 � 2.18(2) Bi/Zn2 2 � 2.159(9)
O2–P 1 � 1.43(3) O1–Bi1 4 � 2.299(1)Cd2 2 � 2.22(2) 2 � 3.41(3)Bi1 1 � 3.70(3)
O3–P 1 � 1.51(4)Cd2 1 � 2.11(4) 2 � 3.29(2)Bi1 2 � 3.41(2)Bi1 1 � 3.65(4)
a The coordination of the disordered PO4 groups is not accurately
known.
Fig. 4 The 31P–17O HMQC (18.8 T) spectrum of BiCd2PO6 was
obtained at a MAS speed of 25 kHz by following the pulse sequence
detailed by Massiot et al.26 An echo was applied to the observed 17O
nuclei with respective 901 and 1801 pulses of 10 and 20 ms. Two 901
pulses of 4.5 ms were then applied on either sides of the 17O 1801 pulse.
The evolution delay was set to 3 ms for an evolution under J-coupling.
A total of 512 scans were accumulated with a recycling delay of 1 s.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 19–22 | 21
discrete chemical shift values appear in the isotropic dimen-
sion. This strongly suggests that some PO4 positions are
privileged, as observed from the single crystal X-ray diffrac-
tion data. For example, two major competing PO4 positions
have been located in Bi1.2M1.2PO5.5, while residual electronic
density on Fourier difference maps is reminiscent of a number
of extra orientations. Again, the current 17O NMR chemical
shift database is not sufficient to fully interpret the spectrum in
the P–17O–M region.
This study highlights the informative data provided by 17O
NMR due to its broad range of chemical shifts compared to
the 31P nucleus. In disordered bismuth phosphates, 17O NMR
clearly provides evidence of preferential PO4 orientations, in
good agreement with the semi-ordering deduced from diffrac-
tion data, which shows modulated microdomains with loss of
the order at long range scales. Of course, the methodology and
conclusions developed here are not restricted to our particular
chemical system, but can be generalized to other partially-
ordered systems, solid solutions, composite structures and
so on. Finally, it is worth stating that, to the best of our
knowledge, a successful 31P–17O through-bond correlation has
been presented here for the first time.
Experimental section
The different oxides reported in this Letter were prepared from
stoichiometric mixtures of Bi2O3, MO (M = Cd, Zn) and
(NH4)2HPO4. To avoid the problem of volatile species, they
were removed by solid state reparative methods, implying
several heating–regrinding steps at temperatures from 200 to
700 1C. The purity of the samples was checked by powder
X-ray diffraction using a Siemens D-5000 diffractometer with
back-monochromatized Cu-Ka radiation. NMR experimental
information is given in the Figure captions. 17O enrichment
was achieved by heating samples at 650 1C for 8 h under17O-enriched water vapor.15
Acknowledgements
The FEDER Region Nord Pas-de-Calais, Ministere de
l’Education Nationale, de l’Enseignement Superieur et de la
Recherche, CNRS, USTL and ENSC-Lille are acknowledged
for funding the NMR spectrometers. M. C. thanks the Region
Nord Pas-de-Calais for financial support.
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22 | New J. Chem., 2009, 33, 19–22 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
A supramolecular sensing system for AgIat nanomolar levels by the
formation of a luminescent AgI–Tb
III–thiacalix[4]arene ternary complexw
Nobuhiko Iki,* Munehiro Ohta, Teppei Tanaka, Takayuki Horiuchi
and Hitoshi Hoshino
Received (in Durham, UK) 22nd September 2008, Accepted 10th November 2008
First published as an Advance Article on the web 1st December 2008
DOI: 10.1039/b816596c
The first example of the detection of AgI ions using supra-
molecular chemistry is demonstrated, in which two thiacalix[4]-
arene ligands are linked by analyte AgI ions and then coordinate
to TbIII
ions to form a luminescent ternary complex, AgI2�TbIII2�
TCAS2, enabling the detection of AgIat concentrations as low
as 3.2�10�9 M.
One of the most significant contributions of supramolecular
chemistry has been the development of a precise strategy to
design fluorescent chemosensors with high selectivities and
sensitivities for heavy metal ions.1 This strategy involves the
covalent joining of a specific binding unit of a metal ion and a
signal-transducing unit (Fig. 1).2 The former is a ligating
group that is carefully selected after considering factors that
will affect its selectivity, such as the affinity of donor atoms to
analyte cations and the stereochemistry of the resulting com-
plex. The latter is a fluorophore, whose photophysical proper-
ties are susceptible to changes such as excimer formation/
dissociation, photoinduced electron transfer, charge transfer
and energy transfer caused by metal binding. The validity of
this strategy, termed the covalent strategy, has been demon-
strated by many of the fluorescent sensors that have been
synthesized.2 For instance, a ratiometric sensor, where pyrene
is attached as a signaling unit to a ligand having N,O donors,
has been designed to enable the detection of AgI ions at
micromolar levels in a 50 : 50 v/v EtOH–water mixture.3
The strategy seems to have been derived on the premise that
two different processes occurs in analyte sensing—recognition
and signaling. Although this strategy is useful, it does not
provide much scope for alternative methods of designing
sensors or sensing systems. In this Letter, we present a system
for sensing AgI ions by the formation of a luminescent
complex using supramolecular chemistry,4 where the analytes
and components are synergistically assembled to function as a
sensor.
Since the development of a facile one-step method to
synthesize thiacalix[4]arene, we have been interested in
its inherent complexing properties and applications.5 For
example, thiacalix[4]arene-p-tetrasulfonate (TCAS, Fig. 2)
reacts with a TbIII ion to form a 1 : 1 complex, TbIII�TCAS (1),
in an aqueous solution at pH 4 8.5 by the ligation of a
bridging sulfur and two adjacent phenol oxygen donors.
Complex 1 exhibits strong luminescence due to the presence
of the TbIII ion, whose excitation energy is transferred from
TCAS in a triplet excited state.6 The luminescence of 1 allows
the detection of the TbIII ion at nanomolar levels.7 Further-
more, TCAS, TbIII and AgI ions form a luminescent ternary
complex, AgI2�TbIII2�TCAS2 (2), at a pH of around 6.8 In this
pH region, only a small fraction of the TbIII ions are com-
plexed by TCAS.6,8 This suggests that AgI can be detected by
measuring the luminescence of complex 2, which is formed in
the presence of TbIII ions and TCAS at a pH of 6 (see the
graphical abstract).
Accordingly, when [TbIII]T = 1.0 � 10�6 and [TCAS]T =
2.0 � 10�6 M at a pH of 6.1 (T = total), the dependence of the
luminescence intensity at 544 nm, assigned as the 5D4 -7F5
transition of TbIII, on the AgI concentration was investigated
(Fig. 3). For a wide range of AgI concentrations, the intensity
increased almost linearly as [AgI]T increased from nanomolar
to sub-micromolar levels. This demonstrates that AgI can be
detected by the formation of ternary complex 2. For higher
[AgI]T levels (42.0 � 10�7 M), the dependence showed a slight
upward convex curve. This can be attributed to the fact that
[AgI]T attains a concentration level equivalent to that of TbIII
and the availability of TbIII ions to form complex 2 is low.
When [AgI]T r 2.0 � 10�8 M, a linear calibration curve was
obtained by least-square fitting, as shown in eqn (1).
Luminescence intensity= 76.5� 108� ([AgI]T/M)+ 437 (1)
Surprisingly, the detection limit (DL) at S/N = 3 was
determined to be 3.2 � 10�9 M (0.35 ppb). This shows that
Fig. 1 Covalent strategy for designing metal sensors.
Graduate School of Environmental Studies, Tohoku University,6-6-07 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan.E-mail: [email protected]; Fax: +81 22-795-7293;Tel: +81 22-795-7222w Electronic supplementary information (ESI) available: Experimentaldetails for sample preparation and ESI-MS of complex 3.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 23–25 | 23
LETTER www.rsc.org/njc | New Journal of Chemistry
the system is more sensitive than covalently designed fluor-
escent sensors, which afford the detection of AgI at the 10�6 M
level.3,9 Notably, the DL of AgI with 2 is lower than that of
flame atomic absorption spectrometry (DL 3 ppb) and as
low as that of inductively-coupled plasma atomic emission
spectroscopy (DL 0.2 ppb).10
The selectivity of this system with regard to AgI ions was
investigated by adding five times the amount of transition
metal cations (M = MnII, FeIII, CoII, NiII, CuII, ZnII, CdII
and PbII) and halide anions (X� = Cl�, Br� and I�) to a
1.0 � 10�7 M AgI ion solution. The luminescence intensity
(at 544 nm), I, was measured and compared to the intensity
measured in the absence of M or X�, I0. As shown in Fig. 4,
the five-fold increase in MnII and ZnII concentration did not
affect the signal intensity of complex 2; however, PbII, CoII
and NiII caused a slight change in its intensity. Notably, CuII
and FeIII ions caused negative interference (�67% and �57%,
respectively). In the TCAS–metal binary systems, CuII and
FeIII ions formed complexes with M : TCAS ratios of 2 : 1 and
1 : 1, respectively, at a pH of 6. If these complexes had been
formed in the present system, 1.75 � 10�7 and 1.5 � 10�7 M of
TCAS would have been available to AgI (1.0 � 10�7 M) to
form complex 2. Therefore, it is likely that CuII and FeIII ions
formed ternary complexes with TCAS and TbIII ions, thereby
reducing the availability of TbIII ions; this results in the for-
mation of an insufficient amount of 2. In addition, such an
M–TbIII–TCAS ternary complex would be non-luminescent
because paramagnetic CuII and FeIII ions readily quench the
excited states of the TCAS ligand. In contrast, CdII caused a
positive deviation (+116%) in the signal. Thus, it follows that
CdII should have formed a luminescent CdII–TbIII–TCAS
ternary complex that is luminescent, since CdII is a non-
quenching ion due to its d10 electronic configuration. In fact,
the CdII–TbIII–TCAS ternary system ([CdII]T = [TbIII]T =
1.0 � 10�6 M, [TCAS] = 2.0 � 10�6 M; pH = 6.5)
yielded a luminescent complex, whose composition was
CdII2�TbIII2�TCAS2 (3), as suggested by electrospray ionization-
mass spectroscopy (ESI-MS) measurements, yielding a peak at
m/z = 1101.5983 that is assignable to [2Cd2+ + 2Tb3+ +
Na+ + 3H+ + 2TCAS8� + H2O]2� (Fig. 5; also see ESIw).In the present system, complex 3, which was formed con-
comitantly, caused an increase in the luminescence. Among
the halide ions, iodide caused a negative (�43%) deviation from
the original intensity, I0, which can be attributed to its strong
ability to form the halo complexes [AgXn](n � 1)� (n = 1–4), as
indicated by their stability constants.11
In metal–ion sensors designed using a covalent strategy, the
roles of each functional group are different (Fig. 1). On the
other hand, in the present AgI sensing system, it is ambiguous
which moiety of 2 is responsible for the functions of binding
and signaling. As shown in the schematic drawing of 2 (Fig. 2),
TCAS has four O and four S donors that form the tetrametal
core, AgI2TbIII
2. Furthermore, there is an antenna present to
absorb photons, the energy from which is eventually trans-
ferred to the TbIII center. Upon excitation, the TbIII center
emits light via an f–f transition. From a structural point of
view, TbIII ions accept two sets of O,S,O donations from the
TCAS ligands. However, it is important to consider that in the
TbIII–TCAS binary system, TbIII does not form a complex
with TCAS at a pH of 6. Thus, analyte AgI is indispensable in
Fig. 2 The structure of TCAS, and complexes 1 and 2.
Fig. 3 Calibration graphs for AgI ions. The inset shows the calibra-
tion curve for the lowest AgI concentrations. Samples: [AgI]T =
0–100 � 10�8 M, [TbIII]T = 1.0 � 10�6 M, [TCAS]T = 2.0 � 10�6 M
and [MES buffer]T = 2 � 10�3 M (pH = 6.11). lex = 323 and
lem = 544 nm.
Fig. 4 The effect of a five-fold increase in concentration of ‘‘foreign
ions’’ added to AgI on the luminescence signal. I and I0 indicate the
luminescence intensity for samples with and without foreign ions,
respectively. Samples: [foreign ion]T = 0 or 5.0 � 10�7 M, [AgI]T =
1.0 � 10�7 M, [TbIII]T = 1.0 � 10�6 M, [TCAS]T = 2.0 � 10�6 M
and [MES buffer]T = 4 � 10�3 M (pH = 5.9). lex = 323 and
lem = 544 nm.
24 | New J. Chem., 2009, 33, 23–25 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
linking two TCAS ligands via S–AgI–S bridges to promote the
coordination of TCAS to TbIII, to form 2. In fact, TCAS
formed a 4 : 2 complex, AgI4�TCAS2, in the binary system at
pH 6.8 In conclusion, multidentate and photon-absorbing
TCAS, luminescent TbIII and analyte AgI, with a linear
coordination geometry, were synergistically assembled to form
a supramolecular structure that is capable of sensing AgI ions
at nanomolar concentrations (see graphical abstract). Since
the sensing function of this system originates from the supra-
molecular nature of complex 2, and not from TCAS and
TbIII individually, complex 2 truly demonstrates the ‘‘supra-
molecular strategy.’’ Here, it is very important to rationally
design molecules so that they form supramolecular assemblies
that display functionalities absent from their individual
components.
Experimental
Procedure for the detection of AgI ions
To a sample solution containing silver(I) nitrate and a
particular foreign ion, if any, appropriate amounts of
aqueous solutions of terbium(III) nitrate, TCAS, pH buffer
(2-morphorinoethanesulfonic acid (MES)) and doubly-
distilled water were added. Before the measurement of its
luminescence spectrum, each sample solution was allowed to
stand for 1 h at room temperature to ensure equilibration. The
luminescence spectra were measured using a Hitachi F-4500
fluorescent spectrometer.
Mass spectrometry
ESI-MS experiments were performed using a Fourier trans-
form ion cyclotron resonance mass spectrometer APEX III
(Bruker). Mass spectra were simulated using the program
iMass for Mac OS X version 1.1.12
Acknowledgements
This study was partly supported by a Grant-in-Aid for
Scientific Research (B) (16350039) from the Japan Society
for the Promotion of Science (JSPS).
References
1 J. M. Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995.2 For reviews, see: A. P. de Silva, H. Q. Nimal Gunaratne,T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T.Rademacher and T. E. Rice, Chem. Rev., 1997, 97, 1515;B. Valeur and I. Leray, Coord. Chem. Rev., 2000, 205, 3;L. Prodi, F. Bolletta, M. Montalti and N. Zaccheroni, Coord.Chem. Rev., 2000, 205, 59.
3 R. H. Yang, W. H. Chan, A. W. M. Lee, P. F. Xia, H. K. Zhangand K. Li, J. Am. Chem. Soc., 2003, 125, 2884.
4 Examples of supramolecular sensing systems can be found in thefollowing reviews: E. V. Anslyn, J. Org. Chem., 2007, 72, 687;T. Hayashita, A. Yamauchi, A. J. Tong, J. C. Lee, B. D. Smith andN. Teramae, J. Inclusion Phenom. Macrocyclic Chem., 2004, 50, 87.
5 N. Morohashi, F. Narumi, N. Iki, T. Hattori and S. Miyano,Chem. Rev., 2006, 106, 5291.
6 N. Iki, T. Horiuchi, H. Oka, K. Koyama, N. Morohashi,C. Kabuto and S. Miyano, J. Chem. Soc., Perkin Trans. 2, 2001,2219.
7 T. Horiuchi, N. Iki, H. Oka and S. Miyano, Bull. Chem. Soc. Jpn.,2002, 75, 2615.
8 N. Iki, M. Ohta, T. Horiuchi and H. Hoshino, Chem.–Asian J.,2008, 3, 849.
9 For other examples, see: H. Tong, L. Wang, X. Jing and F. Wang,Macromolecules, 2002, 35, 7169; J. Raker and T. E. Glass, J. Org.Chem., 2001, 66, 6505.
10 J. D. Ingle, Jr. and S. R. Crouch, Spectrochemical Analysis,Prentice Hall, Englewood Cliffs, NJ, 1988.
11 R. M. Smith and A. E. Martell, Critical Stability Constants,Plenum Press, New York, 1976, vol. 4.
12 U. Rothlisberger, iMass for Mac OS X v. 1.1, 2002 (http://home.datacomm.ch/marvin/iMass/).
Fig. 5 Part of the ESI mass spectrum of complex 3, showing
the isotopomer pattern for [2Cd2+ + 2Tb3+ + Na+ + 3H+ +
2TCAS8� + H2O]2�. (a) Observed pattern for a sample ([TCAS]T =
[CdII]T = [TbIII]T = 2.5 � 10�5 M, [HCl]T = 5 � 10�5 M; pH 5.82
(adjusted with NH3)) and (b) simulated pattern.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 23–25 | 25
Ionic liquids with dual biological function: sweet and anti-microbial,
hydrophobic quaternary ammonium-based saltsw
Whitney L. Hough-Troutman,a Marcin Smiglak,a Scott Griffin,a
W. Matthew Reichert,bIlona Mirska,
cJadwiga Jodynis-Liebert,
dTeresa Adamska,
d
Jan Nawrot,eMonika Stasiewicz,
fRobin D. Rogers*
agand Juliusz Pernak*
f
Received (in Montpellier, France) 30th July 2008, Accepted 29th August 2008
First published as an Advance Article on the web 22nd October 2008
DOI: 10.1039/b813213p
The dual nature of ionic liquids has been exploited to synthesize materials that contain two
independent biological functions by combining anti-bacterial quaternary ammonium compounds
with artificial sweetener anions. The synthesis and physical properties of eight new ionic liquids,
didecyldimethylammonium saccharinate ([DDA][Sac]), didecyldimethylammonium acesulfamate
([DDA][Ace]), benzalkonium saccharinate ([BA][Sac]), benzalkonium acesulfamate ([BA][Ace]),
hexadecylpyridinium saccharinate ([HEX][Sac]), hexadecylpyridinium acesulfamate ([HEX][Ace]),
3-hydroxy-1-octyloxymethylpyridinium saccharinate ([1-(OctOMe)-3-OH-Py][Sac]), and
3-hydroxy-1-octyloxymethylpyridinium acesulfamate ([1-(OctOMe)-3-OH-Py][Ace]), are reported,
as well as the single crystal structures for [HEX][Ace] and [1-(OctOMe)-3-OH-Py][Sac].
Determination of anti-microbial activities is described for six of the ILs. While some exhibited
decreased anti-microbial activity others showed a dramatic increase. For two of the ionic liquids,
[DDA][Sac] and [DDA][ACE], oral toxicity, skin irritation, and deterrent activity was also
established. Unfortunately, both ILs received a Category 4 (harmful) rating for oral toxicity and
skin irritation. However, deterrent activity experiments point to use as an insect deterrent, as both
ILs scored either ‘‘very good’’ or ‘‘good’’ against several types of insects.
Introduction
Ionic liquids (ILs) are currently defined as salts that are
composed solely of cations and anions which melt below
100 1C. These salts have been studied for a variety of applica-
tions such as in electrochemistry,1–3 separation science,4–7
chemical synthesis,8–13 and catalysis,14–16 however, until
recently, very few, if any, ILs had been used as liquid materials
themselves.17,18 In addition, those material applications which
have appeared, typically concentrated on a single desirable
property brought by either the cation or the anion. But ILs, by
definition, have at least two discrete types of ions, both of
which can provide a unique property or function. Thus, our
goal has been to explore how to exploit the dual nature of ILs
by preparing materials that possess two functions, particularly
two biological functions. Here, we present the combination of
anti-bacterial quaternary ammonium compounds (QACs)
with artificial sweeteners.
The anti-bacterial properties of QACs were first discovered
during the late 19th century, amongst carbonium dye com-
pounds, such as auramin, methyl violet, and malachite green.19
Initially, QACs were found to be most effective against gram-
positive organisms, until Jacobs and Heidelberger20–23 further
exploited their anti-bacterial properties against other types of
organisms. It was not until 1935 that the full potential of QACs
was recognized by the chemical community, when the synthesis
of benzalkonium chloride, a long-chain QAC, by Domagk24 and
further characterization of its anti-bacterial activities, proved that
QACs were effective against a wider variety of bacterial strains.
Later, in the 20th century, researchers became more
interested in the synthesis of water-soluble QACs for potential
applications as surfactants,25,26 anti-electrostatic agents,27
anti-corrosive agents,28 disinfectants,29 and phase-transfer
catalysts.30 These newly developed water-soluble QACs
showed anti-bacterial action against not only gram-positive
and gram-negative bacteria, but also pathogen species of fungi
and protozoa.31 These discoveries led to applications for
a The University of Alabama, Department of Chemistry and Center forGreen Manufacturing, Tuscaloosa, AL 35487, USA
bUS Naval Academy, Department of Chemistry, Annapolis,MD 21402, USA
cPoznan University of Medical Sciences, Department ofPharmaceutical Bacteriology, Swiecickiego, 4 60-781 Poznan, Poland
d Poznan University of Medical Sciences, Department of Toxicology,Dojazd 30, 60-631 Poznan, Poland
e Institute of Plant Protection, ul. Wegorka 20, 60-318 Poznan,Poland
f Poznan University of Technology, Faculty of Chemical Technology,pl. Sk!odowskiej-Curie 2, 60-965 Poznan, Poland.E-mail: [email protected]
g The Queen’s University of Belfast, QUILL, School of Chemistry andChemical Engineering, Belfast, Northern Ireland BT9 5AG.E-mail: [email protected]
w Electronic supplementary information (ESI) available: Charac-terization data. Fig. S1: ORTEP (50% probability thermal ellipsoids)of the asymmetric unit of [HEX][Ace]. Fig. S2: Close contacts aroundthe cations in [HEX][Ace]. Fig. S3: p-Stacking modes of the polymericcation in [HEX][Ace]. Fig. S4: p-Stacking mode of the dimeric cationin [HEX][Ace]. Fig. S5: ORTEP (50% probability thermal ellipsoids)of the asymmetric unit of [1-(OctOMe)-3-OH-Py][Sac]. CCDC refer-ence numbers 687477 and 687478. For ESI and crystallographic datain CIF or other electronic format see DOI: 10.1039/b813213p
26 | New J. Chem., 2009, 33, 26–33 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
QACs in wood preservation32–34 and as preservatives in
common household products,35 especially for general environ-
mental sanitation in hospitals and food production facilities.
Furthermore, QACs have been used as penetration enhancers
for transnasal and transbuccal drug delivery, such as nasal
vaccinations.36 The ability of QACs to penetrate and open cell
membranes has been widely used in drug delivery such as
liposomes, which consists of long alkyl chain QACs, and
non-viral gene delivery.37
We have had specific interest in employing the IL concept to
pair the biological activity of a class of compounds such as
QACs, with a second biological activity inherent in the
counterion.38 One such class of ions, which has also seen
independent use in preparing ‘edible’ ILs, includes non-
nutritive sweeteners such as saccharinate and acesulfame.39,40
Salts of these anions are currently used in food products and
are approved as food additives by most national and global
health agencies. Yet, only a handful of quaternary ammonium
saccharinates and acesulfamates have been reported in the
literature.41 Here we demonstrate the concept of preparing ILs
by pairing the biological activity inherent in the cation with a
separate biological function possessed by the anion with
the synthesis, physical properties, anti-microbial activities,
toxicity, and deterrent activity of new QAC-based ILs.
Results and discussion
Synthesis and characterization
Synthesis. Didecyldimethylammonium saccharinate ([DDA]-
[Sac]), didecyldimethylammonium acesulfamate ([DDA][Ace]),
benzalkonium saccharinate ([BA][Sac]), benzalkonium acesulfa-
mate ([BA][Ace]), hexadecylpyridinium saccharinate ([HEX][Sac]),
hexadecylpyridinium acesulfamate ([HEX][Ace]), 3-hydroxy-
1-octyloxymethylpyridinium saccharinate ([1-(OctOMe)-3-OH-
Py][Sac]) and 3-hydroxy-1-octyloxymethylpyridinium acesulfa-
mate ([1-(OctOMe)-3-OH-Py][Ace]) (Fig. 1) were prepared in
high yield as hydrophobic salts from commercially available
QACs benzalkonium chloride ([BA][Cl]), didecyldimethyl-
ammonium chloride ([DDA][Cl]), and hexadecylpyridinium
chloride ([HEX][Cl]), and from one pyridinium salt, 3-hydro-
xy-1-octyloxymethylpyridinium chloride [1-(OctOMe)-3-OH-
Py][Cl], which was prepared by a nucleophilic substitution
reaction of 3-hydroxypyridine by octyl chloromethyl ether
under anhydrous conditions. Each of the cations was paired
with saccharinate or acesulfamate by a stoichiometric metathesis
reaction in aqueous solution, using sodium saccharin ([Na]-
[Sac]) or potassium acesulfame ([K][Ace]). The hydrophobic
Fig. 1 Structures of the synthesized ILs.
Fig. 2 Packing diagram along the a crystallographic axis for [HEX][Ace]
(top) and overlay of the two cations in the asymmetric unit including the
anions with close contacts to each (bottom).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 26–33 | 27
nature of these salts allowed them to be easily extracted from
the aqueous phase into chloroform.
All of the newly prepared ILs were found to be low melting
solids at room temperature with the exception of [DDA]-
containing salts, the only cation without an aromatic ring,
which were found to be liquid at room temperature. The salts
studied are only sparingly soluble in cold and hot water, but
freely soluble and stable in many organic solvents (e.g., chloro-
form, methanol, ethanol, ethyl acetate, N,N-dimethyl-
formamide (DMF), and dimethyl sulfoxide (DMSO)).
Crystal structures. Single-crystal structures for two of the
compounds, [HEX][Ace] and [1-(OctOMe)-3-OH-Py][Sac],
also confirmed the syntheses. Although not the focus of this
paper, interesting packing behavior was observed which may
provide clues to the low melting nature of these compounds in
particular and QAC ILs in general.
The packing diagram for [HEX][Ace] (Fig. 2) reveals that
the cation tails interdigitate to create charge-rich and hydro-
phobic regions. Closer examination indicates that the two
unique cations are not equivalent with slight differences in
the orientation of the hexadecyl tail groups. This modest
difference leads to completely different packing environments.
One cation p-stacks in a polymeric fashion (Fig. 3) and has
only three close contacts with the anions. The second cation
forms a p-stacked dimer with anions capping each open face.
These cations have five close contacts with the anions.
Fig. 4 illustrates the packing in the structure of [1-(OctOMe)-
3-OH-Py][Sac]. Here the strong hydrogen bonding between the
cation and anion dominates and a single cation/anion pair is
found in the asymmetric unit. These hydrogen bonded ion pairs
stack in alternate directions.
Thermal behavior. The thermal properties of the ILs
(Table 1) were determined by differential scanning calorimetry
(DSC) and thermogravimetric analysis (TGA). All of the
synthesized salts exhibited melting points below 100 1C,
allowing their classification as ILs. Interesting phase transition
behavior was observed for [DDA][Sac], [DDA][Ace] and
[HEX][Ace] which was not found for the other ILs. These
three ILs had a detectable glass transition-type transforma-
tion at �33, �53 and �11 1C, respectively. Following glass
transition, samples [DDA][Sac] and [Hex][Ace] exhibited
consecutive crystallization and melting transitions. On the
contrary, [DDA][Ace] was the only IL obtained that did not
exhibit any other thermal transition besides a glass transition.
As seen in Table 1, all the ILs were found to be thermally
stable to temperatures ranging between 160 and 210 1C. One-
step decomposition was found for [BA][Sac], [DDA][Sac],
[1-(OctOMe)-3-OH-Py][Sac] and [1-(OctOMe)-3-OH-Py][Ace].
The anions [Sac]� and [Ace]� normally display a two-step
decomposition, suggesting that the cations, [BA]+, [DDA]+
and [1-(OctOMe)-3-OH-Py]+, play a role in the decomposition
of these ILs resulting in the single decomposition step observed.
Fig. 3 One cation in [HEX][Ace] p-stacks in a polymeric fashion
(interplanar spacing 3.5 and 3.6 A) (top), while the second cation
forms p-stacked dimers (interplanar spacing 3.4 A) with acesulfamate
anions capping both sides (bottom).
Fig. 4 Packing diagram along the a crystallographic axis for
[1-(OctOMe)-3-OH-Py][Sac] (top) and close up of the hydrogen
bonding and alternate stacking of the ion pairs (bottom).
28 | New J. Chem., 2009, 33, 26–33 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Two-step decomposition was observed for samples [HEX]-
[Sac], [DDA][Ace] and [HEX][Ace]. Increase in the thermal
stability (first decomposition step) in these salts, over the
thermal stabilities of the starting materials may indicate an
anion stabilizing effect on the parent cations; [HEX]+ and
[DDA]+. Similarly, the stabilizing effect of the anion can be
observed for the sample of [BA][Ace], which is the only sample
that exhibits a three-step decomposition pathway.
Biological properties
Anti-microbial, anti-bacterial and anti-fungal activities. The
minimum inhibitory concentration (MIC) (Table 2) and mini-
mum bactericidal or fungicidal concentration (MBC) (Table 3)
were determined for [BA][Sac], [DDA][Sac], [BA][Ace] and
[DDA][Ace]. (The starting materials, [BA][Cl] and [DDA][Cl],
which inherently exhibit anti-microbial, anti-bacterial and
anti-fungal activities, included in Tables 2 and 3 for com-
parison.) The activities of the ILs approach those of com-
mercially available [BA][Cl] and [DDA][Cl], although the ILs
were not found to be limited to a specific class of bacteria or
fungi. These same observations have been seen in previous
literature,42 where it was found that the anti-microbial
activities for imidazolium chlorides, tetrafluoroborates, and
hexafluorophosphates were independent of the counterion.
It is thought that 1-alkoxymethylpyridinium chlorides are
strongly active against microbes, yet in previous research,43 it
was concluded that the antimicrobial activities depended on the
substituent at the 3-position of the pyridine ring. Unfortu-
nately, [1-(OctOMe)-3-OH-Py][Cl] and the ILs, [1-(OctOMe)-
3-OH-Py][Sac] and [1-(OctOMe)-3-OH-Py][Ace] exhibited no
antimicrobial activity.
Acute oral toxicities. The acute oral toxicities of [DDA][Ace]
and [DDA][Sac] were determined in three male and three
female Wistar rats, where the rats received a dosage of
300 mg/kg b.w. (mg of substance per kg of body weight) and
2000 mg/kg b.w. of each IL. The ILs were suspended in water
Table 1 Thermal propertiesa
Tg Tc Ts�s Tm Tonset5% Tonset
Ionic liquids[BA][Sac] — 16b — 74 164 204[DDA][Sac] �33 15c — 16 187 214[HEX][Sac] — 30c — 66 207 253/412g
[1-(OctOMe)-3-OH-Py][Sac] — — — 95–98e 206 301[BA][Ace] — 30c �36 90 184 187/249/394g
[DDA][Ace] �53 — — — 189 232/426g
[HEX][Ace] �11 5b — 57 212 267/494g
18c
[1-(OctOMe)-3-OH-Py][Ace] — — — 79–81e 203 267
Starting materialsNa[Sac] — 98c — 120 431 459/541g
K[Ace] — — — 68 190 192/260g
[BA][Cl] — 16bd — — 143 169[DDA][Br]f — — — — 166 196[HEX][Cl] — 45c — 73 184 213[1-(OctOMe)-3-OH-Py][Cl] — — — 68–70e 178 247
a Phase transition points (1C) were measured from transition onset temperatures determined by DSC from the second heating cycle at 5 1C min�1,
after initially heating and then cooling of the samples to �100 1C unless otherwise indicated: Tg = glass transition temperature; Tc =
crystallization temperature; Ts–s = solid–solid transition temperature on heating; Tm = melting point on heating. Decomposition temperatures
were determined by TGA, heating at 5 1Cmin�1 under air atmosphere and are reported as (Tonset 5%) onset to 5 wt%mass loss and (Tonset) onset to
total mass loss. b Transition measured on heating cycle. c Transition measured on cooling cycle. d Transition only during first heating e Visual
melting point range via hot-plate apparatus. f Multiple transitions due to presence of water in starting material. g Multiple decomposition steps.
Table 2 MIC valuesa
Ionic liquid Starting materials
Strain [BA][Sac] [DDA][Sac] [BA][Ace] [DDA][Ace] [BA][Cl] [DDA][Cl]
S. aureus 4 4 4 8 2 2S. aureus (MRSA) 4 4 4 4 2 2E. faecium 8 8 8 8 4 4E. coli 16 16 31 16 8 8M. luteus 8 4 8 8 4 2S. epidermidis 4 4 4 4 2 2K. pneumoniae 4 4 8 4 4 4C. albicans 16 16 16 16 8 8R. rubra 16 16 16 16 8 4S. mutans 0.1 31 1 16 2 2Mean value 8.0 10.7 10.0 10.0 4.4 3.8
a In ppm.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 26–33 | 29
prior to intragastric administration. After receiving the dosage
of 300 mg/kg b.w. for [DDA][Ace] or [DDA][Sac], one male
rat died during the first 24 h, while the other 5 rats remained
alive. But when the dosage was increased to 2000 mg/kg b.w.,
all of the rats died between 24 and 96 h after administra-
tion. Death was preceded by decrease in spontaneous motor
activity, excessive excretion from nostrils, and difficulty of
breathing. The above results indicate the acute toxicity range
for both ILs is between 300–2000 mg/kg b.w. in male and
female rats. Thus, these ILs would be classified as category 4
(harmful) toxins according to standard OECD grading.44
Skin irritation. Skin irritation of [DDA][Ace] and [DDA]-
[Sac] was determined on New Zealand albino rabbits. All of
the exposed animals exhibited defined erythema after 1 h. The
erythema had increased to severe and severe eschar formation
was also observed after 24 h. Although no edema occurred, the
skin irritation of these ILs is defined as category 4 (the highest)
by standard OECD grading.45
Deterrent activity. The deterrent activity of [DDA][Ace] and
[DDA][Sac] toward Tribolium confusum (larvae and beetles),
Sitophilus granarius (beetles) and Trogoderma granarium
(larvae) was determined by using a known method, in which
the amount of food consumed is monitored over a specific time
interval. Three deterrent coefficients had to be calculated from
the average amount of food consumed: (a) the absolute coeffi-
cient of deterrency, A = (CC � TT)/(CC + TT) � 100, (b) the
relative coefficient of deterrency, R = (C � T)/(C + T) � 100,
and (c) the total coefficient of deterrency, which is the sum of
the absolute and the relative coefficients, T=A+R.46 In these
Table 3 MBC valuesa
Ionic liquids Starting materials
Strain [BA][Sac] [DDA][Sac] [BA][Ace] [DDA][Ace] [BA][Cl] [DDA][Cl]
S. aureus 31.2 62.5 31.2 16 62.5 31.2S. aureus (MRSA) 31.2 31.2 31.2 31.2 31.2 31.2E. faecium 16 16 31.2 31.2 31.2 31.2E. coli 62.5 16 125 62.5 62.5 31.2M. luteus 62.5 31.2 62.5 62.5 31.2 31.2S. epidermidis 31.2 16 62.5 31.2 16 31.2K. pneumoniae 62.5 16 31.2 31.2 31.2 16C. albicans 31.2 16 31.2 31.2 16 16R. rubra 62.5 31.2 62.5 62.5 31.2 31.2S. mutans 0.5 62.5 16 125 16 16Mean value 39.1 29.9 48.5 48.5 32.9 26.6
a In ppm.
Table 4 Criteria for the estimation of the deterrent activity based onthe total coefficient
Total coefficient Deterrent activity
200–151 Very good150–101 Good100–51 Medium50–0 Weak
Table 5 Feeding deterrent activity
Ionic liquid Relative coefficient Absolute coefficient Total coefficient Deterrent activity
Sitophilus granarius (beetles)[DDA][Ace] 97.5 57.9 155.5 Very good[DDA][Sac] 57.8 56.6 114.5 GoodAzadirachtina 100.0 74.3 174.3 Very goodLSD0.05
b 57.8 28.8 60.1
Trogoderma granarium (larvae)[DDA][Ace] 94.0 85.0 179.0 Very good[DDA][Sac] 94.2 86.1 180.3 Very goodAzadirachtina 100.0 94.2 194.2 Very goodLSD0.05
b 0.3 7.6 7.8
Tribolium confusum (beetles)[DDA][Ace] 96.2 19.1 115.3 Good[DDA][Sac] 95.0 90.7 186.6 Very goodAzadirachtina 100.0 85.0 185.0 Very goodLSD0.05
b 0.6 9.2 9.0
Tribolium confusum (larvae)[DDA][Ace] 95.0 64.1 159.1 Very good[DDA][Sac] 95.3 88.8 184.1 Very goodAzadirachtina 100.0 88.4 188.4 Very goodLSD0.05
b 2.1 29.4 29.1
a Natural deterrent. b The least significant differences at the 5% level of significance.
30 | New J. Chem., 2009, 33, 26–33 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
equations, CC is the average weight of the food consumed in
the control, TT is the average weight of the food consumed in
the no-choice test, and T and C are the average weights of the
food consumed in the choice test.
The total coefficient value T is compared to standard values
for deterrent activity in Table 4, where a value of 0 equals
neutral activity and a value of +150 to +200 corresponds to
very high deterrent activity. The results of deterrent activity
for [DDA][Ace] and [DDA][Sac] are compared to a natural
deterrent, azadirachtin, in Table 5. The ILs received
either ‘very good’ or ‘good’ deterrent activity for all tested
insects. In particular, [DDA][Sac] exhibited the same deterrent
activity toward Tribolium confusum (larvae and beetles) as
azadirachtin and thus, could be classified as a potential
synthetic insect deterrent.
Conclusions
We have prepared ILs of two biologically active ions by
combining anti-microbial QACs cations with sweetener anions.
Some of these ILs demonstrate properties such as limited water
solubility, high thermal stability, and good deterrent activity
against insects; which suggest potential application as an
insecticide. Although oral toxicity and skin irritation values
were higher than hoped, there is still potential use, not only for
these ILs, but also for new, related ILs which can be prepared
by tuning the composition in such a manner to reduce toxicity.
In general, research in the IL field has begun to shift from
random combinations of ions to a design scheme in which
both the cation and anion are chosen based on the desired
physical, chemical, and biological properties. All procedures
performed on these animals were in accordance with esta-
blished guidelines and were reviewed and approved by the
University of Alabama’s Institutional Animal Care and Use
committee. As our fundamental understanding of IL behavior
increases, more control over the resultant properties of the
salts will be possible, and the number of potential applications,
such as those presented here, will continue to grow.
Experimental
Chemicals and microorganisms
Benzalkonium chloride [BA][Cl] (molecular formula
C6H5CH2N(CH3)2RCl where R = C12H25 (60%) and
C14H29 (40%)), didecyldimethylammonium bromide
[DDA][Br] (tech., 75 wt% gel in water), hexadecylpyridinium
chloride [HEX][Cl] (monohydrate, minimum 99%) and
sodium saccharinate Na[Sac] (hydrate, minimum 98%) were
purchased from Sigma Aldrich. Potassium acesulfamate
K[Ace] (Z 99%) was purchased from Fluka.
The following microorganisms were used: bacteria
Staphylococcus aureus ATCC 6538, Staphylococcus aureus
(MARSA) ATCC 43300, Enterococcus faecium ATCC
49474, Escherichia coli ATCC 2592,2 Micrococcus luteus
ATCC 9341, Staphylococcus epidermidis ATCC 12228,
Klebsiella pneumoniae ATCC 4352, and fungi Candida albicans
ATCC 10231, Rhodotorula rubra PhB and Streptococcus
mutans PCM (Polish Collection of Microorganisms) 2502.
The Rhodotorula rubra was obtained from the Department
of Pharmaceutical Bacteriology, Poznan University of
Medical Sciences, Poland.
General synthesis47
Solid (0.001 mol) Na[Sac] or K[Ace] was dissolved in distilled
water and added to hot aqueous solutions containing
0.001 mol of [BA][Cl], [DDA][Br] or [HEX][Cl]. The mixtures
were stirred at 60 1C for 1 h and then cooled to room
temperature. The hydrophobic product was extracted with
chloroform and purified using distilled water washes, until
chloride or bromide ions were no longer detected in the
product phase using AgNO3. The chloroform was evaporated
and the IL was dried under vacuum.
The starting material 3-hydroxy-1-octyloxymethyl-
pyridinium chloride was prepared according to previous
literature.43 Solid (0.03 mol) K[Ace] or Na[Sac] was dissolved
in distilled water and then added to an aqueous solution
containing 0.03 mol [1-(OctOMe)-3-OH-Py][Cl]. The reaction
was completed by gentle heating and stirring in a water bath
for 2 h. The heat was removed and stirring was continued at
room temperature for 24 h. The mixture was filtered, and the
precipitate was washed with cold distilled water (3� 20 mL) to
give an oil or solid IL. The IL was dried under vacuum, and
recrystallized from ethyl acetate and then dried again under
vacuum. Karl–Fischer analysis indicated the water content of
all dried ILs to be less than 500 ppm.
Thermal analysis
Melting points and other thermal transitions of the ILs were
determined by DSC, with a TA Instruments model 2920
Modulated DSC (Newcastle, DE), cooled with a liquid nitro-
gen cryostat. The calorimeter was calibrated for temperature
and cell constants using indium standard (mp 156.61 1C,
DH = 28.71 J g�1). Data were collected at constant atmos-
pheric pressure where the ILs were placed in aluminum pans
with sample sizes from 5 to 15 mg. An empty sample pan was
used as reference. All experiments were performed at a heating
rate and a cooling rate of 5 1C min�1. The DSC was adjusted
so zero heat flow was between 0 and �0.5 mW, and the
baseline drift was less than 0.1 mW over the temperature
range 0–180 1C.
Thermal decomposition temperatures were measured in the
dynamic heating regime using a TGA, 2950 TA Instrument,
under air atmosphere. The amount of IL used was between
2 and 10 mg in each case, and the samples were heated from
40 to 800 1C at a constant heating rate of 5 1C min�1.
Decomposition temperatures (T5%dec) were determined from
onset to 5 wt% mass loss; this provides a more realistic
representation of thermal stability at elevated temperatures.
X-Ray diffraction
Crystalline samples of [HEX][Ace] and [1-(OctOMe)-3-
OH-Py][Sac] were mounted on a glass fiber on a goniometer
head of a Siemens SMART CCD diffractometer equipped
with a Mo-Ka source (l = 0.71073 A) and a graphite
monochromator. Data collection was conducted at �100 1C
which was achieved by streaming cold nitrogen over the
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 26–33 | 31
crystal. Final unit cell parameters were determined by least-
squares refinement of the hemispherical data set obtained from
20 s exposures. Data were corrected for Lorentz and polariza-
tion effects and absorption using SADABS.48 The initial
structure solution was carried out using the direct methods
option in SHELXTL version 5.49 The positions of all non-
hydrogen atoms were refined anisotropically. The hydrogen
atoms were added and allowed to refine unconstrained in
order to obtain proper close contact interactions.
Crystal data for [HEX][Ace]. C25H42N2O4S; Mr = 466.67;
triclinic, space group P�1; T = 173 K; a = 7.921(3), b =
13.374(5), c= 25.689(10) A, a= 76.755(7), b= 82.225(7), g=89.260(7)1; Z=4; V=2624.2(17) A3;Dc = 1.181 g cm�3; 7459
independent (Rint = 0.0249) and 5755 observed ([I 4 2s(I)])reflections; GooF = 1.070; R1, wR2 [I 4 2s(I)] = 0.0462,
0.1208; R1, wR2 (all data) = 0.0641, 0.1411
Crystal data for [1-(OctOMe)-3-OH-Py][Sac]. C21H28N2O5S;
Mr = 420.51; triclinic, space group P�1; T = 173 K; a =
8.1626(15), b = 8.7141(16), c = 16.756(3) A, a = 81.872(3),
b = 80.780(3), g = 62.850(3)1; Z = 2; V = 1043.7(3) A3; Dc =
1.338 g cm�3; 2969 independent (Rint = 0.0170) and 2515
observed ([I 4 2s(I)]) reflections; GooF = 1.033; R1, wR2
[I4 2s(I)] = 0.0362, 0.0871; R1, wR2 (all data) = 0.0472, 0.0937
Antimicrobial characteristics
Anti-microbial activity was determined by the tube dilution
method. Bacteria strains were cultured in Mueller–Hinton
broth for 24 h and fungi were cultured on Sabouraud agar
for 48 h. Suspensions of the above microorganisms, at a
concentration of 106 cfu mL�1, were prepared from each
culture. Two milliliters of serial twofold dilutions of IL were
inoculated with the above-mentioned suspension to obtain a
final concentration of (1–5) � 105 cfu mL�1.
Growth of the microorganism (or its lack) was determined
visually after incubation for 24 h at 35 1C (bacteria) or 48 h at
22 1C (fungi). The lowest concentration at which there was no
visible growth (turbidity) was determined to be the minimal
inhibitory concentration (MIC). Then, from each tube con-
tent, 10 mL (calibrated loop) was smeared on an agar medium
with inactivates (0.3% lecithin, 3% polysorbate 80, and 0.1%
L-cysteine) and incubated for 48 h at 35 1C (bacteria) or for
5 days at 22 1C (fungi). The lowest concentration of the IL that
killed 99.9% or more of the microorganism was defined as the
minimum biocidal concentration (MBC).
Acute oral toxicity test
The toxicity was tested according to the method of acute toxic
class.44 Three male (250 � 25 g) and three female (170 � 17 g)
Wistar rats were used for each IL tested. The ILs were first
suspended in distilled water and then administered intra-
gastrically at doses of 300 mg/kg b.w. and 2000 mg/kg b.w.
After the dose was administered, the rats were observed for
14 days.
Skin irritation tests
Each IL was tested on 3 male New Zealand albino rabbits,
where the fur was previously removed from the back of the
rabbit. Half a milliliter of the ILs (100%, pure) was distributed
on two 6 cm3 sites of the same animal. The application site was
then covered with a porous gauze dressing and secured in place
with tape. After a 4 h exposure, the dressing was removed and
the application site was gently washed with water. Observa-
tions were then conducted at 1, 24, 48, and 72 h, where the
test sites were evaluated for erythema and edema using a
prescribed scale.45
Feeding deterrent activity tests
Three species of insects were selected for testing: Tribolium
confusum Duv. (larvae and beetles), Sitophilus granarius L.
(beetles), and Trogoderma granarium Ev. (larvae). Insects were
grown on a wheat grain or whole-wheat meal diet in labora-
tory colonies which was maintained at 26 � 1 1C and 60 � 5%
relative humidity. The laboratory assay was conducted
according to the method developed and standardized for storage
insects feeding activity for both choice and no-choice test.46
Wheat wafer discs (1 cm in diameter � 1 mm thick) were
saturated by dipping in either ethanol (96%) only (control) or
in a 1% ethanol solution of [DDA][Ace] or [DDA][Sac]. After
evaporation of the solvent by air-drying (30 min), the wafers
were weighed and offered as the only food source for the
insects over a five day period. The feeding of the insects was
recorded under three conditions: (a) control test (two control
discs (CC)), (b) choice test (a choice between one treated
disc (T) and one control disc (C)), and (c) no-choice test
(two treated discs (TT)). Each of the three experiments was
repeated five times with 3 beetles of Sitophilus granarius,
20 beetles and 10 larvae of Tribolium confusum, and 10 larvae
of Trogoderma granarium. The number of individual insects
depended on the intensity of their food consumption. The
beetles utilized in the experiments were unsexed, 7–10 days
old, and the larvae were 5–30 days old. After five days of
feeding, the discs were reweighed. The data from the experi-
ments have been statistically corrected by an analysis of
variance.
Acknowledgements
This work was supported by Poznan University of Techno-
logy, BW 32-222/2008.
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ISSN 1144-0546
PAPERRudi van Eldik et al.Metal ion-catalyzed oxidative degradation of Orange II by H2O2. High catalytic activity of simple manganese salts
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Metal ion-catalyzed oxidative degradation of Orange II by H2O2. High
catalytic activity of simple manganese salts
Erika Ember, Sabine Rothbart, Ralph Puchta and Rudi van Eldik*
Received (in Montpellier) 6th August 2008, Accepted 25th September 2008
First published as an Advance Article on the web 17th November 2008
DOI: 10.1039/b813725k
In an effort to develop new routes for the clean oxidation of non-biodegradable organic dyes,
a detailed study of some environmentally friendly Mn(II) salts that form very efficient in situ
catalysts for the activation of H2O2 in the oxidation of substrates such as Orange II under mild
reaction conditions, was performed. The studied systems have advantages from the viewpoint of
green chemistry in that simple metal salts can be used as very efficient catalyst precursors and
H2O2 is used as a green oxygen donor reagent. Oxidations were carried out in a glass reactor over
a wide pH range in aqueous solution at room temperature. Under optimized conditions it was
possible to degrade Orange II in a carbonate buffer solution in less then 100 s using 0.01 M H2O2
in the presence of only 2 � 10�5 M Mn(II) salt. To gain insight into the manganese catalyzed
oxidation mechanism, the formation of the active catalyst was followed spectrophotometrically
and appears to be the initiating step in the oxidative degradation of the dye. High valent
manganese oxo species are instable in the absence of a stabilizing coordinating ligand and lead to
a rapid formation of catalytically inactive MnO2. In this context, the role of the organic dye and
HCO3� as potential stabilizing ligands was studied in detail. In situ UV-Vis spectrophotometric
measurements were performed to study the effect of pH and carbonate concentration of the buffer
solution on the formation of the catalytically active species. Electrochemical measurements and
DFT (B3LYP/LANL2DZp) calculations were used to study the in situ formation of the catalytic
species. The catalytic cycle could be repeated several times and demonstrated an excellent stability
of the catalytic species during the oxidation process. A mechanism that accounts for the
experimental observations is proposed for the overall catalytic cycle.
Introduction
Nowadays, one of the major environmental problems con-
cerns the strong increase in xenobiotic and organic substances
that are persistent in the natural ecosystem. Most of these
compounds have an aromatic structure, which makes them
highly stable and thus difficult to degrade.1 A significant
source of environmental pollution is industrial dye waste due
to their visibility and recalcitrance, since dyes are highly
coloured and designed to resist chemical, biochemical and
photochemical degradation.2 About half of the global produc-
tion of synthetic dyes (700 000 t per year) are classified as
aromatic azo compounds that have a –NQN– unit as chromo-
phore in their molecular structure. Over 15% of textile dyes
are lost in waste water streams during the dyeing operation.3
Azo dyes are known to be largely non-biodegradable under
aerobic conditions and to be reduced to more hazardous
intermediates under anaerobic conditions.4 The decolorization
of wastewater has acquired increasingly importance in recent
years, however, there is no simple solution to this problem
because the conventional physicochemical methods are costly
and lead to the accumulation of sludges.5
One approach to solve these problems would be to develop
low-cost, highly efficient, and environmental friendly oxida-
tion catalysts on the basis of transition metal complexes.6,7
Recently, photodegradation methods based on TiO2 as a
photocatalyst,8 beside Fenton systems,9 emerged as one of
the most promising technologies and received increasing atten-
tion due to their practical and potential value in environmental
protection. However, in some cases they are only successful
under specific pH and temperature conditions.
Several studies were performed during the last few years in
order to find good catalysts for the oxidative degradation of
different organic dyes. From an environmental point of view,
first row transition metals are the most challenging. Highly
effective Fe,10,14 Co,11 Cr12 and Mn13 based oxidation catalyst
were developed. In combination with different oxidizing
agents, the decomposition of stable organic substances was
possible. A novel highly active and environmental benign
catalytic system based on Fe-TAML (TAML = tetraamido
macrocyclic ligand) was recently reported by Chahbane et al.14
In many cases tremendous synthetic efforts are required to
obtain an effective catalytic system and in addition the pre-
sence of high concentrations of oxidizing agents is needed.
Among the possible oxidizing agents, H2O2 is one of the most
commonly used owing to its eco-friendly nature. The use of
H2O2 as a green oxidizing agent in these reactions is justified
by a low organic content of the wastewater to be treated and a
Inorganic Chemistry, Department of Chemistry and Pharmacy,University of Erlangen-Nurnberg, Egerlandstr. 1, 91058 Erlangen,Germany
34 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
low reaction temperature, thus requiring the presence of an
adequate catalyst due to the high kinetic activation barrier of
such reactions. Commonly used methods for activation of
H2O2 include the formation of reactive peroxyacids from
carboxylic acids and peroxycarboximidic acid from aceto-
nitrile (Payne oxidation),15 the generation of peroxyisourea
from carbodiimide in the presence of either a weak acid or a
mild base,16 or the use of percarbonate, persulfate or perbo-
rate in strongly basic solution.17 In order to achieve fast
oxidative transformations, the use of large amounts of co-
catalyst additives is often required.18
Among these, the use of percarbonate, a versatile oxidizing
agent, is preferred for environmental reasons.19,20 Oxidation
using environmentally benign oxidants has aroused much
interest,7,21 because chemical industry continues to require
cleaner oxidation, which is an advance over environmentally
unfavoured oxidations and a step up from more costly organic
peroxides.22
In this report, we propose a fast and clean catalytic oxida-
tive degradation of Orange II as model substrate by H2O2 in
aqueous carbonate solution under mild reaction conditions,
pH 8–10 and 25 1C, eqn (1).
ð1Þ
Starting from commercially available Mn(NO3)2 in aqueous
carbonate solution for catalytic applications, various aspects
of the in situ generation of very reactive high valent manganese
intermediates in the presence of H2O2 were studied. Baes and
Mesmer have shown that manganese salts in aqueous solution
are able to form very reactive aquated intermediates.23 More-
over, in an alkaline medium, the introduction of a hydroxy
ligand trans to a water ligand is expected to produce more
labile OH–Mn–H2O species, and their formation (eqn (2)) is
considered to be of major importance for their catalytic
activity.
In the present study, the formation of catalytically inactive
Mn(OH)2 species was observed at higher pH, leading to
deactivation of the producedMn intermediates. The activation
of H2O2 in the presence of manganese salts as a function of pH
and carbonate concentration was therefore monitored using
UV-Vis spectrophotometry. In situ formed, high valent man-
ganese intermediates are known to be highly unstable in the
absence of a spectator ligand. As the study progressed, it was
of importance to investigate the role of the azo dye as a
potential coordinating ligand to stabilize the produced inter-
mediate under different reaction conditions. Electrochemical
measurements and DFT calculations were used to develop
a better understanding of the coordination chemistry of
Orange II. The successful implementation of such catalytic
systems becomes a worthwhile objective when issues such as
environmental compatibility, high atom economy, availability,
and expenses are considered.24
Experimental
Chemicals
Orange II, certified [Acid Orange 7, C.I. 15510, sodium 4-(2-
hydroxy-1-naphthylazo)benzenesulfonate], 99% was supplied
by Sigma–Aldrich and recrystallised from a Et2O/H2O mix-
ture at 4 1C. 2,4,6-Tri-tert-butylphenol (TTBP) 96% was
purchased from Sigma–Aldrich and recrystallised several
times from EtOH/H2O (9 : 1) mixtures prior to use. Hydrogen
peroxide 35 wt% as well as different manganese salt hydrates
used in the experiments, were of analytical grade and provided
by Acros Organics (Germany). Carbonate buffer solutions
were prepared using Millipore Milli-Q purified water.
General procedure
The manganese salts were freshly dissolved in water before
use. To a freshly prepared sodium carbonate solution, an
adequate amount of NaOH was added to adjust the pH of
the solution. Under isothermal conditions, the desired amount
of a concentrated manganese solution was added together with
Orange II, previously dissolved in an aqueous carbonate
solution, and H2O2. In typical measurements, 0.01 M H2O2
was prepared from a 35 wt% solution of H2O2. In addition, to
gain more information on the activation mode of the catalyst,
two further experimental procedures based on different activa-
tion and stabilization modes of the activated catalyst, were
followed. In one, the catalytic active species was generated
in situ in the carbonate buffer solution by addition of the
desired amount of H2O2, followed by the addition of the
corresponding quantity of Orange II to the reaction mixture.
In the other, Orange II was added to the manganese solution
and the formation of an Orange II� � �MnII complex was
observed. The decomposition of the dye was initiated through
the subsequent addition of H2O2. It is important to note that
the catalytic oxidation of the dye by H2O2 could only be
performed in an aqueous carbonate buffer solution. No other
buffer at the same pH, viz. TRIS, TAPS, HEPES or phos-
phate, showed the observed catalytic reaction.
Kinetic study of the manganese catalysed oxidative degradation
of Orange II by H2O2
All kinetic data were obtained by recording time-resolved
UV-Vis spectra using a Hellma 661.502-QX quartz Suprasil
immersion probe attached via optical cables to a 150 W Xe
lamp and a multi-wavelength J & M detector, which records
complete absorption spectra at constant time intervals. In a
thermostated open glass reactor vessel equipped with a mag-
netic stirrer, a 2 � 10�5 M freshly prepared catalyst solution
and 0.01 M H2O2 were added to 40 ml of 5 � 10�5 M dye
at a pH ranging from 8 to 10 at 25 1C. All kinetic measure-
ments were carried out under pseudo-first order conditions
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 35
(i.e. 50 r [H2O2]/[Mn2+] r 1000). The pH of the aqueous
carbonate solution was carefully measured using a Mettler
Delta 350 pH meter previously calibrated with standard buffer
solutions at two different pH values (4 and 10). The kinetics
of the oxidation reaction was monitored at 480 nm. First
order rate constants, where possible, were calculated using
Specfit/32 and Origin (version 7.5) software. To estimate the
effect of the catalyst and H2O2 concentrations on the catalytic
reaction at different carbonate concentrations, stopped-flow
kinetic measurements were carried out using an SX.18MV
stopped-flow instrument from Applied Photophysics.
Spectrophotometric titration
UV-Vis spectra were recorded on a Shimadzu UV-2101
spectrophotometer at 25 1C. A 0.88 cm path length tandem
cuvette with two separate compartments (0.44 cm path length
each), was filled with 1 ml 5� 10�5 M Orange II stock solution
in one, and different concentrations of an aqueous Mn(NO3)2solution in the other compartment. The cuvette was placed in
the thermostated cell holder of the spectrophotometer for
10 min. UV-Vis spectra were recorded before and after mixing
the solutions. The resulting spectrum presents the sum of the
two individual spectra before, and that of the reaction mixture,
after mixing. The observed spectral change is a result of
complex-formation between Mn(II) and Orange II.
Cyclovoltammetric measurements
Cyclovoltammetric (CV) measurements were performed in a
one-compartment three-electrode cell using a gold working
electrode (Metrohm) with a geometrical surface of 0.7 cm2
connected to a silver wire pseudo-reference electrode and a
platinum wire serving as counter electrode (Metrohm).
Measurements were recorded with an Autolab PGSTAT
30 unit at room temperature. The working electrode surface
was cleaned using 0.05 mm alumina, sonicated and washed
with water every time before use. The working volume of 10 ml
was deaerated by passing a stream of high purity N2 through
the solution for 15 min prior to the measurements and then
maintaining an inert atmosphere of N2 over the solution
during the measurements. All CVs were recorded for the
reaction mixture with a sweep rate of 50 mV s�1 at 25 1C.
Potentials were measured in a 0.5 M NaCl/NaOH electrolyte
solution and are reported vs. an Ag/AgCl electrode.
IR measurements
IR spectra were recorded as KBr pellets using a Mattson
Infinity FTIR instrument (60 AR) at 4 cm�1 resolution in
the 400–4000 cm�1 range.
Elemental analysis
The measurements were carried out on an elemental analyzer
Euro EA 3000 instrument from Hekaltech Gmbh. The analy-
tical method is based on the complete instantaneous oxidation
of the sample by ‘‘flash combustion’’ at 1000 1C, which
converts all organic and inorganic substances into combustion
products. The resulting combustion gases are swept into the
chromatographic column by the carrier gas (He) where they
are separated and detected by a thermal conductivity detector.
DFT calculations
Unrestricted B3LYP/LANL2DZp hybrid density functional
calculations,25a–c i.e., with pseudo-potentials on the heavy
elements and the valence basis set25d–f augmented with
polarization functions,25g were carried out using the Gaussian
0326 suite of programs. The relative energies were corrected
for zero point vibrational energies (ZPE). The resulting struc-
tures were characterized as minima by computation of vibra-
tional frequencies, and the wave functions were tested for
stability.
Synthesis of insoluble MnCO3
In a 150 ml round flask 3.36 g (0.4 M) NaHCO3 was dissolved
in 100 ml doubly distilled water and the pH of the solution was
set at 8.5 upon addition of small amounts of concentrated
NaOH solution. To the freshly prepared carbonate solution
1 g (0.04 M) Mn(NO3)2 was added. The mixture was stirred at
room temperature for 15 min during which MnCO3� � �H2O
formed as a white precipitate. The product was filtered and
washed several times with large amounts of water. Yield:
0.44 g MnCO3, 96.2%. IR (KBr pellets): n (cm�1) 3421 (m),
1416 (vs), 862 (s), 725 (m). Elemental analysis (%) for
MnCH2O4: calc.: C 9.03, H 1.52; found: C 9.38, H 1.52.
Synthesis of Orange II� � �MnII complex
In a 50 ml Schlenk tube 0.014 g (2 � 10�3 M) Orange II was
dissolved in 20 ml doubly distilled water and an aqueous
solution of 0.01 g (2 � 10�3 M) Mn(NO3)2 was added
dropwise under continuous stirring. The solution mixture
was kept for several hours at room temperature. The formed
precipitate was filtered and dried at room temperature. Yield:
0.018 g Orange II� � �MnII, 87.1%. IR (KBr pellets): n (cm�1)
3527 (vs), 1619 (s), 1511 (s), 1383 (vs), 1262 (m), 1171 (s),
1120 (s), 1034 (s), 1007 (s), 829 (s), 759 (s), 696 (m), 644 (m),
595 (m). Elemental analysis (%) for MnC16H18O10N3SNa:
calc.: C 36.79, H 3.47, N 8.04, S 6.14, O 30.63; found:
C 29.44, H 3.39, N 8.05, S 4.77, O 30.31.
Synthesis of Orange II� � �MnII� � �Orange II complex
An aqueous solution of 0.005 g (1 � 10�3 M) Mn(NO3)2 was
added under continuous stirring to a 0.014 g (2 � 10�3 M)
Orange II water solution at room temperature. The pale
yellow precipitate was collected by filtration and dried in
air. Yield: 0.017 g Orange II� � �MnII� � �Orange II, 93.7%. IR
(KBr pellets): n (cm�1) 3390 (s), 1619 (s), 1570 (m), 1554 (m),
1520 (vs), 1393 (m), 1260 (m), 1169 (vs), 1119 (vs), 1033 (vs),
1007 (s), 828 (s), 758 (s), 695 (m), 644 (m), 593 (m). Elemental
analysis (%) for MnC32H32O15N5S2Na2: calc.: C 43.1, H 3.62,
N 7.23, S 7.19, O 26.91; found: C 42.99, H 3.75, N 7.23, S 7.00,
O 25.67.
Results and discussion
General observations
A series of experiments were performed in order to investigate
the in situ generation of the highly reactive manganese catalyst
in the oxidative degradation of Orange II by H2O2 under mild
reaction conditions starting with a simple Mn(II) salt.
36 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Oxidation reactions are in general affected by the protonation
state of the substrate, catalyst and oxidant, and the solvent
used. It is further important to note that the studied organic
dye (Orange II) can exist in either one of two tautomeric
forms, or in an equilibrium mixture, depending on the process
parameters. This kind of rapid dynamic equilibrium is relevant
as one dye species may be more reactive than the other. Azo
dyes containing a hydroxyl group in the ortho position to the
azo group within naphthyl or higher fused ring systems, can
exist as azo and hydrazone tautomers,27 with the relative
amounts varying with reaction parameters such as solvent
and temperature.28 Furthermore, in aqueous solution these
species are in a pH dependent equilibrium with a common
anion, in which the negative charge is delocalised throughout
the molecule (see Scheme 1).29 These are chemically distinct
forms which have characteristically different visible spectra,
the azo form absorbs typically at 400–440 nm and the hydra-
zone form at 475–510 nm (see Fig. 1).30
The absorption spectrum of Orange II in an aqueous
carbonate solution shows under the selected reaction condi-
tions (Fig. 1) one main band at 480 nm, which correspond to
the n - p* transition of the azo form. The other two bands at
300 and 270 nm are attributed to the p - p* transition of the
benzene and naphthalene rings, respectively.31 Orange II, due
to the presence of aromatic groups, is very stable, and in the
presence of a powerful bleaching agent such as H2O2,
degradation of dye solutions occurs slowly under specific
reaction conditions. Surprisingly, the oxidation rate was tre-
mendously accelerated by addition of a simple manganese
salt. The reactivity of the in situ formed intermediate
was comparable with the catalytic activity of some earlier
postulated, well known manganese bleach catalysts13,32 and
manganese porphyrins.33 In our work, the formation and
stabilization of the active catalyst was studied in a carbonate
buffer solution.
Complex-formation between Orange II and Mn2+
ortho-Hydroxy aromatic azo dyes, which are bidentate com-
plexing agents are of considerable practical and theoretical
interest because of their ability to form stable chelate com-
plexes with some metal ions.34 It is known that Orange II can
act as a chelating agent since the hydroxy and sulfonate groups
allow a stabilized complex to be formed.35 Addition of Orange
II to a freshly prepared aqueous carbonate solution of a MnII
salt results in significant changes in the UV-Vis spectrum of
Orange II as shown in Fig. 2.
UV-Vis spectra recorded before and after mixing (ca. 5 s
delay) of 5 � 10�5 M Orange II with 5 � 10�5 M Mn(NO3)2showed a significant increase in absorbance at 480, 310
and 228 nm, respectively. The differences before and after
mixing are not profound at low Mn2+ concentrations. On
increasing the Mn2+ concentration, a continuous increase in
DAl=480 nm = A(dye+Mn(II)) � Adye was observed, indicating
the formation of an Orange II� � �Mn2+ species according to
eqn (3). It should be noted that at higher Mn2+ concentration,
a precipitate started to form. The value of Keq was determined
through a constant variation of the Mn2+ concentration. For
a correct determination of the complex-formation constant,
independent measurements were performed at constant man-
ganese concentration where the Orange II concentration was
continuously varied (see Fig. 3C). Independent measurements
were repeated between five and eight times. Selected data are
Scheme 1 Orange II: R = SO3Na; pKA = 11.4, lmax = 480 nm.
Fig. 1 UV-Vis spectrum of 10�4 M Orange II in carbonate buffer
solution at pH 8.5.
Fig. 2 (Blue curve) UV-Vis spectrum of a 5 � 10�5 M Orange II
carbonate (0.1 M HCO3�) solution at pH 8.5 before mixing with a
5 � 10�5 M Mn(NO3)2 solution at pH 8.5. (red curve) UV-Vis
spectrum recorded directly after mixing (ca. 5 s delay).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 37
shown in Fig. 3A, where the solid line represents a fit of eqn (4)
to the data.
Orange IIþMn2þ ÐKeq
ðOrange II � � �MnIIÞ ð3Þ
Ax � A0 = (AN � A0)Keq[Orange II]/(1 + Keq[Orange II])
DA = DANKeq[Orange II]/(1 + Keq[Orange II]) (4)
The values of A0 and AN represent the absorbances of
Orange II and of the complex Orange II� � �MnII, respectively,
and Ax is the absorbance at any MnII concentration. The value
of Keq was calculated from eqn (4) to be (2.9 � 0.9) � 104 M�1,
indicating a relatively weak coordination of the dye to the metal
center. Experimentally, through addition of a 4 � 10�5 M
Mn(NO3)2 solution to a 5 � 10�5 M Orange II aqueous
carbonate solution (0.2 M HCO3�), a decrease in the pH of
the solution from 8.5 to 8.3 was observed, which suggests
phenolic proton release due to Mn(II) coordination to Orange
II with the formation of a six-membered ring structure instead
of coordination to the terminal sulfonato group. At higher
concentrations (above ca. 10�3 M) Orange II forms dimers and
higher aggregates in aqueous solutions,30,36 and has a marked
effect on the observed spectra, particularly UV-Vis and NMR.37
A Benesi-Hildebrand treatment of the optical data to determine
Keq could not be applied since the concentration of Orange II
and MnII were close to each other.38 Using Job’s method,39 the
stoichiometry of the formed complex could be determined.
According to the data shown in Fig. 3B and D, at lower MnII
concentration the formation of a complex with a stoichiometry
of 1 : 1 can be assumed. On increasing the Orange II concen-
tration further, complexes with a higher stoichiometry are
possibly formed (see Fig. 4A and B).
Similar structures have been reported earlier by Nadtochenko
and Kiwi when a Fe3+ salt was added to an Orange II solution
in acidic medium.40 Bauer also reported a TiIV complex,
where TiIV is coordinated by two oxygen atoms from the
sulfonato group and the oxygen of the carbonyl group of the
Fig. 3 (A) Change in absorbance at 480 nm on addition of different concentrations of Mn2+ to 5 � 10�5 M Orange II in aqueous carbonate
solution (0.2 M HCO3�) at pH 8.5 and 22 1C. (B) Job plot analysis for complex-formation between Orange II and Mn2+ in aqueous carbonate
solution (0.2 M HCO3�) at pH 8.5. (C) Spectral changes at 480 nm on addition of different concentrations of Orange II to a freshly prepared
5 � 10�5 M Mn(NO3)2 carbonate solution (0.2 M HCO3�) at pH 8.5 and 22 1C. (D) Job plot analysis for the complex-formation in aqueous
carbonate solution (0.2 M HCO3�).
Fig. 4 (A) Proposed structure for a 1 : 1 Orange II� � �Mn2+ complex
formed in a carbonate buffer solution at a low concentration of Mn2+.
(B) Proposed structure for a 1 : 2 Orange II� � �Mn� � �Orange II
complex formed in a carbonate buffer solution at a high concentration
of Orange II.
38 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
hydrazone tautomer.41 In the enzyme manganese peroxidase,
the double role of Orange II as a stabilizer, forming a complex
with MnIII, and as a substrate that permits the regeneration of
MnII, was recently postulated by Lopez et al.35 Although, the
coordination of organic dyes, viz. Alizarin, Alizarin S42 and
Orange II,3 to several transition metal centres has been known
for years, comparatively little has appeared on their use as
potential stabilizing ligands in oxidative degradation of
organic dyes.
The formed Orange II� � �MnII complex was isolated and the
validity of its composition was confirmed by elemental ana-
lysis. In control experiments the reactivity of the isolated 1 : 1
Orange II� � �MnII and 2 : 1 complexes were studied. The
isolated complexes exhibit the same catalytic activity and
stability under the experimental conditions employed for the
in situ generation of the complex. Due to the weak coordina-
tion mode of the ligand, no differences between the catalytic
activity of the 1 : 1 and 2 : 1 complex were found.
Beside UV-Vis measurements and DFT calculations,
electrochemical measurements were used to study the in situ
formation of highly reactive MnII catalytic species in
the presence of Orange II under the selected experimental
conditions.
CV studies on the complex-formation between Orange II
and Mn2+
CV measurements of a 4 � 10�5 M Mn2+ solution in the
presence of different Orange II concentrations were performed
in order to determine the interaction between the fully aquated
Mn2+ ions and Orange II present in the reaction mixture.
Fig. 5 shows the results of MnII� � �Orange II complex forma-
tion in NaCl electrolyte solution, performed using a standard
three electrode electrochemical setup as described above.
To avoid the oxidation of MnII to MnIV, which precipitates
as MnO2, the potential scan was discontinued at +1.0 V, after
which the reverse scan from +1.0 to �0.8 V was started. The
CVs of Mnaq2+ in the absence of any coordinating substrate
exhibit one quasi-reversible oxidation peak at E = +0.59 V
vs. Ag/AgCl and one quasi-reversible reduction peak at E =
+0.35 V, corresponding to the one electron Mn3+/Mn2+
redox couple. In addition, CV measurements on a freshly
prepared 4 � 10�5 M Orange II electrolyte solution at
pH 8.5 and 22 1C were performed. Orange II, as it can be seen
in Fig. 5, undergoes two electrochemically quasi-reversible,
one-electron reductions with CV half-wave potentials at
Ered1 = �0.19 V and Ered2 = +0.11 V (vs. Ag/AgCl) with a
difference between the cathodic and anodic wave of 0.02 and
0.204 V, respectively. Furthermore, the reduction potential of
Mn3+ decreased from +0.35 V to +0.28 V when Orange II
was added to the solution, indicating the stabilization of
Mn3+ ions. In the presence of a chelating substrate, the
generated Mn3+ complex becomes more stable and the redox
potentials attain lower values.43 When the concentration of
Orange II was increased up to 2 � 10�5 M, the presence of
further reduction peaks along with changes in the oxidation
peak intensity were observed, indicating the formation of
other manganese–Orange II species as specified above.
DFT calculations
To assess the coordination mode of Orange II to the Mn(II)
center, DFT (B3LYP/LANL2DZp) calculations were per-
formed for a series of plausible complexes. Orange II in
aqueous solution under the selected experimental conditions
dissociates into an anionic sulfonate group and a cationic
sodium ion. In the presence of an unsolvated SO3� group
involving charge transfer from the electron-rich sulfonate
group onto the rest of the molecule, may in general not give
satisfactory DFT results.28 Solvent Yellow 14, a model com-
pound for Orange II containing no sulfonate group was
selected for the DFT study of the interaction between the
Mn(II) and the chosen azo dye. A picture of the calculated
conformers of the model compound 1 is shown in Fig. 6.
The optimized geometry of 1a was calculated to be
ca. 5.8 kcal mol�1 lower in energy than that of 1b. Further-
more, the calculated structure of 1a was compared with X-ray
structural data of Solvent Yellow 14.44 A good agreement
between calculated and crystallographically determined struc-
ture was found.
According to the UV-Vis and electrochemical data pre-
sented above, Orange II can coordinate to a fully aquated
Mn2+ center. Different plausible interaction modes of Solvent
Yellow 14� � �MnII (2) and Solvent Yellow 14� � �MnII� � �SolventYellow 14 (3) were studied in detail. Optimized structures of 2
adopting different coordination modes are presented in Fig. 7.
The studied organic dye can coordinate to aquated Mn2+
ion by forming two new bonds, one between Mn2+ and the
deprotonated phenolic OH-group of 1a and the second
between Mn2+ and one of the azo nitrogen atoms, leading
Fig. 5 CVs of a 4 � 10�5 M Mn2+ electrolyte (0.1 M NaCl) solution in the presence of different Orange II concentrations at pH 8.5 (adjusted by
addition of NaOH) and 22 1C.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 39
to the formation of either a planar six-membered (2a) or five-
membered (2b) chelate complex. Furthermore, a second inter-
action mode for 2 involving a hydrogen bond between one
coordinated water molecule and the azo nitrogen atom (2c)
was taken into consideration. The calculated energies indi-
cate that 2a is energetically favoured over 2b by about
3 kcal mol�1. The N–N bond length of 1.30 A for 2a is nearly
identical to that found in the free model molecule 1a (1.28 A),
indicating a weak interaction between the nitrogen atoms and
the positively charged manganese center.
In addition to these structures, DFT calculations were
performed for a further possible interaction of a second dye
molecule with the Mn(II) center leading to the formation of
chelated Mn(II) inner-sphere complexes. Similar transition
metal complexes of ortho-hydroxy azo dyes were prepared
and characterised by Drew and Landquist.45 The introduction
of a second dye molecule is expected to have certain advan-
tages. In addition to the usual stabilization by the chelate-
effect, the introduction of a second molecule of 1a could result
in a protecting effect on the coordination framework. The
optimized structure of 3 is presented in Fig. 8.
The calculated structure of 3 shows a C2-symmetry and the
axial positions are nearly equivalent. The calculated Mn–N
bond lengths in the equatorial plane for the energetically
favoured 2a (2.15 A) and 3 (2.30 A) are comparable with the
X-ray structural data for Mn(II) complexes with nitrogen
containing ligands such as 1,2-bis(imidazol-1-yl)ethane (bim)
(2.213–2.294 A),46a 2-[N,N-bis(2-pyridylmethyl)amoniumethyl]-6-
[N-(3,5-di-tert-butyl-2-oxidobenzyl)-N-(2-pyridylamino)amino-
methyl]-4-methylphenol (H2Ldtb) (2.118–2.237 A)46b and
1,4,7-triazacyclononane (tacn) (2.118–2.146 A).46c
As expected, upon coordination of two dye molecules in 3,
the N–N bond distance becomes longer (1.29 A) than observed
in the crystal structure of 1a due to the partial neutralization
of the delocalized negative charge of the nitrogen atom.
The elongation of the Mn–O bond trans to the azo group
(Mn–O = 2.38 A vs. 2.06–2.27 A for 2, and Mn–O = 2.27/
2.26 A vs. 1.81/2.11 A for 3) exerts a significant trans influence
Fig. 6 Optimized (B3LYP/LANL2DZp) structures of 1a and 1b with a planar geometry and dihedral angles of (a) 180.01 and (b) 178.71 about the
azo group, C–N–N–C.
Fig. 7 Optimized structures of complex 2a, b and c (B3LYP/LANL2DZp).
Fig. 8 Optimized structure of 3 (B3LYP/LANL2DZp).
40 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
opposite to the Mn–N bond. The increased lability of the axial
ligand allows the subsequent interaction of the substituted
transition metal atom with an oxidant, leading to the
rapid formation of active oxidizing species. Moreover, DFT
calculations performed by Blomberg et al.47 suggest that in the
presence of weak-field ligands for Mn(II) and Mn(III), five-
coordination is also accessible whereas Mn(IV) has a much
stronger preference for six-coordination.47
Complex-formation between bicarbonate and Mn(II)
The reactions between bicarbonate ions (HCO3�) and differ-
ent manganese species have been studied for several years,
since aquated Mn2+ cations themselves are actually not able
to catalyze H2O2 disproportionation. Depending on the
HCO3� concentration in the reaction mixture, MnII� � �HCO3
�
complexes of different stoichiometry can be formed. Recently,
it was suggested that only the neutral MnII(HCO3�)2 complex
can facilitate H2O2 disproportionation.48 In this study the
complex-formation reaction between Mn2+ and HCO3� was
monitored using UV-Vis spectrophotometric beside CV mea-
surements as a function of carbonate concentration at pH 8.5.
UV-Vis spectra recorded before and after addition of HCO3�
to an aqueous Mn2+ solution showed the formation of a new
broad band at 300 nm as illustrated in Fig. 9A. The time
course of the absorption band formation is shown in Fig. 9B.
It can be seen from Fig. 9B that the rate of formation of the
manganese carbonate intermediate is enhanced at higher
carbonate concentration. The observed first order rate con-
stants following the induction period in Fig. 9B, are directly
proportional to the [HCO3�] in the range 0.01–0.1 M
(see Fig. 10) with a second order rate constant of (3.6 � 0.2) �10�2 M�1 s�1 at 25 1C. Moreover, the observed induction
period is probably related to the displacement of water from
the first coordination sphere of the fully aquated Mn2+ ion by
HCO3� and subsequent rearrangement of the coordinated
ligand, viz. formation of bidentate carbonate complexes. It
should be noted that under these experimental conditions
(high carbonate concentration and pH 8.5) insoluble MnCO3
is formed as a very fine white precipitate at longer reaction
times. Its composition was confirmed by elemental analysis
and IR spectroscopy.
The reactivity of the produced intermediate was tested in
the oxidative degradation of Orange II by H2O2 at pH 8.5 and
25 1C. During the first 200 s, no change in the reactivity of the
in situ formed manganese intermediate occurs. A significant
time dependent loss in catalytic efficiency of the formed
MnII� � �HCO3� intermediate was observed. An irreversible
deactivation of the catalyst occurs within less than 20 min.
On the other hand, no precipitate formation as well as no
deactivation of the catalytically active manganese intermediate
could be observed in the presence of a coordinating organic
substrate, i.e. Orange II, over a long period of time (1–4 days)
in a high carbonate (0.5 M) containing buffer solution under
these conditions. Moreover, the stabilization of the in situ
formed active catalyst in the presence of an organic substrate
is of considerable practical interest, because its successful
implementation could offer a more efficient alternative for
clean oxidation reactions.
CV measurements of freshly prepared aqueous Mn(NO3)2solutions were performed in the presence of different carbo-
nate concentrations in a 0.1 M NaCl electrolyte solution at
pH 8.5 (adjusted by careful addition of NaOH) and 22 1C. In
the presence of a coordinating substrate, the displacement of a
coordinated water molecule from the manganese coordination
sphere takes place. By coordination of a negatively charged
ligand such as HCO3� to a positively charged metal, the peak
potentials are shifted to more negative potentials compared to
the fully aquated Mn2+ (see Fig. 11A and 12).41 On increasing
the carbonate concentration in solution a decrease in the peak
current intensity occurs concomitantly with peak broadening
because of complexation by carbonate. Typical multiple scan
CVs of a 4 � 10�5 M Mn2+ solution in the presence of 0.2 M
Fig. 9 (A) UV-Vis spectra of an aqueous 4 � 10�4 M Mn2+ solution before (black curve) and after (red curve) addition of 0.4 M HCO3� at pH
8.5 and 25 1C. (B) Time course of the band formation at 300 nm of an aqueous 2� 10�4 MMn2+ solution containing different amounts of HCO3�.
Fig. 10 Plot of observed first order rate constant (kobs) for the
formation of Mn2+� � �HCO3� vs. the bicarbonate concentration in
the presence of 4 � 10�4 M Mn2+ at pH 8.5 and 25 1C.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 41
NaHCO3 and 0.1 M NaCl at pH 8.5 and 25 1C is presented in
Fig. 11B. In the presence of a chelating substrate, the gener-
ated Mn3+ complex becomes more stable and the redox
potentials attain lower values. Moreover, at higher carbonate
concentrations in the reaction mixture the presence of a second
oxidation peak at E = +0.41 V, attributed to the formation
of further complexes such as proposed in eqn (5), was
observed.
½MnIIðH2OÞ6�2þ þHCO �
3 ÐK1
½MnIIðH2OÞ5ðHCO3Þ�þ
½MnIIðH2OÞ5ðHCO3Þ�þþHCO �3 Ð
K2
½MnIIðH2OÞ4ðHCO3Þ2�ð5Þ
By plotting the peak potential E as a function of the
hydrogen carbonate concentration (see Fig. 12), the presence
of different complex species at different carbonate concentra-
tions is revealed.
Carbonate concentration dependence of the catalytic reaction
course
The effect of the carbonate concentration on the oxidative
degradation of the dye was studied at a constant pH of 8.5.
The total carbonate concentration was varied between
0.05 and 0.5 M.
In the present case, the catalytic reaction leads to a square
dependence of kobs on the HCO3� concentration (Fig. 13) with
a third rate constant (8.3 � 0.3) � 10�2 M�2 s�1, suggesting
that 2 equivalents of HCO3� are involved in the oxidation
mechanism. It is suggested, among other possibilities, that one
equivalent of HCO3� is required for the formation of the more
reactive [MnII(H2O)5(HCO3�)]+ intermediate, and the second
equivalent of HCO3� is required for the formation of the more
reactive peroxocarbonate species, known to be a versatile
oxidizing agent. It should also be noticed that no oxidation
of Orange II by H2O2 was observed in the absence of a
carbonate buffer. In the view of these findings we decided to
study the influence of carbonate on the manganese catalyzed
oxidation of Orange II by H2O2 and HCO4�, respectively.
The reaction of carbonate with H2O2 at pH 8.5 and 25 1C
Peroxycarbonate ions, known to be several orders of magni-
tude more reactive toward nucleophilic substrates than H2O2
itself,49 are formed in a relatively fast pre-equilibrium
(K = 0.32 � 0.02 M�1)40 between hydrogen carbonate ions
and H2O2 shown in eqn (6).
HCO3� + H2O2 " HCO4
� + H2O (6)
Moreover, the reaction of H2O2 and HCO3� to form the more
electrophilic HOOCO2� (HCO4
�) occurs rapidly (t1/2 E 300 s)
at near neutral pH and 25 1C.50 This step is also regarded to be
a key aspect of several oxidation reactions.51,52 The higher
Fig. 11 (A) Cyclovoltammograms for 4 � 10�5 MMn2+ solution in an aqueous solution of 0.1 M NaCl and different concentrations of HCO3�.
(B) Typical multiple scan CVs of a 4 � 10�5 M Mn2+ solution in the presence of 0.2 M NaHCO3 and 0.1 M NaCl at pH 8.5 and 22 1C.
Fig. 12 Plot of peak potential E as function of [HCO3�]; E vs.
Ag/AgCl electrode, [Mn2+] = 4 � 10�5 M, [HCO3�] = 0.1–05 M
in 0.1 M NaCl electrolyte solution at pH 8.5 and 22 1C.
Fig. 13 Second-order carbonate concentration dependence of kobs.
Experimental conditions: 2� 10�5 MMn(NO3)2, 5� 10�5 M Orange II,
0.01 M H2O2, pH 8.5, 25 1C.
42 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
reactivity of peroxycarbonate compared to that of H2O2 is
attributed to carbonate being a better leaving group than
hydroxide.40
By performing the oxidation reactions in the presence of
peroxycarbonate instead of H2O2 in a 0.5 M carbonate con-
taining buffer solution at pH 8.5, no difference in the reactivity
was observed (Fig. 14A).
The Mn(II) catalyzed oxidative degradation of Orange II by
using HCO4� as an oxidizing agent could be significantly
enhanced through increasing the total carbonate concentra-
tion in the reaction mixture. This can be explained in terms of
the equilibrium formulated in eqn (6). Based on our experi-
mental observations and aspects reported in the literature41 for
the Mn(II) catalyzed oxidation reaction by H2O2 in a carbo-
nate containing solution, the reaction sequence presented in
Scheme 2 can be suggested to occur.
Complex-formation between Mn2+
and H2O2 in an aqueous
carbonate solution
Addition of H2O2 to hexaaqua Mn2+ in a carbonate solution
leads to significant spectral changes in the UV-Vis spectra
during the reaction (see Fig. 15A). The initial rapid increase
of the intensity of the broad band at 300 nm, as it is illustra-
ted in Fig. 15A, is attributed to the fast formation of
[MnII(H2O)5(HCO3)]+. An isosbestic point at 330 nm suggests
the formation of a new manganese intermediate by addition of
an oxidizing agent, i.e. H2O2. According to our spectroscopic
observations the formed complex with an absorption band at
400 nm could be attributed to a MnIV–Z2-peroxycarbonate
intermediate.53 Based on spectroscopic observations and data
reported in the literature,54 the formed intermediate can be
regarded as most likely to be a high valent manganese com-
plex. Similar Rh,55 Pt56 and Fe57 peroxycarbonate complexes
have been isolated before and were characterized spectro-
scopically. The time course of the absorption band at 400 nm
at different pH is illustrated in Fig. 15B.
In the absence of any stabilizing ligand, the formed complex
rapidly decomposes with the formation of catalytically
inactive MnIVO2 that precipitates from solution (see Fig. 15B).
The decomposition of the active intermediate is accelerated at
higher pH (see Fig. 15B). To ascertain that the formulated
reaction steps in Scheme 2 are valid under our reaction
conditions, a systematic spectroscopic investigation at differ-
ent pH values was performed. Representative data for the
reaction course at 400 nm at pH 8.5 and 9.5 are presented in
Fig. 15B. Contrary to our expectations, an increase of one unit
in pH resulted in an increase of the induction period and a
decrease in the manganese peroxycarbonate complex forma-
tion rate under the mentioned reaction conditions. This could
be partly due to subsequent formation of Mn(OH)2 precipi-
tates at higher pH and to deprotonation of HCO3� that
becomes significant at pH above 8 to 9.51 This results in a
decrease in the HCO3� concentration in the equilibrium
presented in eqn (6), reducing the concentration of peroxy-
carbonate present in solution.
Reactivity profile as function of pH
The reactivity of the catalytic system is generally influenced by
the protonation state of the substrate, the catalyst and oxidiz-
ing agent. In our work the kinetics was studied in 0.4 M
HCO3� containing buffer solution in the pH range between
8.0 and 9.5 at 25 1C. The pH of the carbonate buffer solution
was adjusted carefully using small amounts of concentrated
NaOH solution to avoid dilution. A typical manganese cata-
lyzed oxidative degradation of Orange II by H2O2 in a
carbonate buffer solution is presented in Fig. 16A. The
catalytic degradation is usually complete within 1–10 min
Fig. 14 (A) Spectral changes observed at 480 nm for the 2 � 10�5 MMn(NO3)2 catalyzed oxidative degradation of 2.5 � 10�5 M Orange II in the
presence of (black curve) 0.01 M H2O2 and (red curve) 0.01 M HCO4�, respectively, at pH 8.5 and 0.5 M total carbonate concentration.
(B). Comparison of the absorbance changes at 480 nm vs. time for the 2 � 10�5 MMn2+ catalyzed oxidative degradation of 5 � 10�5 M Orange II
by 0.01 M H2O2 at pH 8.5 and different carbonate concentrations.
Scheme 2 In situ formation of catalytically active Mn intermediates
in the presence of hydrogen peroxide in a carbonate containing
aqueous solution at pH 8.5 and 25 1C.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 43
depending on the pH of the solution, the catalyst concentra-
tion, and the H2O2 and carbonate concentrations. The decom-
position of the dye was followed by monitoring the spectral
changes at 480 nm. The depletion of the band at 480 nm is in
general correlated with cleavage (heterolytic or homolytic) of
the azo group leading to colorless oxidation products due to
the induced discontinuity in the conjugation of the p-system in
the dye molecule. The inset in Fig. 16A shows the first
spectrum of Orange II before the addition of the catalyst
and H2O2, and the final spectrum recorded after 250 s.
A decrease in the intensity of the two other bands at
270 and 300 nm was observed, showing that further bleaching
also occurs under these reaction conditions. The isolation and
characterization of reaction products is extremely difficult and
requires large synthetic efforts, particularly as different reac-
tion intermediates tend to react further under experimental
conditions. A comparison of the reaction course at different
pH values is shown in Fig. 16B.
The Mn(II) catalyzed decolorization and oxidative decom-
position of Orange II was found to be sensitive to the pH of
the solution. According to our experimental data, an increase
in pH resulted in a slight decrease in the reaction rate under
the above-mentioned reaction conditions and the highest
reactivity is observed at a pH between 8.2 and 8.6
(see Fig. 17). Increasing the pH to 49 leads to a decrease in
the oxidation rate for the bicarbonate-activated peroxide,
which is presumably the result of the deprotonation of
HOOCO2� to form CO4
2�, a less electrophilic oxidant.58
At even higher pH, the decomposition of the peroxide is
accelerated and may reduce the oxidation reaction rate.
Contrary to our expectations, the observed rate constants
for the decolorization reaction of Orange II are similar to
the destruction rate constants of naphthalene and benzene
rings, long-lived intermediates, under the studied conditions
(see Fig. 17). Thus, for a complete oxidation of these stable
molecules higher concentrations of oxidant and catalyst are
required.
A similar screening using MnCl2, Mn(Ac)2 and Mn(SO4)2showed identical catalytic activity in the oxidative degradation
of Orange II by H2O2. In all cases, the manganese catalyzed
oxidative degradation of Orange II is favored by moderate
alkaline pH values and vanishes completely at very high or
very low (strong acidic) values. According to the experimental
observations mentioned above, the manganese catalyzed
oxidative degradation of Orange II by H2O2 in a carbonate
containing solution is considerably inhibited at higher
pH values due to the lower formation of the high valent
manganese Z2-peroxycarbonate complex (see Fig. 15B).
Fig. 15 (A) UV-Vis spectra recorded for the reaction of 2 � 10�4 M Mn(NO3)2 with 0.01 M H2O2 in a 0.5 M HCO3� containing solution at
pH 8.4 and 25 1C. (B) Comparison of typical absorbance at 400 nm vs. time plots at pH 8.5 (black curve) and 9.5 (red curve).
Fig. 16 (A) UV-Vis spectra of a 2 � 10�5 MMn(NO3)2 catalyzed oxidative degradation of 5� 10�5 M Orange II by 0.01 MH2O2 in a 0.4 M total
carbonate containing solution at pH 8.5 and 25 1C. The inset in Fig. 16A shows the first spectrum of Orange II before the addition of the catalyst
and H2O2, and the final spectrum recorded after 250 s. (B) Comparison of absorbance at 480 nm vs. time plots for the 2 � 10�5 M Mn(NO3)2catalyzed oxidative degradation of 5 � 10�5 M Orange II by 0.01 M H2O2 in a 0.4 M total carbonate containing solution at different pH values
and 25 1C.
44 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Effect of the manganese concentration on the oxidative reaction
course
To evaluate the effect of the catalyst concentration on the
manganese catalyzed oxidative degradation of Orange II by
H2O2 under catalytically relevant experimental conditions,
kinetic studies were performed for solutions in which the
carbonate containing water solution with various amounts
of Mn(NO3)2 was added in the presence of 0.01 M H2O2 to a
5 � 10�5 M Orange II solution at 25 1C. The obvious
accelerating ability of the HCO3� ions prompted us to study
the catalytic reaction course in more detail at four different
carbonate concentrations. The in situ produced catalyst con-
centration dependence was studied at 480 nm using in situ
UV-Vis spectroscopic measurements and the kinetic traces
could be adequately fitted to a single exponential function.
Plots of the observed rate constant as a function of [Mn2+] at
different carbonate concentrations are presented in Fig. 18.
As it is evidenced in Fig. 18, the [Mn2+] dependences of the
observed rate constants for the manganese catalyzed oxidative
degradation of Orange II by H2O2 in a low carbonate con-
centration containing solution (0.1–0.3 M HCO3�) are
strongly curved (higher K values, see Table 1) and reach a
limiting value at higher catalyst concentration. In contrast,
similar data at higher carbonate concentrations (0.4–0.5 M
HCO3�) result in a less curved dependence of kobs on the
catalyst concentration, i.e. lower K values (see Table 1). The
observed rate profile can be explained by the general reaction
mechanism proposed in Scheme 2 and simplified in Scheme 3.
The observed rate law for the proposed reaction steps in
Scheme 3 is given by eqn (7). The calculated k and K values
from the non-linear concentration dependences in Fig. 18 are
summarized in Table 1.
kobs ¼kK ½MnðIIÞ�
1þ K ½MnðIIÞ� ð7Þ
Effect of the H2O2 concentration on the manganese-catalyzed
oxidative degradation of Orange II
The effect of H2O2 on the oxidation reaction course was
studied by varying its initial concentration over a wide range,
between 5 and 30 mM (Fig. 19). At lower H2O2 concentrations
(1 and 5 mM) a fast oxidation reaction occurs in the first few
seconds followed by a rapid consumption of H2O2 resulting
finally in a partial and inefficient decolorization of the dye.
This prompted us to study the H2O2 concentration effect on
the catalytic oxidation of the dye at higher concentrations of
H2O2. The kobs values were calculated from a single exponen-
tial fit to the absorbance at 480 nm vs. time plots and showed a
linear dependence on the initial H2O2 concentration over the
studied concentration range.
Stability of the in situ formed catalyst
In control experiments the stability of the in situ generated
catalyst was studied by repeated addition of dye and H2O2 to a
solution of 2 � 10�5 M Mn(NO3)2 at pH 8.5 (0.4 M HCO3�)
and 25 1C (see Fig. 20A and B).
As it can be seen in Fig. 20A, the catalytic cycle could be
repeated several times without any significant loss of activity
during the oxidation reaction, indicating an excellent stability
of the in situ formed catalyst. After the fifth cycle the reactionFig. 18 Mn(NO3)2 concentration dependence of kobs. Reaction con-
ditions: 5 � 10�5 M Orange II, 0.01 M H2O2, pH 8.5 and 25 1C.
Table 1 The constants k and K for theMn(NO3)2 catalyzed oxidationof Orange II by H2O2 at pH 8.5 and 25 1C (see Scheme 3)
[HCO3�]/M k/s�1 10�3K/M�1
0.1 0.0033 34.60.3 0.032 17.60.4 0.051 17.80.5 0.138 15.2
Scheme 3 Proposed reactions steps for the formation of the cata-
lytically active manganese intermediate in the presence of H2O2 in a
carbonate containing solution.Fig. 17 Plot of observed rate constant (kobs) calculated for the
decoloring reaction followed at 480 and 300 nm, respectively. Experi-
mental conditions: 2 � 10�5 M Mn(NO3)2, 5 � 10�5 M Orange II,
0.01 M H2O2, 0.4 M total carbonate and 25 1C.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 45
solution containing the active catalyst was allowed to stay at
ambient temperature for 48 h. Subsequently, the catalytic
activity of the in situ formed manganese complex was evalu-
ated again by performing the oxidation reaction in the
presence of freshly added Orange II and H2O2. The experi-
mental results illustrated in Fig. 20B provide clear evidence for
the high efficiency of the in situ formed catalyst under the
above mentioned experimental reaction conditions.
Mechanistic aspects of the manganese-catalyzed oxidative
degradation of Orange II by H2O2 in carbonate solution
Throughout this study, the oxidation reactions were carried
out in a thermostated open glass reactor vessel at ambient
temperature in aqueous hydrogen carbonate containing solu-
tions. The readily available manganese salts, the mild reaction
conditions and the operation simplicity and practicability
allow for an easy and green oxidative degradation of the
studied organic dye. In control experiments the catalytic
activity of the in situ generated manganese complex was
investigated under an inert atmosphere. By performing the
catalytic reaction in a closed glass reactor under inert reaction
conditions no change in the decomposition reaction rate was
noticed. A comparison of the reaction course carried out
under different experimental conditions is illustrated in
Fig. 21.
By performing the reaction under inert reaction conditions
no significant differences in the decomposition reaction rate was
observed, indicating that HO� or HOO� radical formation
is not prevalent for this oxidation reaction. This is further
supported by the observation that addition of radical traps
such as TTBP had no effect on the reaction course (see Fig. 21).
Taking into account all obtained spectroscopic and kinetic
data, the following reaction schemes can be proposed for the
Mn2+ catalyzed oxidative degradation of Orange II by H2O2
in carbonate solution under catalytically relevant experimental
conditions.
A key feature of the proposed reaction mechanism outlined
in Scheme 4 is that the overall oxidation of Orange II occurs in
a two electron oxidation step leading to the formation of a
relatively stable high-valent MnQO intermediate and transfer
of the oxo group to the substrate. Most of the earlier reported
papers22,59 on the oxidation reaction catalyzed by several
isolated and structurally well defined manganese complexes
have emphasized the formation of a high-valent MnQO
intermediate by the reaction of manganese with the appro-
priate oxidant. According to our observations, HCO3� ions
are involved in two catalytically relevant reactions. HCO3�
ions react with aquated MnII present in solution to form a
catalytically active Mn–HCO3� complex. HCO3
� is also in-
volved in a fast equilibrium with H2O2 to form HOOCO2�,
a versatile heterolytic oxidant. In the following step, through
nucleophilic attack of the oxidizing agent on the MnII center, a
MnII–Z2-peroxycarbonate complex is formed. The remaining
coordination sites in the first shell will be occupied by water
and hydroxyl at a pH between 8 and 10. The principal mode of
the formation of relatively stable high-valent MnQO inter-
mediates is believed to involve the heterolytic cleavage of the
peroxide bond, as shown in Scheme 4. An important role in
the stabilization of the formed MnQO species is played by the
electron donating bicarbonate ions. This may also account for
the unique requirement of HCO3� in the oxidative decom-
position of Orange II catalyzed by simple manganese salts.
The further coordination of the substrate followed by an
oxygen transfer step along with the second electron, leads to
the formation of several oxidation products and finally to the
regeneration of the catalyst. It must be noted that in the
Fig. 19 H2O2 concentration dependence of kobs. Reaction conditions:
5 � 10�5 M Orange II, 2 � 10�5 M Mn(NO3)2, pH 8.5 and 25 1C.
Fig. 20 (A) Spectral changes observed at 480 nm for the repeated addition of 5 � 10�5 M Orange II to a 2 � 10�5 M Mn(NO3)2 solution in the
presence of 0.01 M H2O2 at pH 8.5 and 0.4 M total carbonate concentration. (B) Spectral changes observed at 480 nm for a new addition of
5 � 10�5 M Orange II and 0.01 M H2O2 to a 48 h old reaction mixture containing the catalyst solution under the same experimental conditions as
mentioned in A.
46 | New J. Chem., 2009, 33, 34–49 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
absence of a catalyst, the oxidative degradation of Orange II
by addition of an electrophilic bleaching agent, HOOCO2�,
occurs very slowly under certain reaction conditions. The
oxidation mechanism involves nucleophilic attack of the dye
at the electrophilic oxygen of HOOCO2�. In aqueous solution,
proton transfer can lead to the displacement of HCO3� and
the slow formation of oxidized substrate.
If substrate binding to MnII occurs before the addition of
HOOCO2� to the catalyst solution, following reactions can be
assumed to take place during the reaction cycle under the
chosen experimental conditions.
In line with the concerns mentioned above, the first step in
Scheme 5 involves the prior coordination of Orange II to MnII
and formation of MnII–Orange II complexes of different
stoichiometry, followed by nucleophilic attack of the oxidant
on the MnII center leading to the formation of Orange
II–MnII–peroxycarbonate species. The subsequent scission of
the peroxo bond leads to the formation of high-valent oxo
intermediates, as formulated in Scheme 4. In this case, the
formed MnIVQO intermediate is stabilized by Orange II, an
electron rich organic molecule with chelating capacity. The
importance of Orange II as an equatorial ligand is also to
favor the heterolytic scission of the peroxo bond leading to the
MnIVQO intermediate and bicarbonate.
Conclusions
A fast and environmentally benign method for the oxidative
degradation of Orange II could be achieved using H2O2 in
conjunction with catalytic amounts of relatively non-toxic
manganese salts as catalyst precursors in a carbonate contain-
ing aqueous solution under mild reaction conditions. Screen-
ing and spectroscopic methods allowed us to study the
catalytic reaction course and to identify some key features of
the reaction that reflect upon its mechanism. Our study
revealed that the oxidative degradation of the model substrate
Orange II is catalytic only in carbonate containing aqueous
solution. No other buffer containing aqueous solution could
induce the oxidative degradation of Orange II by H2O2 and
this led to the implication of peroxycarbonate as a key
molecular entity. The reported experimental data suggests that
the in situ formed high-valent manganese intermediate posses-
sing one hydrogen carbonate ligand is able to activate
H2O2, but decomposes rapidly with the formation of neutral
MnCO3, which precipitates from solution as an insoluble
white solid. One of the main factors affecting the process
efficiency was the stabilization of the catalytically active Mn
complex. Furthermore, by addition of Orange II, the forma-
tion of MnII� � �Orange II complexes with different stoichio-
metry was observed. The simultaneous s,p-coordination of
the organic dye is well-precedented, and recent DFT studies
support this type of complex formation.28 The catalytic
Scheme 4 Proposed reaction mechanism for the Mn(II) catalyzed
oxidative degradation of Orange II by H2O2 in a carbonate containing
aqueous solution at pH between 8–9 and 25 1C.
Scheme 5 Proposed reaction mechanism involving first substrate
coordination to MnII in a pre-equilibrium step during the catalyzed
oxidative degradation of Orange II by H2O2 in a carbonate containing
aqueous solution at pH between 8–9 and 25 1C.
Fig. 21 Comparison of typical absorbance at 480 nm vs. time plots of
a 2� 10�5 MMn(NO3)2 catalyzed oxidative degradation of 5� 10�5 M
Orange II by 0.01 M H2O2 in a 0.4 M HCO3� containing solution at
pH 8.5 and ambient temperature performed in the presence of atmos-
pheric oxygen (black curve), inert atmosphere (red curve) and TTBP
(blue curve), respectively.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 47
activity of the formed intermediates was tested under catalytic
reaction conditions.
The kinetic investigations performed at different pH could
provide relevant information about the nature of the oxidizing
agent involved in the reaction. It was found that the pH is a
critical issue for the rate of the oxidation process due to its
influence on the deprotonation of the bicarbonate ions, the
formation of peroxycarbonate in solution, and the deprotona-
tion of aquated Mn2+. The ongoing studies are presently
complemented by investigations on different organic sub-
strates with various functional groups in order to determine
the influence of substrate modification on the catalytic
reaction cycle. DFT studies beside further kinetic and spectro-
scopic investigations should contribute to a better understanding
of the catalytic system.
Acknowledgements
The authors kindly acknowledge fruitful discussions with
Dr Anette Nordskog and Dr Wolfgang von Rybinski, Henkel
KGaA, Dusseldorf, Germany.
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 34–49 | 49
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PAPERT. Yong-Jin Han et al.The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene in a 3-ethyl-1-methylimidazolium acetate–DMSO co-solvent system
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Submit your work now!Supporting the
The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene
in a 3-ethyl-1-methylimidazolium acetate–DMSO co-solvent system
T. Yong-Jin Han,* Philip F. Pagoria, Alexander E. Gash, Amitesh Maiti,
Christine A. Orme, Alexander R. Mitchell and Laurence E. Fried
Received (in Gainesville, FL, USA) 17th June 2008, Accepted 6th August 2008
First published as an Advance Article on the web 18th September 2008
DOI: 10.1039/b810109d
Ionic liquids have previously been shown to dissolve strong inter- and intramolecular hydrogen-
bonded solids, including natural fibers. Much of this solubility is attributed to the anions in ionic
liquids, which can disrupt hydrogen bonding. We have studied the solubility and recrystallization
of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a very strong inter- and intramolecular hydrogen-
bonded solid, in various ionic liquid solvent systems. We discovered that acetate-based ionic
liquids were the best solvents for dissolving TATB, while other anions, such as Cl�, HSO4� and
NO3� showed moderate improvements in the solubility compared to conventional organic
solvents. Ionic liquid–DMSO co-solvent systems were also investigated for dissolving and
recrystallizing TATB.
1. Introduction
Ionic liquids (ILs) have recently been shown to be ideal
solvents for dissolving hydrogen-bonded solids, including
cellulose1 and natural fibers.2,3 The use of imidazolium-based
cations with halides as counter-anions has significantly im-
proved the solubilities of these natural products. Successful
dissolution of these highly hydrogen-bonded solids is largely
attributed to the ability of ILs’ anions to act as hydrogen bond
acceptors and disrupt the hydrogen bonds in these materials.1
With a graphite-like crystalline structure,4 1,3,5-triamino-
2,4,6-trinitrobenzene (TATB) is one of the most strongly
hydrogen-bonded solids known. Owing to its inter- and intra-
molecular hydrogen bonds, both in-plane and out-of-plane
(see Fig. 1), the solubility of TATB in conventional organic
solvents is minuscule. With a capacity to dissolve 70 ppm
(0.007% w/v) at room temperature,5 DMSO is the best con-
ventional organic solvent known to dissolve TATB. Super-
acids, such as concentrated sulfuric acid, have been shown to
dissolve up to ca. 240 000 ppm (24% w/v) at room tempera-
ture,5 but due to their highly corrosive nature are often
avoided. There is a need to find a desirable solvent for TATB
as it has become necessary to control the particle size, as well
as the morphology, of TATB crystals.
TATB is of particular interest in the energetic materials
(EM) community due to its extreme insensitivity to impact,
shock and heat, while providing a good detonation velocity.6
This combination of insensitivity with good performance
characteristics makes TATB an ideal insensitive high explosive
(IHE) in numerous applications. TATB has also attracted
researchers from the field of optics, due to its unexpectedly
strong secondary harmonic generation (SHG) efficiency.7 The
source of the nonlinear optical (NLO) property of TATB has
been a topic of intense discussion,8,9 since the original crystal
structure determined by Cady and Larson showned4 TATB to
have a centrosymmetric structure with the space group P�1,
Z = 2, which is incompatible with NLO activity. Some have
attributed the NLO activity of TATB to a small amount of a
second, presently unidentified, TATB polymorph mixed in
with the bulk centrosymmetric TATB crystals.10,11 Therefore,
identifying a suitable solvent system that can increase the
Fig. 1 The crystal structure of TATB, a centrosymmetric structure
with space group P�1, Z = 2. (a) A–B plane view, (b) C plane view.
Chemistry, Materials, Earth and Life Sciences Directorate, LawrenceLivermore National Laboratory, Livermore, CA 94551, USA.E-mail: [email protected]
50 | New J. Chem., 2009, 33, 50–56 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
solubility of TATB may also allow a new opportunity to
crystallize and isolate the potential second polymorph with
exceptional SHG efficiency.
Herein, we report the solubility of highly hydrogen-bonded
TATB in both commercially available and custom synthesized
imidazolium-based ILs. In particular, 3-ethyl-1-methylimida-
zolium acetate (EMImOAc) was extensively investigated in
its pure form, as well as in combination with DMSO as a
co-solvent.
2. Experimental
2.1 Materials
3-Ethyl-1-methylimidazolium chloride (EMImCl), 3-butyl-1-
methylimidazolium chloride (BMImCl), 3-ethyl-1-methyl-
imidazolium acetate (EMImOAc), 3-ethyl-1-methylimidazolium
nitrate (EMImNO3), 3-butyl-1-methylimidazolium hydrogen
sulfate (BMImHSO4) and DMSO were purchased from
Sigma-Aldrich, and used without purification unless otherwise
noted. Vacuum distillation was performed on EMImOAc to
remove any impurities prior to experiments.
3-Allyl-1-methylimidazolium chloride (AllylMImCl) was
synthesized according to a published report.12 3-(Methoxy-
methyl)-1-methylimidazolium chloride (MeOMImCl) was
synthesized using a modification of the procedure reported
for the synthesis of AllylMImCl.
Synthesis of 3-(methoxymethyl)-1-methylimidazolium chloride
(MeOMImCl). Into a 500 mL round-bottomed flask equipped
with a stirrer bar, argon inlet and addition funnel, was
dissolved 1-methylimidazole (25 g, 0.31 mol) in trichloro-
ethylene (100 mL). With stirring, chloromethyl methyl ether
(35 g, 0.43 mol) was added dropwise over a 0.5 h period. The
mixture was warmed and a turbid, two-layer mixture formed.
The mixture was refluxed for 2 h, cooled and poured into a
separating funnel. The organic layer was separated, filtered and
the solvent removed under vacuum at 45 1C to yield a
tan-beige viscous liquid (52 g).
2.2 Solubility measurements
Small scale solubility tests (o10 mg) of TATB in ILs
were monitored with a Nikon optical microscope equipped
with a temperature controlled heating stage, under cross-
polarized light.
Large scale solubility measurements were performed using a
three-necked round-bottomed flask in a silicone oil bath
at a constant temperature of 100 1C. Due to its high density
(1.93 g cm�3) and bright yellow color, visual inspection of
TATB particles in solutions was easily achieved with the aid of
a hand-held flashlight.
2.3 Crystallization
A non-agitated cooling crystallization method was employed
to grow TATB crystals from a DMSO–EMImOAc co-solvent
system. Typically, in a 250 mL round-bottomed flask equipped
with a drying tube and a thermocouple, TATB (4 g) was
added, along with 100 g of DMSO–EMImOAc (80 : 20 w/w).
The solution was slowly heated to 90 1C with constant stirring.
Once all of the TATB had dissolved, the solution was slowly
cooled back down to room temperature without stirring.
Occasionally, an Omega (series 2010) programmable controller
was used to control the cooling rate.
For a typical anti-solvent crystallization, 20 mL of an 80 : 20
DMSO–EMImOAc solution was placed in a four-necked
100 mL round-bottomed flask equipped with an overhead
stirrer, drying tube, thermocouple and septum inlet. To this
was added TATB (0.5 g), and the mixture was stirred and
heated slightly (50 1C) until all of the TATB had dissolved and
a red-orange solution had formed. The temperature of the
sample was maintained at the desired temperature using a
J-KEM temperature controller. The mixture was stirred slowly
as a solution of acetic acid (4 g) in dry DMSO (40 mL) was
added via a syringe and long needle connected to a syringe
pump, set to deliver at 2 mL h�1. The resulting TATB was
collected by suction filtration, and washed with water (25 mL)
and MeOH (10 mL) to yield 0.46 g of a yellow microcrystalline
solid. Raman spectroscopy was used to determine the purity of
the recrystallized TATB.
3. Results
3.1 Solubility of TATB in ILs
There are certain advantages that ILs have over conventional
solvents that make them an attractive alternative for the
dissolution of TATB. ILs, because of their inherent low vapor
pressure and high-temperature stability, have reduced environ-
mental and safety concerns compared to conventional
organic solvents. Also, in theory, the IL is recoverable after
precipitation or distillation of impurities from it.
The solubility of TATB was first investigated in BMImCl,
since BMImCl has previously been shown to dissolve
cellulose,1 Bombyx mori silk fibers2 and wool keratin fibers3
in relatively high concentrations (10, 13.2 and 4 wt%, respec-
tively at 100 1C). A solution of 0.5 wt% of TATB in BMImCl
was stirred rapidly at 100 1C for 20 h. However, at the end of
the 20th hour, there were still TATB particles present in the
flask. The color of the solution was only slightly yellow
(the color of the original TATB powder), signifying that only
a small amount of TATB had dissolved. Similar results were
observed for other ILs with Cl� anions, including EMImCl
and custom synthesized AllylMImCl (see Table 1). As noted
previously, short chain-substituted imidazolium-based ILs
with Cl� anions have been effective in dissolving natural
polymers. The hydrogen bond-accepting Cl� anion is thought
to be the crucial component in disrupting hydrogen bonding in
the biopolymer.1 However, for TATB the hydrogen bond
disruption caused by the Cl� ions was not strong enough to
significantly dissolve TATB particles.
In an attempt to improve the solubility of TATB, a new
imidazolium-based cation, 3-methoxymethyl-1-methylimida-
zolium chloride (MeOMImCl), was synthesized. Unlike the
BMIm and EMIm cations, which may have limited, if any,
hydrogen bond-accepting capability, the ether side chain of
MeOMImCl is a hydrogen bond acceptor13 and may assist in
disrupting the strong hydrogen bonding of TATB. However,
when 0.5 wt% of TATB was added to MeOMImCl and heated
with stirring at 100 1C for 20 h, no significant quantity of
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 50–56 | 51
TATB dissolved, similar to BMImCl and EMImCl, which was
visually evident. This result suggests that even with an active
cation, the overall hydrogen bond-accepting capacity of
MeOMImCl is not significant enough to disturb the hydrogen
bonding network of TATB crystals.
The effects of anions other than Cl� in dissolving TATB
were also examined. For this study, BMImHSO4, EMImNO3,
and EMImOAc were selected and tested. These ILs were
chosen for their anions’ hydrogen bond-accepting capability.
As anticipated, BMImHSO4 and EMImNO3 had very similar
results compared to BMImCl, each showing less than 0.5 wt%
solubility of TATB at 100 1C. However, EMImOAc showed a
surprisingly good solubility of TATB. At 100 1C in a large
scale test, EMImOAc was able to dissolve up to 10 � 1.0 wt%
of TATB, confirmed by visual inspection. There was, however,
a noticeable difference in the color of the acetate solution when
compared to the solutions from the other anions (Fig. 2A
inset). When TATB was added to EMImOAc and heated, the
entire mixture turned a dark blood-red color, whereas in the
other ILs, no color change was observed (at times, some
turned slightly yellow, the original color of the TATB crys-
tals). The source of this color change was investigated by
UV-vis spectrophotometry. As seen in Fig. 2A, TATB added
to EMImOAc (diluted 100 times with DMSO) clearly shows a
pronounced peak at lmax = 409 nm, whereas TATB dissolved
in DMSO only shows a TATB absorbance at lmax = 357 nm.
The origin of the peak at lmax = 409 nm can be assigned to a
s-complex. We also carried out a Raman spectroscopy measure-
ment of the s-complex (Fig. 2B). The peaks observed at
807 and 1149 cm�1 correspond well to a previously reported
signature of a s-complex.14 The formation of a s-complex
with TATB was described during the synthesis of TATB by the
vicarious nucleophilic substitution of hydrogen.15 Selig also
assigned the absorption band at 409 nm to a s-complex
between strong bases and TATB.5
3.2 Crystallization of TATB
The primary need for a solvent system that will readily dissolve
TATB is to improve overall processability. More specifically,
high solubility is necessary to produce high quality crystals
from a supersaturated solution of TATB. Therefore, crystal-
lization experiments were performed using EMImOAc via a
non-agitated cooling method. An optical microscope fitted
with a heating stage was used to study the recrystallization of
TATB in EMImOAc. A few drops of TATB particles in
EMImOAc (4 wt% solution) were placed on a cover slip on
a heating stage. The mixture was heated to 100 1C and kept at
this temperature until all of the particles had dissolved (Fig. 3a
and b). The homogeneous solution was cooled slowly by
natural convection. From the saturated solution, crystals
started to emerge when the temperature reached 70 1C. Over
time, single, well-faceted crystals of TATB appeared and grew
larger (Fig. 3c and d). These crystals were far better than the
starting TATB crystals, which were almost all aggregates with
few, if any, well defined facets.
Table 1 The solubility of TATB in various IL systems at 100 1C
IL R X� TATB solubility (wt%)
BMImCl CH3CH2CH2CH2 Cl� o0.5EMImCl CH3CH2 Cl� o0.5AllylMImCl CH2QCH Cl� o0.5MeOMImCl CH3OCH2 Cl� o0.5BMImHSO4 CH3CH2CH2CH2 HSO4
� o0.5EMImNO3 CH3CH2 NO3
� o0.5EMImOAc CH3CH2 CH3COO� 10
Fig. 2 (A) UV-vis spectra of TATB dissolved in DMSO and the
DMSO–EMImOAc system. The inset shows a photograph of TATB
dissolved in DMSO (left) and in EMImOAc (right). (B) Raman
spectra of (a) TATB, (b) EMImOAc in DMSO, (c) TATB dissolved
in EMImOAc–DMSO solution; the peaks at 807 and 1149 cm�1 are
signatures of a s-complex.
52 | New J. Chem., 2009, 33, 50–56 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Similar recrystallization experiments were performed on a
larger scale (100 mL volume). However, due to the viscosity of
EMImOAc at room temperature, it was difficult to filter and
isolate the recrystallized TATB. In order to lower the viscosity
of EMImOAc, DMSO was added as a co-solvent. When
DMSO was added, the solubility of TATB decreased linearly
with respect to the DMSO concentration (Fig. 4).
However, even with the DMSO concentration as high as
80 wt%, the solubility of TATB was still significantly high,
approximately 4 wt%. Recrystallization experiments were
performed using an 80 : 20 DMSO–EMImOAc solution
(80 wt% DMSO, 20 wt% EMImOAc). Upon heating this
solution with TATB to 90 1C, a color change was once again
observed, signifying the formation of a s-complex. Once the
added amount of TATB had fully dissolved, the solution was
allowed to cool to room temperature by natural convection,
allowing crystals to form. The recrystallized TATB was re-
covered by simple vacuum filtration. It was visually apparent
that the filtrate contained a significant amount of the s-complex.
Therefore, the addition of excess water or another proton
donor (i.e. acetic acid) was necessary in order to fully recover
the remaining TATB dissolved (ca. 1 wt%) in the filtrate. SEM
micrographs of the recrystallized TATB crystals showed good
crystal morphology (Fig. 5a) compared to the starting crystals
(Fig. 5b). The crystal sizes of the recrystallized TATB ranged
from 10–50 mm. On the other hand, the water crash-precipi-
tated crystals showed an irregular crystal morphology, with
crystal sizes that ranged from sub-500 nm–5 mm (Fig. 5c). The
Raman spectrum of the recrystallized TATB crystals con-
firmed that the structure of the recrystallized TATB matched
well with that of the starting material (Fig. 6).
Besides the non-agitated cooling method of TATB crystal-
lization, we also investigated an anti-solvent crystallization
method. As seen from the non-agitated crystallization method
above, a s-complex, which forms when TATB is dissolved in
EMImOAc, requires a proton source to fully convert it back to
TATB at room temperature. Thus, we employed acetic acid as
an anti-solvent to provide the necessary proton for the reac-
tion. Acetic acid, a weak acid, was chosen to limit the rate of
reaction to avoid the crash precipitation of TATB. Preliminary
experiments showed that the concentration and rate of addi-
tion of acetic acid is critical in controlling the overall size of
the recrystallized TATB. The overall morphology of the
TATB crystals formed by this method showed a significant
improvement compared to the starting materials. By carefully
controlling the rate of addition, significantly large TATB
crystals (o500 mm) could be formed via this method.
Fig. 3 Optical images of TATB dissolving and recrystallizing in
EMImOAc: (a) at room temperature, (b) at 100 1C, (c) at 70 1C and
(d) cross-polarized light view of image (c).
Fig. 4 The solubility curve of TATB in the DMSO–EMImAOc
system.
Fig. 5 SEM micrographs of TATB (a) recrystallized from EMImOAc,
(b) starting material and (c) H2O-precipitated material.
Fig. 6 Raman spectra of (a) starting TATB and (b) recrystallized
TATB.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 50–56 | 53
4. Discussion
In order to determine the ineffectiveness of ILs in solubilizing
TATB compared to cellulose, the cohesive energy density
(CED) of the two systems was compared. CED is often
expressed in its square-root form, known as the solubility
parameter, d. For cellulose, a variety of measurements, in-
cluding mechanical and surface free energy measurements,
suggest a value of d B 25 MPa12.16 For TATB, the heat
of sublimation (i.e. cohesive energy per molecule) is
B40.2 kcal mol�1.17 This, coupled with a molar volume of
221.2 A3 in the crystal phase,4 yields a value of dB 35.5 MPa12.
In other words, the CED (= d2) of TATB is approximately
2 times that of cellulose, explaining why the former is more
difficult to dissolve than the latter. The above-obtained solu-
bility parameter can be used as an approximate tool to screen
solvents for TATB. As an example, we note that the conven-
tional water-soluble IL, BMIm+BF4�, has a solubility para-
meter near to d = 26.5 MPa12.18 Given that TATB has a much
higher value of d, we expect the solubility of TATB to be poor
in such prototypical solvents in the absence of chemical
modification. In order to understand the reason for the higher
CED in TATB, we employed first-principles density functional
theory (DFT) using the program DMol3 19–22 to compute the
interlayer van der Waals binding and the intralayer (inter-
molecular) hydrogen bond contribution to the total cohesive
energy. We found that these two energies were comparable,
with the van der Waals contribution being almost 90% that of
the hydrogen bond contribution. The hydrogen bonds them-
selves have an average strength of B3.5 kcal mol�1, slightly
stronger than the hydrogen bonds in cellulose.23
The remarkable solubility of TATB in EMImOAc com-
pared to other ILs was initially very puzzling. Since the cation
of the ILs doesn’t seem to affect the solubility of TATB, we
concluded that the acetate moiety plays a key role in solubiliz-
ing TATB. TATB dissolved in EMImOAc produces a deep red
color, observed at lmax = 409 nm. The origin of this peak can
be assigned to a s-complex. There are many reviews on the
mechanism of the formation of s-complexes in intermolecular
nucleophilic displacement reactions involving electrophilic,
nitro-activated aromatic substrates.24 The mechanism gener-
ally involves the addition of a nucleophile to a position on the
electrophilic aromatic ring that results in the stabilization of
the negative charge by an ortho- and/or para-substituted nitro
group. The structure of the s-complex is shown in Fig. 7 and
consists of a cyclohexadienyl anion, in which the carbon center
that undergoes substitution is converted to an sp3-hybridized
center. The resulting negative charge may be delocalized into
the nitro groups, thus stabilizing the s-complex. Most studies
on the formation of s-complexes investigated 1-substituted-
2,4-dinitro- or 1-substituted-2,4,6-trinitrobenzenes, and very
few s-complexes of fully-substituted aromatic rings are
known. In the TATB molecule, because of its high-symmetry,
there are three equivalent positions at which the acetate anion
may react to produce the s-complex. The s-complex would be
stabilized by the presence of the three nitro groups at the 2-, 4-
and 6-positions relative to the tetrahedral carbon containing
the acetate group. In addition, the stability of the s-complex
relative to TATB would be enhanced by relieving steric
crowding on the TATB ring of the adjacent amino and nitro
groups upon forming the tetrahedral carbon center at the site
of base addition.
TATB added to EMImCl does not form a s-complex. In
order to understand the difference between the action of the
acetate and chloride anions on TATB, we carried out DFT-
based investigations using a state-of-the-art quantum chemical
conductor-like screening model (COSMO)25 and its extension
to real solvents (COSMO-RS).26 This model computes the
chemical potential of a solute in its own environment and in
solvent environments. From the difference between these
chemical potentials, one can estimate the solubility of the
solute in the solvent. Details of the procedure are described
elsewhere.27 Table 2 (column 2) displays the computed solu-
bility of TATB in EMImCl and EMImOAc, respectively. The
computed solubility in EMImCl is in line with the observed
low solubility (i.e. o0.5 wt%) in this solvent. In contrast, the
computed solubility in EMImOAc is 250 times smaller than
the experimentally observed value of 10 wt% at 100 1C. This
result, in conjunction with color changes observed in the
acetate IL solution, indicates that while TATB dissolves in
its pure form in EMImCl, it undergoes some chemical reaction
during its dissolution in EMImOAc. We have also computed
the possibility of a deprotonation mechanism for the observed
solubility in EMImOAc. To do this, we have investigated one
of the simplest reactions, i.e. an NH2 group of TATB loses a
proton to a neighboring anion of the IL (thereby forming an
acetic acid molecule in the acetate IL or a HCl molecule in the
chloride IL), while the unpaired cation of the IL binds to the
ortho position of the deprotonated TATB anion. Column 3 of
Table 2 lists the computed heat of reaction for such a chemical
process using the program Dmol3.20–22 The reaction is highly
endothermic and clearly prohibitive in the chloride IL, but
exothermic and likely to occur in the acetate IL. The above
results can be qualitatively explained based on the stronger
basicity of an OAc� group compared to Cl�. The computed
UV-vis spectrum (using the semi-empirical program
Fig. 7 Schematic of s-complex formation from TATB.
Table 2 COSMO-RS results for TATB dissolution in EMImOAcand EMImCl
SolventTATB solubilityat 100 1C (wt%)a DEdeprotonation/kcal mol�1b
EMImOAc 0.04 �1.6EMImCl 0.10 +22.0
a 1 wt%=1 g 100 mL�1= 10 g L�1. b Energy of the reaction: TATB+
EMIm+Anion� - EMIm+[TATBdeprotonated]� + H-Anion; DE is
positive (negative) for an endothermic (exothermic) reaction.
54 | New J. Chem., 2009, 33, 50–56 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
ZINDO)28 of the deprotonated TATB displayed a sharp peak
at B410 cm�1, which is also in excellent agreement with our
experimental observations. Therefore, we cannot at this point
discount the possibility of alternative chemical pathways of
s-complex formation and the deprotonation mechanism.
We have also attempted to dissolve cellulose in EMImOAc.
Although a recent report29 showed a high solubility of cellu-
lose (Avicel PH-101) in EMImOAc (15 wt%) at 110 1C, the
solubility of our cellulose (Eastman Kodak) in EMImOAc at
100 1C was less than 0.5 wt%. This discrepancy can be
attributed to different cellulose sources and therefore the level
of recalcitrance of the cellulose tested. Our cellulose experi-
ment result supports the idea that the mechanism of solubility
for TATB in EMImOAc is indeed by chemical modification
(rather than by hydrogen bond disruption). It is important to
note that ILs can potentially modify the solute, as with TATB,
to increase its solubility. Therefore, one must be very cautious
in determining the solubility of various solutes in ILs to make
sure that chemical modification of the solute is not the cause of
the observed increase in solubility.
Crystallization of TATB via the non-agitated cooling
method in EMImOAc resulted in an improved morphology
of the TATB crystals obtained compared to the starting
materials. Cooling by natural convection yielded crystals in
the size range of 10–50 mm (Fig. 5a). However, when the
cooling rate was controlled, larger crystals were obtained. As
seen in Fig. 8, when the crystallization solution was cooling at
a rate of 1 1C min�1, 200–500 mm sized crystals were obtained.
One drawback of the cooling crystallization method is that at
room temperature, the amount of recovered TATB is less than
the original amount of TATB added, due to dissolved TATB
in the 80 : 20 solution; the addition of a protic solvent is
necessary to recover the remaining TATB. Thus, an anti-
solvent crystallization scheme was employed as an alternative.
As mentioned above, during our initial attempts to recrystal-
lize of TATB from DMSO–EMImOAc solution, the recovery
of the TATB was rather poor because it is soluble in the
mixture at a 1 wt% level at room temperature. The most
effective anti-solvents of all those tested were hydroxylic
compounds such as organic alcohols and acids. These solvents
provided a proton source that released the acetate from the
s-complex and precipitated the TATB. In addition, some
inorganic acids, such as sodium hydrogen phosphate and boric
acid, were also found to be effective. A limiting factor in the
ability of these inorganic salts to act as an efficient anti-solvent
was their solubility in DMSO. Some had limited solubility,
rendering them less effective in precipitating TATB in good
yields. The addition of gaseous CO2 to the solvent mixture also
precipitated TATB in excellent yields. It is not clear whether
the CO2 acted to neutralize the mixture, making it less basic,
or actually acted as a counter-solvent to precipitate the TATB.
The use of gaseous CO2 is attractive because of its cost and
availability, but it was hard to control the particle size of the
recrystallized TATB when adding CO2 in gaseous form.
The anti-solvent of choice was acetic acid because it was
reasoned that it could be removed from the IL to yield
recovered EMImOAc without contamination from other salts.
Preliminary results show that crystal size and shape are
strongly dependent on the rate of addition and the concentra-
tion of the anti-solvent. Detailed information regarding the
crystallization of TATB via the anti-solvent method will be
published elsewhere.
5. Conclusion
ILs previously shown to dissolve highly hydrogen-bonded
solids were ineffective with TATB. This may be due to the
cohesive energy of TATB, which is almost 2 times that of
cellulose. The remarkable solubility of TATB in EMImOAc
was attributed to the formation of a s-complex or to the
deprotonation of TATB. Owing to the basicity and nucleo-
philicity of the OAc� anion, the s-complex could easily form
in EMImOAc, but not in the presence other anions such as
Cl�. Therefore, the solubility of TATB in EMImOAc is
proportional to the concentration of EMImOAc. The dis-
solved s-complex can revert back to TATB, either via cooling
or by the addition of an anti-solvent. The recrystallized TATB
shows a much improved crystal morphology compared to the
starting material. We are currently performing experiments to
further control the crystallization of TATB by the anti-solvent
crystallization method.
Acknowledgements
This work performed under the auspices of the US Depart-
ment of Energy by Lawrence Livermore National Laboratory
under Contract DE-AC52-07NA27344. The project 06-SI-005
was funded by the Laboratory Directed Research and Develop-
ment Program.
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56 | New J. Chem., 2009, 33, 50–56 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Supramolecular synthesis of some molecular adducts of 4,40-bipyridineN,N0-dioxidew
Kapildev K. Arora, Mayura S. Talwelkar and V. R. Pedireddi*
Received (in Durham, UK) 8th May 2008, Accepted 8th September 2008
First published as an Advance Article on the web 29th October 2008
DOI: 10.1039/b807853j
Molecular adducts (1a–1e) of 4,40-bipyridine N,N0-dioxide, 1, respectively with cyanuric acid,
trithiocyanuric acid, 1,3,5-trihydroxybenzene (phloroglucinol), 1,3-dihydroxybenzene (resorcinol)
and 1,2,4,5-benzenetetracarboxylic acid have been reported. The major interactions observed in
the structures 1a–1e are N–H� � �O, N–H� � �S, O–H� � �O and C–H� � �O, in the form of homomeric
and heteromeric patterns of the constituents, either as a single or cyclic hydrogen-bonded motifs.
While in the adduct 1a, both homomeric and heteromeric units of both the constituents were
observed, no heteromeric interactions were observed in 1b and 1c. In addition, in 1b, homomeric
aggregation of molecules of 1 occurred in association with water molecules. However, while
heteromeric interactions prevail between the constituents in 1d and 1e, only one of the
co-crystallizing species gave homomeric interactions (4,40-bipyridine N,N0-dioxide in 1d; 1,2,4,5-
benzenetetracarboxylic acid in 1e). Further, in either type of the patterns, the cyclic motifs are
formed as a pair-wise hydrogen bonds comprising of strong and weak hydrogen bonds
(N–H� � �O/C–H� � �O or O–H� � �O/C–H� � �O). In three-dimensions, the ensembles of molecules
yield planar sheets, ladders and pseudorotaxane type assemblies.
Introduction
Design and synthesis of molecular complexes/adducts employ-
ing noncovalent interactions such as hydrogen bonds, which is
broadly defined as supramolecular synthesis, aims at creation
of exotic functional solids and in this connection, exploration
of novel ligands is a continuous process.1 Thus, a variety of
ligands of different molecular dimensions and functional
properties were utilized for the preparation of numerous
supramolecular assemblies of exotic architectures as reported
in the recent literature.2 Among those, 4,40-bipyridine (bpy) is
well studied, especially as a spacer molecule, both in organic
and organic–inorganic hybrid complexes. It was mainly due to
the ability of bpy to form either O–H� � �N only or O–H� � �N/
C–H� � �O pair-wise hydrogen bonds and also dative bonds
with metal ions in conjunction with carboxyl/carboxylate and
many other functional moieties.3
In further exploration and thrust to identify other spacer
molecules, compounds that mimic bpy topologically, for ex-
ample, 1,2-bis(4-pyridyl)ethene and ethane, 1,3-bis(4-pyridyl)-
propane etc., evolved as novel ligands for the preparation of
the tailor-made supramolecular assemblies of desired archi-
tectures and properties.4 Also, in recent times, 4,40-bipyridine
N,N0-dioxide (N-oxide derivative of bpy), 1, has been well
considered in the synthesis of coordination assemblies, but
corresponding organic supramolecular assemblies are limited.5
Since the N-oxide, 1 is a potential hydrogen bond acceptor to
establish interaction with complementary functionalities such as
–OH, –COOH, –NH, –CONH2 etc., it is rather surprising that
1 was not utilized, so effectively, in the supramolecular synthesis
of organic assemblies, as only a few reports are known in the
literature.6 Apart from it, the native structure of 1 itself is not
known in the literature. Thus, we are interested to elucidate the
structure of 1 and also study its application in the molecular
recognition and supramolecular synthesis with different organic
functional moieties such as –OH, –COOH, which are well
known to yield discrete molecular recognition patterns.1c,3b,d
In this direction, our attempts to obtain single crystals of
suitable quality for structure elucidation of 1 are not successful
yet, but co-crystallization experiments of 1 with cyanuric acid,
trithiocyanuric acid, 1,3,5-trihydroxybenzene (phloroglucinol),
1,3-dihydroxybenzene (resorcinol) and 1,2,4,5-benzenetetra-
carboxylic acid, possessing different functional moieties, as
shown in Chart 1, gave molecular complexes in the form of
single crystals. The structural features of these unusual
molecular adducts, unravel by single-crystal X-ray diffraction
methods, are described in this article.
Results and discussion
Solid state structure of molecular complex, 1a, of 4,40-bipyridine
N,N0-dioxide, 1 and cyanuric acid (CA)
Co-crystallization of 1 and cyanuric acid, CA, from a methanol
solution gave good quality single crystals, 1a, in a 1:2 ratio of the
reactants and it was characterized by X-ray diffraction methods.
The pertinent crystallographic information is given in Table 1.
Solid State & Supramolecular Structural Chemistry Unit, Division ofOrganic Chemistry, National Chemical Laboratory, Dr. Homi BhabhaRoad, Pune, 411008, India. E-mail: [email protected];Fax: +91 20 25892629; Tel: +91 20 25902097w Electronic supplementary information (ESI) available: ORTEPdiagrams of 1a–1e. Search overview details for Cambridge StructuralDatabase (CSD). CCDC reference numbers 672332–672336. For ESIand crystallographic data in CIF or other electronic format see DOI:10.1039/b807853j
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 57–63 | 57
PAPER www.rsc.org/njc | New Journal of Chemistry
Analysis of molecular packing reveals that in the complex
1a, each molecule of 1 establish interaction with two dimers of
CA, as shown in Fig. 1, by forming two different pair-wise
hydrogen bonding patterns of N–H� � �O (H� � �O, 1.70 and
1.71 A; N� � �O, 2.69 and 2.68 A) and C–H� � �O (H� � �O, 2.38
and 2.44 A; C� � �O, 3.34 and 3.33). Such a recognition pattern
gave a three-dimensional structure, as stacked layers, which is
shown in Fig. 1(b).
However, the arrangement of molecules in a typical sheet is
quite intriguing. Although 1 and CA established heteromeric
pattern, each one in turn form one-dimensional crinkled tapes,
through homomeric pattern by holding the adjacent molecules,
as shown in Fig. 2. While CA molecules form homomeric
patterns through cyclic N–H� � �O hydrogen bonds, with
H� � �O distances being in the range, 1.70–2.02 A (N� � �O,
2.60–2.85 A), molecules of 1 gave such patterns through a
cyclic pattern of C–H� � �O hydrogen bonds and the corres-
ponding H� � �O distances are 2.36 and 2.40 A, (C� � �O, 3.31
and 3.33 A). Further, the molecular tapes of 1 and CA are
arranged alternatively in two-dimensional sheets. In fact, the
homomeric patterns observed for 1 and CA are the most
commonly observed arrangement in many of their molecular
complexes.7 It is interesting to note that pure crystal structure
of CA also is due to the aggregation of such molecular tapes,8
as observed in 1a, held together by single N–H� � �O hydrogen
bonds, as shown in Fig. 2(b). However, such an inference
could not be established about the arrangement of molecules
of 1 as its pure crystal structure is not known. However, since
Chart 1
Table 1 Crystallographic details of crystal structures of molecular adducts, 1a–1e
1a 1b 1c 1d 1e
Formula C10H8N2O2: C10H8N2O2: 1.5(C10H8N2O2): 2(C10H8N2O2): C10H8N2O2:2(C3H3N3O3) 2(C3H3N3S3):2(H2O) C6H6O3 2(C6H6O2):4(H2O) C10H6O8
Mr 446.35 578.74 408.38 668.65 442.33Crystal morphology Blocks Blocks Blocks Rectangular blocks BlocksCrystal color Colorless Colorless Pale-yellow Colorless ColorlessCrystal system Triclinic Monoclinic Triclinic Triclinic MonoclinicSpace group P�1 C2/c P�1 P�1 P21/ca/A 8.218(3) 22.129(8) 10.111(2) 7.129(1) 12.926(5)b/A 9.299(4) 13.217(5) 10.277(2) 10.253(2) 7.948(3)c/A 12.168(5) 8.531(3) 10.405(2) 23.220(4) 19.059(7)a/1 91.93(1) 90 70.61(1) 82.15(1) 90b/1 91.44(1) 105.82(1) 84.88(1) 85.26(1) 106.54(1)g/1 108.10(1) 90 61.60(1) 70.40(1) 90V/A3 882.7(6) 2400.6(15) 902.7(3) 1582.7(5) 1877.0(1)Z 2 4 2 2 4Dc/g cm�3 1.679 1.601 1.502 1.403 1.565T/K 298(2) 298(2) 298(2) 298(2) 273(2)l(Mo-Ka) 0.71073 0.71073 0.71073 0.71073 0.71073m/mm�1 0.138 0.612 0.112 0.109 0.1282y range/1 46.60 46.68 56.54 46.54 56.56Limiting indices �9 r h r 9 �24 r h r 24 �13 r h r 13 �7 r h r 7 �15 r h r 17
�10 r k r 8 �14 r k r 14 �13 r k r 13 �11 r k r 10 �10 r k r 6�13 r l r 11 �9 r l r 7 �13 r l r 13 �25 r l r 25 �25 r l r 24
F(000) 460 1192 426 704 912No. reflns measured 3845 5055 10278 6950 10778No. unique reflns [R(int)] 2526 [0.0281] 1739 [0.0229] 4062 [0.0418] 4524 [0.0333] 4347 [0.0238]No. reflns used 1983 1539 3342 1999 3401No. parameters 345 193 344 465 345Reflection 7.32 9.01 11.80 9.73 12.6GOF on F2 1.043 1.139 1.038 0.821 1.018R1 [I 4 2s(I)] 0.0612 0.0353 0.0558 0.0438 0.0480wR2 0.1520 0.0896 0.1571 0.0971 0.1196Drmax, min/e
� A�3 0.38, �0.44 0.44, �0.39 0.26, �0.34 0.24, �0.23 0.249, �0.288
58 | New J. Chem., 2009, 33, 57–63 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
the majority of N-oxide structures possess the homomeric
patterns of 1, as shown in Fig. 2(a), following the analogy
observed for CA, the pure structure of 1 could be visualized as
a combination of such tapes and this may provide means to
establish the structure of 1 by other methods, such as powder
X-ray diffraction techniques, as it fails to yield single crystals
so far, without additional molecules (either solvent of crystal-
lization or co-crystallizing agent).
Thus, 1a could be visualized as a representative example for
the combination of unity and diversity with the observation of
homomeric and heteromeric patterns of both the co-crystal-
lizing species simultaneously. Also, the dual role of N-oxide 1,
as a spacer and structure directing, could be established, unlike
4,40-bipyridine, which often play a role of spacer, except in the
recently reported assemblies, wherein it acts as a guest.9 In
order to corroborate such features through a large number of
molecular complexes of 1, co-crystallization of it with trithio-
cyanuric acid, TCA, which is an analogue of CA, has been
carried out, expecting formation of an iso-structural complex
with that of 1a, by which relative competition for homomeric
and heteromeric patterns could also be programmed.
Solid state structure of adduct, 1b, of 4,40-bipyridine
N,N0-dioxide, 1 and trithiocyanuric acid (TCA)
N-oxide, 1 gave co-crystals with TCA as a hydrate and it has
been labeled as 1b. Further, the asymmetric unit consists of
1:2 ratio of the reactants, and the important crystallographic
information is given in Table 1. The molecular arrangement in
two- and three-dimensions in the crystal structure of 1b is
shown in Fig. 3.
In 1b, three-dimensional structure is alike in 1a, but through
stacked crinkled sheets (Fig. 3), rather than planar sheets.
Further, in contrast to the structure of 1a, a heteromeric pattern
between the molecules of 1 and TCA is not observed. Instead,
the interaction between 1 and TCA is established through water
molecules. Thus, TCA forms N–H� � �O hydrogen bonds
(H� � �O, 1.66 A, N� � �O, 2.61 A) with water molecules, while 1
forms O–H� � �O hydrogen bonds (H� � �O, 1.86 and 1.91 A with
corresponding O� � �O, 2.73 and 2.70 A), as shown in Fig. 3(b).
Such an ensemble ultimately self-assembles, leading to the
formation of two-dimensional sheets with tapes of TCA mole-
cules separated by the aggregates of 1 and water. Within each
molecular tapes of TCA, the adjacent molecules are held
together by N–H� � �S hydrogen bonds with H� � �S distances of
2.52 and 2.54 A (N� � �S distances of 3.39 and 3.41 A).
To evaluate, further, the nature of the variable hydrogen-
bonding patterns of 1 in the presence of other molecular
entities with potential hydrogen bond donor functionalities,
co-crystallization of 1 with 1,3,5-trihydroxybenzene (THB)
which may be regarded as analogue of CA in its enol form,
as shown below, has been carried out.
Supramolecular assembly in molecular complex, 1c, of
4,40-bipyridine N,N0-dioxide, 1, and 1,3,5-trihydroxybenzene
(phloroglucinol), THB
Co-crystallization of 1 and THB from a methanol solution
gave a molecular complex, 1c in a 3:2 ratio of the reactants 1
Fig. 1 (a) Molecular recognition between 1 and CA in the crystal structure of 1a. (b) Three-dimensional arrangement of molecules in the crystal
structure of 1a, in the form of stacked layers.
Fig. 2 (a) Molecular tapes of 1 and CA through homomeric patterns which are held together by heteromeric in the structure of 1a. (b)
Arrangement of molecules in the crystal structure of CA.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 57–63 | 59
and THB. Analysis of three-dimensional packing reveals
several quite exciting features, especially a pseudorotaxane
type network in the form of a host–guest type assembly, as
shown in Fig. 4.
Although each THB interacts with three molecules of 1,
forming a heteromeric pattern by O–H� � �O hydrogen bonds
with H� � �O distances of 1.71, 1.73 and 1.75 A (O� � �O, 2.63,
2.60, 2.67 A), as shown in Fig. 5(a), the homomeric patterns
formed by both 1 and THB play a crucial role in the formation
of ultimate exotic structure in 1c. The homomeric pattern of
THB is shown in Fig. 5(b) and the corresponding patterns of 1
are shown in Fig. 6.
The molecules of THB were found to be yielding a molecular
tape, through homomeric pattern, constituted by C–H� � �Ohydrogen bonds (see Fig. 5(b)), which is, in fact, unknown
either in its pure structure or in its molecular complexes.10
Further, two molecules of 1 in the asymmetric unit of 1c also
form molecular tapes independently. Interestingly, while one of
these remains like infinite tapes, the tapes belonging to the
second molecule are held together by cyclic C–H� � �O hydrogen
bonding patterns constituting layers with void space (Fig. 6). In
those cavities the tapes of THB molecules fit like a thread,
yielding a pseudorotaxane type structure (Fig. 4(b)). Earlier,
in our investigations on 1,10-phenanthroline complexes, we
demonstrated the feasibility of such structures entirely engraved
by noncovalent interactions.11
Thus, molecular complex, 1c further demonstrates the
elegancy of noncovalent synthesis to mimic the ensembles
known to exist for decades, often, being synthesized by con-
ventional means. Looking at the tapes formed by THB, it
appears that such tapes could be even possibly synthesized by
dihydroxybenzene as well, which may possibly also can yield a
pseudorotaxane type structure as observed in 1c. Hence, co-
crystallization of 1 with 1, 3-dihydroxybenzene (DHB) has
been carried out.
Molecular complex, 1d, of 4,40-bipyridine N,N0-dioxide, 1 and
1,3-dihydroxybenzene, DHB
N-Oxide, 1 and DHB form co-crystals, 1d, in a 1:1 ratio along
with two molecules of water and crystallize in triclinic space
group, P�1. The three-dimensional arrangement of these mole-
cules is indeed quite interesting with a stair-case type structure.
A typical arrangement is shown in Fig. 7.
A detailed analysis of the arrangement reveals that both the
symmetry independent molecules of 1, form homomeric pat-
terns independently, as observed in 1a and 1c, yielding mole-
cular tapes through C–H� � �O hydrogen bonds (H� � �O, 2.40
and 2.51; 2.47 and 2.51 A with corresponding C� � �O, 3.31 and
3.38 A; 3.40 and 3.40 A). Infinite tapes corresponding to a
particular symmetry are only shown in Fig. 8(a), for the
purpose of clarity, while the tapes of the other symmetry
independent molecules is shown in the inset of Fig. 8(a). The
tapes correspond to both the symmetry independent mole-
cules, are held together by two water molecules through
O–H� � �O (H� � �O, 1.67 A; O� � �O, 2.77 A) and C–H� � �O
Fig. 3 (a) Stacking of layers comprising of molecules of 1 and TCA in the crystal structure of 1b. (b) Two-dimensional arrangement of molecules
showing the molecular tapes of TCA separated by the molecules of 1 and water, which are held together by O–H� � �O hydrogen bonds.
Fig. 4 (a) Pseudorotaxane type network in the crystal structure of 1c, with void space being filled by a molecular tape of 1. Schematic
representation is shown as inset. (b) A typical pseudorotaxane network with molecules of 1 as rings and molecules of THB as rods.
60 | New J. Chem., 2009, 33, 57–63 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(H� � �O, 2.54 A; C� � �O, 3.31 A) hydrogen bonds, constituting
cavities. The water molecules, in turn, are held together by
O–H� � �O hydrogen bond with a H� � �O distance of 1.94 A
(O� � �O, 2.83 A). In the cavities, two DHB molecules, which
are held together by C–H� � �O (H� � �O, 2.90 and 2.91 A; C� � �O,
3.51 and 3.52 A) hydrogen bonds are situated. These DHB
molecules are further glued to the tapes of 1 by O–H� � �O and
C–H� � �O hydrogen bonds. Such adjacent ensembles are
further held together, as shown in Fig. 8(a), by water mole-
cules connecting the two molecular tapes corresponding to
the same symmetry molecules by O–H� � �O and C–H� � �Ohydrogen bonds. A schematic representation of the arrange-
ment is shown in Fig. 8(b).
Thus, in complex 1d, only the molecules of 1 aggregated to
yield homomeric patterns, while DHB remains as monomers
forming interactions with 1 yielding heteromeric patterns.
Taking into account the facile formation of ladders and
stair-case type structures by 4,4 0-bipyridine (bpy) with
–COOH functionality, and in particular, the recent reports
of preparation of such architectures by co-crystallizing bpy
with 1,2,4,5-benzenetetracarboxylic acid (BTCA),12 further
studies have been directed to create supramolecular assembly
of 1 and BTCA.
Supramolecular assembly in molecular complex, 1e, of
4,40-bipyridine N,N0-dioxide, 1, and
1,2,4,5-benzenetetracarboxylic acid, BTCA
Co-crystallization of 1 and BTCA gave a 1:1 molecular com-
plex, 1e. In this structure (Fig. 9), in two-dimensional arrange-
ment, each molecule of 1 interacts with BTCA forming
heteromeric pattern through the formation of O–H� � �O/
C–H� � �O hydrogen bonding patterns, H� � �O, 1.60/2.30;
1.49/2.59 A (O� � �O, 2.53/3.23; 2.48/3.53 A). But, molecules
of 1 did not undergo homomeric aggregation, in the structure
of 1e. In contrast, molecules of BTCA show homomeric
recognition pattern through well known R22(8) hydrogen
bonding pattern, with H� � �O distances of 1.67 and 1.70 A
(O� � �O, 2.63 and 2.65 A), via the remaining –COOH groups,
that did not interact with the molecules of 1.
Thus, the arrangement ultimately could be visualized as
sheets with layers of molecules of BTCA stuffed by the
molecules of 1 with appreciable void space. However, in
three-dimensional arrangement, the adjacent layers are
arranged in such a manner that molecules from the adjacent
layers effectively fill the void space; thus, 1e could not yield a
channel structure. It is noteworthy to mention that among all
the structures studied in this series (1a–1e), molecules of 1 did
not undergo homomeric recognition only in the structure of 1e,
perhaps, due to the strong interaction between –COOH and
N - O moieties, thus exhibiting the ability of 1 also to
perform the role of spacer, like its analogue bpy, and suggests
the importance of the complementarity between the functional
groups undergoing the molecular recognition process.
Fig. 5 (a) Molecular recognition between 1 and THB, yielding heteromeric patterns. (b) Homomeric pattern of THB.
Fig. 6 Homomeric patterns of N-oxide, 1 in the crystal structure of 1c.
Fig. 7 Three-dimensional packing of molecules in the crystal structure of 1d.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 57–63 | 61
Conclusions
In this study, we have shown the ability of 4,40-bipyridine
N,N0-dioxide to yield different types of supramolecular assem-
blies from simple stacked sheet structures to pseudorotaxane
and stair-case type structures depending upon its interaction
with the co-crystallizing agents. Unlike its analogue, bpy, the
N-oxide shows preference for the homomeric patterns, although
its spacer role is visualized in the structure 1e. Further, ob-
servation of the homomeric patterns formed by 1 in the crystal
structures, 1a–1d, and also in some of the examples found in the
literature, it may be possible to extrapolate it to predict the
three-dimensional structure of 1 as a stacked sheets with each
sheet as an aggregation of molecular tapes formed by the
mutual recognition of the adjacent molecules through C–H� � �Ohydrogen bonds. Thus, we strongly believe that this can be a
good starting model to determine the three-dimensional struc-
ture of 1 by other techniques such as powder X-ray diffraction
methods or by computational procedures and we have already
initiated process in this direction.
Experimental
Preparation of molecular adducts of the molecular complexes,
1a–1e
All the chemicals used in this study were obtained from
commercial suppliers and used as such without any further
purification. The solvents employed for the crystallization
purpose were of spectroscopy grade of highest available
purity. Co-crystals have been prepared by dissolving 4,40-
bipyridine N,N0-dioxide, 1, and cyanuric acid, trithiocyanuric
acid, 1,3,5-trihydroxybenzene, 1,3-dihydroxybenzene and
1,2,4,5-benzenetetracarboxylic acid in 1:1 or 1:2 ratio either
in CH3OH or H2O as solvent and slowly evaporating the
obtained solution. Single crystals were obtained over a period
of 48 h in all the cases. In typical preparation, 0.0941 g
(0.5 mmol) of 1 and 0.127 g (0.5 mmol) of 1,2,4,5-benzenetetra-
carboxylic acid were dissolved in 15 mL of CH3OH by gently
warming on a water bath. The resultant solution was kept for
evaporation at ambient conditions by protecting the conical
flask from external mechanical disturbances and within 48 h,
colorless and good quality crystals of 1e, were obtained that
are suitable for studies by single-crystal X-ray diffraction
methods.
Crystal structure determination of 1a–1e
Good quality single crystals of 1a–1e have been chosen by
viewing under microscope and glued to a glass fiber using an
adhesive to mount on a goniometer of Bruker single crystal
X-ray diffractometer equipped with APEX CCD detector. The
data collection was smooth in all the cases without any
complications and all the crystals were found to be stable
throughout data collection period. The intensity data were
processed using Bruker suite programmes, SAINT,13 followed
Fig. 8 Arrangement of molecules within a two-dimensional layer in the crystal structure of 1d.
Fig. 9 (a) Two-dimensional arrangement of molecules in the crystal structure of 1e. (b) Stacking of sheets in three-dimensions.
62 | New J. Chem., 2009, 33, 57–63 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
by absorption correction by SADABS.14 The structures were
solved by using XS and refined by least-square methods using
XL.15 All the non-hydrogen atoms were refined by anisotropic
methods and the hydrogen atoms were either refined or placed
in the calculated positions. All the structural refinements
converged to good R-factors as listed in Table 1.
Acknowledgements
We thank Department of Science and Technology (DST) for
the financial support and also greatly acknowledge Professor
Judith A. K. Howard (Durham, UK) for her generous support
to Mayura by awarding scholarship. Also one of us (K. A.)
thanks Council of Scientific and Industrial Research (CSIR),
for the Research Fellowship.
References
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5 A search performed on Cambridge Structural Database (CSD)using version 1.10, retrieved 140 entries possessing 4,40-bipyridineN,N0-dioxide, in which 118 are found to be organometallic while 22are only the organic molecular complexes (see ESIw).
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13 SAINT, Version 6.02; Bruker AXS, Inc., Analytical X-raySystems, 5465 East Cheryl Parkway, Madison, WI 53711-5373,2000.
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 57–63 | 63
Synthesis and characterisation of bulky guanidines and
phosphaguanidines: precursors for low oxidation state metallacyclesw
Guoxia Jin,b Cameron Jones,*a Peter C. Junk,a Kai-Alexander Lippert,b
Richard P. Roseab
and Andreas Stascha
Received (in Durham, UK) 29th May 2008, Accepted 20th August 2008
First published as an Advance Article on the web 9th October 2008
DOI: 10.1039/b809120j
Reactions of alkali metal amides or phosphides with the bulky carbodiimide, ArNQCQNAr
(Ar = C6H3Pri2-2,6), followed by aqueous work-ups, have yielded several guanidines,
ArNC(NR2)N(H)Ar (R = cyclohexyl (GisoH) or Pri (PrisoH); NR2 = cis-NC5H8Me2-2,6
(PipisoH)), a bifunctional guanidine, {ArNCN(H)Ar}2{m-N(C2H4)2N} (Pip(GisoH)2), and two
phosphaguanidines, ArNC(PR2)N(H)Ar (R = cyclohexyl (CyP-GisoH) or Ph (PhP-GisoH)).
A very bulky guanidine, ArNC{N(Ar)SiMe3}N(H)Ar (ArSi-Giso), and an aryl coupled
bifunctional guanidine, {ArN(H)C(NPri2)NC6H2Pri2-2,6-}2 (PrisoH)2, have been prepared by
other routes. All compounds have been crystallographically characterised and shown to exist in
a number of isomeric forms in the solid state. These appear to be largely retained in solution.
The deprotonation of GisoH with BunLi in either hexane or THF led to crystallographically
characterised dimeric and monomeric complexes respectively, viz. [Li{Li(k2-N,N0-Giso)2}] and
[Li(THF)(Z1-N,Z3-Ar-Giso)]. Deprotonation of PrisoH and Pip(GisoH)2 with K[N(SiMe3)2] gave
the unsolvated polymer, [{K(Z1-N,Z6-Ar-Priso)}N], and the solvated complex,
[{K(THF)2}{Pip(Giso)2}{K(THF)3}], respectively.
Introduction
The coordination chemistry of anionic amidinate
([RNC(R)NR]�, R = H, alkyl, aryl etc.) and guanidinate
([RNC(NR2)NR]�) ligands has been extensively studied, giving
rise to numerous complexes incorporating metals from across the
periodic table.1 In these, the ligands have displayed an impressive
array of coordination modes which depend upon the nature and
bulk of the substituents (R), and the metal involved. This
structural diversity is one of the main factors that have led
to such complexes finding many applications in catalysis,2–4
materials science5 and synthesis,1 to name but a few.
Recent developments in this area have concentrated on the use
of very bulky amidinates to stabilise low nuclearity s- and
p-block metal complexes which show significant potential as,
for example, lactide polymerisation catalysts.2 Of most note here
is the Piso� ligand, [ArNC(But)NAr]�, which incorporates
sterically demanding 2,6-diisopropylphenyl (Ar) substituents at
its N-centres and a tert-butyl group on the backbone carbon.
The spatial profile and ligating abilities of this ligand have
been likened to those of b-diketiminates, the most commonly
utilised examples of which also possess N–Ar substituents,
e.g. [(ArNCR)2CH]� (R = Me or But).6 Although complexes
of b-diketiminates are widely used in catalytic processes, they are
perhaps more notable for their capacity to kinetically stabilise
complexes containing low oxidation state metal centres. A salient
illustration of this is the synthesis and structural characterisation
of the homologous series of monomeric, N,N0-chelated group 13
metal(I) complexes, [:M{(ArNCMe)2CH}] (M = Al, Ga, In or
Tl),7 which have shown remarkable further chemistry.
In contrast to b-diketiminates, bulky amidinates (e.g. Piso�)
had rarely been employed in the preparation of low oxidation
state metal complexes. In 2005, we began to address this
paucity with the preparation of the group 13 metal(I) com-
plexes [:M(Piso)] (M = In or Tl).8 However, unlike their
b-diketiminate counterparts, [:M{(ArNCMe)2CH}], the Piso�
ligand in these complexes is localised and chelates the metal
centre in an Z1-N,Z3-arene-fashion. In addition, the analogous
GaI and AlI complexes could not be stabilised. These results
suggested that related, but bulkier ligands would need to be
accessed to enforce N,N0-chelation and allow stabilisation of
lighter group 13 metal(I) centres. To this end, the very large
guanidinate ligand, [ArNC(NCy2)NAr]� (Giso�; Cy = cyclo-
hexyl), was developed and used in the syntheses of the
remarkably stable monomeric four-membered heterocycles,
[:M(k2-N,N0-Giso)] (M = Ga or In; N.B. the Al(I) heterocycle
has not yet been accessed),9 the coordination chemistry of
which was later explored.10 In addition to the increased steric
bulk of Giso� over Piso�, the greater stabilising ability of the
guanidinate can be attributed to the fact that it is a more
N-electron rich donor than the amidinate, a result of it
possessing a zwitterionic resonance form containing two nega-
tively charged N-donor centres, viz. [Cy2N+QC(N�Ar)2].
a School of Chemistry, PO Box 23, Monash University, 3800 VIC, Australiab School of Chemistry, Main Building, Cardiff University, Cardiff,UK CF10 3AT
w Electronic supplementary information (ESI) available: ORTEP dia-grams for 2 and 3. Crystallographic data (excluding structure factors)for the structures of 1–12. CCDC reference numbers 704662 (1),704663 (2), 704664 (3), 704665 (4�2CHCl3), 704666 (5), 704667 (6),704668 (7), 699384 (8�hexane), 704669 (9), 704670 (10), 704671 (11),704672 (12�2THF). For ESI and crystallographic data in CIF or otherelectronic format see DOI: 10.1039/b809120j
64 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
Over the last three years we have extended our application
of Giso�, and a range of other Ar-substituted guanidinate and
phosphaguanidinate ([ArNC(PR2)NAr]�)11 ligands, to the
stabilisation of heterocyclic complexes containing low oxida-
tion state metal centres from all blocks of the periodic table
(e.g. Mg(I),12 Ge(I),13 As(I),14 various d-block metal(I)15 and
f-block metal(II)16 species) with considerable success. More-
over, we have used these ligands in the synthesis of a variety of
gallyl–metal complexes, including examples exhibiting un-
precedented Ga–Zn17 and Ga–Sn18 bonds. In all these studies,
the ligands have been prepared by the deprotonation of
neutral guanidines or phosphaguanidines with alkali metal
reagents. Although some preliminary details of the synthesis of
the neutral ligand precursors have been previously been des-
cribed by us,9–16 it seemed that a full report of the preparation
and characterisation of these compounds would aid other
researchers seeking to harness their unique properties for their
own purposes. The value of this is highlighted by the fact that
prior to our involvement in this field, only one guanidine
bearing 2,6-diisopropylphenyl substituents at its N-centres,
viz. ArNC{N(H)Ar}2, had appeared in the literature.19 Here,
we report on the synthesis, structures and properties of eight
N–Ar substituted guanidines and phosphaguanidines, and
some of their alkali metal derivatives.
Results and discussion
(i) Synthesis of bulky guanidines and phosphaguanidines
A number of synthetic routes are known for the preparation
of guanidines.1 One of the most versatile of these involves
the addition of metallated amides to carbodiimides
(RNQCQNR), followed by aqueous work-up. Here, this
route has been employed to synthesise the guanidines GisoH
(1), PrisoH (2), PipisoH (3), as well as the bifunctional
guanidine, Pip(GisoH)2 (4), in high to quantitative yields
(Scheme 1). In all preparations, THF was used as the solvent
and the initial addition reactions were carried out at either
ambient temperature and/or under reflux conditions.
It appears that this route does have steric and electronic
limitations, as the attempted addition of some amides to
the carbodiimide (ArNQCQNAr) were not successful. For
example, lithiated cis-2,6-dimethylpiperidine adds to the
carbodiimide to give compound 3, whereas lithiated 2,2,6,6-
tetramethylpiperidine does not react with ArNQCQNAr in
THF at reflux. Moreover, M[N(SiMe3)2] (M = Li, Na or K)
do not react with ArNQCQNAr under similar conditions,
though these reagents are known to add to smaller carbodii-
mides at room temperature.20
Although considerably less sterically demanding than some
of the amide precursors mentioned above, lithium carbazolyl
did not react with ArNQCQNAr in THF at reflux, and only
carbazole and the carbodiimide were recovered after work-up.
This lack of reactivity probably derives from the lower nucleo-
philicity of the aromatic carbozyl anion, relative to the bulkier
amides used in the preparation of 1–3.
Interest in the coordination chemistry of phosphaguanidi-
nates, [RNC(PR 02)NR]�, has recently begun to escalate.1d,21
One of the main reasons behind this is that the phosphino
group of these ligands is pyramidal, unlike the planar amino
substituent of guanidinates. Therefore, the zwitterionic reso-
nance form of these ligands, [R02P+QC(N�R)2], does not play
a significant role in their chemistry. As a result, phospha-
guanidinates are coordinatively versatile, and in many of their
complexes the phosphino group acts a P-lone pair donor.1d,21
Despite this emerging importance, there had been no reports
of N–Ar substituted phosphaguanidinates or phospha-
guanidines in the literature. We have reversed this situation
with the synthesis of CyP-GisoH, 5, and PhP-GisoH, 6, via the
addition of the relevant lithium phosphide to ArNQCQNAr
(Scheme 1). Aqueous work-ups of these compounds were
performed under an inert atmosphere to prevent oxidation
of the phosphorus atom. However, we have found that the
products can be handled in moist air as solids or in solution
without significant oxidation occurring, as judged by 31P
NMR spectroscopy. It is noteworthy that the addition of
phosphines to smaller carbodiimides to form phospha-
guanidines, in the presence of catalytic amounts of s-block
amide or alkyl bases, has recently been reported.22,23
Although the addition of metal amides to ArNQCQNAr is
a versatile route to bulky guanidine compounds, its limitations
centre on the bulk of the reacting amide complex (as men-
tioned above). Because of this, a different approach was used
Scheme 1 Reagents and conditions: (i) ArNQCQNAr, THF, 20 1C
or reflux; (ii) H2O.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 65
to synthesise the exceedingly bulky guanidine, ArSi–GisoH 7
(Scheme 2). This involved lithiation of the known guanidine,
ArNC{N(H)Ar}2, the product of which was subsequently
quenched with Me3SiCl in THF at reflux to give 7 in
good yield.
One further bifunctional guanidine has been prepared in this
study via a route not involving carbodiimide addition. Though
this synthesis was originally not intended, it is moderately
yielding, reproducible and thus is included here. In an attempt
to form a Mn(II) complex of Priso�, K[Priso] was reacted with
commercially available MnI2 in THF. This, instead led to the
isolation of the aryl-coupled guanidine, (PrisoH)2 8, in a 30%
yield (Scheme 3) without aqueous work-up. When the reaction
was repeated with a pure sample of [MnI2(THF)3], compound
8 was not obtained. Presumably, the commercially sourced
MnI2 initially employed, was contaminated with significant
amounts of higher oxidation state manganese species. It is
believed that the reaction of the impure MnI2 with K[Priso] led
to the oxidative coupling of two Priso� anions through aryl
para-positions on each. This seems reasonable in light of the
fact that we have recently shown that Priso� can coordinate
the Rh(COD) fragment (COD = 1,5-cyclooctadiene) solely
through one aryl substituent in a Z5-cyclohexadienyl fashion.15
A Mn(4II)-Priso complex in which the ligand exhibits this
cyclohexadienyl binding mode can easily be envisaged as an
intermediate in the oxidative coupling that gave 8. The possi-
bility that 8 was alternatively formed via the oxidative cou-
pling of two Priso� anions by a diiodine contaminant in the
impure sample of MnI2 was examined and discounted.
(ii) Structural and spectroscopic properties of prepared
compounds
The crystal structures of all compounds 1–8 have been deter-
mined (see Fig. 1–6 for the molecular structures of 1, 4–8;
those of 2 and 3 can be found in ESIw). The compounds
display solid state structures comparable to those of previously
characterised guanidines and phosphaguanidines.1,21 Each of
the guanidines, 1–3, possesses a close to planar backbone
amino (–NR2) fragment which in no case is co-planar with
the CN3 core of the molecule. Therefore, any interaction of the
amino N-lone pair within the p-system of the largely localised
guanidine CN3 backbone must be limited. It is noteworthy
that the –NR2 fragments of 4 are significantly more distorted
from planar than those of the monofunctional guanidines.
Similarly, the two phosphaguanidines display distorted pyra-
midal phosphorus centres, the lone pairs of which are direc-
tional and therefore cannot be involved with the p-system of
their localised CN2P cores. The bond lengths and angles
within these core fragments (see Table 1) are consistent with
these descriptions.
Several different isomeric forms of the compounds have
been identified in this study. To allow comparisons with
related amidines, the backbone unit (R2N or R2P) has been
defined as the lower priority in determining the stereo-configu-
ration of the compounds (see refs. 1d and 1e for a description
of the four isomeric and tautomeric forms of amidines, viz.
Z-anti, Z-syn, E-anti and E-syn). The guanidines, 1–3 (see
Fig. 1 for the structure of 1), and the phosphaguanidine, 5
(Fig. 3), exist in the Z-anti-form which is common for guani-
dines but not for uncoordinated phosphaguanidines which
normally occur in the solid state in their E-syn-form.1d,21
Indeed, this is the isomer adopted by the phosphaguanidine,
6, in the solid state (Fig. 4). In contrast, the extremely bulky
guanidine, 7 (Fig. 5), crystallises in the rarely observed Z-syn-
form, probably because of steric buttressing of its aryl groups
by the larger N(Ar)SiMe3 substituent. It is of note that the
Z-syn-isomer of amidines with very bulky backbone C-substitu-
ents have been previously reported, e.g. (tript)C{N(H)R}(NR)
(tript = 9-triptycenyl, R = Cy or Pri).24 Both the bifunctional
amidines, 4 and 8 (Fig. 2 and 6, respectively), exist in the
solid state as Z-anti-,Z-anti-isomers, as has been previously
documented for bifunctional amidines.1
Often, amidines and guanidines will be present in solution in
more than one of their four possible isomeric forms. This can
Scheme 2 Reagents and conditions: (i) BunLi, THF; (ii) Me3SiCl,
THF reflux.
Scheme 3 Reagents and conditions: (i) K[N(SiMe3)2], THF; (ii) MnI2,
THF.
Fig. 1 Molecular structure of 1 (25% thermal ellipsoids are shown;
hydrogen atoms, except H(1), omitted for sake of clarity).
66 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
lead to complicated NMR spectra for such compounds.
However, the guanidines and phosphaguanidines, 1–6, display
relatively simple 1H and 13C{1H} NMR spectra, which are
suggestive of only one, or predominantly one, isomer occur-
ring in solution. These spectra imply that each compound has
two chemically inequivalent Ar substituents, and that both
alkyl or aryl groups on the backbone –ER2 (E = N or P)
groups are equivalent. If the compounds retain their solid state
isomeric forms in solution, which seems likely, the latter
observation requires their –ER2 groups to partially rotate on
the NMR timescale, thus leading to the compounds possessing
averaged mirror planes incorporating their ECN2 fragments.
Although the isomeric forms adopted by the guanidines,
1–4, in solution cannot be certain without two-dimensional
NMR experiments, some insight into the solution conforma-
tions of the phosphaguanidines, 5 and 6, can be gained from
their 1H NMR spectra. That for 5 shows only one isomer, the
NH resonance of which exists as a doublet (3JPH = 14.1 Hz;31P{1H} NMR: d �2.9 ppm). The spectrum of 6 reveals the
compound to exist as two isomers in solution in an approxi-
mately 90 : 10 ratio. The NH resonance of the major isomer
(31P{1H} NMR: d �18.5 ppm) is a singlet, while that for
the minor isomer (31P{1H} NMR: d �13.3 ppm) is a doublet
(3JPH = 18.2 Hz). In an excellent paper on phosphaguanidinate
solution behaviour, Coles et al. have shown that isomer
interconversion can readily occur by one or more of a number
of possible pathways.21e Importantly, they also showed that
the closely related phosphaguanidine, Cy2PC{N(H)Pri}(NPri),
Fig. 2 Molecular structure of 4 (25% thermal ellipsoids are shown; hydrogen atoms, except H(1), omitted for sake of clarity). Symmetry
operation:0 �x + 1, �y + 1, �z.
Fig. 3 Molecular structure of 5 (25% thermal ellipsoids are shown;
hydrogen atoms, except H(2), omitted for sake of clarity).
Fig. 4 Molecular structure of 6 (25% thermal ellipsoids are shown;
hydrogen atoms, except H(1), omitted for sake of clarity).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 67
is present in solution in both its E-syn- (major) and Z-anti-
(minor) forms (14 : 1 ratio at 298 K). The NH resonance of the
E-syn-form shows no coupling to the P-centre, while that of
the minor Z-anti-isomer does (3JPH = 14.5 Hz). Accordingly,
we conclude that compound 5 exists solely as its Z-anti-form
in solution (as in the solid state), whereas the major solution
state isomeric form of 6 is E-syn (as in the solid state), and the
minor form is Z-anti.
Many of the signals in the 1H NMR spectrum of ArSi-
GisoH, 7, are very broad and suggest one or more dynamic
processes are occurring in solution. Despite efforts, the spec-
trum could not be resolved, and thus we could not shed light
on the nature of the dynamic behaviour. One possibility,
however, is that it involves a restricted rotation of the Ar
and/or SiMe3 groups about the N–C or N–Si bonds of 7. In
this respect, it should be noted that similar solution dynamic
behaviour has been observed for the closely related com-
pound, ArNC{N(H)Ar}2, an exhaustive variable-temperature
NMR study of which showed this behaviour to be derived
from restricted rotation of its three Ar groups.19 Another
possibility for 7 is that there is a fluxional interconversion
between two or more isomers of the compound, which is
occurring at close to the NMR timescale. This seems less
likely, however, when the imposing sterics of the compound
are taken into account.
Little information could be gained from the solution NMR
spectra of the bifunctional guanidine, 8. These are very
complicated and point towards more than one isomer existing
Fig. 5 Molecular structure of 7 (25% thermal ellipsoids are shown;
hydrogen atoms, except H(3), omitted for sake of clarity). Selected
bond lengths (A) and angles (1): Si(1)–N(1) 1.7762(16), N(1)–C(1)
1.410(2), C(1)–N(2) 1.285(2), C(1)–N(3) 1.383(2); N(2)–C(1)–N(3)
130.87(17), N(2)–C(1)–N(1) 116.38(16), N(3)–C(1)–N(1) 112.73(16),
C(1)–N(1)–C(5) 119.99(15), C(1)–N(1)–Si(1) 119.94(12),
C(5)–N(1)–Si(1) 119.81(12).
Fig. 6 Molecular structure of 8 (25% thermal ellipsoids are shown; hydrogen atoms, except H(1) and H(6), omitted for sake of clarity). Selected
bond lengths (A) and angles (1): N(1)–C(1) 1.391(3), C(1)–N(3) 1.290(4), C(1)–N(2) 1.378(4), N(4)–C(44) 1.290(3), N(5)–C(44) 1.383(4),
N(6)–C(44) 1.387(4); N(3)–C(1)–N(2) 121.1(2), N(3)–C(1)–N(1) 122.2(3), N(2)–C(1)–N(1) 116.7(3), C(1)–N(2)–C(17) 120.2(2), C(1)–N(2)–C(14)
119.8(2), C(17)–N(2)–C(14) 115.5(2), C(44)–N(5)–C(45) 119.5(2), C(44)–N(5)–C(48) 119.9(2), C(45)–N(5)–C(48) 116.0(2), N(4)–C(44)–N(5)
120.8(3), N(4)–C(44)–N(6) 122.0(3), N(5)–C(44)–N(6) 117.3(2).
Table 1 Selected bond lengths (A) and angles (1) for 1–6 (E = N or P)
1 2 3 4 5 6
ArNQC 1.290(2) 1.2911(16) 1.285(2) 1.287(2) 1.2909(19) 1.311(2)ArN–C 1.384(3) 1.3910(16) 1.394(2) 1.373(2) 1.375(2) 1.346(2)C–ER2 1.388(2) 1.3807(16) 1.385(2) 1.398(2) 1.8708(17) 1.8798(18)
ArN–CQN 121.26(17) 122.02(11) 124.10(17) 124.67(15) 123.26(14) 121.51(16)R2E–CQN 121.66(18) 120.57(11) 119.91(16) 119.84(15) 121.76(11) 119.98(13)R2E–C–N 117.08(17) 117.42(10) 115.99(16) 115.48(14) 114.96(11) 118.51(13)P
angles about E 353.3 357.0 353.5 341.9 302.3 304.4
68 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
in solution. For example, several overlapping N–H resonances
were seen in its 1H NMR spectrum, where only one would be
expected if it retained its solid state Z-anti-, Z-anti-isomeric
form in solution. As a result, the spectra proved difficult to
assign.
(iii) Metallation of bulky guanidines and phosphaguanidines
The guanidines and phosphaguanidines prepared here (with
the exception of ArSi-Giso 7), can be easily deprotonated
by standard metallation procedures. The reactions of these
ligands with one equivalent of BunLi or K[N(SiMe3)2] proceed
rapidly and near quantitatively in common solvents such as
hexane, toluene, THF or diethyl ether at ambient temperature
or below. The solvent and metal involved in the reaction can
have a striking bearing on the nuclearity of the formed
complex, and the conformation adopted by the guanidinate
or phosphaguanidinate ligand. This is important as it can
influence the product obtained from, for example, further salt
metathesis reactions of these alkali metal complexes with other
metal halides. In this study, we have structurally and spectro-
scopically characterised four lithium or potassium salts of the
ligands prepared above.
The lithiation of GisoH, 1, with BunLi in hexane led to the
solvent free dimeric complex, 9, whilst in THF the monomeric
solvated complex, 10, was formed (Scheme 4). In contrast,
metallation of PrisoH, 2, with K[N(SiMe3)2] in toluene
afforded the polymeric, solvent free complex, 11, whereas
metallation of Pip(GisoH)2 with the same reagent in THF
gave the solvated complex, 12 (Scheme 4). The NMR spectro-
scopic data for 9–11 are more symmetrical than their solid
state structures (vide infra) would suggest and imply that
fluxional processes are occurring in solution that are rapid
on the NMR timescale. This is not uncommon for alkali-metal
amidinates and guanidinates,1 and therefore no efforts were
made to investigate these dynamic behaviours by variable
temperature NMR studies. Once crystallised from the reaction
mixture, compound 12 has negligible solubility in normal
deuterated solvents (including D8-THF) and therefore no
meaningful NMR spectroscopic data could be obtained for
this compound.
The molecular structure of 9 is depicted in Fig. 7 and shows
it to be dimeric with two different lithium coordination
environments. Li(1) is coordinated by two chelating Giso�
ligands that have largely localised N(1)–C(1)–N(2) fragments.
The Li(1)–N bond lengths of 2.072(2) A (to N(2) and N(2)0)
and 2.240(5) A (to N(1) and N(1)0), although different, lie
within the normal range for amidinate and guanidinate N–Li
interactions.25 The two more distant N-atoms (N(1) and
N(1)0) also coordinate the bent two-coordinate Li(2) centre
with short interactions (1.954(4) A). The coordination sphere
of the both Li atoms is completed by agostic interactions to
ligand hydrogen atoms; Li(1) has two such interactions (both ca.
2.23 A), whereas Li(2) has four (from ca. 2.03 A to ca. 2.27 A).
When these close contacts are taken into account, both
Li-centres can be thought of as having heavily distorted
octahedral geometries. A survey of the Cambridge Crys-
tallographic Database revealed two similar dimeric lithium ami-
dinates, [Li{k2-N,N0-(SiMe3)NC(R)N(SiMe3)}2{Li(OEt2)}]
(R = C6H5CF3-4 or C6H5F-2),26 though the non-chelated
Li centre of both is further coordinated by an ether molecule.
Scheme 4 Reagents and conditions: (i) BunLi, hexane (Cy = cyclo-
hexyl); (ii) BunLi, THF; (iii) K[N(SiMe3)2], toluene; (iv) K[N(SiMe3)2],
THF.
Fig. 7 Molecular structure of 9 (25% thermal ellipsoids are shown;
hydrogen atoms omitted for sake of clarity). Selected bond lengths (A)
and angles (1): N(1)–C(1) 1.394(3), N(2)–C(1) 1.323(3), N(3)–C(1)
1.409(3), N(1)–Li(2) 1.954(4), N(1)–Li(1) 2.240(5), N(2)–Li(1)
2.072(2); N(2)–C(1)–N(1) 114.3(3), N(2)–Li(1)–N(1) 63.78(12),
N(2)0–Li(1)–N(1) 119.6(2), N(1)0–Li(2)–N(1) 121.7(4). Symmetry
operation:0 �x, y, �z + 1/2.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 69
The molecular structure of monomeric 10 is shown in Fig. 8.
The localised guanidinate ligand is acting as an amide that
coordinates the Li atom in an Z1-fashion through N(2).
In addition, there is an approximately Z3-interaction of the
Li-centre with the Ar-substituent of N(1). The coordi-
nation sphere on the Li(1) is completed by one THF molecule.
A similar coordination mode (but minus the coordi-
nated THF) has been reported for the thallium(I) complex,
[Tl(Z1-N,Z3-Ar-Giso)].8
Like the structure of 10, the guanidinate moieties of the
potassium complexes, 11 and 12 (Fig. 9 and 10, respectively),
adopt the Z-anti-configuration but with more localised
coordinated NCN fragments. In addition, the arene-K inter-
actions in both are close to Z6-, as opposed to the Z3-Ar-Li
coordination seen in 10. In 11, this leads to a one-dimensional
polymeric structure in which one Ar-group of each ligand
bridges two K-centres. Compound 12 is monomeric, and in
addition to arene and N-attachments, one K-centre is coordi-
nated by two THF molecules, while the other is ligated by
three. All the distances to the K-centres in both complexes are
in the normal range.25
Conclusion
In conclusion, the synthesis and characterisation of a variety
of guanidine, bifunctional guanidine and phosphaguanidine
compounds, all bearing 2,6-diisopropylphenyl N-substituents,
have been described. In the solid state, the Z-anti-isomeric
form is observed for all guanidines, except in one extremely
bulky example, ArSi-GisoH 7. The sterics of this necessitate
it occurring as the rarely observed Z-syn-isomer. Of the
phosphaguanidinates, the bulkier example, CyP-GisoH 5,
crystallises in the Z-anti-form, while PhP-GisoH, 6, adopts
the E-syn-conformation. In solution, most of the described
compounds appear to retain their stereochemistry, though in
some cases isomer mixtures were observed. Several of the
prepared compounds have been deprotonated with alkali
metal reagents and the resulting salts crystallographically
characterised. In the case of the deprotonation of GisoH 1
with BunLi, the nuclearity and guanidinate coordination mode
displayed by the formed complexes are dependent upon the
reaction solvent employed. We are currently systematically
exploring the use of bulky guanidinates and phosphaguanidi-
nates, prepared from the neutral compounds 1–8, for the
stabilisation of low oxidation metallacycles incorporating
metals from all blocks of the periodic table.
Experimental
General considerations
All manipulations were performed under an inert atmosphere
(dinitrogen or argon) using Schlenk or glove box techniques.
Aqueous organic work-ups were carried out in air, except those
for the phosphaguanidines, 5 and 6. Melting points were
determined in sealed capillaries under a dinitrogen atmosphere,
except those for the guanidines, 1–4, which were determined in
open capillaries. Reaction solvents were dried over potassium
or Na/K alloy prior to use, except dichloromethane and chloro-
form which were used as received. Mass spectra were recorded
at the EPSRC National Mass Spectrometric Service, Swansea
University. Microanalyses were obtained from either Medac
Ltd or Campbell Microanalytical, Ottago. IR spectra were
Fig. 9 Molecular structure of 11 (25% thermal ellipsoids are shown;
hydrogen atoms omitted for sake of clarity). Selected bond lengths (A)
and angles (1): K(1)–N(1) 2.755(3), K(1)–Ar centroid 3.077(1), K(1)0–Ar
centroid 2.945(1), C(1)–N(2) 1.329(5), C(1)–N(3) 1.402(5), N(1)–C(1)
1.340(5); N(2)–C(1)–N(1) 121.7(3), N(2)–C(1)–N(3) 115.1(3),
N(1)–C(1)–N(3) 123.2(3), C(1)–N(3)–C(26) 122.0(3), C(1)–N(3)–C(29)
121.5(3), C(26)–N(3)–C(29) 114.7(3), C(1)–N(1)–K(1) 128.2(2). Sym-
metry operation:0 x � 1/2, �y + 1/2, �z.
Fig. 8 Molecular structure of 10 (25% thermal ellipsoids are shown;
hydrogen atoms omitted for sake of clarity). Selected bond lengths (A)
and angles (1): N(1)–C(1) 1.3149(16), C(1)–N(2) 1.3587(16), C(1)–N(3)
1.4092(16), Li(1)–N(2) 1.943(3), Li(1)–C(2) 2.290(3), Li(1)–C(3)
2.458(3), Li(1)–C(7) 2.591(3), O(1)–Li(1) 1.889(3); N(1)–C(1)–N(2)
121.56(11), N(1)–C(1)–N(3) 117.46(11), N(2)–C(1)–N(3) 120.98(11),
C(1)–N(3)–C(32) 117.05(10), C(1)–N(3)–C(26) 120.82(10),
C(32)–N(3)–C(26) 115.51(10), C(1)–N(2)–Li(1) 117.59(11).
70 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
recorded using a Nicolet 510 FT-IR spectrometer as Nujol
mulls between NaCl plates. 1H and 13C{1H} NMR spectra were
recorded on either Bruker DXP400, Bruker DPX300, Jeol
Eclipse 300 or Bruker WM250 spectrometers and were refer-
enced to the resonances of the solvent used. 31P{1H} NMR
spectra were recorded on a Jeol Eclipse 300 spectrometer and
were referenced to external 85% H3PO4. Cy2NH, Pri2NH,
cis-2,6-dimethylpiperidine and piperazine were obtained com-
mercially, dried over molecular sieves, and distilled under
dinitrogen prior to use. K[N(SiMe3)2] was prepared by treating
(SiMe3)2NH with KH in toluene at 20 1C. ArNQCQNAr27
and ArNC{N(H)Ar}219 were synthesised according to literature
procedures. All other reagents were obtained from commercial
sources and used as received.
Preparation of GisoH 1
BunLi (5.33 cm3 of a 1.6 M solution in hexanes, 8.52 mmol)
was added to a solution of Cy2NH (1.58 g, 1.73 cm3,
8.69 mmol) in THF (40 cm3) at 20 1C over 5 min and the
resultant solution stirred for 1 h. ArNQCQNAr (3.00 g,
8.27 mmol) was then added, the suspension stirred for
15 min, followed by heating at reflux for 1.5 h (or alternatively
stirred at room temperature for 4 h). All volatiles were
removed under reduced pressure and diethyl ether (40 cm3)
and H2O (10 cm3) added to the residue. The mixture was
stirred for 30 min to give two clear solution phases. The
organic phase was separated and the aqueous layer was
extracted with CH2Cl2 (3 � 30 cm3). The combined organic
phases were dried (MgSO4), filtered, and volatiles evaporated
from the filtrate under vacuum. The oily residue solidified
upon standing to give 1 as colourless crystals (yield 4.40 g,
98%). The product can be recrystallised from hot hexane
(yield 80%); mp 140–141 1C. 1H NMR (300 MHz, 298 K,
CDCl3): d 0.91 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.08–0.90
(m, 8 H, CH2), 1.21 (d, J=6.8 Hz, 6 H, CH(CH3)2), 1.36 (d, J=
6.8 Hz, 6 H, CH(CH3)2), 1.38 (d, J = 6.8 Hz, 6 H,
CH(CH3)2), 1.47–1.70 (m, 8 H, CH2), 2.05 (m, 4 H,
CH2CHN), 2.97 (tt, J = 11.7, 3.3 Hz, 2 H, CHN), 3.22 (sept,
J = 6.8 Hz, 2 H, CH(CH3)2), 3.32 (sept, J = 6.8 Hz, 2 H,
CH(CH3)2), 4.95 (s, 1 H, NH), 6.89–7.17 (m, 6 H, ArH); 1H
NMR (250 MHz, 298 K, C6D6): d 0.96 (d, J = 6.8 Hz, 6 H,
CH(CH3)2), 1.12–1.32 (m, 6 H, CH2), 1.44 (d, J= 6.8 Hz, 6 H,
CH(CH3)2), 1.50–1.68 (m, 2 H, CH2), 1.54 (d, J = 6.8 Hz, 12
H, CH(CH3)2), 1.75–1.92 (m, 8 H, CH2), 2.21–2.44 (m, 4 H,
CH2), 3.23 (tt, J = 11.7, 3.3 Hz, 2 H, CHN), 3.60 (sept, J =
6.8 Hz, 4 H, CH(CH3)2), 5.32 (s, 1 H, NH), 7.06–7.44 (m, 6 H,
ArH); 13C{1H} NMR (75.5 MHz, 298 K, CDCl3): d 21.6
(CH(CH3)2), 22.5 (CH(CH3)2), 24.9 (CH2), 26.0 (CH(CH3)2),
26.1 (CH(CH3)2), 27.1 (CH(CH3)2), 28.6 (CH(CH3)2), 29.0
(CH2), 32.6 (CH2), 58.0 (HCN), 121.6, 122.8, 123.5, 126.9,
135.9, 140.0, 145.5, 145.6, (ArC), 148.0 (CN3),13C{1H} NMR
(75.5 MHz, 298 K, C6D6): d 21.7 (CH(CH3)2), 22.3
(CH(CH3)2), 25.2 (CH2), 26.2 (CH(CH3)2), 27.3 (CH(CH3)2),
28.7 (CH(CH3)2), 29.3 (CH(CH3)2), 32.9 (CH2), 39.8 (CH2),
58.2 (HCN), 122.6, 123.3, 123.7, 127.1, 136.1, 139.9, 145.5,
145.6 (ArC), 148.5 (CN3); IR (Nujol): n/cm�1 = 3384 (m),
1614 (s), 1583 (s), 1259 (m), 1163 (m), 1110 (m), 1072 (m),
986 (m), 954 (w), 894 (m), 799 (m), 761 (m), 700 (w);
MS/APCI: m/z (%) = 544.7 (MH+, 100).
Preparation of PrisoH 2
A procedure analogous to that used to prepare 1 was em-
ployed, but using Pri2NH (colourless crystals: crude yield
99%; ca. 90% after recrystallisation); mp 144–145 1C; 1H
NMR (250 MHz, 298 K, CDCl3): d 0.89 (d, J = 6.8 Hz, 6 H,
CH(CH3)2), 1.12 (overlapping d, J = 6.8 Hz, 18 H,
CH(CH3)2), 1.20 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.37 (d,
J = 6.8 Hz, 6 H, CH(CH3)2), 3.17 (sept, J = 6.8 Hz, 2 H,
CH(CH3)2), 3.25 (sept, J = 6.8 Hz, 2 H, CH(CH3)2), 3.49
(sept, J = 6.8 Hz, 2 H, CH(CH3)2), 4.80 (s, 1 H, NH),
6.80–7.18 (m, 6 H, ArH); 1H NMR (400 MHz, 298 K,
C6D6): d 0.98 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.36 (over-
lapping d, J = 6.8 Hz, 18 H, CH(CH3)2), 1.51 (d, J = 6.8 Hz,
6 H, CH(CH3)2), 1.54 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 3.68
(sept, J = 6.8 Hz, 6 H, CH(CH3)2), 5.25 (s, 1 H, NH),
7.09–7.39 (m, 6 H, ArH), 13C{1H} NMR (75.5 MHz, 298 K,
CDCl3): d 21.6 (CH(CH3)2), 21.9 (NCH(CH3)2), 22.7
(CH(CH3)2), 24.7 (CH(CH3)2), 25.7 (CH(CH3)2), 28.2
Fig. 10 Molecular structure of 12 (25% thermal ellipsoids are shown; hydrogen atoms and isopropyl groups omitted for sake of clarity). Selected
bond lengths (A) and angles (1): K(1)–O(1) 2.681(3), K(1)–O(2) 2.698(3), K(1)–O(5) 2.780(3), K(1)–N(1) 2.823(2), K(2)–O(3) 2.646(3), K(2)–O(4)
2.710(3), K(2)–N(5) 2.735(3), K(1)–Ar centroid 3.007(1), K(2)–Ar centroid 2.915(1), N(1)–C(1) 1.328(4), N(2)–C(1) 1.321(4), N(3)–C(1) 1.437(4),
N(4)–C(30) 1.426(4), N(5)–C(30) 1.336(4), N(6)–C(30) 1.322(4); N(2)–C(1)–N(1) 124.6(3), N(2)–C(1)–N(3) 114.8(3), N(1)–C(1)–N(3) 120.6(2),
C(1)–N(1)–K(1) 123.88(18), C(30)–N(5)–K(2) 129.42(18), N(6)–C(30)–N(5) 123.6(3), N(6)–C(30)–N(4) 115.2(2), N(5)–C(30)–N(4) 121.2(2).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 71
(CH(CH3)2), 28.8 (CH(CH3)2), 47.7 (HCN), 121.7, 122.7,
123.6, 126.9, 135.4, 139.8, 145.3, 145.8 (ArC), 148.3 (CN3);13C{1H} NMR (100.6 MHz, 298 K, C6D6): d 22.2 (CH(CH3)2),
22.5 (NCH(CH3)2), 23.1 (CH(CH3)2), 25.5 (CH(CH3)2), 26.0
(CH(CH3)2), 28.8 (CH(CH3)2), 29.7 (CH(CH3)2), 48.3 (HCN),
123.2, 123.8, 124.3, 127.7, 136.1, 140.3, 145.9, 146.2 (ArC),
149.1 (CN3); IR (Nujol): n/cm�1 = 3364 (m), 1608 (s), 1580
(s), 1303 (m), 1245 (m), 1184 (m), 1154 (m), 1109 (m), 1046
(m), 1002 (m), 932 (m), 828 (m), 798 (m), 767 (m), 714 (m);
MS/APCI: m/z (%) = 464.4 (MH+, 100).
Preparation of PipisoH 3
A procedure analogous to that used to prepare 1 was em-
ployed, but using cis-2,6-dimethylpiperidine (colourless crys-
tals: crude yield 98%; ca. 88% after recrystallisation); mp
128–130 1C. 1H NMR (400 MHz, 298 K, CDCl3): d 0.89 (d,
J E 6.1 Hz, 6 H, NCH(CH3)), 1.11 (d, J = 6.8 Hz, 6 H,
CH(CH3)2), 1.16 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.18–1.76
(m, 6 H, CH2), 1.26 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 3.12
(sept, J = 6.8 Hz, 2 H, CH(CH3)2), 3.16 (sept, J = 6.8 Hz, 2
H, CH(CH3)2), 3.70 (mc, 2 H, NCH(CH3)), 4.85 (s, 1 H, NH),
6.88–7.18 (m, 6 H, ArH); 1H NMR (400MHz, 298 K, C6D6): d1.01 (d, J E 6.0 Hz, 6 H, NCH(CH3)), 1.28–1.73 (m, 6 H,
CH2), 1.42 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.49 (d, J = 6.8
Hz, 6 H, CH(CH3)2), 1.54 (d, J = 6.8 Hz, 6 H, CH(CH3)2),
1.56 (d, J= 6.8 Hz, 6 H, CH(CH3)2), 3.55 (sept, J= 6.8 Hz, 4
H, CH(CH3)2), 4.11 (mc, 2 H, NCH(CH3)), 5.34 (s, 1 H, NH),
7.11–7.39 (m, 6 H, ArH); 13C{1H} NMR (75.5 MHz, 298 K,
CDCl3): d 14.4 (CH2), 20.8 (NCH(CH3)), 21.5 (CH(CH3)2),
22.9 (CH(CH3)2), 24.1 (CH(CH3)2), 25.6 (CH(CH3)2), 28.2
(CH(CH3)2), 28.9 (CH(CH3)2), 30.0 (CH2), 48.3 (HCN), 121.8,
122.6, 123.5, 126.7, 135.1, 139.4, 145.3, 145.6 (ArC), 149.8
(CN3);13C{1H} NMR (100.6 MHz, 298 K, C6D6): d 15.0
(CH2), 21.4 (NCH(CH3)), 22.2 (CH(CH3)2), 23.4 (CH(CH3)2),
25.0 (CH(CH3)2), 25.9 (CH(CH3)2), 28.9 (CH(CH3)2), 29.8
(CH(CH3)2), 30.7 (CH2), 49.0 (HCN), 123.3, 123.7, 124.3,
127.6, 135.9, 140.0, 145.8, 146.1 (ArC), 150.7 (CN3); IR
(Nujol): n/cm�1 = 3378 (m), 1616 (s), 1579 (s), 1303 (m),
1258 (m), 1183 (m), 1145 (m), 1169 (m), 1079 (m), 1023 (m),
934 (m), 803 (m), 765 (m), 755 (m); MS/APCI: m/z (%) =
476.4 (MH+, 100).
Preparation of Pip(GisoH)2 4
BunLi (5.00 cm3 of a 1.6 M solution in hexanes, 8.00 mmol) was
added to a solution of piperazine (0.339 g, 3.94 mmol) in THF
(40 cm3) at 20 1C over 5 min and the resultant solution stirred
for 1 h. ArNQCQNAr (2.93 g, 8.08 mmol) was then added
and the mixture stirred for 30 min, before being heated at
reflux for 2 h. After cooling to ambient temperature, water
(ca. 3 cm3) was added and volatiles removed under reduced
pressure. More water (ca. 30 cm3) and CH2Cl2 (60 cm3) were
then added to the residue and the mixture vigorously stirred
until two clear solution phases were formed. The organic
phase was separated and the aqueous layer was extracted with
CH2Cl2 (3� 30 cm3). The combined organic phases were dried
(MgSO4), filtered and volatiles removed from the filtrate under
reduced pressure. The residue was recrystallised from CHCl3at –30 1C to give 4 as colourless crystals (yield: 1.88 g, 75%);
mp 196–198 1C; 1H NMR (400 MHz, 298 K, CDCl3): d 0.89
(br d, J=6.8 Hz, 12 H, CH(CH3)2), 1.00 (d, J=6.8 Hz, 12 H,
CH(CH3)2), 1.15 (br d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.23 (d,
J= 6.8 Hz, 12 H, CH(CH3)2), 2.89 (br s, 8 H NCH2), 3.04 (mc
of overlapping sept., J=6.8 Hz, 8 H, CH(CH3)2), 4.93 (s, 2 H,
NH), 6.90–7.16 (m, 12 H, ArH); 13C{1H} NMR (100.6 MHz,
298 K, CDCl3): d 22.8 (CH(CH3)2), 23.3 (CH(CH3)2), 24.5
(CH(CH3)2), 25.7 (CH(CH3)2), 28.8 (CH(CH3)2), 28.9
(CH(CH3)2), 47.3 (NCH2), 123.1, 123.4, 124.3, 127.3, 134.1,
140.1, 144.4, 145.2 (ArC), 150.8 (N3C); IR (Nujol): n/cm�1 =3391 (m), 1623 (s), 1585 (m), 1261 (m), 1196 (m), 1145 (m),
1109 (m), 1041 (m), 988 (m), 935 (m), 840 (m), 799 (m), 759
(m); MS/APCI: m/z (%) = 811.4 (MH+, 100).
Preparation of CyP-GisoH 5
BunLi (4.00 cm3 of a 1.6 M solution in hexanes, 6.40 mmol) was
added to a solution of Cy2PH (1.27 g, 6.40 mmol) in THF
(20 cm3) at 0 1C over 5 min. The resultant solution was stirred
for 1 h at room temperature. A solution of ArNQCQNAr
(2.54 g, 6.28 mmol) in THF (15 cm3) was then added to the
mixture which was subsequently heated at reflux for 1.5 h.
After cooling, degassed water (1 cm3) was added, the mixture
vigorously stirred for 1 h, and all volatiles removed under
reduced pressure. The residue was extracted with warm hexane
(2 � 50 cm3). The extract was dried over MgSO4, then filtered
and concentrated to ca. 15 cm3. Slow cooling of the filtrate to
�30 1C overnight yielded colourless crystals of 5 (yield: 2.85 g,
81%); mp 150–152 1C. 1H NMR (400 MHz, 298 K, CDCl3): d0.81 (d, J= 6.7 Hz, 6 H, CH(CH3)2), 1.09 (d, J= 6.7 Hz, 6 H,
CH(CH3)2), 1.10–1.25 (m, 8 H, CH2), 1.23 (d, J= 6.7 Hz, 6 H,
CH(CH3)2), 1.25 (d, J = 6.7 Hz, 6 H, CH(CH3)2), 1.58–2.04
(m, 14 H, CHP and CH2), 3.00 (sept., J = 6.7 Hz, 2 H,
CH(CH3)2), 3.18 (sept., J = 6.7 Hz, 2 H, CH(CH3)2), 5.44 (d,
JPH = 14.1 Hz, 1 H, NH), 6.92–7.18 (m, 6 H, ArH); 13C{1H}
NMR (100.6 MHz, 298 K, CDCl3): d 22.3 (CH2), 22.4 (CH2),
25.2 (CH(CH3)2), 26.1 (CH(CH3)2), 27.0 (CH(CH3)2), 27.8
(CH(CH3)2), 27.9 (CH(CH3)2), 28.0 (CH(CH3)2), 28.1 (CH2),
28.8 (CH2), 29.1 (CH2), 29.1 (CH2), 32.2 (d, J = 20 Hz, CH2),
33.7 (d, J = 13.2 Hz, CH2), 123.3, 123.4, 123.5, 128.4, 133.9,
139.0, 145.2, 147.2 (ArC), 160.1 (d, J = 13.1 Hz, backbone
PCN2);31P{1H} NMR (121 MHz, 298 K, C6D6): d –2.9 (s); IR
(Nujol): n/cm�1 = 3354 (NH), 1620 (m), 1592 (m), 1568 (s),
1324 (m), 1259 (s), 1173 (m), 1109 (m), 1043 (m), 934 (m),
884 (m), 852 (m), 799 (s), 756 (s); MS/EI: m/z (%) = 560.4
(M+, 4), 517.4 (M+ � C3H7, 100). Accurate mass (EI), m/z:
calc. for M+: 560.4254, found: 560.4251.
Preparation of PhP-GisoH 6
BunLi (2.80 cm3 of a 1.6 M solution in hexanes, 4.52 mmol)
was added to a solution of Ph2PH (0.85 g, 4.56 mmol) in THF
(10 cm3) at �70 1C over 5 min then warmed to room
temperature and stirred for 2 h. To the resultant red solution
was added ArNQCQNAr (1.61 g, 4.43 mmol) in THF
(10 cm3) at �70 1C. The mixture was subsequently heated
under reflux for 1.5 h. It was then cooled to room temperature
and ca. 0.3 cm3 degassed H2O was added with stirring.
Volatiles were removed in vacuo and the residue extracted
into diethyl ether (80 cm3) and filtered. The filtrate was
72 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
concentrated and stored at –30 1C to give colourless blocks of
6 (yield: 1.66 g, 68%); mp 160–162 1C. 1H NMR (400 MHz,
298 K, CDCl3): d 0.83 (4 � overlapping d, J = 6.8 Hz, 24 H,
CH3), 2.78 (sept, J= 6.8 Hz, 2 H, CH), 3.15 (sept, J= 6.8 Hz,
2 H, CH), 5.60 (s, 1 H, NH), 6.85–7.51 (m, 16 H, Ar–H);13C{1H} NMR (100.6 MHz, 298 K, CDCl3): d 21.9, 22.1, 24.4,25.4 (CH(CH3)2), 28.5, 28.8 (CH(CH3)2), 122.2, 122.8, 123.0,
123.1, 127.6, 128.0, 128.4, 129.1, 129.7, 137.4, 138.7, 145.9,
146.1, 146.4 (ArC), 155.6 (J= 16.1 Hz, PCN2);31P{1H} NMR
(121 MHz, 298 K, CDCl3,): d �18.5; MS/APCI, m/z (%): 549
(M+, 100); IR (Nujol): n/cm�1 = 1607 (s), 1579 (s), 1434 (m),
1258 (s), 1185 (m), 1099 (m), 742 (m), 693 (m); C37H45N2P
requires: C 80.99%, H 8.27%, N 5.10%, found: C 80.84%, H
8.38%, N 5.25%.
Preparation of ArSi-GisoH 7
BunLi (1.64 cm3 of a 1.6 M solution in hexanes, 2.62 mmol)
was added to a solution of ArNC{N(H)Ar}2 (1.35 g, 2.50 mmol)
in THF (15 cm3) at room temperature over 5 min. The solution
was then stirred for 1 h. Me3SiCl (0.36 g, 2.85 mmol)
was added at room temperature and the mixture subsequently
heated at reflux for 2.5 h. All volatiles were removed under
reduced pressure and the residue was extracted into warm
hexane (60 cm3). The solution was concentrated under reduced
pressure to ca. 12 cm3 and cooled to 4 1C to obtain colourless
crystals of 7 (yield 0.96 g, 63%); mp 257–258 1C. 1H NMR
(400 MHz, 298 K, CDCl3): d �0.3 (v br s, 9 H, Si(CH3)3),
0.92–0.64 (m, 12 H, CH(CH3)2), 1.14 (d, J = 6.8 Hz, 12 H,
CH(CH3)2), 1.17 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 2.81 (sept,
J = 6.8 Hz, 2 H, CH(CH3)2), 3.54–3.14 (m, 4 H, CH(CH3)2),
5.59 (s, 1 H, NH), 7.28–6.54 (m, 9 H, ArH); 13C{1H} NMR
(75.5 MHz, 298 K, CDCl3): only resonances of one aryl
substituent are resolved. Others, as well as those for the SiMe3group, are too broad to be detected. d 23.2, 26.0, 28.2,
(CH(CH3)2 and CH(CH3)2), 122.4, 126.6, 134.2, 145.5
(ArC), 146.8 (CN3); IR (Nujol): n/cm�1= 3378 (m), 1618
(s), 1578 (s), 1378 (m), 1246 (m), 1223 (m), 1107 (m), 1007 (m),
970 (m), 843 (m), 822 (m), 752 (m); MS/EI: m/z (%) = 611
(M+, 14), 596 (M+ � CH3, 5), 568 (M+ � C3H7, 15), 539
(M+ � SiMe3, 15), 496 (M+ � SiMe3 � C3H6, 18).
Preparation of (PrisoH)2 8
A solution of K[N(SiMe3)2] (0.65 g, 3.24 mmol) in THF
(10 cm3) was added to PrisoH 2 (1.50 g, 3.24 mmol) in THF
(10 cm3) at 20 1C and the mixture stirred for 1 h. A solution of
impure MnI2 (Aldrich Chemical Company, 1.00 g, 3.24 mmol)
in THF (20 cm3) was then added at �78 1C and the reaction
mixture slowly warmed to room temperature overnight. All
volatiles were removed in vacuo and the residue was extracted
with hexane (40 cm3). Filtration, concentration and slow
cooling overnight to �30 1C yielded colourless crystals of 8
(yield 0.44 g, 30%); mp 223–225 1C. 1HNMR (400MHz, 298 K,
C6D6): d 0.81–1.01 (m of overlapping br d, 18 H, CH(CH3)2),
1.05–1.47 (m of overlapping broad d, 54 H, CH(CH3)2),
3.11–3.49 (m of overlapping br sept, 12 H, CH(CH3)2),
4.74–4.91 (m, 2 H, NH), 6.88–7.29 (m, 10 H, ArH); 13C{1H}
NMR (100.6 MHz, 298 K, C6D6): d 21.83, 21.87, 22.70, 22.75,
24.73, 25.69, 28.12, 28.28, 28.81, 28.94, 31.63 (CH(CH3)2 and
CH(CH3)2), 47.60 (CHN), 121.32, 121.41, 121.89, 122.68,
123.55, 123.61, 139.69, 139.78, 140.12, 145.59, 145.78 (ArC),
148.24, 148.33 (CN3), NB: more than one isomer present. Only
major resonances reported with tentative assignments; IR
(Nujol): n/cm�1 = 3364 (m), 1611 (s), 1589 (s), 1376 (s),
1342 (m), 1261 (m), 1184 (m), 1111 (m), 999 (m), 870 (m),
802 (m), 761 (m), 715 (m); MS/EI: m/z (%) = 924.7 (M+, 14),
881.7 (M+ –C3H7, 52). Accurate mass (EI), m/z: calc. for M+:
924.7691, found: 924.7688; CHN: C62H96N6 requires: C
80.46%, H 10.45%, N 9.08%; found: C 79.77%, H 10.99%,
N 9.31%.
Preparation of [Li{Li(Giso)2}] 9
BunLi (0.70 cm3 of a 1.6 M solution in hexanes, 1.12 mmol)
was added over 5 min to a solution of GisoH 1 (0.58 g, 1.07
mmol) in hexane (20 cm3) at 20 1C. The resultant solution was
stirred for 30 min then concentrated under reduced pressure to
ca. 8 cm3. It was then stored at 4 1C overnight to afford
colourless crystals of 9 (yield: 0.42 g, 71%); mp 190–192 1C
(melts with slow decomposition); 1H NMR (300 MHz, 298 K,
C6D6): d 0.85–1.17 (m, 16 H, CH2), 1.18 (d, J = 6.8 Hz, 24 H,
CH(CH3)2), 1.49 (d, J = 6.8 Hz, 24 H, CH(CH3)2), 1.78–1.48
(m, 16 H, CH2), 2.03 (m, 8 H, CH2CHN), 3.35 (br t, J E11 Hz, 4 H, CHN), 3.57 (br sept, J= 6.8 Hz, 8 H, CH(CH3)2),
7.26–6.94 (m, 12 H, ArH); 13C{1H} NMR (75.5 MHz, 298 K,
C6D6): d 23.7, 25.0, 26.9, 27.9, 28.7, (CH2), CH(CH3),
CH(CH3)), 35.1 (CH2), 58.6 (HCN), 120.8 (ArC), 124.0
(ArC), 141.3 (ArC), 150.2 (br, ArC), 160.6 (v br, CN3);7Li NMR (155.5 MHz, 298 K, C6D6): d 2.6 (s); IR (Nujol):
n/cm�1 = 1612 (s), 1583 (s), 1236 (s), 1156 (m), 1110 (m), 1027
(m), 933 (m), 895 (m), 792 (m), 748 (m); MS/EI: m/z (%) =
543.7 (GisoH+, 5), 500 (GisoH+ � C3H6, 62).
Preparation of [Li(THF)(Giso)] 10
BunLi (2.00 cm3 of a 1.6 M solution in hexanes, 3.20 mmol)
was added over 5 min to a solution of GisoH 1 (1.71 g, 3.14
mmol) in THF (20 cm3) at 0 1C. The solution was then stirred
for 1 h and volatiles removed under reduced pressure. Hexane
(15 cm3) was added to the residue and the resultant solution
concentrated to ca. 6 cm3. This was filtered and cooled to
�30 1C to yield large colourless crystals of 10. Concentration
of the supernatant solution at room temperature yielded
another crop of 10 (yield 1.52 g; 78%); mp 208–210 1C. 1H
NMR (400 MHz, 298 K, C6D6): d 0.97 (mc, 4 H, THF-CH2),
1.27 (br mc, 12 H, CH(CH3)2), 1.30–1.45 (m, 6 H, CH2), 1.63
(d, 3JHH = 6.8 Hz, 12 H, CH(CH3)2), 1.71 (mc, 2 H, CH2),
1.93 (mc, 4 H, CH2), 2.06 (mc, 4 H, CH2), 2.52 (mc, 4 H, CH2),
2.63 (mc, 4 H, THF-OCH2), 3.38 (mc, 2 H, NCH), 3.85 (sept, J
= 6.8 Hz, 4 H, CH(CH3)2), 6.98 (t, J = 7.5 Hz, 2 H, p-ArH),
7.26 (d, J= 7.5 Hz, 4 H,m-ArH); 13C{1H} NMR (100.6 MHz,
298 K, C6D6): d 22.8 (CH(CH3)2), 23.4 (CH2), 25.3 (CH2), 26.3
(CH2, THF), 27.1 (CH(CH3)2), 32.3 (CH2), 56.5 (NCH), 66.7
(OCH2), 118.8, 122.2, 140.1, 149.7 (ArC), 156.6 (backbone,
CN3);7Li NMR (116.8 MHz, 298 K, C6D6): d 1.64 (s);
IR (Nujol): n/cm�1 = 3378 (m), 1618 (s), 1578 (m), 1378
(m), 1246 (s), 1228 (m), 1198 (m), 1107 (m), 1008 (m), 970 (m),
843 (m), 822 (m), 752 (m); MS/EI: m/z (%) = 543.7
(GisoH+, 100).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 73
Preparation of [{K(Priso)}N] 11
Toluene (30 cm3) was added to a mixture of PrisoH 2 (1.02 g,
2.20 mmol) and K[N(SiMe3)2] (0.45 g, 2.26 mmol) and the
resultant suspension stirred vigorously for 4 h at room tem-
perature. All volatiles were removed under reduced pressure
and the residue washed with hexane (15 cm3). Recrystallisation
from a toluene solution at�30 1C yielded colourless crystals of
11 (yield 0.95 g, 86%); mp 4300 1C. 1H NMR (400 MHz, 298
K, C6D6): d 1.08 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.43 (d,
J = 6.8 Hz, 12 H, CH(CH3)2), 1.51 (d, J = 6.8 Hz, 12 H,
CH(CH3)2), 3.41 (sept, J= 6.8 Hz, 2 H, CH(CH3)2), 3.68 (two
overlapping sept, J = 6.8 Hz, 4 H, CH(CH3)2), 6.76–7.18 (m,
6 H, ArH); 13C{1H} NMR (100.6 MHz, 298 K, C6D6): d 22.7
(NCH(CH3)2), 24.0 (CH(CH3)2), 24.2 (CH(CH3)2), 27.4
(CH(CH3)2), 47.0 (HCN), 117.3, 122.5, 141.1, 145.5 (ArC),
153.2 (CN3); IR (Nujol): n/cm�1 = 1613 (s), 1584 (m), 1261
(m), 1152 (m), 1098 (m), 933 (m), 779 (m); MS/EI: m/z (%) =
501.3 (M+, 3), 420.3 (M+ � K � C3H6, 100). Accurate mass
(EI), m/z: calc. for M+: 501.3480, found: 501.3484.
Preparation of [{K(THF)2}{Pip(Giso)2}{K(THF)3}] 12
A solution of K[N(SiMe3)2] (0.336 g, 1.68 mmol) in THF
(15 cm3) was added to a solution of Pip(GisoH)2 4 (0.65 g,
0.801 mmol) in THF (25 cm3) at 20 1C. The resultant mixture
was stirred for 1 h, concentrated to ca. 15 cm3 and then cooled
to �30 1C to afford colourless crystals of 12 (yield 0.46 g,
52%); mp 4300 1C; IR (Nujol): n/cm�1 = 1620 (s), 1584 (m),
1238 (m), 1195 (m), 1050 (m), 987 (m), 840 (m), 799 (m), 758
(m), 736 (m); MS/APCI: m/z (%) = 811.4 (Pip(GisoH)2H+,
100). N.B. The very low solubility of 12 in common deuterated
solvents precluded the acquisition of meaningful NMR data.
X-Ray crystallography
Crystals of 1–12 suitable for X-ray structural determination
were mounted in silicone oil. Crystallographic measurements
were made using a Nonius Kappa CCD diffractometer. The
structures were solved by direct methods and refined on F2 by
full-matrix least squares (SHELX97)28 using all unique data.
Hydrogen atoms have been included in calculated positions
Table 2 Crystal data for compounds 1–12
Compound 1 2 3 4�2CHCl3 5 6
Empirical formula C37H57N3 C31H49N3 C32H49N3 C56H80Cl6N6 C37H57N2P C37H45N2PMr 543.86 463.73 475.74 1049.96 560.82 548.72T/K 123(2) 150(2) 150(2) 150(2) 150(2) 150(2)Crystal system Monoclinic Orthorhombic Monoclinic Monoclinic Monoclinic TriclinicSpace group P21/n Pbca P21/c P21/c P21/n P�1a/A 12.265(3) 18.397(4) 19.236(4) 13.042(3) 10.960(2) 10.847(2)b/A 17.424(4) 15.542(3) 16.327(3) 12.030(2) 26.459(5) 10.942(2)c/A 15.775(3) 20.168(4) 19.536(4) 18.989(4) 12.934(3) 14.156(3)a/1 90 90 90 90 90 96.42(3)b/1 90.43(3) 90 106.01(3) 91.97(3) 112.61(3) 101.60(3)g/1 90 90 90 90 90 102.50(3)V/A3 3371.2(12) 5767(2) 5898(2) 2977.7(10) 3462.6(12) 1585.4(6)Z 4 8 8 2 4 2Dc/Mg m�3 1.072 1.068 1.072 1.171 1.076 1.149m(Mo-Ka)/mm�1 0.062 0.062 0.062 0.328 0.105 0.114F(000) 1200 2048 2096 1120 1232 592No. reflections collected 38 325 19 664 21 080 10 581 14 712 10 001No. independent reflns 7339 5343 11498 5520 7517 5420Rint 0.1167 0.0382 0.0500 0.0272 0.0299 0.0306Final R1 (I 4 2s(I)) 0.0629 0.0435 0.0603 0.0465 0.0479 0.0464Final wR2 (all data) 0.1584 0.1069 0.1527 0.1147 0.1227 0.1159
Compound 7 8�hexane 9 10 11 12�2THF
Empirical formula C40H61N3Si C68H110N6 C74H112Li2N6 C41H64LiN3O C31H48KN3 C82H132K2N6O7
Mr 612.01 1011.62 1099.58 621.89 501.82 1392.14T/K 123(2) 150(2) 123(2) 150(2) 123(2) 150(2)Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Orthorhombic MonoclinicSpace group P21/c P21/c C2/c P21/c P212121 P21/na/A 35.510(7) 15.467(3) 20.707(4) 18.807(4) 11.462(2) 24.500(5)b/A 9.9877(2) 22.956(5) 12.031(2) 11.783(2) 11.997(2) 16.473(3)c/A 21.966(4) 19.774(4) 26.802(5) 18.773(4) 21.319(4) 20.494(4)a/1 90 90 90 90 90 90b/1 104.59(3) 111.87(3) 104.33(3) 113.20(3) 90 93.48(3)g/1 90 90 90 90 90 90V/A3 7456(3) 6516(2) 6469(2) 3823.8(13) 2931.6(10) 8256(3)Z 8 4 4 4 4 4Dc/Mg m�3 1.090 1.031 1.129 1.080 1.137 1.120m(Mo-Ka)/mm�1 0.093 0.059 0.064 0.063 0.204 0.168F(000) 2688 2240 2416 1368 1096 3040No. reflections collected 58 137 16 169 18 157 24 208 22 486 27 961No. independent reflns 16 069 11 404 5651 8282 5060 14 497Rint (0.0810) (0.0423) (0.1428) (0.0304) (0.1036) (0.0408)Final R1 (I 4 2s(I)) 0.0546 0.0755 0.0669 0.0501 0.0737 0.0713Final wR2 (all data) 0.1380 0.1828 0.1301 0.1236 0.1371 0.1858
74 | New J. Chem., 2009, 33, 64–75 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(riding model) for all structures, with the exception of the
methyl hydrogens of C(21) and C(24) in the structure of 11
which were not included in the refinement. Two crystallo-
graphically independent molecules were refined in the asym-
metric units of the crystal structures of 3 and 7. No significant
geometric differences were found between the two molecules in
each structure and therefore only the metrical parameters for
one molecule from each structure are reported here. The Flack
parameter for the crystal structure of compound 11 is 0.01(6).
Crystal data, details of data collections and refinement are
given in Table 2.
Acknowledgements
We gratefully acknowledge financial support from the Aus-
tralian Research Council (fellowships for C. J. and A. S.), the
Leverhulme Trust (fellowship for A. S.), the Erasmus scheme
of the European Union (travel grant for K. L.), the Royal
Society (fellowship for G. J.), and the US Air Force Asian
Office of Aerospace Research and Development. Thanks also
go to the EPSRC Mass Spectrometry Service, Swansea.
References
1 For general references on the structure and reactivity of amidinateand guanidinate complexes, see: (a) J. Barker and M. Kilner,Coord. Chem. Rev., 1994, 133, 219; (b) F. T. Edelmann, Coord.Chem. Rev., 1994, 137, 403; (c) P. J. Bailey and S. Price, Coord.Chem. Rev., 2001, 214, 91; (d) M. P. Coles, Dalton Trans., 2006,985; (e) P. C. Junk and M. L. Cole, Chem. Commun., 2007, 1579,and references therein.
2 N. Nimitsiriwar, V. C. Gibson, E. L. Marshall, A. J. P. White,S. H. Dale and M. R. J. Elsegood, Dalton Trans., 2007, 4464.
3 S. R. Foley, Y. Zhou, G. P. A. Yap and D. S. Richeson, Inorg.Chem., 2000, 39, 924.
4 S. Dagorne, I. A. Guzei, M. P. Coles and R. F. Jordan, J. Am.Chem. Soc., 2000, 122, 274.
5 J. Barker, N. C. Blacker, P. R. Phillips, N. W. Alcock,W. Errington and M. G. H. Wallbridge, J. Chem. Soc., DaltonTrans., 1996, 431.
6 L. Bourget-Merle, M. F. Lappert and J. R. Severn, Chem. Rev.,2002, 102, 3031.
7 (a) C. Cui, H. W. Roesky, H.-G. Schmidt, M. Noltemeyer, H. Haoand F. Cimpoesu, Angew. Chem., Int. Ed., 2000, 39, 4274;(b) N. J. Hardman, B. E. Eichler and P. P. Power, Chem. Commun.,2000, 1991; (c) M. S. Hill and P. B. Hitchcock, Chem. Commun.,2004, 1818; (d) M. S. Hill, P. B. Hitchcock andR. Pongtavornpinyo, Dalton Trans., 2005, 273.
8 C. Jones, P. C. Junk, J. A. Platts, D. Rathmann and A. Stasch,Dalton Trans., 2005, 2497.
9 C. Jones, P. C. Junk, J. A. Platts and A. Stasch, J. Am. Chem. Soc.,2006, 128, 2206.
10 S. P. Green, C. Jones and A. Stasch, Inorg. Chem., 2007, 46, 11.11 G. Jin, C. Jones, P. C. Junk, A. Stasch and W. D. Woodul, New J.
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Chem. Commun., 2006, 3978.14 S. P. Green, C. Jones, G. Jin andA. Stasch, Inorg. Chem., 2007, 46, 8.15 C. Jones, D. P. Mills and A. Stasch, Dalton Trans., 2008,
4799.16 D. Heitmann, C. Jones, P. C. Junk, K.-A. Lippert and A. Stasch,
Dalton Trans., 2007, 187.17 C. Jones, R. P. Rose and A. Stasch, Dalton Trans., 2007, 2997.18 S. P. Green, C. Jones, K.-A. Lippert, D. P. Mills and A. Stasch,
Inorg. Chem., 2006, 45, 7242.19 R. E. Boere, R. T. Boere, T. Masuda and G. Wolmershauser, Can.
J. Chem., 2000, 78, 1613.20 Z. Lu, G. P. A. Yap and D. S. Richeson, Inorg. Chem., 1999, 38,
5788.21 See for example (a) M. P. Coles and P. B. Hitchcock, Chem.
Commun., 2002, 2794; (b) J. Grundy, M. P. Coles and P. B.Hitchcock, Dalton Trans., 2003, 2573; (c) N. E. Mansfield,M. P. Coles and P. B. Hitchcock, Dalton Trans., 2005, 2833;(d) N. E. Mansfield, M. P. Coles and P. B. Hitchcock, DaltonTrans., 2006, 2052; (e) N. E. Mansfield, J. Grundy, M. P. Coles,A. G. Avent and P. B. Hitchcock, J. Am. Chem. Soc., 2006, 128,13879.
22 W.-X. Zhang, M. Nishiura and Z. Hou, Chem. Commun., 2006,3812.
23 M. R. Crimmin, A. G. M. Barrett, M. S. Hill, P. B. Hitchcock andP. A. Procopiou, Organometallics, 2008, 27, 497.
24 R. J. Baker and C. Jones, J. Organomet. Chem., 2006, 691, 65.25 As determined from a survey of the Cambridge Crystallographic
Database, May, 2008.26 C. Knapp, E. Lork, P. G. Watson and R. Mews, Inorg. Chem.,
2002, 41, 2014.27 K. Ogawa and M. Akazawa, Jpn. Pat. Appl., JP 91-208987910517,
1993.28 G. M. Sheldrick, SHELX-97, University of Gottingen, 1997.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 64–75 | 75
The hydrogen bond acidity and other descriptors for oximes
Michael H. Abraham,*aJavier Gil-Lostes,
aJ. Enrique Cometto-Muniz,
b
William S. Cain,bColin F. Poole,
cSanka N. Atapattu,
cRaymond J. Abraham
d
and Paul Leonardd
Received (in Durham, UK) 9th July 2008, Accepted 20th August 2008
First published as an Advance Article on the web 9th October 2008
DOI: 10.1039/b811688a
The solvation descriptors for cyclohexanone oxime and acetone oxime have been obtained from
measurements on water–solvent partitions, and gas–liquid chromatographic retention data. These
yield values of 0.33 and 0.37 for the Abraham hydrogen bond acidity, A, in reasonable agreement
with a value of 0.37 for cyclohexanone oxime obtained by our recent NMR method. The other
descriptors E, S, B, L and V have also been obtained for cyclohexanone oxime and acetone
oxime, and have been estimated for a number of other oximes as well. The value for A, the
overall or effective hydrogen bond acidity of the oximes is reasonably close to the 1 : 1 hydrogen
bond acidity, a2H = 0.39 to 0.46, that can be deduced from previous literature measurements on
oximes, and to the 1 : 1 hydrogen bond acidity, a2H = 0.43 for another NOH compound,
N,N-dibenzylhydroxylamine, that again can be deduced from literature measurements.
Introduction
The oximes were important derivatives of aldehydes and
ketones, often used for identification in the 19th and early
20th century. Their use as derivatives has declined, but a
number of oximes are important. Nifuroxime is a drug, and
diacetylmonooxime is a cholinesterase reactivator. In order to
predict physicochemical and biochemical properties of the
oximes, a knowledge of their Abraham descriptors1,2
(or solvation parameters) is needed. One of the key descriptors
is the overall, or effective, hydrogen bond acidity, A, in which
we were particularly interested, especially as we have recently
developed a new method for the experimental determination
of this parameter.3 In this work, we showed that the difference
(Dd) in the 1H NMR chemical shift of a protic hydrogen in
DMSO vs. CDCl3 solvent is directly related to the hydrogen
bond acidity. This correlation was valid over 54 compounds
and 72 protic hydrogens varying from cyclohexane to the OH
proton of phenol. An important advantage of the NMR
method is that it allows the determination of A values for
individual protic hydrogens in multifunctional solutes.
As we have pointed out,1 the overall or effective hydrogen
bond acidity, A, is the important type of acidity when con-
sidering processes in which a solute is in dilute solution and
surrounded by solvent molecules, or is present in the gas phase
as an isolated molecule. A related acidity is the 1 : 1 hydrogen
bond acidity, a2H, in which a solute complexes with a hydrogen
bond base in an inert solvent such as tetrachloromethane.1,4
The defining equations for a2H are eqn (1),4 where K is the 1 : 1
complexation constant for an acid against a reference base B,
eqn (2) in which logK is put on a general scale of hydrogen
bond acidity KAH, and finally eqn (3) in which KA
H is
transformed into the a2H scale. In eqn (2), LB and DB are
the fitting coefficients.
A–H + :B - A–H� � �B; K (1)
logK (for an acid against a reference base B) = LB log
KAH + DB (2)
a2H = (1.1 + KA
H)/4.636 (3)
The term (1.1 + KAH) serves to define the origin of the scale
where a2H = 0 for zero acidity, and the factor 4.636 is used
only to provide a suitable range of the scale. A number of
equations on the lines of eqn (2) were constructed for various
reference bases.
The only acid–base measurements that seem to have been
made on oximes are those of Ossart et al.,5 who measured 1 : 1
complexation constants for a number of oximes against the
base tetrahydrofuran in tetrachloromethane. The 1 : 1 com-
plexation constants, K, in units of mol�1 dm3, are in Table 1,
together with the corresponding values of a2H that we have
deduced from the LB and DB values for the base tetrahydro-
furan4 in Table 2, through eqn (2) and (3). Feuer et al.6 have
measured 1 : 1-complexation constants for the NOH com-
pound N,N-dibenzylhydroxylamine against a number of
hydrogen bond bases in tetrachloromethane, as shown in
Table 2, where we give the deduced values of a2H.
aDepartment of Chemistry, University College London, 20 GordonStreet, London, UK WC1H OAJ. E-mail: [email protected]: [email protected]
bChemosensory Perception Laboratory, Department of Surgery(Otolaryngology), University of California, San Diego, La Jolla,CA 92093-0957, USA. E-mail: [email protected]
cDepartment of Chemistry, Wayne State University, Detroit,MI 48202, USA. E-mail: [email protected]: [email protected]
dChemistry Department, The University of Liverpool, P.O. Box 147,Liverpool, UK L69 3BX. E-mail: [email protected]: [email protected]
76 | New J. Chem., 2009, 33, 76–81 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
Results
The complexation constants of Ossart et al.5 can be trans-
formed into KAH and then into a2
H values through eqn (2) and
(3). The deduced values of a2H range from 0.39 to 0.46 as
shown in Table 1. Similarly, the complexation constants of
Feuer et al.6 yield the a2H values given in Table 2. No equation
on the lines of eqn (2) has been constructed for benzene as a
reference base, and so we are left with three independent
values of a2H for N,N-dibenzylhydroxylamine. There is not
very good agreement, but we can say that the 1 : 1 hydrogen
bond acidity of N,N-dibenzylhydroxylamine is around 0.43
units. Once a2H is known, the general equation, eqn (4),7 can
be used to estimate the 1 : 1 complexation constant of the
oximes or of the hydroxylamine with any base for which the
1 : 1 hydrogen bond basicity b2H has been determined.8–11
logK = (7.354a2Hb2
H) � 1.094 (4)
Of more practical utility is the overall hydrogen bond acidity,
A, which is one of the descriptors in our linear free energy
relationships, LFERs, eqn (5) and (6).1,2
SP = c + eE + sS + aA + bB + vV (5)
SP = c + eE + sS + aA + bB + lL (6)
In eqn (5) and (6), the independent variables are solute
descriptors as follows. E is the solute excess molar refractivity
in units of (cm3 mol�1)/10, S is the solute dipolarity/polariz-
ability, A and B are the overall or summation hydrogen bond
acidity and basicity, V is the McGowan characteristic volume12 in units of (cm3 mol�1)/100 and L is the logarithm of the gas
to hexadecane partition coefficient at 25 1C. Eqn (5) is used for
transfer of solutes from one condensed phase to another, and
eqn (6) is used for processes that involve the transfer of solutes
from the gas phase to a solvent phase. The dependent variable,
SP, is a set of solute properties in a given system. For example,
SP in eqn (5) could be the water-to-octanol partition coeffi-
cient, as logPoct, and SP in eqn (6) could be a gas-to-solvent
partition coefficient or some measure of gas chromatographic
retention. The coefficients in eqn (5) and 6 are evaluated
through multiple linear regression analysis (MLRA).
The use of eqn (5) and (6) in the determination of descrip-
tors has been described in detail,2 and numerous examples are
available.13–16 In brief, equations on the lines of eqn (5) and (6)
are set up for a number of physicochemical processes, using
solutes whose descriptors are known. The SP values for the
investigated compound are then obtained by experiment for
the same processes under exactly the same conditions as used
in the calibration experiments. There are six descriptors that
are required for any compound. However, V can be calculated
from atomic and bond contributions,1,12 and E can then be
obtained by one of a variety of methods. If the refractive index
of the liquid compound at 20 1C is available, E can be
obtained directly. Otherwise E can be calculated by addition
of fragments, either by hand or by a commercial program,17 or
can be obtained from a calculated refractive index.18
Cyclohexanone oxime and acetone oxime are solids, but a
number of lower oximes are liquids whose refractive index has
been measured,19 and for which we have calculated E, see
Table 3. Also included are values of E calculated from the
ACD refractive index,18 and values of E calculated through
the PharmaAlgorithm (PHA) program.17 The ACD values are
all too low, but the PHA values show good agreement with the
experimental values. We take the PHA value of 0.58 for
cyclohexanone oxime and a value of 0.39 for acetone oxime
(slightly larger than that for butanone oxime).
This then leaves four descriptors, S, A, B and L to be
obtained by experiment. In principle, if four values of SP are
obtained in four calibrated systems, we have four unknowns
(S, A, B and L) that can be deduced from four equations. In
practice, it is much better to have a larger number of equations
and then to find the best solution of the equations by trial-and-
error, the best solution being the values of the descriptors that
provide the best fit of calculated and experimental SP values.
We used the procedure in Microsoft ‘Solver’ to obtain the best
fit descriptors. We can extend the number of equations
through eqn (7), where Ps is a water-to-solvent partition
coefficient, Ks is the corresponding gas-to-solvent partition
coefficient, and Kw is the corresponding gas-to-water partition
coefficient. In the case of a solvent such as octanol, that takes
Table 2 Values of LB and DB in eqn (2), the 1 : 1 complexationconstant, K, in tetrachloromethane and derived values of a2
H forN,N-dibenzylhydroxylamine
Base LB DB K (ref. 6) a2H
Triethylamine 1.0486 0.0517 14 0.462Diethyl ether 0.7129 �0.3206 2.3 0.444Dimethyl sulfoxide 1.2399 0.2656 11 0.372Benzene N/A N/A 0.5Tetrahydrofuran 0.8248 �0.1970
Table 3 Some experimental and calculated values of E for oximes
Oxime Z(20) V E(exptl.)aACD(calc.)
PHA(calc.)
Formaldehyde oxime 0.3650 0.37Acetaldehyde oxime 1.4264 0.5059 0.390 0.300 0.40Propanal oxime 1.4303 0.6468 0.366 0.293 0.40Butanal oxime 1.4367 0.7877 0.357 0.288 0.40Isobutanal oxime 0.7877 (0.37) 0.41Acetone oxime 0.6468 (0.39) 0.296 0.38Butanone oxime 1.4431 0.7877 0.383 0.292 0.38Pentan-2-one oxime 1.4455 0.9286 0.369 0.290 0.37Pentan-3-one oxime 1.4465 0.9286 0.375 0.290 0.37Hexan-2-one oxime 1.4470 1.0695 0.354 0.288 0.37Heptan-4-one oxime 1.4475 1.2104 0.335 0.288 0.37Cyclopentanone oxime 0.8200 (0.58) 0.59Cyclohexanone oxime 0.9609 (0.58) 0.728 0.58
a Values in parenthesis are estimated.
Table 1 Values of the 1 : 1 complexation constant, K, for someoximes against tetrahydrofuran in tetrachloromethane, and the corres-ponding values of a2
H
Oxime K (ref. 5) a2H
Acetaldehyde oxime 3.75 0.44Acetone oxime 3.51 0.43Butanone oxime 4.08 0.45Cyclohexanone oxime 2.45 0.39Acetophenone oxime 4.24 0.45Benzophenone oxime 4.49 0.46Benzaldehyde oxime (b) 4.65 0.46
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 76–81 | 77
up a considerable amount of water when in equilibrium with
water, both logPs and logKs refer to the water-saturated
octanol. Then eqn (7) can be applied provided that logKw as
obtained for pure water is the same for water saturated with
octanol. There is a considerable amount of experimental
evidence that logKw is indeed the same, within any realistic
experimental error, for water and octanol saturated water,20
and so eqn (7) can be applied to wet octanol as well as to
solvents that take up only very small quantities of water.
logPs = logKs � logKw (7)
If we allow the value of logKw to float, we have increased the
number of ‘descriptors’ to be determined from four to five.
However, the logPs values for the four solvents listed in
Table 4 Coefficients in the equations used to calculate descriptors for cyclohexanone oxime, and the corresponding observed and calculatedvalues (Ps is the water-to-solvent partition coefficient, Ks is the corresponding gas-to-solvent partition coefficient, Kw is the corresponding gas-to-water partition coefficient, k is the gas to stationary phase partition coefficient, tr
0 is the retention time relative to the standard)
SP
System SP c e s a b v/l Obs Calc
Water–octanol logPs 0.088 0.562 �1.054 0.034 �3.460 3.814a 0.988 1.031Water–chloroform logPs 0.327 0.157 �0.391 �3.191 �3.437 4.191a 0.821 0.944Water–hexane logPs 0.361 0.579 �1.723 �3.599 �4.764 4.344a �0.599 �0.773Water–toluene logPs 0.143 0.527 �0.720 �3.010 �4.824 4.545a 0.260 0.232Gas–waterb logKw �0.994 0.577 2.549 3.813 4.841 �0.869a 5.115 5.011Gas–octanol logKs �0.198 0.002 0.709 3.519 1.429 0.858 6.103 6.181Gas–chloroform logKs 0.116 �0.467 1.203 0.138 1.432 0.994 5.936 6.141Gas–hexane logKs 0.292 �0.169 0.000 0.000 0.000 0.979 4.516 4.423Gas–toluene logKs 0.121 �0.222 0.938 0.467 0.099 1.012 5.375 5.423Gas–waterc logKw �1.271 0.822 2.743 3.904 4.814 �0.213 5.115 4.979CW-20M log tr
0 �3.270 0.144 1.420 1.950 0.000 0.467 0.824 0.752OV-275 log tr
0 �2.822 0.355 1.650 1.797 0.325 0.341 1.106 1.133Hp-Innowax log tr
0 �2.675 0.033 1.290 1.703 �0.051 0.386 0.765 0.704DEGS log tr
0 �3.296 0.327 1.568 1.882 0.297 0.424 0.964 0.939HP-5 80 log k �1.927 �0.051 0.360 0.303 0.000 0.636 1.258 1.215100 log k �1.970 �0.022 0.329 0.243 0.000 0.573 0.916 0.869120 log k �2.008 0.000 0.305 0.200 0.000 0.518 0.613 0.570160 log k �2.552 0.050 0.229 0.145 0.000 0.389 �0.557 �0.589SPB-Octyl 80 log k �2.645 0.165 0.062 0.000 0.000 0.703 0.600 0.543100 log k �2.719 0.181 0.057 0.000 0.000 0.644 0.267 0.219120 log k �2.738 0.189 0.076 0.000 0.000 0.578 �0.016 �0.063160 log k �1.980 0.174 0.059 0.000 0.000 0.431 0.084 0.036180 log k �1.996 0.182 0.060 0.000 0.000 0.391 �0.104 �0.147200 log k �1.965 0.186 0.048 0.000 0.000 0.350 �0.250 �0.302240 log k �1.979 0.192 0.052 0.000 0.000 0.287 �0.530 �0.581Rtx-440 80 log k �2.452 �0.038 0.505 0.389 0.000 0.667 1.001 0.990100 log k �2.537 0.000 0.461 0.316 0.000 0.613 0.647 0.630120 log k �2.584 0.021 0.427 0.271 0.000 0.559 0.337 0.317160 log k �2.419 0.046 0.336 0.211 0.000 0.427 �0.168 �0.176180 log k �2.398 0.048 0.312 0.192 0.000 0.382 �0.368 �0.376200 log k �2.403 0.067 0.288 0.181 0.000 0.346 �0.549 �0.550220 log k �2.479 0.077 0.270 0.174 0.000 0.323 �0.730 �0.739240 log k �2.393 0.098 0.226 0.156 0.000 0.284 �0.842 �0.854DB-1701 160 log k �2.119 �0.007 0.553 0.575 0.000 0.409 0.238 0.331180 log k �2.078 �0.001 0.511 0.488 0.000 0.362 0.024 0.106200 log k �2.083 0.020 0.471 0.419 0.000 0.328 �0.164 �0.092220 log k �2.070 0.039 0.428 0.356 0.000 0.295 �0.333 �0.270Rxi-50 160 log k �2.104 0.124 0.592 0.283 0.000 0.390 0.264 0.279180 log k �2.110 0.145 0.536 0.258 0.000 0.352 0.059 0.062200 log k �2.118 0.160 0.486 0.250 0.000 0.319 �0.114 �0.127220 log k �2.111 0.169 0.446 0.216 0.000 0.288 �0.297 �0.296240 log k �2.093 0.181 0.402 0.192 0.000 0.259 �0.446 �0.44480 log k �2.192 0.090 0.807 0.398 0.000 0.623 1.448 1.409120 log k �2.236 0.117 0.713 0.302 0.000 0.505 0.778 0.755140 log k �2.242 0.143 0.648 0.269 0.000 0.455 0.504 0.479HP-Innowax 160 log k �2.568 0.215 1.157 1.544 0.000 0.356 0.634 0.645180 log k �2.383 0.202 0.998 1.363 0.000 0.299 0.367 0.374200 log k �2.350 0.204 0.926 1.198 0.000 0.265 0.133 0.142220 log k �2.334 0.209 0.854 1.071 0.000 0.237 �0.077 �0.067DB-225 160 log k �2.784 0.055 0.980 0.853 0.000 0.340 �0.210 �0.120180 log k �2.833 0.074 0.909 0.776 0.000 0.311 �0.354 �0.372200 log k �2.826 0.091 0.842 0.691 0.000 0.278 �0.600 �0.586220 log k �2.775 0.096 0.754 0.612 0.000 0.251 �0.731 �0.754a These coefficients are for v, the remainder are for l. b Eqn (5). c Eqn (6).
78 | New J. Chem., 2009, 33, 76–81 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Table 4 then yield four extra logKs values, and in addition we
have two equations, one from eqn (5) and one from eqn (6) for
logKw, making an extra six equations. In Table 4 are given the
systems that we have used for cyclohexanone oxime, the coeffi-
cients in eqn (5) and (6), and the observed and calculated SP
values. The extra equations lead to a total of 53 equations for
which the SP values can be fitted with a standard deviation, SD,
of only 0.063 log units with the descriptors shown in Table 5.
For acetone oxime, we have the GLC data obtained at UCL.
We also have an equation derived from the retention indices, I,
obtained by Zenkevich21 on Porapak Q for a large number of
volatile compounds. Application of eqn (6) yielded eqn (8).
I = 154.68 � 69.354E + 38.611B + 175.622L (8)
N = 214, R2 = 0.9873, SD = 28.7, F = 2702.6
In eqn (8), N is the number of compounds, R is the correlation
coefficient, SD is the standard deviation and F is the F-statis-
tic. There is also a set of GLC data on a Perkin–Elmer column
that includes acetone oxime.22 The relevant equation is
eqn (9), making a total of 16 equations for acetone oxime.
Details of the calculations for acetone oxime are in Table 6;
the standard deviation between observed and calculated values
is only 0.040 log units.
I = 83.84 � 19.68E + 63.46S + 118.44A + 11.85B
+ 196.853L (9)
N = 48, R2 = 0.9880, SD = 13.9, F = 713.13
The 1H NMR spectra of oximes in CDCl3 and DMSO
solvents have been recorded previously. There is exchange
between the NH and OH protons in hydroxylamines in
DMSO solution which was noted by Feuer et al.6 in their
measurements of the self-association of these compounds in
this solvent. However the OH chemical shift in oximes in
DMSO solution is independent of concentration and this was
used by Kurtz and D’Silva23 in their estimation of the pKa of
twenty oximes in DMSO solvent. The 1H NMR data of ca.
forty oximes in CDCl3 solution, including acetone and cyclo-
hexanone oxime are given in the Aldrich Spectral catalogue.24
The OH proton chemical shift is always very deshielded,
for example acetone oxime 9.97 ppm, cyclohexanone oxime
9.78 ppm. Very similar shifts are obtained in DMSO solution:
10.12,23 10.14 (this work) for acetone oxime, and 10.02,23
10.05 (this work) for cyclohexanone oxime. The values
for chloroform are for relatively concentrated solutions
(8/10%, weight to volume,24 i.e. for cyclohexanone oxime
0.9 mol dm�3). The chemical shift of the OH proton in oximes
in CDCl3 solvent is known to be concentration dependent6 due
to intermolecular hydrogen bonding; thus a dilution experi-
ment was performed in CDCl3 solution on cyclohexanone
oxime to obtain the N dilution chemical shift required for
this study. The oxime concentration was decreased until
the OH chemical shift showed very little change with concen-
tration (Table 7). The concentrations were measured by
using the integral of the a-CH2 protons of the oxime with
respect to the residual CHCl3 peak. The results are given in
Table 7. The plot of d(OH) vs. concentration is linear until a
dilution of ca. 0.06 mol dm�3 is reached when the plot is
essentially independent of concentration. Thus the value of
4.45 ppm may be regarded as the N dilution chemical shift in
this experiment. However the OH peak of the oxime at the
lowest concentration measured was a broad peak of intensity
2H, with respect to the a-CH2 protons of the oxime
(see above). This value was interpreted as due to the oxime
OH (intensity 1) plus an equal amount of water protons
present despite careful drying of the CDCl3 solvent over
molecular sieves. There is rapid exchange on the NMR time
scale between the oxime OH proton and the water protons
to give the broad peak observed. The chemical shift of this
peak is therefore the weighted average of the chemical shifts of
the oxime OH and the water protons. Thus eqn (10) applies
where dobs, d and d2 are the observed chemical shift and
the chemical shifts of the oxime OH and the water protons
at these concentrations and n1 and n2 the mole fractions of the
two species.
dobs = n1d1 + n2d2 (10)
The N dilution chemical shift of water in CDCl3 solvent is
1.56 ppm25 and inserting this in eqn (10) with dobs = 4.45 ppm
and n1 = n2 = 1/2 gives the N dilution value for the OH
shift in cyclohexanone oxime as 7.34 ppm. This value,
when inserted into the A vs. Dd, eqn (3), gives an A value
of 0.37.
Table 5 Solvation descriptors for cyclohexanone and acetone oxime
Oxime E S A B V L logKw
Cyclohexanone oxime 0.58 0.90 0.33 0.61 0.9609 4.320 5.11Acetone oxime 0.39 0.66 0.37 0.56 0.6488 2.557 4.46
Table 6 Observed and calculated values for acetone oxime (seeTable 4 for definitions)
SP
System SP Obs. Calc.
Water–octanol logPs 0.120 0.154Water–chloroform logPs �0.351 �0.264Water–hexane logPs �1.725 �1.740Water–toluene logPs �0.960 �1.002Gas–watera logKw 4.464 4.472Gas–octanol logKs 4.584 4.580Gas–chloroform logKs 4.113 4.137Gas–hexane logKs 2.739 2.744Gas–toluene logKs 3.504 3.484Gas–waterb logKw 4.464 4.452CW-20M log tr
0 �0.287 �0.354OV-275 log tr
0 0.058 0.129HP-Innowax log tr
0 �0.227 �0.217DEGS log tr
0 �0.152 �0.181Porapak Q21 I/100 5.980 6.009See text22 I/100 6.700 6.748
a Eqn (5). b Eqn (6).
Table 7 d(OH) vs. concentration of cyclohexanone oxime in CDCl3
Conc. (mol dm�3 � 10�2) 2.00 6.97 9.26 11.76 20.0d(OH) 4.45 4.68 5.77 6.27 8.82
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 76–81 | 79
Discussion
The descriptors for cyclohexanone oxime have been derived
from fits to 53 equations and can be regarded as soundly based.
Those for acetone oxime are based on 16 equations, and so
should also be quite reliable. The value of the hydrogen bond
acidity descriptor, A, is 0.33 or 0.37 for cyclohexanone oxime
and 0.37 for acetone oxime, as compared to the 1 : 1 hydrogen
bond acidity 0.39 and 0.43, respectively, see Table 1, and 0.43
for the NOH compound, N,N-dibenzylhydroxylamine, see
Table 2. For alcohols, A and a2H do not differ too much :
0.37 and 0.32 for propan-1-ol, 0.33 and 0.33 for isopropanol,
and 0.31 and 0.32 for tert-butanol. Hence, for N,N-dibenzyl-
hydroxylamine we expect A to be near 0.43 units. The hydro-
gen-bond acidity of the two types of NOH compound, the
oximes and the hydroxylamines, are thus quite close.
The value of 0.37 for the hydrogen bond acidity of cyclo-
hexanone oxime by the NMRmethod is a little higher than the
value of 0.33 from the GLC and partition measurements.
However, the NMR method is rendered more difficult than
usual because of the large concentration dependence of the
chemical shift in CDCl3, and the necessity of obtaining the N
dilution chemical shift of the oxime from the observed shift
due to the oxime and water. For other acyclic oximes, we
suggest that an A-value of 0.35 could be taken.
In the calculation of the descriptors for the oximes, we used
the method of fitting by trial-and-error. If, for a given oxime,
we have four unknown descriptors S, A, B and L, then four
equations of the type of eqns (5) and (6) would suffice to yield
values for the four descriptors. It is obviously better to have
more equations, but then the solution can only be obtained by
trial-and-error. We used the ‘Solver’ add-on programme in
Microsoft Excel to obtain the best-fit descriptors. Inspection
of Table 4 shows that the various equations that can be used in
the calculation of descriptors have very different coefficients.
The larger the coefficient the more accurately can the corre-
sponding descriptor be obtained. Several of the GLC phases
have reasonably large values of the s- and a-coefficients,
because they are dipolar and are hydrogen bond bases and
so they are useful in the determination of the S and A
descriptors: note that the solvent hydrogen bond basicity is
complementary to the solute hydrogen bond acidity. However,
the values of the a-coefficients for the GLC phases are never
more than 2.0, whereas a number of other processes, including
partitions from water to non-polar solvents, have a-coeffi-
cients numerically almost twice as large. It is therefore an
advantage to include water-to-solvent partitions in the set of
equations when calculating S and A. Of course, since there are
no commercially available GLC stationary phases with any
significant hydrogen bond acidity (the b-coefficients are zero),
it is then absolutely essential to include other processes such as
water to solvent partitions in order to obtain the B descriptor.
For a few other oximes, water-to-octanol partition coeffi-
cients26 and retention data by Zenkevich21 are available, and
we give in Table 8 approximate values for descriptors, with A
fixed at 0.35 for the acyclic oximes, and at 0.33 for
cyclopentanone oxime.
Reversed phase HPLC systems have been used instead of
water-to-solvent systems in the calculation of descriptors,27
but this is only possible if rather unusual HPLC systems are
used. Du et al.28 and Valko et al.29 have shown that most of the
common isocratic elution and gradient elution systems have
similar coefficients, with rather small a-coefficients. Hence if
HPLC systems are used, it is preferable to include some
water-to-solvent partition systems as well as GLC systems.
Probably the best set of experimental data to use in order to
obtain all the descriptors is a combination of retention data on
GLC stationary phases and partition coefficients in a number
of water-to-solvent partition systems, as we have used here.
Experimental
Partition coefficients
Cyclohexanone oxime and acetone oxime were used as
received. Solvents were pre-equilibrated with water, and the
water saturated with the solvent and the solvent saturated with
water were used in the experiments. Dilute solutions of the
oximes in water were gently shaken with the organic solvent
and left to equilibrate at 25 1C for 30 min. Portions of the
organic layer and the aqueous layer were carefully withdrawn
using hypodermic syringes and directly injected into a Perkin-
Elmer F-33 gas chromatograph with a stationary phase of
Carbowax 20M at 101 1C. The volumes withdrawn (Vo and
Vw) were arranged so that the area under the GC peaks was
almost the same for the aqueous and organic layers. The ratio
of the areas (Ao/Aw) could then be taken as the ratio of the
quantities of oxime in the withdrawn volumes (Qo/Qw). Then
the partition coefficient, P, is given by P = (Qo/Vo)/
(Qw/Vw) = (Ao/Vo)/(Aw/Vw). The partition coefficients in each
water-to-solvent system are given in Table 9; this includes a
value for the water-to-octanol partition coefficient from the
MedChem data base.26 From the replicate measurements we
Table 8 Approximate solvation descriptors for some oximes
Oximes E S A B V L logKw
Cyclopentanone oxime 0.580 0.94 0.33 0.61 0.8200 3.700 5.23Acetaldehyde oxime 0.390 0.50 0.35 0.54 0.5059 1.931 3.98Propanal oxime 0.366 0.52 0.35 0.54 0.6468 2.498 3.92Butanal oxime 0.357 0.58 0.35 0.54 0.7877 3.149 3.96Isobutanal oxime 0.370 0.59 0.35 0.57 0.7877 2.992 4.13Butanone oxime 0.383 0.71 0.35 0.56 0.7877 3.173 4.40
Table 9 Partition coefficients for cyclohexanone oxime and acetoneoxime between water and various solvents
Solvent logP logP takenCyclohexanone oxime
Octanol 0.988 0.988Toluene 0.260 0.260Chloroform 0.805, 0.818, 0.839 0.821Hexane �0.570, �0.596, �0.630 �0.599
Acetone oxime
Octanol 0.1226
Toluene �0.980, �0.982 �0.981Chloroform �0.297 �0.297Hexane �1.784, �1.669, �1.751 �1.725
�1.738, �1.682
80 | New J. Chem., 2009, 33, 76–81 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
estimate that the standard deviation is about 0.03–0.04 log
units. In the GC experiments, a flame ionisation detector was
used; we encountered no particular problems in the analysis of
the aqueous solutions.
GLC retention data
At UCL, four GLC stationary phases were each calibrated
using 45–65 solutes of known descriptors: CW-20M at 101 1C,
DEGS at 87 1C, HP-Innowax at 100 1C and OV-275 at 89 1C.
The obtained coefficients are in Table 4, together with coeffi-
cients for all the other equations used. Cyclohexanone oxime
or acetone oxime were then injected onto a given phase
together with standard compounds as references, and reten-
tion data obtained under the same conditions as the calibra-
tion. The coefficients in Table 4 refer to log tr0, where tr
0 is the
retention time relative to the standard. The internal standards
were heptanol for CW-20M, DEGS, and HP-Innowax and
hexanol for OV-275. A number of secondary standards were
also used. At Wayne State, retention factors at 20 1C intervals
over the temperature range 60–140 or 180–240 1C were
obtained with an Agilent Technologies HP-6890 gas chromato-
graph (Palo Alto, CA, USA) fitted with a split/splitless injector
and flame ionization detector. Nitrogen was used as carrier gas
at a constant linear velocity of 40 cm s�1 and methane
was used to determine the column hold-up time. Measure-
ments were made for seven different stationary phases on
30 m � 0.25 mm I.D. open-tubular columns with a film thick-
ness of 0.25 mm for 60–140 1C and 1.00 mm for 180–240 1C.
The system constants at each temperature were determined by
calibration using 60–100 varied compounds exactly as before30
and are summarized with the retention factors for cyclo-
hexanone oxime in Table 4; k in log k is the gas to stationary
phase partition coefficient.
NMR experiments
These were conducted exactly as described before.3 All the
compounds and solvents were obtained commercially. The
CDCl3 and DMSO solvents were commercial samples (Sigma-
Aldrich). The CDCl3 was bought in 1 ml ampoules and used
directly in the experiments. Solutions of B10 mg mL�1
concentration were run with TMS as internal standard in
DMSO solvent. The 1H spectra were obtained on a Bruker
Avance 400 MHz NMR spectrometer operating at 400.13 MHz.
Typical running conditions were 128 transients, spectral width
3300 Hz and 32 K data points, giving an acquisition time of
5 s. The FIDs were zero-filled to 64 K. The spectra were first
order, and the assignments were straightforward.
Acknowledgements
This work was supported in part by Philip Morris USA, Inc.,
and Philip Morris International.
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 76–81 | 81
Electrochemical methodology for determination of imidazolium ionic
liquids (solids at room temperature) properties: influence of the
temperaturew
M. P. Stracke,aM. V. Migliorini,
aE. Lissner,
aH. S. Schrekker,
aD. Back,
b
E. S. Lang,bJ. Dupont*
aand R. S. Goncalves*
a
Received (in Gainesville, FL, USA) 17th July 2008, Accepted 29th August 2008
First published as an Advance Article on the web 14th October 2008
DOI: 10.1039/b812258j
A set of six imidazolium ionic liquids (1a–b, 2a–c, 3), that were solids at room temperature, were
characterized by electrical impedance spectroscopy to obtain information about their polarization
resistance (Rp), conductivity (s) and charge transfer activation energy (Ea). These experiments
were performed at different temperatures in a glass micro-cell, equipped with three platinum
electrodes. The observed conductivities were due to charge transfer processes of molecular oxygen
at the electrode surface and mass transfer processes within the IL matrix. Higher temperatures
resulted for all ionic liquids in increased conductivities. X-Ray diffraction of the ionic liquids 2a–c
suggested that a higher degree of supramolecular two-dimensional organization, higher density, is
related to an easier oxygen-electrode approximation, lower Ea. Two distinct temperatures ranges
were observed. The larger conductivity increases in the higher temperature range were explained
by melting (ILs 1–2) and fluxional behavior/reorientation phenomena of the ionic liquids and are
due to enhanced oxygen diffusion (IL 3). In general, the understanding of imidazolium ionic
liquid electrochemical properties could facilitate the development of new applications.
1. Introduction
The discovery of air- and water-stable imidazolium room-
temperature ionic liquids (RTILs) by the suitable choice of the
anion initiated intensive research efforts towards their appli-
cation.1 Further attractive physical and chemical properties of
the imidazolium RTILs include,2–6 a negligible vapor pressure;
low inflammability; thermal stability; liquidity over a wide
temperature range; easy recycling; and being a good solvent
for a wide variety of organic and inorganic chemical com-
pounds. Besides, imidazolium RTILs are ‘‘designable’’ as
structural modifications in both the cation (especially the
1 and 3 positions of the imidazolium ring) and anion permit
the tuning of properties such as, e.g., miscibility with water
and organic solvents,7 melting point and viscosity.3 This
adaptability is also responsible for the easy preparation of
task-specific imidazolium ionic liquids, ionic liquids that con-
tain a specific functionality covalently incorporated in either
the cation or anion.8–11 As a result, applications of imidazolium
RTILs are numerous and found in the fields of, for instance,
extraction and separation processes,4,12,13 synthetic chemistry,4,6
catalysis (organometallic,5,6,14,15 transition-metal nanoparticle,14–19
bio20), and materials science.4,21
Another important imidazolium RTIL research area is in
the field of electrochemistry, which is due to their chemical and
electrochemical stability, wide electrochemical windows, and
high electrical conductivities and ionic mobilities.3–6,22–24
Electrochemical applications of imidazolium RTILs as
electrolytes are found in, e.g., fuel cells,25 electrodeposition,26
capacitors,27–29 solar cells,30,31 batteries32 and water electro-
lysis for hydrogen generation.33 However, the use of imida-
zolium RTILs could suffer from sealing problems due to
leakage issues. Possible alternatives are, e.g., imidazolium RTIL
polymer homologues such as gel34 or solid35 polyelectrolytes,
and imidazolium RTILs confined in silica-derived networks
(ionogels)36 and polymers.27 Without doubt, the direct appli-
cation of imidazolium ionic liquids (ILs), that are solids at
room temperature, instead of imidazolium RTILs, would be
another attractive option. As a consequence, we were inter-
ested in the electrochemical properties of imidazolium ILs
(solids at room temperature). In general, understanding the
physicochemical properties of ILs is of great importance
to provide information about their application scope.37,38
Herein, we report the results obtained with the imidazolium
ILs 1–3, presented in Fig. 1, which can be divided in two
classes: (1) hydrophilic ILs 1a–b and 3, and (2) hydrophobic
ILs 2a–c. Electrical impedance spectroscopy (EIS), a non-
destructive technique, was used to determine their temperature
dependent polarization resistance (Rp), conductivity (s) and
charge transfer activation energy (Ea).
a Laboratory of Electrochemistry, Laboratory of Molecular Catalysisand Laboratory of Technological Processes and Catalysis, Instituteof Chemistry, Universidade Federal do Rio Grande do Sul, Av. BentoGoncalves 9500, P.O. Box 15003, CEP: 91501-970 Porto Alegre-RS,Brazil. E-mail: [email protected]; E-mail: [email protected];Fax: +55-51-3308-7304; Fax: +55-51-3308-7304;Tel: +55-51-3308-6321; Tel: +55-51-3308-7236
bDepartamento de Quımica, Laboratorio de Materiais Inorganicos,Universidade Federal de Santa Maria, CEP: 97105-900 SantaMaria-RS, Brazil
w Electronic supplementary information (ESI) available: Experimentalsection. CCDC 607218 (2a: room temperature), 607812 (2b: roomtemperature) and 671958 (2c: 100 K). For ESI and crystallographicdata in CIF or other electronic format see DOI: 10.1039/b812258j
82 | New J. Chem., 2009, 33, 82–87 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
2. Experimental
2.1 Imidazolium ionic liquids
The de-aerated imidazolium ILs 1a–b,39,40 2a–c41–44 and 345
were prepared according to known procedures, and the NMR
spectral data were in agreement with the literature data.
Recrystallizations were performed to obtain high purity ILs
as white solids at room temperature.
2.2 Electrical impedance spectroscopy
The device used to perform the electrical impedance measure-
ments of the room-temperature ionic solids consisted of a
home-made glass micro-cell (Fig. 2) with a free area of
0.65 cm2, equipped with three platinum wire electrodes. This
micro-cell was inserted in a three-way round-bottom flask
allowing the control of the gas atmosphere and humidity.
The working electrode was located at the center of the micro-
cell, the counter electrode was placed at the full length of the
inner wall, and the reference electrode was located in between
the working and counter electrodes. A computer-controlled
potentiostat Autolab PGSTAT 30 was connected to the ionic
solid in the glass-cell by the corresponding electrodes, and the
temperature were kept under control. The electrical impedance
spectra were measured over the frequency sweep range from
50 kHz to 5 Hz and the amplitude of the applied sine wave
voltage was 10 mV. The experimental data were corrected
by the software, taking into consideration the influence of
connecting cables and other parasite capacitances, to obtain
the polarization resistance (Rp) of the samples. The RP values
were obtained from the intercepts of the electrode impedance
arc on the real impedance axis and were used to calculate the
corresponding conductivities (s).
2.3 Differential scanning calorimetry
The melting points of the ILs 1a–b and 2a–c were determined
using a TA Instruments DSC 2010 differential scanning
calorimeter, equipped with a manual cooling unit. The DSC
instrument was calibrated using an indium primary standard.
An average sample weight of 7–12 mg was sealed in an
aluminium pan in a nitrogen-filled glove box. The DSC
measurements were carried out under a nitrogen atmosphere.
The melting points (Tm, determined at the maximum of the
endothermic peaks) were determined on heating in the second
heating run.
2.4 X-Ray diffraction studies
Crystallographic data were collected at room temperature
and/or �100 1C on a Bruker Kappa Apex II CCD diffracto-
meter using Mo-Ka radiation (l = 0,71073 A). The experi-
mental set-up did not allow full rotations. Hence, the data sets
are of lower coverage. Crystal structures were refined with full-
matrix least squares on F2 using all data (SHELXTL crystal
structure solution software). Non-hydrogen atoms were
refined anisotropically. Hydrogen atoms were fixed on geo-
metrically ideal positions during the refinement. The free
refinement of hydrogen atom parameters gave low data/
parameter ratios and led to high correlations. Relevant crystallo-
graphic data, and collection and refinement details, are
compiled in Table S5 of ESI.w The structures presented in
Fig. 6 were obtained from the original X-ray data using the
DIAMOND software (version 2.1c, Crystal Impact GbR,
http://www.crystalimpact.com/diamond/).
3. Results and discussion
3.1 Impedance spectrum analysis
A home-made glass micro-cell (Fig. 2), equipped with three
platinum wire electrodes, was used for the electrical impedance
spectroscopy measurements of the imidazolium ILs 1–3
(Fig. 1). Furthermore, the partial oxygen pressure of the gas
atmosphere was kept constant. The Nyquist plots of IL
[PhC3MIm][NTf2] 2b at different temperatures are presented
in Fig. 3(a). As for most of the ILs 1–3, electrical impedance
spectroscopy measurements with 2b afforded partial semi-
circles. An equivalent circuit is proposed taking into account
that there exists a semicircle corresponding to one time constant
that represents an electrochemical circuit with two resistances
and one parallel combination of phase constant (CPE, Fig. S1,
ESIw). In contrast, complete semicircles were observed with IL
[C2O2MIm][Cl] 3 at higher temperatures (Fig. 3(b)). Perfor-
mance of these electrical impedance spectroscopy measure-
ments under vacuum resulted in confuse and irreproducible
Fig. 1 Imidazolium ionic liquids (solid at room temperature) applied
in this work.
Fig. 2 Illustration of the home-made glass micro-cell: (a) top view;
(b) section.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 82–87 | 83
Nyquist plots. This strongly suggested that a charge transfer
process of molecular oxygen at the platinum electrode surface
was responsible for the observed phenomena, which is repre-
sented by the equilibrium reaction of Scheme 1.
This was further supported by the Nyquist plots obtained
when the experiments were performed under a pure argon
atmosphere and a pure oxygen atmosphere (Fig. S2, ESIw).The charge transfer process was not observed under an argon
atmosphere. However, this process did take place in the
presence of a pure molecular oxygen atmosphere.
The polarization resistance (RP) values were determined by
fitting the obtained impedance semicircles. The Rp values
represent the polarization resistances related to the charge
transfer process of oxygen on the platinum electrode surface,
since the platinum electrode is inactive under the applied
conditions. For all ILs 1–3, RP decreased with increasing
temperatures. Eqn (1) was used to convert RP into the
conductivity (s) of oxygen within the ILs, where l (0.1 cm)
and A (3.14 � 10�2 cm2) represent the length and active
surface area of the working platinum electrode, respectively.
These conductivities were due to charge transfer processes and
transport phenomena of molecular oxygen and were not
related to the ionic conductivities of the bulk ILs. This strategy
was applied to determine the activation energies of the oxygen
Fig. 3 (a) Nyquist diagram of [PhC3MIm][NTf2] 2b at 19 1C (’),
26 1C (K), 42 1C (m) and 60 1C (window); (b) Nyquist diagram of
[C2O2MIm][Cl] 3 at 5 1C (’), 17 1C (K), 31 1C (m), 34 1C (E) and
42 1C (.).
Scheme 1 Charge transfer processes of molecular oxygen at the
platinum electrode surface.
Fig. 4 Conductivities of (a) IL [PhC3MIm][NTf2] 2b and (b) IL
[C2O2MIm][Cl] 3 at different temperatures.
Fig. 5 Arrhenius conductivity plot of IL [PhC3MIm][NTf2] 2b.
84 | New J. Chem., 2009, 33, 82–87 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
redox processes on the platinum electrode surface as
described below.
s = l/RPA (1)
Fig. 4(a) and (b) show the conductivities of the ILs
[PhC3MIm][NTf2] 2b and [C2O2MIm][Cl] 3 at different
temperatures. The same conductivity–temperature correlation
was observed for all ILs 1–3. Higher temperatures resulted in
higher conductivities. As such, the transport of the species
involved in the charge transfer reaction is temperature depen-
dent. Furthermore, the conductivity was characterized by two
distinct temperature dependences: (1) small conductivity in-
creases in the lower temperature range; and (2) large conducti-
vity increases in the higher temperature range. In case of the ILs
2b and 3, these dependences showed their intersection at 42 and
35 1C, respectively, which indicates that the transport processes
are differently affected below and above this temperature.
It was found that the experimental conductivity data of the
lower temperature range fitted the conventional Arrhenius
eqn (2), where Ea is the activation energy for the charge
transfer process. Fig. 5 shows the Arrhenius conductivity plot
of IL 2b and the activation energies calculated from the
Arrhenius formula are presented in Table 1. The hydrophilic
ILs showed the higher charge transfer activation energies,
which decreased in the order: [C2O2MIm][Cl] 3 4[C10MIm][Mes] 1b 4 [C4MIm][Mes] 1a 4 [Ph2C2MIm][NTf2]
2a4 [PhC2MIm][NTf2] 2c4 [PhC3MIm][NTf2] 2b. Now, it is
important to remember that these activation energies were
measured in the presence of atmospheric oxygen. The values of
51.6 kJ mol�1 (0.53 eV) to 110 kJ mol�1 (1.14 eV) are very
close to those observed for charge transfer processes of oxygen
at polycrystalline oxide surfaces,46 LSCF-SDC composite47
and multi-metallic electrodes.48 Apparently, the determined IL
charge transfer processes are due to electrochemical reactions
of molecular oxygen at the electrode surface.49
ln s = ln s0 � (Ea/RT) (2)
3.2 X-Ray diffraction studies
The charge transfer processes involving molecular oxygen
should be the same for all ILs 1–3. As a consequence, it is
reasonable to infer that the IL crystalline structure influences
the transport of molecular oxygen inside the crystal. The
crystal data concerning the ILs 2a–c are listed in Table S5 (ESIw)
and their structures at room temperatures are presented in
Fig. 6. The electrostatic interactions of IL 2a generate a
tri-dimensional structural organization (Fig. 6(a)). In contrast,
the existing interactions in the ILs 2b and 2c are of
two-dimensional nature, generating structures in the form of
layers as can be verified in Fig. 6(b) and (c). This structural
organization at room temperature is reflected by the
density of these ILs at room temperature, which decreases
in the order: [PhC3MIm][NTf2] 2b (d = 1.553 g cm�3) 4[PhC2MIm][NTf2] 2c (d = 1.539 g cm�3) 4 [Ph2C2MIm]-
[NTf2] 2a (d= 1.47 g cm�3). This suggests that a higher degree
of two-dimensional organization as in IL 2b results in a more
dense packing. However, the observed activation energies
decrease in exactly the opposite order: [Ph2C2MIm][NTf2]
2a 4 [PhC2MIm][NTf2] 2c 4 [PhC3MIm][NTf2] 2b. As a
consequence, it is possible to infer that the diffusion of
molecular oxygen is faster in two-dimensional organized ILs.
Importantly, it is not possible to verify the formation of
structures in the form of channels or tunnels.
3.3 Differential scanning calorimetry
The melting points of the ionic liquids 1–3 were determined by
differential scanning calorimetry (DSC) to check if there exists
a correlation with their temperature dependent conductivities
(Table 1). Most of these ionic liquids have melting points that
are close to their intersection temperatures as determined from
the conductivity plots (e.g. Fig. 4). This indicates that the
change from the slowly to the faster changing conductivity is
most likely due to the changeover from the solid to the liquid
state. In strong contrast, IL [C2O2MIm][Cl] 3 showed an
intersection temperature (42 1C, Fig. 4(b)) far below
its melting point (197 1C). As a consequence, IL 3 was not
melted at the beginning of the second temperature range. This
behavior allows us to infer that the faster increasing conduc-
tivity in the second temperature range of IL 3 should be
associated with the oxygen diffusion inside the crystal arrays.
A possible explanation could be an increase in fluxional
behavior/reorientation phenomena in the solid state, which
enhances the molecular oxygen diffusion.50,51 This was further
supported by the low degree of organization of IL 2c observed
at 25 1C by X-ray diffraction, and high quality data were only
obtained at 100 K due to a more defined organization.
4. Conclusions
In conclusion, electrical impedance spectroscopy is a suitable
analytical tool for the determination of important imida-
zolium IL properties, including polarization resistance (Rp),
conductivity (s) and activation energy (Ea) for a charge
transfer reaction involving molecular oxygen. Increased tem-
peratures result in higher conductivities, showing two distinct
temperature ranges. The detected conductivities were due to
charge transfer processes of molecular oxygen at the platinum
electrode surface and mass transfer processes of oxygen inside
the IL matrix. Comparison of the oxygen charge transfer
process activation energies with the X-ray diffraction data of
2a–c suggests that the oxygen mobility in the ionic liquids
(solids at room temperature) is affected by their nature
of structural supramolecular organization: tri-dimensional
Table 1 Activation energy, conductivity intersection and meltingpoint of the ILs 1–3
Entry IL Eaa/kJ mol�1 Ea
a/eV Tisb/1C Tm
c/1C
1 [C4MIm][Mes] 1a 78.1 0.81 63 772 [C10MIm][Mes] 1b 79.0 0.82 31 573 [Ph2C2MIm][NTf2] 2a 73.7 0.76 40 624 [PhC3MIm][NTf2] 2b 51.6 0.53 42 505 [PhC2MIm][NTf2] 2c 56.6 0.58 28 416 [C2O2MIm][Cl] 3 110 1.14 42 197 (204)d
a Activation energy calculated from the Arrhenius formula. b Tem-
perature at the intersection of the low- and high-temperature range of
the temperature dependent conductivity. c Melting point determined
by differential scanning calorimetry on heating. d Ref. 42.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 82–87 | 85
vs. two-dimensional. Furthermore, the changeover from the
solid to the liquid state and fluxional behavior/reorientation
phenomena in the solid state are most likely the responsible
factors for the faster increasing conductivity in the second
temperature range. As such, electrical impedance spectroscopy
could accelerate the discovery of new electrochemical ionic
liquid (solid at room temperature) applications and the sub-
stitution of ionic liquids where beneficial.
Acknowledgements
The authors thank the CNPq for financial support.
Fig. 6 X-Ray diffraction crystal structures of (a) [Ph2C2MIm][NTf2] 2a (room temperature); (b) [PhC3MIm][NTf2] 2b (room temperature) and
(c) [PhC2MIm][NTf2] 2c (100 K).
86 | New J. Chem., 2009, 33, 82–87 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 82–87 | 87
A new family of biocompatible and stable magnetic nanoparticles:
silica cross-linked pluronic F127 micelles loaded with iron oxides
Zhaoyang Liu,* Jun Ding and Junmin Xue*
Received (in Montpellier, France) 18th June 2008, Accepted 4th September 2008
First published as an Advance Article on the web 15th October 2008
DOI: 10.1039/b810302j
A new family of magnetic nanoparticles, silica cross-linked pluronic F127 micelles loaded with
iron oxides having the properties of high biocompatibility, physical and chemical stability, high
magnetism, and low-cost production, have been synthesized.
1. Introduction
Iron oxide (IO) nanoparticles are emerging as promising
candidates for various biomedical applications, such as mag-
netic resonance imaging (MRI),1 targeted drug delivery,2
hyperthermia treatment,3 the labelling and sorting of cells,4
and the separation of biochemical products,5 due to their
superparamagnetic properties. Most of these applications
require the nanoparticles to be biocompatible, water soluble,
and physically and chemically stable in a physiological environ-
ment.6 To date, the most promising synthetic strategy for
iron oxide nanoparticles is based on the high temperature
decomposition of iron salts in the presence of organic solvents,
which can produce monodisperse and highly crystalline IO
nanoparticles.7 However, their uses in biomedicine are quite
limited because the particles synthesized through this route
can only be dispersed in hydrophobic solvents. Before bio-
medical applications are possible, they have to be transferred
into an aqueous medium. Moreover, the reactivity of iron oxide
particles have been shown to greatly increase as their dimen-
sions are reduced to the nano scale. Therefore, it is necessary
to engineer the surface of IO nanoparticles to improve
their biocompatibility, solubility and stability in physiological
environments for various biomedical applications.8
Several natural and synthetic polymers have been employed
to coat the surface of IO nanoparticles to transfer their surface
wettability. These polymers include dextran,9 lipids,10 dendri-
mers,11 polyethylene glycol (PEG)12 or polyethylene oxide
(PEO),13 and polyvinylpyrrolidone (PVP).14 All the polymers
used are known to be biocompatible and able to promote the
dispersion of IO nanoparticles in an aqueous medium. How-
ever, these polymer coatings are not robust and can be
detached from particle surfaces easily under in vivo condi-
tions.10,12 To improve the stability of the polymer coatings
in vivo, a cross-linking technique has been developed.15 For
example, the stability of dextran coatings on IO nanoparticles
can be improved when the dextran polymer chains are chemi-
cally cross-linked. Although cross-linking is considered a
promising method for strengthening the polymer coatings of
IO nanoparticles,16–19 this method requires multiple synthetic
steps (multi-pot).18 Therefore, a simple and one-pot method is
in demand.
In this work, we have developed a simple and one-pot
method to fabricate a new family of biocompatible and stable
magnetic nanoparticles that are coated with a hybrid layer of
silica cross-linked pluronic F127 (SCL-P@IO). Pluronic F127
(PF127) is an ABA-type triblock copolymer consisting of
hydrophobic poly(propylene oxide) (PPO) and hydrophilic
PEO. The PEO blocks present a high biocompatiblity by
effectively preventing aggregation, the adsorption of proteins,
the adhesion to tissues, and recognition by the reticulo-
endothelial system in vivo.20 Silica has been extensively studied
as an inorganic coating for a long period of time due to its rich
surface chemistry, which means it is able to conjugate biofunc-
tional moieties easily. Compared to polymer coatings, silica
coatings are more chemically stable and resistant to diffusion
for encapsulated components. PF127 copolymer and silica
have also been selected as suitable surface coating candidates
because they are highly safe in vivo and have been approved by
the Food and Drug Administration.20,21
A double-layer coating of PEO and silica on the surface of
IO nanoparticles is proposed, as shown in Fig. 1a. Like
conventional mesoporous silica synthesis using PF127 surfac-
tants,22 the silica was controlled so as to be deposited on the
interior PEO blocks of the PF127 micelle, leaving the exterior
PEO blocks stretched out in aqueous media. Therefore, a
double-layer structure of PEO and silica on the surfaces of
the IO nanoparticles was formed (Fig. 1a). The advantages of
the resulting magnetic nanoparticles are follows: (1) high
biocompatibility and stability due to the presence of PEO
blocks on the surface of the nanoparticles, (2) high chemical
and physical stability due to the robust and dense silica cross-
linked micelles, and (3) simple and low-cost synthesis, since
silica cross-linking is much easier in comparison with tradi-
tional polymer cross-linking, and since both PF127 and the
silica precursor are commercially available. Therefore, the
present magnetic nanoparticles possess great potential in a
variety of biomedical applications.
2. Experimental
2.1 Materials
Dioctyl ether, oleic acid, iron(III) chloride, tetraethoxysilane
(TEOS), diethoxydimethylsilane (Me2Si(OEt)2, DEDMS) and
Department of Materials Science and Engineering, NationalUniversity of Singapore, Singapore, 117576, Republic of Singapore.E-mail: [email protected]. E-mail: [email protected];Fax: +65 67763604; Tel: +65 65164655
88 | New J. Chem., 2009, 33, 88–92 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
pluronic F127 (PF127) were purchased from Aldrich
Chemical Co. Fibroblasts 3T3 were purchased from ATCC.
RPMI-1640 medium, Dulbecco’s modified Eagle’s medium
(DMEM), fetal bovine serum (FBS), L-glutamine, penicillin
and streptomycin were purchased from Sigma. All other
solvents and chemicals were purchased from Aldrich and used
as received.
2.2 Synthesis of IO nanoparticles (Fe3O4)
FeCl3�6H2O (3.3 mmol) and sodium oleate (10 mmol) were
dissolved in a mixture of ethanol (25 mL), de-ionized water
(20 mL) and hexane (45 mL). After refluxing for 4 h at 62 1C,
the iron oleate complex was washed with de-ionized water
three times. The iron oleate complex (3.3 mmol) and oleic acid
(1.67 mmol) were dissolved in dioctyl ether (20 mL) at 70 1C.
After heating for 1.5 h at 290 1C, ethanol (30 mL) was added
to the mixture, and the nanoparticles were collected by
centrifugation at 6000 rpm. The nanoparticles were washed
with hexane and ethanol three times. Finally, the nanoparticles
were dispersed in hexane (40 mL) and oleic acid (100 ml).
2.3 Synthesis of SCL-P@IO nanoparticles
A hexane solution (0.2 mL) of IO nanoparticles was added to
an aqueous solution (8 mL) of PF127 (1.3 g). After 3 h of
stirring at room temperature, the mixture was dried under
nitrogen gas. The obtained powder could be readily redis-
persed in de-ionized water (8 mL) with shaking. Then, a 0.3 M
HCl solution (0.4 g) and TEOS (0.2 g) were added to the
mixture with stirring. After stirring at room temperature for
48 h, DEDMS (0.1 g) was added. Stirring was continued for
another 3 h.
2.4 Cell culture
The cell viability of the nanoparticles was carried out by
testing the viability of 3T3 fibroblasts after incubation with
DMEM, supplemented with 10% FBS, 1 mM L-glutamine and
100 IU mL�1 penicillin via an 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl tetrazolium bromide (MTT) assay. Mouse macro-
phage cells (RAW 264.7) were used to assess the cellular
uptake of the nanoparticles. The RAW 264.7 cells were
cultured in RPMI-1640 medium, supplemented with 10%
FBS, 2 mM L-glutamine, 100 IU mL�1 penicillin and
100 mg mL�1 streptomycin. The cell concentrations were
determined by hemacytometry, and the Fe concentrations
were determined by Thermal Jarrell Ash Duo Iris inductively-
coupled plasma optical emission spectrometer (ICP-OES).
2.5 Characterization
TEM measurements were taken using a JEOL JEM 3010
instrument. The hydrodynamic diameters of the nanoparticles
were measured by a Malvern Zeta Sizer Nano S-90 dynamic
light scattering (DLS) instrument. TGA analyses were per-
formed by a TA Instruments Q500 thermogravimetric analyzer.
IR studies were run on an ATI Mattson Infinity Series
FT-IR spectrophotometer. Magnetic properties were mea-
sured on a superconducting quantum interference device
(SQUID, Quantum Design, USA) and a Lakeshore 7300 series
vibrating sample magnetometer (VSM). The fluorescence
emission spectra of pyrene were measured by a fluorescence
photometer (FP-777 Jasco) at 254 nm excitation. 29Si NMR
spectra were recorded with an Advance 500 Bruker spectro-
meter at 99.36 MHz. The pulse length was 6 ms (theta = p/6)with 6 s repetitions.
3. Results and discussion
3.1 TEM, XRD and29Si NMR
In a typical synthesis, 10.5 nm monodisperse and hydrophobic
Fe3O4 nanoparticles were synthesized separately (Fig. 1b).23
The as-synthesized Fe3O4 nanoparticles were coated with a
layer of oleic acid, which made them only soluble in hydro-
phobic solvents (Fig. 1b inset photo). With the addition of
PF127 surfactants, these polymeric surfactants self-assembled
into a micellar structure, encapsulating the IO nanoparticles in
their cores. The hydrophobic PPO block in the middle of the
PF127 associated with the alkyl tail of the oleic acid through a
hydrophobic interaction, while the two hydrophilic PEO
blocks stretched out in aqueous media (Fig. 1a). Then, TEOS
Fig. 1 a: Synthetic scheme for silica cross-linked pluronic F127
micelles loaded with IO nanoparticles (SCL-P@IO). Left: an as-
synthesized hydrophobic IO nanoparticle. Right: an IO nanoparticle
with its surface covered by a double-layer of PEO and silica. b: A TEM
of as-synthesized hydrophobic IO nanoparticles. The inset photo
shows that the IO nanoparticles can only be dispersed in hexane. c:
A TEM of SCL-P@IO nanoparticles. The right bottom inset is a
higher magnification TEM of typical SCL-P@IO nanoparticles. The
inset photo shows that the SCL-P@IO nanoparticles can be readily
dispersed in water. d: Size distribution histogram of the nanoparticles
in c. e: XRD patterns of IO and SCL-P@IO nanoparticles. f: 29Si
NMR spectra corresponding to samples (a) with and (b) without the
addition of DEDMS, respectively.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 88–92 | 89
was added as a silica precursor to polymerize and cross-link
the PF127 micellar shells.
Fig. 1c shows a TEM image of the SCL-P@IO nanoparti-
cles. The formation of well-defined core/shell morphologies is
readily confirmed, since the Fe3O4 within the micelle cores is
more electron-dense than the silica/PF127 hybrid shell.
A higher magnification TEM of typical SCL-P@IO nano-
particles is shown in the right bottom of Fig. 1c. These
nanoparticles have a number-average diameter of around
21 nm, as shown in the histogram in Fig. 1d, with an ultrathin
(about 5 nm) silica shell deposited outside the Fe3O4 nano-
particles. A size distribution analysis, as shown in the
histogram in Fig. 2a, reveals that the spherical NPs are
monodisperse and have an average size of 7.9 � 1.5 nm. The
inset photo shows that the resulting nanoparticles can be
readily dispersed in water. The XRD patterns of the IO and
SCL-P@IO nanoparticles (Fig. 1e) can be assigned to the
(220), (311), (400), (422), (511) and (440) reflections of the
spinel structure of magnetite (JCPDS no. 19-0629). The broad
band at 20–301 is due to the presence of amorphous
silica, while the labelled peaks are associated with Fe3O4
nanocrystals.
The condensation of silicate during the preparation was
studied by NMR techniques. Fig. 1f (a) and (b) correspond to
the sample with and without the addition of DEDMS, respec-
tively. In the 29Si NMR spectra, three peaks at ca. �94, �104and �114 ppm are assigned to Q2, Q3 and Q4 species with
progressively increasing cross-linking (condensation).24 After
automatic calculation of the integrated area, the Q4 : Q3 ratio
decreased from 0.91 (b) to 0.83 (a), indicating a slightly lower
condensation of silicate with the addition of DEDMS.
3.2 DLS and FT-IR
The obtained SCL-P@IO nanoparticles were characterized by
DLS. The DLS measurements of the IO and SCL-P@IO
nanoparticles are shown in Fig. 2a. The hydrodynamic
diameter of the SCL-P@IO nanoparticles is 43.3 nm, which
is larger than that measured by TEM in Fig. 1c. This is
because the light scattering measurement includes the PEO
chains stretching out into the aqueous solution, which cannot
be observed by TEM due to the low contrast of the PEO
polymers.25 This result also confirms the double-layer struc-
ture of PEO and silica on the surface of SCL-P@IO nano-
particles instead of just a single layer of silica; that is, the silica
is deposited on the interior PEO chains, while the exterior
PEO chains are stretched out into the aqueous solution, as
suggested in Fig. 1a. The surface coating of the SCL-P@IO
nanoparticles was further studied by IR analysis. As shown
in Fig. 2b, silica formation is confirmed, since a band at
1080 cm�1, assigned to Si–O–Si, is observed for these
SCL-P@IO nanoparticles.26 After calcination at 700 1C, the
characteristic band of C–H at 1726 cm�1 disappears com-
pletely, while the band assigned to thermally stable silica is still
observed.
3.3 Magnetism characterization
The magnetic properties of the IO and SCL-P@IO nanopar-
ticles were examined at room temperature by using a VSM. As
shown in Fig. 3a, the saturated magnetization of the IO and
SCL-P@IO nanoparticles were 63.1 and 28.3 emu g�1, res-
pectively. The reduction in saturated magnetization for the
SCL-P@IO nanoparticles accounts for the diamagnetic
properties of the silica and the PF127 shell surrounding
the IO cores. The inset photo in Fig. 3a shows the magnetic
manipulation ability of the SCL-P@IO nanoparticles.
When an external magnet is placed beside the glass vial, the
aqueous dispersion of SCL-P@IO nanoparticles could be
directed towards the magnet. This efficient magnetism will
allow these nanoparticles to be useful in many biomedical
applications, such as targeted delivery and separation. The
magnetization change of the SCL-P@IO nanoparticles with
storage time was monitored by VSMmeasurements. As shown
in Fig. 3b, the saturated magnetization of the SCL-P@IO
nanoparticles was almost constant (at around 28 emu g�1)
during 90 d storage, suggesting that the PF127/silica hybrid
coating is dense enough to be non-permeable, preventing the
encapsulated IO cores from degrading and leading to lower
magnetism.
3.4 Cell viability and uptake
The biocompatibility of the SCL-P@IO nanoparticles was
examined by the cell viability of 3T3 fibroblast lines through
Fig. 2 a: Hydrodynamic sizes of IO and SCL-P@IO nanoparticles in
aqueous solution determined by DLS measurements. b: IR spectra of
PF127 triblock copolymer (top), SCL-P@IO nanoparticles (middle)
and SCL-P@IO nanoparticles after calcination at 700 1C (bottom).
The IR spectra of the SCL-P@IO nanoparticles are characteristic of
both the silica network (Si–O–Si stretch at 1080 cm�1) and the
copolymer (C–H stretch at 1730 cm�1). This C–H band disappears
after calcination.
Fig. 3 a: Magnetization curves (M–H) of IO and SCL-P@IO nano-
particles. The inset photo shows that the SCL-P@IO nanoparticles
can be driven by an external magnet. b: The magnetization change of
the SCL-P@IO nanoparticles with storage time, as observed by VSM
measurements.
90 | New J. Chem., 2009, 33, 88–92 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
an MTT assay. As shown in Fig. 4a, the SCL-P@IO nano-
particles were biologically inert up to an iron concentration of
1000 mg mL�1. This result indicates that the SCL-P@IO
nanoparticles are highly non-toxic and biocompatible. When
injected into the bloodstream, nanoparticles are often con-
sidered as an intruder by the innate immunity system, and can
be readily recognized and become engulfed by the macrophage
cells. The nanoparticles will then be removed from the blood
circulation system, and lose their efficiency in diagnostics and
therapeutics.
Fig. 4b shows the uptake of the oleic acid-stabilized (Oleic
acid-IO) and PEO-stabilized (SCL-P@IO) nanoparticles
by macrophage cells with an initial Fe concentration of
0.23 mg mL�1. The Oleic acid-IOs were quickly internalized
into the cells within 24 h, with an uptake of 163 pg Fe cell�1.
The amount taken in by the cells decreased with time because
of the rapid growth and division of the macrophage cells.
After grafting with PEO, the SCL-P@IO nanoparticles’
uptake by macrophage cells was much lower, at only
3 pg Fe cell�1, compared with Oleic acid-IO nanoparticles.
The very low uptake of SCL-P@IO nanoparticles could be
due to surface PEO grafting of the SCL-P@IO nanoparticles
lowering the adsorption of the proteins and decreasing the
possibility of macrophage recognition.
3.5 Stability test
The stability of the SCL-P@IO nanoparticles under physio-
logical conditions was also studied by DLS measurements.
The size change of the SCL-P@IO nanoparticles with incuba-
tion time in phosphate-buffered saline (PBS) plus 10% FBS
were monitored. As shown in Fig. 5a, the sizes of SCL-P@IO
nanoparticles were almost constant over 90 d incubation,
indicating that these nanoparticles did not aggregate and were
fairly dispersed in the physiological medium. This is mainly
attributed to the anti-aggregation and anti-biofouling proper-
ties of the PEO blocks of PF127 on the surfaces of SCL-P@IO
nanoparticles. The stability of micelles under dilution is also
a big issue because they are highly diluted in vivo after
administration. Pyrene is an effective fluorescent probe to test
micelle stability. The ratio between the first (375 nm) and third
(386 nm) emission intensities (Im1/Im3) of the pyrene spectrum
depends on the environmental polarity of the solvent.27 Here,
the fluorescence spectra of pyrene molecules encapsulated in
silica-cross-linked PF127 micelles were measured as a function
of PF127 surfactant concentration (different dilution levels) to
study the micelle stability. As shown in Fig. 5b, the low and
almost constant Im1/Im3 ratio (about 1.2 : 1) meant that the
silica deposition effectively cross-linked the PF127 micellar
chains and stabilized the micelles from dissociation under
dilution.
4. Conclusions
In conclusion, we have fabricated a new family of magnetic
nanoparticles based on silica cross-linked PF127 block co-
polymer micelles loaded onto IO nanoparticles. The advan-
tages of high biocompatibility, physical and chemical stability,
high magnetism, and the low-cost of production of these new
magnetic nanoparticles make them promising for a wide range
of biomedical applications, such as bioimaging, bioseparation
and drug delivery.
Acknowledgements
This work was supported by the Singapore MOE’s ARF Tier 1
funding WBS R-284-000-050-133.
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92 | New J. Chem., 2009, 33, 88–92 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Novel thiophene-conjugated indoline dyes for zinc oxide solar cells
Takuya Dentani,aYasuhiro Kubota,
aKazumasa Funabiki,
aJiye Jin,
b
Tsukasa Yoshida,cHideki Minoura,
cHidetoshi Miura
dand Masaki Matsui*
a
Received (in Montpellier, France) 28th May 2008, Accepted 21st August 2008
First published as an Advance Article on the web 16th October 2008
DOI: 10.1039/b808959k
The application of a series of thiophene-conjugated indoline dyes for zinc oxide solar cells,
prepared by the one-step cathode deposition template method, was examined. The introduction
of thiophene ring(s) into D131-type indoline dye improved the cell performance due to their
appropriate energy levels and bathochromic shift in the UV-vis absorption band on zinc oxide.
It is important for the oxidation potential (Eox) of dyes to have a more positive value than
ca. 0.25 V vs. Fc/Fc+ in acetonitrile in order to show a high (470%) incident photon-to-
current efficiency.
Introduction
Organic dyes, such as coumarins,1 styryls,2 polyenes,3 dimethyl-
fluorenyl-containing derivatives4 and indoline derivatives,5
have been reported to act as good sensitizers for titanium
oxide. Bathochromic organic dyes, such as squaryliums,6
phthalocyanines7 and heptamethinecyanines,8 have also been
reported to sensitize semiconductors. In particular, D149
has been reported to show the highest solar-light-to-electricity
conversion efficiency (Z) of 9.0% among organic dyes.5a
One promising approach to improve the performance of
sensitizers is the expansion of the p-conjugation system to
absorb more photons. The introduction of ethylene and
thiophene units into chromophores is a good methodology
to expand p-conjugation.9 On the other hand, a convenient
preparation process for zinc oxide thin films has been
reported.10 The key point of this method is the formation
of porous zinc oxide films at low temperature (o70 1C).
Indoline dyes D131, D102 and D149, in which cyanoacrylic,
monorhodanic and double rhodanic acids are used as
anchor moieties, respectively, are known to show good
performances.5f We report herein the application of novel
thiophene-conjugated indoline dyes having a series of anchor
moieties to zinc oxide dye-sensitized solar cells.
Results and discussion
Synthesis of indoline dyes
Thiophene-conjugated indoline dyes 20–28 were synthesized,
as shown in Scheme 1. Compound 1 was allowed to react with
NBS (2) to give 3, followed by a reaction with thiophene
boronic acids esters 4–7 to provide 8–11, which were formy-
lated to give 12–15. These compounds were allowed to react
with cyanoacetic, mono- and double-rhodanic acids 16–19 to
provide 20–28. D131, D102 and D149 were prepared in a
similar way.
UV-vis absorption and fluorescence spectra
The UV-vis absorption and fluorescence spectra of 20–28,
D131, D102 and D149 are shown in Fig. 1, Fig. 2 and
Fig. 3. The results are also listed in Table 1. All the indoline
dyes showed first and second absorption bands at around 500
and 400 nm, respectively. The first absorption maximum
(lmaxfirst) of monothiophene derivatives 20, 23, 24, 25 and 26
were more bathochromic than thiophene-free derivatives
D131, D102 and D149. Interestingly, no further bathochromic
shift was observed for di- and trithiophene derivatives 21, 22,
27 and 28 compared to monothiophene derivatives 20, 23, 24,
25 and 26, respectively. The molar absorption coefficients at
the first absorption band (efirst) of 20–28 were less than those of
thiophene-free derivatives D131, D102 and D149. The half-
widths of 20–28 (99–146 nm) were larger than those of D131,
D102 and D149 (65–79 nm). No marked difference in efirst
among mono-, di- and trithiophene derivatives was observed,
being in the range 37 700 to 47 900. The second absorption
maximum (lmaxsecond) of thiophene derivatives 20–28 showed
a bathochromic shift, and at the same time, their molar
absorption coefficients (esecond) were larger with increasing
numbers of thiophene units. No remarkable differences in
the UV-vis absorption spectra between 20 and 23, and between
25 and 26, were observed. The fluorescence maximum (Fmax)
showed a bathochromic shift by the introduction of a
thiophene unit.
Electrochemical properties
The oxidation potentials (Eox) ofD131,D102,D149 and 20–25
were measured by using an Ag/Ag+ electrode in acetonitrile to
compare the energy levels of Eox and Eox � E0–0 of the dyes,
the I�/I3� potential, and the conduction band of zinc oxide.
aDepartment of Materials Science and Technology, Faculty ofEngineering, Gifu University, Yanagido, Gifu 501-1193, Japan.E-mail: [email protected]; Fax: +81 58 293 2794;Tel: +81 58 293 2601
bDepartment of Chemistry, Faculty of Science, Shinshu University,3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
c Environmental and Renewable Energy System Division, GraduateSchool of Engineering, Gifu University, Yanagido, Gifu 501-1193,Japan
dChemicrea Co. Ltd., 2-1-6 Sengen, Tsukuba, Ibaragi 305-0047,Japan
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 93–101 | 93
PAPER www.rsc.org/njc | New Journal of Chemistry
Fc/Fc+ was used as a standard. The Eox of ferrocene was
observed at +0.13 V vs. Ag/Ag+ in acetonitrile. Fig. 4 shows
that the Eox of 20 was observed at +0.38 V vs. Ag/Ag+ in
acetonitrile, corresponding to +0.25 V vs. Fc/Fc+ in aceto-
nitrile. The I�/I3� potential level was observed at +0.09 V vs.
Ag/Ag+ in acetonitrile, corresponding to �0.04 V vs. Fc/Fc+
in acetonitrile.
The potential level of Eox � E0–0, where E0–0 represents the
intersection of the normalized absorption and fluorescence
spectra in solution, is considered to correspond to the LUMO
energy level.9 The E0–0 of 20 was observed at 589 nm,
corresponding to 2.11 eV. Therefore, the Eox � E0–0 value of
20 was calculated to be�1.86 V vs. Fc/Fc+ in acetonitrile. The
energy levels of free indoline dyes measured in solution
differed from those of adsorbed ones. Unfortunately, ferro-
cene and indoline dyes on a zinc oxide-coated ITO electrode
did not give distinct redox responses due to a slow charge
transfer process. Hence, the Eox of ferrocene and indoline dyes
could not be determined. The Eox and Eox � E0–0 of all the
indoline dyes are listed in Table 1.
Scheme 1 The synthesis of indoline dyes 20–28.
Fig. 1 UV-vis absorption and fluorescence spectra of indoline dyes
D131, 20, 21, 22 and 23 at a concentration of 1.0 � 10�5 mol dm�3 in
chloroform. Solid and dotted lines represent UV-vis absorption and
fluorescence spectra, respectively.
Fig. 2 UV-vis absorption and fluorescence spectra of indoline dyes
D102 and 24 at a concentration of 1.0� 10�5 mol dm�3 in chloroform.
Solid and dotted lines represent UV-vis absorption and fluorescence
spectra, respectively.
94 | New J. Chem., 2009, 33, 93–101 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
UV-vis absorption and IR spectra of 20
The UV-vis absorption spectra of 20 are shown in Fig. 5. The
lmaxfirst of 20 in chloroform and on zinc oxide were observed at
519 and 449 nm, respectively. Thus, large hypsochromic shift
of lmaxfirst was observed on zinc oxide. The lmax
first of 20 in the
presence of an equimolar amount of triethylamine (TEA) in
chloroform was observed at 470 nm, there being slightly more
bathochromic than that on zinc oxide.
FTIR spectra of 20 are shown in Fig. 6. The IR spectrum of
20 in a potassium bromide disk showed an absorption band at
around 1680 cm�1, which was assigned to a carbonyl stretch-
ing absorption. When indoline dye 20, adsorbed onto a zinc
oxide film, was scraped off and its IR spectrum was measured
in a potassium bromide disk, the absorption band at around
1680 cm�1 disappeared and new absorption was observed at
around 1600 cm�1. This spectrum is similar to that of the
triethylammonium salt of 20, in which the absorption band at
around 1600 cm�1 is assigned to the asymmetric stretch
absorption of the carboxylate anion. It was also observed
that indoline dye 20 showed negative solvatochromism
in solution (lmaxfirst = 516 (toluene), 519 (chloroform),
Fig. 3 UV-vis absorption and fluorescence spectra of indoline dyes
D149, 25, 26, 27 and 28 at a concentration of 1.0 � 10�5 mol dm�3 in
chloroform. Solid and dotted lines represent UV-vis absorption and
fluorescence spectra, respectively.
Table 1 Optical and electrochemical properties of indoline dyes
Compound lmax/nm (e)a Fmax/nma RFIb Eox vs. Fc/Fc
+ in MeCN/V Eox � E0–0 vs. Fc/Fc+ in MeCN/V
D131 463 (55 400) 591 83 +0.41 �2.00325 (15 600)
20 519 (43 300) 659 77 +0.25 �1.86373 (27 300)
21 517 (37 700) 712 27 +0.23 �1.81393 (38 300)
22 519 (41 700) 701 4 +0.22 �1.83409 (47 100)
23 523 (47 300) 653 203 +0.25 �1.85373 (29 100)
D102 514 (54 700) 621 68 +0.37 �1.83368 (25 200)
24 548 (41 400) 702 80 +0.25 �1.75388 (37 100)
D149 550 (68 000) 636 100 +0.30 �1.79395 (32 000)
25 571 (43 500) 717 78 +0.24 �1.67410 (34 800)
26 568 (45 600) 713 49 —c —c
408 (40 500)27 564 (42 000) 743 10 —c —c
405 (41 900)28 550 (47 900) 727 3 —c —c
412 (48 900)
a Measured on 1.0 � 10�5 mol dm�3 of substrate in chloroform at 25 1C. b Relative fluorescence intensity. c Not measured due to low solubility.
Fig. 4 The electrochemical measurement of 20 in acetonitrile (2 ml)
containing tetrabutylammonium perchlorate (0.1 mol dm�3). Ag/Ag+
in acetonitrile was used as a reference electrode. Platinum wire
was used as the working and counterelectrode. The scan rate was
100 mV s�1.
Fig. 5 The UV-vis absorption spectra of 20 in chloroform and on
zinc oxide.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 93–101 | 95
529 (dichloromethane), 465 (DMSO), 453 (acetonitrile) and
464 nm (methanol)). These results indicate that the hypso-
chromic shift of 20 on zinc oxide is mainly attributed to the
formation of a bidentate complex between the carboxylate and
zinc. The polar zinc oxide surface could also be attributed to
the hypsochromic shift.
Photoelectrochemical properties
The cell performance ofD131-type indoline dyes was examined.
The normalized UV-vis absorption spectra on zinc oxide
and action spectra are shown in Fig. 7. The results are also
listed in Table 2. The cell performance was improved in the
presence of cholic acid (CA), a co-adsorbate that can inhibit
the aggregation of dyes on zinc oxide due to carboxylic acid
and hydrophobic moieties. The UV-vis absorption spectra of
20 and 23 in the absence and presence of CA are depicted in
Fig. 7(a). In the case of 20, a broad absorption at around
530 nm decreased in the presence of CA, indicating the
prevention of aggregation on zinc oxide. Meanwhile, only
slight differences in the absorption bands between the absence
and presence of CA were observed for 23. The Z values of 20
and 23 in the absence of CA were 3.13 and 3.30%, respectively
(Table 2, runs 3 and 7). Those in the presence of CA were 3.78
and 3.36%, respectively (Table 2, runs 2 and 6). Thus, the Zvalues of 20 and 23 were improved by 21 and 2% in the
presence of CA, respectively. These results suggest that the
hexyl group in 23 is very effective in inhibiting aggregation on
zinc oxide. In the cases of 21 and 22, aggregation formation
decreased in the presence of CA, resulting in an improved cell
performance (Table 2, runs 4 and 5). The absorption bands of
20, 21, 22 and 23 on zinc oxide were more bathochromic than
that of D131, as shown in Fig. 7(b). The action spectra show
the sensitization of zinc oxide by 20, 21, 22 and 23 at around
550 nm, whereas no sensitization was observed for D131 at
around 550 nm, as depicted in Fig. 7(c). The incident photon-
to-current efficiency (IPCE) in the presence of CA was in the
following dye order: 20 (83.1%) 4 23 (78.2%), D131 (77.8%)
4 21 (69.1%) 4 22 (55.5%) (Table 2, runs 1, 2, 4–6). The
short-circuit photocurrent densities (Jsc) of 21 (8.15 mA cm�2),
20 (8.09 mA cm�2), 23 (7.42 mA cm�2) and 22 (6.69 mA cm�2)
were higher than that of D131 (5.55 mA cm�2). The fill factor
(ff) was lowered by introducing a thiophene unit. Con-
sequently, the Z value was in the following order of dyes:
20 (3.78%) 4 23 (3.36%), 21 (3.19%) 4 D131 (2.60%) 4 22
(2.08%). Thus, an improvement in cell performance was
successfully observed for a series of D131-type thiophene-
conjugated indoline dyes. The improved cell performance of
20, 21 and 23, compared with D131, mainly came from the
bathochromic shift in the absorption band and a high IPCE
(470%) to increase Jsc.
Next, the cell performance of D102 and 24 was examined
(Table 2, runs 8–10). The UV-vis absorption and action
spectra are shown in Fig. 8. The absorption band of 24 was
more bathochromic than that of D102. The absorption spec-
trum of 24 in the absence of CA clearly showed a broad
absorption at around 600 nm, suggesting the formation of
aggregates. Fig. 8(b) shows the sensitization of zinc oxide by
24 at around 630 nm. However, the IPCE value of 24 was
lower than that of D102 so as not to increase Jsc. The open-
circuit voltage (Voc) and ff of 24 were lower than those of
D102 (Table 2, runs 8 and 9). Thus, no improvement in
cell performance was observed for D102-type thiophene-
conjugated indoline dyes.
Fig. 6 FTIR spectra of 20: (a) 20, (b) 20 in the presence of zinc oxide
and (c) the triethylammonium salt of 20.
Fig. 7 (a) Normalized UV-vis absorption spectra of 20 and 23 on zinc
oxide in the absence and presence of CA, (b) normalized UV-vis
absorption spectra of D131, 20, 21, 22 and 23 on zinc oxide in the
presence of CA and (c) action spectra of D131, 20, 21, 22 and 23 in the
presence of CA.
96 | New J. Chem., 2009, 33, 93–101 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Finally, the cell performance ofD149-type indoline dyes was
examined. The UV-vis absorption and action spectra of D149,
25, 26, 27 and 28 are shown in Fig. 9. In this case, the
difference in the UV-vis absorption bands of 25 and 26 in
the absence and presence of CA was small compared with
those in the cases of 20 and 23, as shown in Fig. 9(a). The Zvalues of 25 and 26 in the presence of CA were higher than
those in the absence of CA (Table 2, runs 12–15). Fig. 9(b)
shows that 25, 26, 27 and 28 are more bathochromic than
D149. Fig. 9(c) indicates that though the sensitization of zinc
oxide was observed for 25, 26, 27 and 28 at around 670 nm,
Fig. 8 (a) Normalized UV-vis absorption spectra of D102 and 24 on
zinc oxide in the absence and presence of CA, and (b) action spectra of
D102 and 24 in the presence of CA.
Table 2 Physical properties of indoline dyes
Run Compound CAa lmax/nm Abs.b IPCE (%) Jsc/mA cm�2 Voc/V ff Zc (%)
1 D131 2 405 3.36 77.8 5.55 0.66 0.71 2.602 20 2 449 2.48 83.1 8.09 0.69 0.68 3.783 20 0 459 1.96 71.4 7.09 0.65 0.68 3.134 21 2 461 2.16 69.1 8.15 0.63 0.62 3.195 22 2 457 2.44 55.5 6.69 0.59 0.53 2.086 23 2 450 2.07 78.2 7.42 0.66 0.68 3.367 23 0 452 2.07 76.2 7.58 0.65 0.67 3.308 D102 2 476 3.20 77.1 9.00 0.65 0.66 3.889 24 2 514 1.94 48.6 7.33 0.62 0.63 2.8310 24 0 539 1.54 42.4 6.44 0.59 0.58 2.2011 D149 2 521 3.08 81.2 11.08 0.68 0.57 4.2312 25 2 547 1.76 43.4 6.85 0.54 0.64 2.3513 25 0 555 1.65 35.9 5.38 0.50 0.62 1.6814 26 2 546 1.25 37.5 5.85 0.62 0.68 2.4515 26 0 561 1.21 37.7 5.55 0.57 0.65 2.0716 27 2 546 1.26 29.7 4.40 0.59 0.66 1.7117 28 2 542 1.45 26.1 3.67 0.56 0.67 1.36
a Equivalents of cholic acid with respect to dye. b Absorbance at absorption maximum on zinc oxide. c Action spectra and I–V characteristics
under AM 1.5 irradiation (100 mW cm�2).
Fig. 9 (a) Normalized UV-vis absorption spectra of 25 and 26 on zinc
oxide in the absence and presence of CA, (b) normalized UV-vis
absorption spectra of D149, 25, 26, 27 and 28 on zinc oxide in the
presence of CA, and (c) action spectra of D149, 25, 26, 27 and 28 in the
presence of CA.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 93–101 | 97
their IPCE values were lower than that of D149. Thus, no
improvement in cell performance was observed for the series
of D149-type thiophene-conjugated indoline dyes (Table 2,
runs 11, 12, 14, 16 and 17).
Relationship between IPCE and Eox, Eox � E0–0
To examine why only D131-type thiophene-conjugated indo-
line dyes showed improved cell performances, the relationship
between IPCE and energy levels was examined. Fig. 10(a)
shows the relationship between IPCE and Eox. Indoline dyes
D131, 20, 21, 23, D102 and D149, of which the Eox levels were
more positive than the ca. +0.25 V vs. Fc/Fc+ in acetonitrile,
showed high (470%) IPCE values. The potential level of
I�/I3� was observed at �0.04 V vs. Fc/Fc+ in acetonitrile.
Fig. 10(b) shows the relationship between IPCE and Eox �E0–0. It was also found that indoline dyes D131, 20, 21, 23,
D102 and D149 showed high IPCE values. It is reported that
the potential levels of the conduction band of titanium oxide
and the I�/I3� redox are �0.5 and +0.4 V vs. NHE, respec-
tively, there being an energy gap of 0.9 V.9,11 The conduction
band level of zinc oxide is similar to that of titanium oxide.
Therefore, the level of zinc oxide is considered to be �0.94 V
vs. Fc/Fc+ in acetonitrile, which is much more positive than
the Eox � E0–0 levels of all the indoline dyes, the energy gap
between Eox � E0–0 and the conduction band levels being
larger than 0.7 V. It is suggested that an energy gap larger than
0.2 V between Eox and I�/I3�, and Eox � E0–0 and the
conduction band levels, respectively, are required.9 Thus,
though the Eox � E0–0 level of all the indoline dyes are
sufficiently negative, their Eox levels are critical for the sensi-
tization cycle to proceed. No marked difference in the
Eox levels among the thiophene-conjugated derivatives 20
(+0.25 V), 21 (+0.23 V), 22 (+0.22 V), 23 (+0.25 V), 24
(+0.25 V) and 25 (+0.24 V) was observed in solution.
However, their Eox level on zinc oxide could differ from that
in solution. As the Eox level of D131 (+0.41 V vs. Fc/Fc+ in
MeCN) was more positive than those of D102 (+0.37 V) and
D149 (+0.30 V) in solution, those ofD131-type derivatives 20,
21, 22 and 23 might be more positive than those of D102- and
D149-type derivatives 24, 25, 26, 27 and 28 on zinc oxide. The
Eox levels of D102, 20, 21 and 22 were observed at +0.37,
+0.25, +0.23 and +0.22 V vs. Fc/Fc+ in acetonitrile,
respectively. This suggests that the Eox level can negatively
shift with increasing numbers of thiophene units on zinc oxide.
Therefore, the Eox levels of D131-type mono- and dithiophene
derivatives 20, 21 and 23 could be more positive than those of
D102- and D149-type derivatives, and the redox potential of
I�/I3� on zinc oxide could show an improved cell perfor-
mance. As a result, indoline dyes 20, 21 and 23 could show
better performances than D131 due to larger Jsc values. The
Eox levels of D102- and D149-type thiophene-conjugated
indoline dyes 24, 25, 26, 27 and 28 might be too negative on
zinc oxide, despite their bathochromic shift in the UV-vis
absorption spectrum on zinc oxide. In order to improve the
performance of indoline dyes, it is important to design deri-
vatives of them having more positive Eox level.
Conclusion
A series of D131-, D102- and D149-type thiophene-conjugated
indoline dyes were examined as sensitizers for zinc oxide solar
cells, prepared by the one-step cathode deposition template
method. Among the series of thiophene-conjugated indoline
dyes, D131-type indoline dyes improved cell performance.
This could have been due to their positive Eox levels. In order
to improve the performance of D102- and D149-type indoline
dyes, it is important to design derivatives of them having more
positive Eox levels.
Experimental
General
Melting points were measured with a Yanagimoto MP-52
micro-melting-point apparatus. NMR spectra obtained using
a JEOL JNM-ECX 400P spectrometer. EI and FAB MS
spectra were recorded on a JEOL MStation 700 spectrometer.
UV-vis absorption and fluorescence spectra were acquired on
Hitachi U-3500 and F-4500 spectrophotometers, respectively.
Cyclic voltammetry was carried out using an EG&G Princeton
Applied Research Potentiostat/Galvanostat (Model 263A)
driven by the M270 software package. One-step cathode electro-
deposition was undertaken using a Hokuto-Denko HSV-100
potentiostat system. The photoelectrochemical measurements
of solar cells were performed on a Bunko-Keiki CEP-2000
system. The I–V curve measurements of solar cells were
performed on an EKO Instruments I–V curve tracer MP-160
and Grating spectroradiometer LS-100.
Electrochemical measurements
The electrochemical measurements of indoline dyes D131, 20,
21, 22, 23, D102, 24, D149, 25, ferrocene and potassiumFig. 10 The relationship between IPCE and energy levels: (a) IPCE
vs. Eox and (b) IPCE vs. Eox � E0–0.
98 | New J. Chem., 2009, 33, 93–101 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
iodide, were performed in acetonitrile. The oxidation potential
(Eox) was measured by using three small-sized electrodes.
Ag/Ag+ was used as a reference electrode. Platinum wire
was used as the working and counterelectrode. Acetonitrile
solutions (2 ml) of dyes containing tetrabutylammonium
perchlorate (0.1 mol dm�3) were prepared. Dry argon
gas was introduced into the solution for 10 min. The electro-
chemical measurements were then performed at a scan rate
of 100 mV s�1.
Preparation of the zinc oxide solar cell
An aqueous potassium chloride solution (300 ml, 0.1 mol dm�3)
was electrolyzed at �1.0 V vs. SCE with bubbling oxygen
gas at 70 1C for 30 min. Platinum was used as a counter-
electrode. To the pre-electrolyzed film was added an
aqueous solution of zinc chloride. The concentration of zinc
chloride was adjusted to 5 mmol dm�3. Then, the film was
again electrodeposited in the solution at �1.0 V vs. SCE at
70 1C for 20 min with bubbling oxygen gas. To the electro-
deposited film was added an aqueous solution of eosin Y
(0.050 mmol dm�3). The film was electrodeposited at �1.0 V
vs. SCE at 70 1C for 30 min with bubbling oxygen gas. The film
was kept in a dilute aqueous potassium hydroxide solution
(pH 10.5) for 24 h to remove adsorbed eosin Y. The film was
then dried at 100 1C for 1 h. The thin film was immersed in a
chloroform solution of dye (1 � 10�4 mol dm�3) and kept at
ambient temperature for 1 h to adsorb dyes 20–28 onto the
zinc oxide. In the cases of D131, D102 and D149, the film was
immersed in an acetonitrile–tert-butyl alcohol 1 : 1 mixed
solution (0.5 mmol dm�3). Then, the film was washed with
chloroform. In the cases of D131,D102 andD149, the film was
washed with an acetonitrile–tert-butyl alcohol 1 : 1 mixed
solution. The films were dried under an air atmosphere at
ambient temperature. The film was used as the working
electrode. A platinum spattered film was used as the counter-
electrode. The cell size was 5.0 � 5.0 mm. Thermosetting resin
was put around the cell. An acetonitrile–ethylene carbonate
(v/v = 1 : 4) mixed solution containing tetrabutylammonium
iodide (0.5 mol dm�3) and iodine (0.05 mol dm�3) was used as
the electrolyte.
Photoelectrochemical measurements
Action spectra were measured under monochromatic light
with a constant photon number (5 � 1015 photon cm�2 s�1).
I–V characteristics were measured under illumination with
AM 1.5 simulated sun light (100 mW cm�2) through a shading
mask (5.0 � 4.0 mm).
Synthesis of dyes
Materials. 1,2,3,3a,4,8b-Hexahydro-4-[4-(2,2-diphenylethenyl)-
phenyl]cyclopent[b]indole (1) was supplied from Chemicrea
Co. Ltd. N-Bromosuccinimide (NBS, 2) and 2-(4,4,5,5-tetra-
methyl-1,3,2-dioxaborolan-2-yl)thiophene (4) were purchased
from Wako Pure Chemical Industries Ltd. 5-(4,4,5,5-Tetra-
methyl-1,3,2-dioxaborolan-2-yl)-2,20-bithiophene (5), 5-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)-2,2 0,5 0,200-terthiophene
(6) and cyano acetic acid (16) were purchased from Aldrich
Co. Ltd. Rhodanine-3-acetic acid (17) was purchased from
Tokyo Kasei Co. Ltd. Compound 19 was synthesized in the
similar procedure to that described for 18.12 3-Hexyl-2-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene (7)13
and 3,5-(di-tert-butyl)benzylamine14 were synthesized as des-
cribed in the literature. D131, D102 and D149 were prepared
in a similar way, as described in the literature.5c,e
Synthesis of 3. To a dry acetone solution (23 ml) of 1
(980 mg, 2.37 mmol) was added NBS (423 mg, 2.38 mmol)
at 0 1C under an argon atmosphere. The mixture was stirred at
room temperature for 3 h. The reaction mixture was poured
into water (20 ml) and extracted with chloroform (3 � 50 ml).
The extract was washed with brine (2 � 50 ml) and dried over
anhydrous sodium sulfate. The solvent was removed in vacuo.
The crude product was purified by silica gel column chromato-
graphy (chloroform–hexane = 1 : 3) to afford 3 as a pale
yellow solid. Yield 96%, mp 81–83 1C. dH (400 MHz, CDCl3,
Me4Si): 1.42–1.49 (1 H, m), 1.61–1.65 (1 H, m), 1.79–1.87
(3 H, m), 1.96–2.02 (1 H, m), 3.76–3.79 (1 H, m), 4.65–4.69
(1 H, m), 6.83 (1 H, d, J = 8.4 Hz), 6.92 (1 H, s), 6.99–7.01
(4 H, m), 7.09 (1 H, d, J= 8.4 Hz), 7.16 (1 H, s) and 7.24–7.40
(10 H, m). m/z (EI) = 493 (M+ + 2, 100), 491 (M+, 98), 464
(69), 462 (67), 413 (55), 384 (52) and 178 (42).
Synthesis of 8–11. To a THF solution (10 ml) of 3 (492 mg,
1.0 mmol) were added boronic acid esters 4–7 (1.20 mmol),
tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.05 mmol)
and a 2 M aqueous potassium carbonate solution (0.8 ml). The
mixture was refluxed (8: 12 h, 9: 20 h, 10: 20 h and 11: 20 h)
under an argon atmosphere. After cooling, chloroform
(100 ml) was added to the reaction mixture and it was then
filtered through Celite. The filtrate was next poured into
water (50 ml). The chloroform layer was washed with brine
(3 � 50 ml) and dried over anhydrous sodium sulfate. The
solvent was removed in vacuo and the crude product purified
by silica gel column chromatography (8: chloroform–hexane =
4 : 3 � 1, chloroform � 1; 9: chloroform–hexane = 1 : 1 � 1,
chloroform–hexane = 2 : 5 � 1; 10: chloroform–hexane =
1 : 1 � 1, chloroform–hexane = 3 : 5 � 2; 11: chloroform–
hexane = 8 : 11 � 1, chloroform–hexane = 1 : 3 � 2) to give
8–11 as a yellow solid. The physical and spectral data are
shown below.
8. Yield 72%, mp 204–206 1C. dH (400 MHz, CDCl3,
Me4Si): 1.46–1.51 (1 H, m), 1.62–1.67 (1 H, m), 1.79–1.94
(3 H, m), 2.00–2.07 (1 H, m), 3.81–3.86 (1 H, m), 4.70–4.73
(1 H, m), 6.93 (1 H, s), 6.98–7.06 (6 H, m), 7.15 (1 H, s),
7.16–7.17 (1 H, m) and 7.26–7.39 (12 H, m). m/z (EI) = 495
(M+, 100), 466 (24) and 248 (8).
9. Yield 49%, mp 105–107 1C. dH (400 MHz, CDCl3,
Me4Si): 1.39–1.47 (1 H, m), 1.55–1.59 (1 H, m), 1.69–1.84
(3 H, m), 1.91–2.00 (1 H, m), 3.69–3.73 (1 H, m), 4.58–4.61
(1 H, m), 6.91–7.03 (8 H, m), 7.08–7.10 (3 H, m) and 7.21–7.34
(12 H, m). m/z (FAB) = 578 (MH+).
10. Yield 53%, mp 106–109 1C. dH (400 MHz, CDCl3,
Me4Si): 1.48–1.59 (1 H, m), 1.62–1.66 (1 H, m), 1.82–1.93
(3 H, m), 2.03–2.06 (1 H, m), 3.80–3.88 (1 H, m), 4.67–4.78
(1 H, m), 6.94 (1 H, s), 6.98–7.11 (10 H, m), 7.17 (1 H, d,
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 93–101 | 99
J = 3.4 Hz), 7.21 (1 H, d, J = 4.8 Hz) and 7.27–7.41
(12 H, m). m/z (FAB) = 660 (MH+).
11. Yield 56%, mp 57–61 1C. dH (400 MHz, CDCl3, Me4Si):
0.89 (3 H, t, J = 6.8 Hz), 1.30–1.34 (6 H, m), 1.42–1.52
(1 H, m), 1.59–1.64 (3 H, m), 1.78–1.90 (3 H, m), 1.97–2.07
(1 H, m), 2.58 (2 H, t, J = 7.6 Hz), 3.78–3.82 (1 H, m),
4.66–4.69 (1 H, m), 6.73 (1 H, s), 6.92–7.04 (7 H, m) and
7.22–7.40 (12 H, m). m/z (FAB) = 580 (MH+).
Synthesis of 12–15. To DMF (4 ml) was added phosphorous
oxychloride (352 mg, 2.30 mmol) at 0 1C. To the solution was
then added a DMF solution (14 ml) of 8–11 (0.84 mmol) at
0–5 1C. The mixture was heated at 75 1C (12: 2 h, 13: 4 h, 14:
20 h and 15: 2 h). After the reaction was complete, the reaction
mixture was poured into ice–water (100 ml) and neutralized
with aqueous sodium hydroxide. The product was extracted
with chloroform (3 � 50 ml). The extract was washed with
brine (2 � 50 ml) and water (2 � 50 ml), and dried over
anhydrous sodium sulfate. The solvent was removed in vacuo
and the product purified by silica gel column chromatography
(2 � chloroform) to afford 12–15 (12: orange solid, 13: red
solid, 14: red solid and 15: orange solid). The physical and
spectral data are shown below.
12. Yield 90%, mp 112–114 1C. dH (400 MHz, CDCl3,
Me4Si): 1.47–1.53 (1 H, m), 1.65–1.67 (1 H, m), 1.82–1.89
(3 H, m), 2.07–2.11 (1 H, m), 3.81–3.85 (1 H, m), 4.76–4.79
(1 H, m), 6.94 (1 H, s), 6.96 (1 H, d, J = 8.5 Hz), 7.01 (2 H, d,
J = 8.8 Hz), 7.05 (2 H, d, J = 8.8 Hz), 7.23–7.39 (13 H, m),
7.68 (1 H, d, J = 4.1 Hz) and 9.80 (1 H, s). m/z (EI) = 523
(M+, 100), 495 (56), 373 (52) and 344 (31).
13. Yield 74%, mp 115–117 1C. dH (400 MHz, CDCl3,
Me4Si): 1.44–1.53 (1 H, m), 1.59–1.66 (1 H, m), 1.77–1.91
(3 H, m), 2.00–2.09 (1 H, m), 3.79–3.81 (1 H, m), 4.70–4.73
(1 H, m), 6.93 (1 H, s), 6.95 (1 H, d, J = 8.5 Hz), 6.99 (2 H, d,
J = 8.9 Hz), 7.03 (2 H, d, J = 8.9 Hz), 7.08 (1 H, d, J =
3.9 Hz), 7.18 (1 H, d, J = 3.9 Hz), 7.24–7.40 (13 H, m), 7.62
(1 H, d, J = 4.1 Hz) and 9.82 (1 H, s). m/z (FAB) =
606 (MH+).
14. Yield 26%, mp 230–232 1C. dH (400 MHz, CDCl3,
Me4Si): 1.46–1.54 (1 H, m), 1.62–1.68 (1 H, m), 1.79–1.86
(3 H, m), 1.98–2.02 (1 H, m), 3.77–3.99 (1 H, m), 4.46–4.69
(1 H, m), 6.38–7.40 (23 H, m), 7.57–7.58 (1 H, m) and 9.78
(1 H, s). m/z (FAB) = 688 (MH+).
15. Yield 96%, mp 66–68 1C. dH (400 MHz, CDCl3, Me4Si):
0.89 (3 H, t, J = 7.0 Hz), 1.30–1.39 (6 H, m), 1.45–1.48
(1 H, m), 1.61–1.73 (3 H, m), 1.79–1.90 (3 H, m), 2.02–2.05
(1 H, m), 2.91 (2 H, t, J = 7.0 Hz), 3.79–3.83 (1 H, m),
4.73–4.77 (1 H, m), 6.93 (1 H, s), 6.94 (1 H, d, J = 8.2 Hz),
7.00 (2 H, d, J = 8.9 Hz), 7.04 (2 H, d, J = 8.9 Hz), 7.06
(1 H, s), 7.23–7.40 (12 H, m) and 9.95 (1 H, s). m/z (FAB) =
608 (MH+).
Synthesis of 20, 21, 22 and 23. In the cases of 20, 21 and 23,
to an acetonitrile solution (6 ml) of 12, 13 and 14 (0.30 mmol)
were added cyano acetic acid (100 mg, 1.18 mmol)
and piperidine (46 mg, 0.54 mmol). In the case of 22, to
an acetonitrile–chloroform (1 : 1) mixed solution (80 ml) of
14 (107 mg, 0.16 mmol) were added cyano acetic acid (97 mg,
1.14 mmol) and piperidine (776 mg, 9.11 mmol). The mixture
was then refluxed (20: 2 h, 21: 2 h, 22: 23 h and 23: 17 h). After
cooling, the solvent was removed in vacuo and the residue
dissolved in chloroform. To the solution was added 1 M
aqueous hydrochloric acid (0.4 ml) and water (50 ml), and
the mixture stirred at room temperature for 30 min. The
chloroform layer was separated, washed with water (3 � 50 ml)
and dried over anhydrous sodium sulfate. The solvent was
removed in vacuo and the product purified by silica gel column
chromatography (20: chloroform–methanol = 8 : 1 � 1, 10 :
1 � 2; 21: chloroform–methanol = 10 : 1 � 3; 22:
chloroform–methanol = 10 : 1 � 1, 8 : 1 � 3; 23: chloroform–
methanol = 10 : 1 � 3) to afford 20, 21, 22 and 23 as a purple
solid. The physical and spectral data are shown below.
20. Yield 64%, mp 268–271 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.23–1.32 (1 H, m), 1.59–1.68 (2 H, m), 1.79–1.84 (2 H,
m), 1.99–2.08 (1 H, m), 3.82–3.86 (1 H, m), 4.86–4.90 (1 H, m),
6.97 (1 H, d, J = 8.7 Hz), 7.02 (2 H, d, J = 8.5 Hz), 7.07
(1 H, s), 7.11 (2 H, d, J = 8.5 Hz), 7.19–7.22 (2 H, m),
7.28–7.36 (5 H, m), 7.41–7.48 (4 H, m), 7.57–7.59 (2 H, m),
7.95 (1 H, d, J = 3.4 Hz) and 8.43 (1 H, s). m/z (FAB) =
591.2106 (MH+, C39H31N2O2S requires 591.2106).
21. Yield 62%, mp 194–198 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.28–1.35 (1 H, m), 1.58–1.69 (2 H, m), 1.81–1.86
(2 H, m), 2.00–2.07 (1 H, m), 3.81–3.85 (1 H, m), 4.81–4.84
(1 H, m), 6.98 (1 H, d, J = 9.2 Hz), 7.00 (2 H, d, J = 9.1 Hz),
7.06 (1 H, s), 7.09 (2 H, d, J = 9.1 Hz), 7.20–7.21 (2 H, m),
7.28–7.53 (13 H, m), 7.82 (1 H, br s) and 8.28 (1 H, br s). m/z
(FAB) = 673.1974 (MH+, C43H33N2O2S2 requires 673.1983).
22. Yield 79%, mp 266–269 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.29–1.36 (1 H, m), 1.61–1.70 (2 H, m), 1.84–1.87
(2 H, m), 2.00–2.05 (1 H, m), 3.81–3.85 (1 H, m), 4.80–4.83
(1 H, m), 6.98 (1 H, d, J = 6.3 Hz), 7.00 (2 H, d, J = 7.8 Hz),
7.06 (1 H, s), 7.08 (2 H, d, J = 7.8 Hz), 7.20–7.22 (2 H, m),
7.28–7.47 (13 H, m), 7.60–7.62 (2 H, m), 7.98 (1 H, d, J=3.4 Hz)
and 8.49 (1 H, s). m/z (FAB) = 755.1831 (MH+,
C47H35N2O2S3 requires 755.1861).
23. Yield 93%, mp 240–243 1C. dH (400 MHz, DMSO-d6,
Me4Si): 0.84 (3 H, t, J = 6.0 Hz), 1.20–1.30 (7 H, m),
1.57–1.65 (4 H, m), 1.76–1.84 (2 H, m), 1.97–2.06 (1 H, m),
2.74 (2 H, t, J = 7.2 Hz), 3.78–3.82 (1 H, m), 4.82–4.86
(1 H, m), 6.93 (1 H, d, J = 8.2 Hz), 6.99 (2 H, d, J = 8.6 Hz),
7.04 (1 H, s), 7.07 (2 H, d, J = 8.6 Hz), 7.17–7.19 (2 H, m),
7.26–7.34 (5 H, m), 7.38–7.45 (4 H, m), 7.50 (1 H, s), 7.54
(1 H, s) and 8.25 (1 H, s). m/z (FAB) = 675.3117 (MH+,
C45H43N2O2S requires 675.3045).
Synthesis of 24, 25, 26, 27 and 28. To an acetic acid solution
(4 ml) of 12–14 (0.30 mmol) was added rhodanine derivatives
17–19 (0.32 mmol). The mixture was heated at 120 1C and
ammonium acetate (0.88 mmol) added, after which it
was refluxed for 2 h. After cooling, the reaction mixture was
poured into water (20 ml). The resulting precipitate was
filtered and washed with water, and the crude product purified
by silica gel column chromatography (24: chloroform–methanol=
8 : 1 � 3; 25: chloroform–methanol = 8 : 1 � 2; 26:
100 | New J. Chem., 2009, 33, 93–101 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
chloroform–methanol = 8 : 1 � 9; 27: chloroform–methanol =
8 : 1 � 5; 28: chloroform–methanol = 8 : 1 � 3) to afford
compound 24, 25, 26, 27 and 28 as a purple solid. The physical
and spectral data are shown below.
24. Yield 89%, mp 175–178 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.29–1.33 (1 H, m), 1.59–1.68 (2 H, m), 1.81–1.84
(2 H, m), 2.00–2.05 (1 H, m), 3.81–3.85 (1 H, m), 4.69 (2 H, s),
4.84–4.88 (1 H, m), 6.95 (1 H, d, J= 8.5 Hz), 7.01 (2 H, d, J=
8.3 Hz), 7.06 (1 H, s), 7.09 (2 H, d, J = 8.3 Hz), 7.19–7.21
(2 H, m), 7.28–7.34 (5 H, m), 7.39–7.49 (4 H, m), 7.57–7.58
(2 H, m), 7.77 (1 H, d, J = 3.9 Hz) and 8.10 (1 H, s). m/z
(FAB) = 697.1647 (MH+, C41H33N2O3S3 requires 697.1653).
25. Yield 31%, mp 4 300 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.14 (3 H, t, J = 6.9 Hz), 1.25–1.37 (1 H, m),
1.60–1.68 (2 H, m), 1.80–1.84 (2 H, m), 2.01–2.08 (1 H, m),
3.82–3.86 (1 H, m), 3.98–4.00 (2 H, m), 4.69 (2 H, s), 4.84–4.87
(1 H, m), 6.96 (1 H, d, J = 8.5 Hz), 7.00 (2 H, d, J = 9.3 Hz),
7.07 (1 H, s), 7.08 (2 H, d, J = 9.3 Hz), 7.20–7.55 (13 H, m),
7.68 (1 H, d, J = 3.9 Hz) and 8.02 (1 H, s). m/z (FAB) =
824.1757 (MH+, C46H38N3O4S4 requires 824.1745).
26. Yield 81%, mp 4 300 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.24–1.29 (1 H, m), 1.25 (18 H, s), 1.59–1.87 (2 H, m),
1.85–1.87 (2 H, m), 2.01–2.09 (1 H, m), 3.83–3.87 (1 H, m),
4.61 (2 H, s), 4.85–4.88 (1 H, m), 5.19 (2 H, s), 6.98 (1 H, d,
J= 8.5 Hz), 7.00 (2 H, d, J= 8.8 Hz), 7.07 (1 H, m), 7.10 (2 H,
d, J= 8.8 Hz), 7.19–7.48 (14 H, m), 7.53 (1 H, s), 7.57 (1 H, d,
J = 3.9 Hz), 7.72 (1 H, d, J = 4.1 Hz) and 8.07 (1 H, s). m/z
(FAB) = 998.3133 (MH+, C59H56N3O4S4 requires 998.3154).
27. Yield 95%, mp 4 300 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.22–1.35 (1 H, m), 1.23 (18 H, s), 1.57–1.66 (2 H, m),
1.78–1.85 (2 H, m), 1.95–2.05 (1 H, m), 3.73–3.79 (1 H, m),
4.33 (2 H, s), 4.74–4.78 (1 H, m), 5.10 (2 H, s), 6.91 (1 H, d,
J = 8.5 Hz), 6.99 (2 H, d, J = 8.3 Hz), 7.03 (1 H, s), 7.04
(2 H, d, J = 8.3 Hz), 7.17–7.54 (18 H, m), 7.62 (1 H, s) and
7.94 (1 H, s). m/z (FAB) = 1080.3016 (MH+, C63H58N3O4S5requires 1080.3031).
28. Yield 32%, mp 4 300 1C. dH (400 MHz, DMSO-d6,
Me4Si): 1.22–1.33 (1 H, m), 1.26 (18 H, s), 1.59–1.68 (2 H, m),
1.80–1.84 (2 H, m), 1.97–2.03 (1 H, m), 3.78–3.83 (1 H, m),
4.46 (2 H, s), 4.77–4.81 (1 H, m), 5.17 (2 H, s), 6.96 (1 H, d,
J = 8.5 Hz), 6.98 (2 H, d, J = 9.1 Hz), 7.05 (1 H, s), 7.06
(2 H, d, J = 9.1 Hz), 7.19–7.54 (20 H, m), 7.71 (1 H, s) and
8.02 (1 H, s). m/z (FAB) = 1162.2795 (MH+, C67H60N3O4S6requires 1162.2908).
Acknowledgements
This work was financially supported in part by Grants-in-Aid
for Science Research (no. 19550185) from the Japan Society
for the Promotion of Science (JSPS).
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 93–101 | 101
Gold imidazolium-based ionic liquids, efficient catalysts for
cycloisomerization of c-acetylenic carboxylic acids
Florentina Neat-u,a Vasile I. Parvulescu,a Veronique Michelet,b Jean-Pierre Genet,b
Alexandre Goguetcand Christopher Hardacre
cd
Received (in Durham, UK) 22nd July 2008, Accepted 8th September 2008
First published as an Advance Article on the web 20th October 2008
DOI: 10.1039/b812580e
Ionic liquid stabilized gold(III) chloride is shown to be a very active catalyst in the cyclization
of sterically hindered and unhindered acetylenic carboxylic acid substrates even in the absence
of a base.
Introduction
Ionic liquids (ILs) have received significant attention recently
because they exhibit several advantages over molecular
solvents with respect to their environmental impact.1 Catalytic
reactions in ILs have been examined for at least 20 years and
have been used for a wide variety of carbon–carbon bond
forming reactions, which were the first to be undertaken in this
media, and a number of good reviews cover the area of ILs.2–6
The extensive interest stems from the fact that the properties
of ionic liquids may be tuned in order to suit a particular
application by varying the cation–anion combination system-
atically and thereby are useful engineering solvents. In addi-
tion, for chemical reactions, the ionic liquid provides an ionic
environment which can significantly alter the reactivity and
selectivity of processes compared with molecular solvents.7
The transition metal-catalyzed cyclization of 4-alkynoic
acids constitutes a major route8 for the construction of
5-membered exocyclic lactones and has been the subject of a
large number of investigations.9–14 Recently, a very attractive
route to perform this reaction under mild conditions in the
presence of gold was reported.15,16 In our laboratory, the
catalytic properties of AuCl and AuCl3 for gem-substituted
substrates, in the absence of base, was described15 as well as
the use of two heterogeneous systems Au2O317 and Au/beta.18
These systems were found to be active for both substituted and
unsubstituted substrates. In addition, the optimized hetero-
geneously catalyzed system was found to be recyclable.22
Whilst gold has been shown to be highly active, it commonly
undergoes significant deactivation due to the ease by which it
may change its oxidation state and, in the case of nanoparti-
cles, the catalyst particle size leading to instability in the form
of the active catalyst.19 Therefore, modalities which can
enhance the stability are extremely important for practical
applications.20 These can be in the form of the solvent used or
the nature of the support.21 For example, stabilization of gold
in the form of nanoparticles in ionic liquids by imidazolium
derivatives has been reported.22–25
In this report the behavior of a 4 wt% Au/beta catalyst and
a series of 1,3-dialkylimidazolium tetrachloroaurate salts in
ionic liquids as catalysts for the cyclization of acetylenic
substrates has been studied. Gold has recently been reported
as a catalyst in ionic liquids in the hydration of phenyl-
acetylene26,27 and the syntheses of substituted 3(2H)-furanones,27
2,5-dihydrofurans28 and substituted indoles.29 However, with
the exception of the Co2(CO)8-catalyzed intramolecular and
intermolecular Pauson–Khand annelation using 1-butyl-3-
methylimidazolium hexafluorophosphate ([C4mim][PF6]) and
tetrafluoroborate ([C4mim][BF4]) ionic liquids as solvents, no
other related reactions to the cyclization of acetylenic sub-
strates have been reported in ILs, to date.30
Experimental
Catalysts preparation
1. Au-beta catalyst. The catalyst was prepared by stirring
1 g of beta zeolite (PQ Corporation) for 3 h with 100 cm3 of 1 M
NH4NO3 at 353 K.22 The slurry was filtered off and carefully
washed with deionized water, dried for 6 h at 333 K and
calcined for 24 h at 773 K. Deposition of gold was performed
using the deposition–precipitation method. The support
(1 g) was added to 100 cm3 of an aqueous solution of HAuCl4(2.1 � 10�3 M) at 343 K which had previously adjusted to a
pH = 8.5 with 0.2 M NaOH. The temperature of the slurry
was maintained at 343 K under vigorous stirring for 3 h.
Thereafter, the sample was filtered off, washed with deionized
water to remove the free chloride and then dried under
vacuum at 333 K for 24 h. The resultant catalyst contained
4 wt% Au as determined by ICP-AES analysis. This catalyst
has been used as a reference material in these experiments.
2. Ionic liquids synthesis. Gold ionic liquids were
synthesized using the method reported previously by Hasan
et al.25 Four 1-alkyl-3-methylimidazolium tetrachloroaurate
([Cnmim][AuCl4], n = 2, 4, 6, 18) ionic liquids were prepared
by adding a 10% molar excess of [Cnmim]Cl to tetrachloroauric
aDepartment of Chemical Technology and Catalysis, University ofBucharest, B-dul Regina Elisabeta 4-12, 030016 Bucharest, Romania.E-mail: [email protected]; Fax: +40 21 4010241
b Laboratoire de Synthese Selective Organique et Produits Naturels,ENSCP, UMR 7573, 11 rue P. et M. Curie, F-725231 Paris Cedex 05,France. E-mail: [email protected]; Fax: +33 1 44071062
c CenTACat School of Chemistry and Chemical Engineering, Queen’sUniversity, Stranmillis Road, Belfast, Northern Ireland,UK BT9 5AG
dQUILL School of Chemistry and Chemical Engineering, Queen’sUniversity, Stranmillis Road, Belfast, Northern Ireland, UK BT9 5AG.E-mail: [email protected]; Fax: +44 28 90974687
102 | New J. Chem., 2009, 33, 102–106 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
acid (HAuCl4�4H2O, Alfa Aesar) resulting in the rapid
formation of a yellow solid. Following heating to above
its melting points with stirring for 0.5 h, the product was
purified by recrystallization from benzene–acetonitrile in the
volume ratio of 4 : 1. [Cnmim]Cl were prepared in house using
standard literature methods.31 Trihexyltetradecylphospho-
nium hydrogen sulfate ([P66614][HSO4]) was supplied by Cytec.
1-Butyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}-
imide ([C4mim][NTf2]) and trihexyltetradecylphosphonium
bis{(trifluoromethyl)sulfonyl}imide ([P66614][NTf2]) were
formed by metathesis from [C4mim]Cl and [P66614]Cl (Cytec),
respectively, according to literature methods.32 The base func-
tionalized ionic liquid 5-diisopropylamino-3-oxapentyl)-
dimethylethylammonium bis{(trifluoromethyl)sulfonyl}imide
(BIL) shown in Fig. 1 was synthesized as previously re-
ported.33 In all cases prior to reaction the ionic liquids were
dried under vacuum at 50 1C overnight. All ionic liquids
contained o0.16 wt% water determined by Karl–Fischer
analysis and o5 ppm halide by suppressed ion chromato-
graphy. All other reagents were used as received.
Catalyst characterization
The solid catalysts were characterized by nitrogen adsorption–
desorption isotherms at 77 K (Micromeritics ASAP 2000) after
out-gassing the samples at 393 K for 12 h.
The XPS spectra were recorded using a Kratos Axis
UltraDLD spectrometer with monochromatic Al-Ka radia-
tion. The data were analyzed using Casa-XPS (v2.3.13)
employing a Shirley-background subtraction prior to fitting.
EXAFS data were collected at the Synchrotron Radiation
Source in Daresbury, UK, using station 9.3. The spectra were
recorded at the Au LIII edge using a double crystal Si(111)
monochromator. Scans were collected and averaged. Data
were processed using EXCALIB which was also used to
convert raw data into energy vs. absorption data. EXBROOK
was used to remove the background. The analysis of the
EXAFS was performed using EXCURV98.34 The gold con-
centration was determined by ICP-AES.
Catalytic tests
Typically 0.26 mmol of acetylenic acid was stirred with 2.5 mol%
[Cnmim][AuCl4] dissolved in 0.5 g [Cnmim]Cl in air at
room temperature, until completion of the reaction. After
the completion of the reaction, the reaction products
were extracted three times with diethyl ether and the
solvent completely removed under vacuum to give the
corresponding lactone. 1H and 13C NMR were recorded
on a Bruker AV 300 instrument operating at 300 Hz to
identify the products. The measured NMR spectra for
3-phenyl-5-methylene-g-butyrolactone (2a), 3-n-butyl-3-ethoxy-
carbonyl-5-methylene-g-butyrolactone (2b), 3-methoxycarbonyl-
5-methylene-3-(3 0-phenylprop-2 0-enyl)-g-butyrolactone (2c),3-allyl-3-methoxycarbonyl-5-methylene-g-butyrolactone (2d), 3-
benzyl-3-ethoxycarbonyl-5-methylene-g-butyrolactone (2e) and
3-methoxycarbonyl-5-methylene-g-butyrolactone (2f) were in
good agreement were those reported previously.19–21 In all
cases, no cyclization is observed in the absence of any of the
gold catalysts irrespective of the solvent used.
Results and discussion
Catalysts characterization
The beta zeolite used in these experiments had a surface area
of 464 m2 g�1 and a pore volume of 0.96 cm3 g�1. After the
deposition of gold (4 wt%) the surface area decreased to
383 m2 g�1 and the pore volume to 0.80 cm3 g�1. TEM
analysis of this material shown an uniform size distribution
with an average of 3 nm. The characterization of IL-stabilized
gold(III) chloride was examined using TEM, XPS and
EXAFS. Fig. 2 shows the XPS spectra of the Au 4f photo-
electron emission corresponding to the mixture of the catalyst
([C6mim][AuCl4]) with the ionic liquid [C6mim]Cl after the
reaction. The binding energies of Au 4f7/2 and Au 4f5/2 levels
were located at 90.0 eV and 86.3 eV, respectively. EXAFS of
[C6mim][AuCl4] dissolved in [C6mim]Cl showed a single peak
at 0.22 nm associated with 4 chlorine atoms in the first
coordination shell. During reaction, this peak decreases
slightly and a small decrease in the white line of the XANES
is observed. This variation may indicate that chlorine is being
replaced by a lighter element such as coordination by the
substrate during reaction, as would be expected. TEM analysis
is in agreement with the XPS and EXAFS measurements and
showed no nanoparticle formation. These observations are
Fig. 1 Schematic of the cation of the basic ionic liquid (BIL) used as
solvent for the cyclization of the functionalized acetylenic substrates
1a and 1b.
Fig. 2 The XPS spectra in the Au 4f region of the [C6mim][AuCl4]
after reaction.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 102–106 | 103
consistent with the presence of a dissolved Au(III) species with
B4 chlorines in the first coordination sphere.35
Catalytic tests
Table 1 shows the activity of Au/beta in a range of ionic
liquids for the cyclization of the functionalized acetylenic
substrates 1a and 1b.
Although cycloisomerization of substrate 1a did occur in the
BIL and [P66614][HSO4] with conversions of 75 and 70%,
respectively, (Table 1, entries 1, 2), the ILs could not be
separated from the reaction products due to the high solubility
of the ionic liquid–substrate mixture in diethyl ether. In the
case of the reaction performed in [C4mim][NTf2] and
[P66614][NTf2], the ionic liquid could only be partially sepa-
rated from the reactants and products and showed conversion
of the substrate of 80% and 70%, respectively (Table 1, entries
3, 4). In each case, the conversions were obtained from NMR
determination in the ionic liquid. [C6mim]Cl was found to
separate efficiently from diethyl ether and the cycloisomeriza-
tion of 1a (Table 1, entry 5) resulted in the desired compound
2a in 79% isolated yield.
Due to the ease of workup [C6mim]Cl was also examined as
a medium for the cyclization of 1b over Au/beta. From an
analysis of the 1H NMR, a conversion of 91% was obtained
with an isolated yield of the lactone of 58% (Table 1,
entry 6). Similar activities and selectivities were also found in
conventional molecular solvents, such as acetonitrile (Table 1,
entry 7).
The heterogeneously catalyzed reaction results were com-
pared with the use of the ionic liquid as a catalyst in the form
of the tetrachloroaurate based ionic liquids. Since [C6mim]-
[AuCl4] is a solid at room temperature, [C6mim]Cl was used as
solvent. The results are summarised in Table 2.
To date, it has only been possible to exclude a base from the
homogeneous reaction conditions if the two substituents on a
tetrahedral centre were of a significant size, as understood by
the Thorpe–Ingold effect.36 In the case of the ionic liquid
catalyst system, all the g-acetylenic carboxylic acids examined
were cleanly transformed to the corresponding g-alkylideneg-butyrolactones. Moreover, similar activity and selectivity
was found for the ionic liquid catalyst compared with
the homogeneous AuCl catalysts system in acetonitrile.15
Irrespective of the alkenyl side chain length the lactones were
isolated in 85–96% yields (Table 2, entries 1–5) even at room
temperature. In all cases, the catalytic amount of gold ionic
liquid used in these reactions was equivalent to the amount
used under heterogeneous conditions. No side reactions were
observed on the alkenyl side chains during the course of the
reaction.
Using the gold based ionic liquid system, complete trans-
formations of 2-prop-2-ynylmalonic acid monomethyl ester 1f
with an 84% isolated yield (Table 2, entry 6) and of 2-phenyl-
pent-4-ynoic acid 1a with an 96% isolated yield (Table 2, entry 7)
after 1 h at room temperature were obtained. Similar results
were found for the reaction of 1a in the presence of [C2mim]-
[AuCl4], [C4mim][AuCl4] and [C18mim][AuCl4] at room
temperature. These results for unsubstituted substrates are
comparable with those obtained under heterogeneous Au2O3
conditions (3 h),21 or homogeneous AuCl/K2CO3 conditions
(2 h)20 and show significant advantages over other homo-
geneous gold chloride based catalysts.19 In the case of the
homogeneous catalysts, the formation of degradation pro-
ducts or the corresponding methylketone was observed for
the sterically unhindered substrates and the reaction only
occurred in the presence of a base. In the ionic liquid catalyzed
reactions, excellent reactivity was found without the need for
additives. Furthermore, the IL-catalysts were recycled three
times without any loss in conversion or yields.
A comparison of the homogeneous reaction (Table 2, entries
7 and 1) with that of the heterogeneous reaction (Table 1,
entries 5 and 6) indicates that the former is more active
requiring a lower temperature and resulting in a higher con-
version/yield after 1 h. This is reflected in the turnover
frequencies (TOF) for the homogeneous catalysts compared
with the supported catalysts which are B19.8 h�1 (at RT) and
B1.3 h�1 (at 40 1C), respectively, for the formation of 2b, for
example. The lower rate is unlikely to be due to mass transfer
Table 1 Cyclization of functionalized acetylenic substrate overAu/beta in a range of ionic liquids
Entry R1 R2 Solvent Product Yielda (Conv.) (%)
1 Ph H BIL 2a (75)b
2 Ph H [P66614][HSO4] 2a (70)b
3 Ph H [P66614][NTf2] 2a (70)b
4 Ph H [C4mim][NTf2] 2a (80)b
5 Ph H [C6mim]Cl 2a 79 (83)6 CO2Et n-Bu [C6mim]Cl 2b 58 (91)7 CO2Et n-Bu CH3CN 2b 60 (90)
a Isolated yield. b IL inseparable from the system.
Table 2 Au-catalyzed cyclization of functionalized carboxylic acids
Entry R1 R2 Product Temp./1C Time/h Yielda (%)
1 CO2Et n-Bu 2b RT 1 962 CO2Me Cinnamyl 2c 40 2 903 CO2Me Allyl 2d RT 2 914 CO2Et Bn 2e RT 1 855 CO2Et Bn 2e RT 2 956 CO2Me H 2f RT 1 847 Ph H 2a RT 1 96
a Isolated yield.
104 | New J. Chem., 2009, 33, 102–106 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
limitations in the heterogenous case which has been observed
in other solid catalyzed reactions in ionic liquids37 as the
acetonitrile reaction (Table 1, entries 6 and 7) also shows
reduced activity. The higher TOF may be expected due to the
inaccessibility of the bulk gold atoms; however, even taking
into account the lower dispersion of the heterogeneous cata-
lyst, which contains 3 nm gold particles, the homogeneous
catalyst has a higher intrinsic activity compared with the
heterogeneous system.
Scheme 1 shows a proposed mechanism for the gold based
ionic liquid catalyzed reaction. From the XPS and EXAFS,
the active catalyst is thought to be Au3+ which activates the
acetylenic group.20 The ionic liquid provides a medium which
eliminates the use of a base. This role of the ionic liquid may
be to shift the acid equilibrium of the starting material to
favour the carboxylate anion, either by hydrogen bonding
with the chloride, for example, or via stabilizing the anion in
the ionic environment. This increase in concentration of the
active intermediate allows reaction and activation of the
carbon–carbon triple bond by the Au3+ centre and nucleo-
philic addition to the alkyne. After the cyclization a hydrogen
mediated demetalation ends the catalytic cycle. It should be
noted that the scheme does not preclude the possibility that the
cation of the ionic liquid may play an important role in
creating the active catalyst. For example, imidazolium based
ionic liquids have been shown to form carbenes with homo-
geneous catalysts in C–C bond forming reactions.10
Conclusions
Gold chloride based ionic liquids have been shown to be very
active catalysts in the cyclization of acetylenic substrates. The
ionic liquid medium prevents nanoparticle formation via
stabilization of the gold in the form of isolated species by
chlorine coordination. The ionic liquid also allows activation
of the carboxylic acid in the starting material and provides a
medium which eliminates the need for added base in order to
cyclize unhindered acetylenic carboxylic acid.
Acknowledgements
This work was financially supported by the Consiliul National
al Cercetarii Stiintifice din Invatamantul Support (CNCSIS)
and the Centre National de la Recherche Scientifique (CNRS),
a Portfolio partnership from the EPSRC and an EU transna-
tional grant. CCLRC are thanked for providing EXAFS
beamtime.
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Scheme 1 The mechanism of cyclization of acetylenic carboxylic acid
using Au3+ derived catalysts. It should be noted that representation of
the gold as [Au] is for illustrative purposes only and will exist in the
form of a [AuClx]y+ complex.
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106 | New J. Chem., 2009, 33, 102–106 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Magnetically moveable bimetallic (nickel/silver) nanoparticle/carbon
nanotube composites for methanol oxidationw
Guan-Ping Jin,*ab Ronan Baron,a Neil V. Rees,a Lei Xiaoa
and Richard G. Compton*a
Received (in Durham, UK) 22nd August 2008, Accepted 18th September 2008
First published as an Advance Article on the web 31st October 2008
DOI: 10.1039/b814630f
Multi-walled carbon nanotubes (CNTs) functionalized both by nickel and silver nanoparticles
were obtained using a single step chemical deposition method in an ultrasonic bath. The new
composite material was characterized by means of scanning electron microscopy (SEM), X-ray
diffraction (XRD) and cyclic voltammetry (CV). The electroactivity of the bi-functionalized CNTs
multi-walled carbon nanotubes was assessed in respect to the electrooxidation of methanol. It was
found that the carbon nanotube supported silver nanoparticles have significantly higher catalytic
properties than the bulk metal of the same surface area. Furthermore, it was shown that the
presence of only a very small proportion of magnetic nickel nanoparticles (1.5% of the total
number of metallic nanoparticles) allows the bi-functionalized carbon nanotubes to be moved
magnetically in solution, making them easily recoverable after use whilst keeping an optimal
electrocatalytic surface area.
1. Introduction
The synthesis of magnetic nanomaterials has attracted con-
siderable attention in the last few years. One of the reasons for
that interest is that magnetic material can be moved using a
magnet and which makes the considered material recoverable
both for economical and environmental issues.1–4 Nanomater-
ials that can be magnetically driven are also very promising
for medical applications, such as drug delivery5 or complex
biomanipulations.6
The functionalization of carbon materials with magnetic
particles is particularly attractive due to the properties and
wide use of carbon materials. In particular, magnetic nano-
particles have been synthesized on the surface of carbon
nanotubes using various different methodologies.6–10
As far as the use of magnetic nanomaterials in electro-
chemistry is concerned, there have been only a limited number
of reports on the matter. Most notably Willner et al. studied
the use of hydrophobic magnetic nanoparticles capable of
blocking an electrode surface11–13 and Wang et al. addressed
the use of magnetic nickel nanoparticles both for on-demand
control of electrocatalytic processes and to reduce electrode
surface fouling.14–16
A lot of interest is devoted to methanol electrocatalytic
oxidation as it can be used in fuel cells and both bulk silver and
silver nanoparticles are known to be efficient electrocatalysts
for methanol oxidation in alkaline solutions17,18 with less
poisoning observed than at platinum materials.19 However,
even though silver is much less expensive than platinum its
cost remains an issue.
In order to get the benefits of both the magnetic properties
of magnetic nanoparticles and the catalytic properties of
AgNPs we designed a hybrid material, which contains both.
NiNPs and AgNPs were synthesized on CNTs using a one-
pot chemical deposition in an ultrasonic bath using a
methodology recently developed in our laboratory for the
synthesis of NiNPs on glassy carbon microspheres.20 To
date, this publication is the first report of the bi-functionaliza-
tion of CNT with NiNPs and AgNPs. In addition, the
electrocatalytic oxidation of methanol at the new hybrid
material was studied.
2. Experimental
2.1 Reagents and equipment
Bamboo-like multi-walled carbon nanotubes (CNTs, diameter
30 � 10 nm, 5–20 mm length, o95% purity) were purchased
from NanoLab (Brighton, MA, USA). Nickel(II) chloride
(NiCl2, 99.9%) was obtained from Alfa Aesar (Heysham,
UK). L-Ascorbic acid (99.7%) and silver nitrate were supplied
by BDH (Poole, UK). Nafion was purchased from Aldrich
(Poole, UK). Acetonitrile (ACN) was supplied by Sigma-
Aldrich (Gillingham, UK). All the reagents were used without
further purification. All solutions were prepared using purified
water from Vivendi UHQ grade water system with a resistivity
of not less than 18.2 MO cm.
Electrochemical measurements were recorded using an
Autolab PGSTAT 30 computer-controlled potentiostat with
a standard three-electrode setup. Either a home-made 4 mm
aDepartment of Chemistry, Physical and Theoretical ChemistryLaboratory, Oxford University, South Parks Road, Oxford,UK OX1 3QZ. E-mail: [email protected];Fax: 0044-1-865 275410; Tel: 0044-1-1865 275413
bAnhui Key Laboratory of Controllable Chemistry Reaction &Material Chemical Engineering, School of Chemical Engineering,Hefei University of Technology, Hefei, 230009, P. R. China.E-mail: [email protected]; Fax: 0086-0551-2902450;Tel: 0086-551-2901450
w Electronic supplementary information (ESI) available: Videos S1–3.See DOI: 10.1039/b814630f
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 107–111 | 107
PAPER www.rsc.org/njc | New Journal of Chemistry
diameter disc paraffin-impregnated graphite electrode21 or a
0.08 mm diameter disk bulk silver served as working electro-
des. Paraffin-impregnated graphite electrodes have similar
behaviour than other common graphite electrodes and have
been chosen here because they are easy to fabricate and it is
easy to renew their surface by a polishing step. A platinum
wire was used as a counter electrode, and a silver wire used as
the reference electrode completed the cell assembly. The
paraffin-impregnated graphite electrode surface was renewed
by successive mechanical polishing steps on alumina powders
(Micropolish II, Buehler) of 1 to 0.3 mm in diameter. The
electrode was sonicated for 5 min in deionized water after each
polishing step. All experiments were carried at a temperature
of 20 � 1 1C. All the solutions were degassed with nitrogen
prior to the electrochemical recordings.
Scanning electron microscopy (FEG-SEM, tungsten fila-
ment as electron source, acceleration voltage 20 keV) images
and energy dispersion X-ray spectra analysis were performed
using a JEOL 6300 F instrument. X-Ray diffraction patterns
(XRD) were collected on a PANalytical X’Pert instrument
with 40 kV and 40 mA settings.
Sonication was obtained using a D-78224 Singen/Htw
sonicator (50/60 Hz, 80 W, UK).
2.2 Ultrasonic synthesis of silver and nickel nanoparticles
on CNTs
The nickel and silver nanoparticles were synthesized onto
the surface of CNTs using the following protocol: The CNTs
were sonicated in conc. HClO4 + HNO3 (3:7, v:v) for
7 h in order to oxidize their surface, they were then filtered
and extensively washed with deionized water to pH 7, and
dried in air. Then, 2.9 mg NiCl2, 1.7 mg AgNO3 and 2.0 mg
oxidized CNTs were added to 60 mL of acetonitrile in an
airtight glass flask. The mixture was sonicated for one hour.
4.0 mg of L-ascorbic was then added in the flask and the pH
was adjusted to 5.2 using 1 M NaOH. The reaction was
allowed to proceed for 5 min at 65 1C under sonication.
Finally, the products were separated by centrifugation,
washed with acetonitrile and deionized water to remove any
unreacted species. The multi-walled carbon nanotubes deco-
rated with silver and nickel nanoparticles (AgNPs,NiNPs/
CNTs) were allowed to air-dry for 24 h prior to use. Multi-
walled carbon nanotubes decorated only with silver (AgNPs/
CNTs) or nickel nanoparticles (NiNPs/CNTs) were obtained
using the same method.
2.3 Modification of the paraffin-impregnated graphite
electrodes with CNTs
Films of CNTs on the surface of paraffin-impregnated
graphite electrodes were obtained as follows: 2 mg of CNTs
decorated with nanoparticles was suspended in 2 mL of
Nafion (0.05%) and acetonitrile solution to form a ‘‘casting’’
suspension. The casting suspension was then briefly sonicated
for 2 min in order to disperse the CNTs decorated with
nanoparticles. Some of the suspension was then pipetted onto
the surface of a freshly polished paraffin-impregnated graphite
electrodes and let to dry in air.
2.4 Movement of the AgNPs,NiNPs/CNTs composite
material
The AgNPs,NiNPs/CNTs (AgNPs/CNTs, NiNPs/CNTs)
composite materials were pipetted onto a 1.0 mm thick glass
surface with some water. A magnet (NdFeB alloy rod magnet,
purchased from e-magnets UK Ltd, Sheffield, UK) was posi-
tioned directly below the glass surface and moved by an
electronic motor. The directed movement of the nanocom-
posites was observed and recorded using an optical microscope
with a Bressler Visiomar video camera (160� magnification
using a 320 � 240 pixel frame).
3. Results and discussion
3.1 Synthesis and microscopic characterization of the
nanoparticle-modified CNTs
The synthesis of the silver and nickel nanoparticles on the
surface of the CNTs was obtained following the steps noted in
Scheme 1. First the CNTs are treated with concentrated nitric
and perchloric acids to generate carboxylic groups on their
edges and defects. The negatively charged sites chelate silver
and nickel cations added to the solution. It is then expected
that the addition of ascorbic acid as a mild reducing agent in
the presence of ultrasound results in the production of small
nickel and silver nanostructures on the surface of the CNTs.
Similar experimental routes were followed for the synthesis of
nickel or silver nanoparticles separately on the CNTs.
A scanning electronic microscopy analysis of the samples
reveals that silver and nickel nanoparticles of 100 nm in
diameter in average are obtained on the CNTs (Fig. 1). The
EDX (Fig. 2) and XRD spectra of the samples (Fig. 3) confirm
the presence of both silver and nickel nanoparticles. It can be
noticed that the peaks for Ni (111) and Ag (111) are larger
than the other peaks, which reveals that the most common
nanoparticles on the CNTs are face-centered cubic (fcc)
nickel and silver. The average crystallite size calculated using
Scherrer’s equation from the width at half peak maximum for
the NiNPs is 30 � 25, and 25 � 15 nm, respectively for the
Scheme 1 Preparation of multi-walled carbon nanotubes (CNTs)
functionalized both by nickel and silver nanoparticles using a single
step chemical deposition method in an ultrasonic bath and subsequent
immobilization of the new composite material on an electrode surface.
108 | New J. Chem., 2009, 33, 107–111 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
NiNPs/CNTs and the AgNPs,NiNPs/CNTs and 20 � 10 nm
for the AgNPs of the AgNPs/CNTs and the AgNPs,NiNPs/
CNTs. It can be further stated on the nature of the silver and
nickel nanoparticles that those particles are distinct and do not
crystallise in the form of alloys, as it is well known that Ni and
Ag are immiscible in both the solid and liquid phases.22
3.2 Electrode modification and characterization
The electrode surfaces were modified by the decorated CNTs
in a Nafion film by following the protocol described in the
Experimental section. The electrode surfaces can be charac-
terized electrochemically by oxidizing the metallic nanoparti-
cles. Some metal oxides have a well-defined and specific
reduction potential and the corresponding reduction peak
can be used to estimate the surface area of specific metals.
Fig. 4 shows the cyclic voltammograms that were obtained in
0.1 M NaOH for the various modified electrodes. It can
be observed that the voltammogram corresponding to the
AgNPs,NiNPs/CNTs modified electrode corresponds to the
superposition of the characteristic features of both the AgNPs/
CNTs and the NiNPs/CNTs modified electrodes. Using the
literature values of 790 and 270 mC cm�2 for the charge passed
per unit area of surface area of nickel and silver,23–25 we can
estimate the total surface area of each of the metals for the
AgNPs,NiNPs/CNTs/Nafion material. The average loading
of the nickel and silver nanostructures on the CNTs were
estimated to be, respectively in the order of 3.4 � 10�2 and
2.2 cm2 mg�1. Which then shows that, for nanoparticles of
about the same size, the NiNPs represent only 1.5% of the
total number of nanoparticles.
3.3 Electrocatalysis
The electroactivity of the mono- and bi-functionalized multi-
walled carbon nanotubes was assessed and compared with the
Fig. 1 SEM images of the multi-walled carbon nanotubes functionalized both by nickel and silver nanoparticles (AgNPs,NiNPs/CNTs). The
square on Fig. 1(A) indicates where the EDX spectrum in Fig. 2 was obtained.
Fig. 2 EDX spectra of (A) AgNPs,NiNPs/CNTs, (B) NiNPs/CNTs
and (C) AgNPs/CNTs.
Fig. 3 XRD spectra of (a) Ni/CNTs, (b) AgNPs/CNTs and (c)
AgNPsNi/CNTs.
Fig. 4 Cyclic voltammetry (30th cycle) in 0.1 M NaOH at a 4 mm
diameter paraffin-impregnated graphite electrode modified with
(a) 20 mL CNTs/Nafion, (b) 20 mL NiNPs/CNTs/Nafion, (c) 20 mLAgNPs/CNTs/Nafion and (d) 80 mL AgNPs,NiNPs/CNTs/Nafion
casting solutions. Scan rate: 50 mV s�1.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 107–111 | 109
electroactivity of bulk silver macroelectrodes in respect
to the electrooxidation of methanol. The cyclic voltam-
mograms obtained for the second cycle are shown in Fig. 5.
We choose to present the second cycle as a non-negligable
decrease in intensity (ca. 25%) is observed from the first cycle
to the second one. Measurements show a decrease of less
than 10% is then observed between the second and the
twentieth cycle. The electrochemical characterization of the
modified electrode surfaces, conducted independently as
described above, provides valuable data to compare the
electrocatalytic efficiency of the different materials. Indeed,
the catalytic currents obtained can be normalized with the
total metal surface area to provide the current density per unit
of electroactive surface (Table 1). The data reported in Table 1
show that the AgNPs/CNTs/Nafion- and AgNiNPs/CNTs/
Nafion-modified electrodes have similar properties, with a
current density about more than ten times higher than the
current density obtained at the bulk silver macroelectrode.
Such a higher electrocatalytic property can partially be
explained by the higher substrate diffusion that we expect to
observe at dispersed nanoparticles.26–31 Furthermore it has to
be said from the results reported in Table 1 that the experi-
mental results show that NiNPs and AgNPs have similar
electrocatalytic properties towards the electrooxidation of
methanol.
3.4 Characterization of magnetically driven movement of the
AgNPs,NiNPs/CNTs composites
The possibility of magnetically recovering the electrocatalytic
nanomaterial was explored by assessing the possibility to move
it with a magnet using the setup described in the Experimental
section. As it can be seen in Fig. 6 and Video S1 (ESIw), withthe shift of a magnet positioned directly below the glass
surface, the AgNPs,NiNPs/CNTs composites move from right
bottom to middle, then, to left up in the video screen,
suggesting an obvious movement for AgNPs,NiNPs/CNTs
composites on the surface of glass. The same test was
undertaken for the NiNPs/CNTs and AgNPs/CNTs nano-
composites. A similar response can be seen for NiNPs/CNTs
composites (Video S2, ESIw). However, no move was observed
for AgNPs/CNTs nanocomposites (Video S3, ESIw). It is thenpossible to conclude that the bifunctionalisation of the CNTs
provides the possibility to magnetically drive them to a specific
location in a solution. This added property to the new
electroactive nanomaterial allows, for example, the recovery
of the catalyst once the reaction has taken place.
4. Conclusions
Multi-walled carbon nanotubes functionalized either by nickel or
silver nanoparticles or by both were obtained using a single step
chemical deposition method in an ultrasonic bath. The electro-
activity of the bi-functionalized CNT multi-walled carbon nano-
tubes was assessed in respect to the electrooxidation of methanol.
It was found that they have significantly higher catalytic proper-
ties than the bulk silver of the same surface area. Furthermore, it
was shown that the addition of a minute fraction (1.5%) of
NiNPs in respect to the total number of nanoparticles adds to
their electrocatalytic properties the possibility to easily move
them in solution using a magnet. The bi-functionalized carbon
nanotubes are then easily recoverable after use.
Table 1 Catalytic performance for methanol oxidation of variouselectrode architectures; A is the metal total surface area estimated byelectrochemical oxidation of the surface, Ip is the peak current valuemeasured for a voltammetric scan obtained at 50 mV s�1 in 0.56 Mmethanol and 0.1 M NaOH and Jp is the corresponding currentdensity in respect to the total surface of silver
Electrode A/cm2 Ip/mA Jp/mA cm�2
Ag bulk 0.16 � 0.05 9.28 � 10�2 0.58 � 0.2NiNPs/CNTs/Nafion 0.29 � 0.1 3.00 10.3 � 2AgNPs/CNTs/Nafion 0.30 � 0.1 3.3 11.0 � 2AgNPs,NiNPs/CNTs/Nafion 0.56 � 0.2 4.14 7.4 � 2
Fig. 6 Optical microscopy images of the AgNPs,NiNPs/CNTs material, taken at 10 s time-intervals and following the movement of a magnet
going forward (images (A) to (C)) and then going backward (images (D) to (F)). These pictures were extracted from Video S1 (ESIw).
Fig. 5 Second cycle cyclic voltammetric curves obtained in 0.56 M
methanol and 0.1 M NaOH at a 0.08 mm diameter silver electrode
(curve a) and at a 4 mm diameter paraffin-impregnated graphite
electrode modified with casting solutions made of 80 mL CNTs/Nafion
(curve b), 80 mL NiNPs/CNTs/Nafion (curve c), 80 mL AgNPs/CNTs/
Nafion (curve d) and 120 mL AgNPs,NiNPs/CNTs/Nafion (curve e).
Scan rate: 50 mV s�1.
110 | New J. Chem., 2009, 33, 107–111 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Acknowledgements
G.-P. J. gratefully acknowledges financial support from
Natural Science Foundation of Anhui Province of China
(No. 070415210), Science and Technology Program Founda-
tion of Hefei City (No. 20071032), and Doctor Foundation of
Hefei University of Technology (2005). R. B. and N. V. R. are
grateful to EPSRC for funding.
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 107–111 | 111
Microwave-assisted facile synthesis of discotic liquid crystalline
symmetrical donor–acceptor–donor triads
Satyam Kumar Gupta, V. A. Raghunathan and Sandeep Kumar*
Received (in Durham, UK) 23rd May 2008, Accepted 11th July 2008
First published as an Advance Article on the web 8th September 2008
DOI: 10.1039/b808750d
We report the synthesis and characterization of two series of novel triphenylene–anthraquinone-
based symmetric discotic liquid crystalline trimers. These triads were prepared using microwave
dielectric heating. Conventional heating under similar reaction conditions failed to produce
desired products. To the best of our knowledge, these are the first donor–acceptor–donor triads
in which all the three components represent discotic mesogenic moieties. Chemical structures of
these discotic oligomers have been characterized by spectral techniques and elemental analysis.
The thermotropic liquid crystalline properties of these donor–acceptor–donor triads were
investigated by polarizing optical microscopy and differential scanning calorimetry. They exhibit
a columnar mesophase over a wide range of temperature. The columnar hexagonal mesophase
structure of these discotic oligomers has been elucidated with the help of X-ray diffraction studies.
Introduction
The notable improvement in the performance of electronic
devices based on organic semiconductors has attracted great
interest in recent years.1 The improved efficiency of organic
devices has origins ranging from appropriate molecular design
to well-defined structured layers essential for effective charge
transport. Recently there have been tremendous efforts to
achieve both p-type (hole conducting) and n-type (electron
conducting) properties in organic semiconducting materials
which are crucial for molecular electronics. One elegant
approach for such materials is to covalently link electron
donor and electron acceptor components at molecular level.
These kinds of materials are expected to behave as intrinsic,
non-composite p/n-type semiconductors. Such chemical tailor-
ing could lead to the development of other molecular archi-
tectures and it is envisaged that the combination of covalent
chemistry and self-assembly will be crucial for the develop-
ment of nano-engineered functional materials for electronic
applications.1 Among the diverse semiconductors, discotic
liquid crystals (DLCs) play an important role in the design
of electronic devices.2 Discotic liquid crystals are unique
nanostructures with remarkable electronic and optoelectronic
properties. Due to the co-facial stacking of aromatic cores,
disc-like molecules self organize into one dimensional colum-
nar wire and these columns in turn arrange themselves in
various two-dimensional lattices. The transport along the
columnar axis is much faster than between the columns. Due
to their relatively high charge carrier mobility, tendency to
form highly order films of various thickness and self healing of
defects owing to their dynamic nature, discotic mesogens have
been considered as attractive candidates for applications in
organic electronic devices such as photovoltaic solar cells, light
emitting diodes and field effect transistors.2
Microwave-assisted high-speed chemical synthesis has
attracted a considerable amount of attention in the past decade.
Almost all types of organic reactions have been performed
using the efficiency of microwave-flash heating. This is not
only due to the fact that reactions proceed significantly faster
and more selectively than under conventional thermal condi-
tions but also because of the operational simplicity, high yield
of products and cleaner reactions with easier work-up. A large
number of review articles provide extensive coverage of the
subject.3 Recently we and others have reported the synthesis
of a variety of liquid crystalline materials using microwave
dielectric heating.4
Very recently a great deal of attention is being paid to liquid
crystal oligomers.5 The physical properties of liquid crystalline
oligomers are significantly different from those of conven-
tional low molar mass liquid crystals. Their purification and
characterization are simple, and due to the restricted motion
of their components liquid crystal oligomers provide and
stabilize a variety of fluid phases with fascinating functions.
Further, an oligomeric approach provides a wide flexibility in
molecular design towards multifunctional liquid crystals.
However, compared to the number of calamitic oligomers,
discotic oligomers are rare. In this context we are interested in
the design and synthesis of novel functional discotic oligo-
meric materials and their mesophase behavior. Our molecular
design is such that it contains the well studied electron rich
triphenylene moiety6 and electron deficient anthraquinone7 as
the hole and electron transporting components, respectively.
These molecular double-cables, owing to their incommensu-
rate core sizes, may stack one on top of the other in the
columns to give columnar versions of double cable polymers,8
which could eventually provide side-by-side percolation
pathways for electrons and holes in solar cells. Here, we
report the synthesis and mesomorphism of novel triphenylene–
anthraquinone–triphenylene discotic liquid crystalline symmetric
Raman Research Institute, C.V. Raman Avenue, Sadashivanagar,Bangalore, 560 080, India. E-mail: [email protected];Fax: +91 80 23610492; Tel: +91 80 23610122
112 | New J. Chem., 2009, 33, 112–118 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
trimers. To the best of our knowledge, these are the first
donor–acceptor–donor triads in which all the three compo-
nents represent discotic mesogenic moiety.
Experimental
General information
Chemicals and solvents (AR quality) were used as received
without any further purification. Microwave irradiation was
performed in an unmodified household microwave oven.
(LG, MS-192W). However, commercial microwave reactors
for organic reactions are now available which provides
adequate mixing and control of reaction parameters such as
temperature and pressure. Column chromatographic separa-
tions were performed on silica gel (230–400 mesh). Thin layer
chromatography (TLC) was performed on aluminum sheets
precoated with silica gel (Merck, Kieselgel 60, F254). Chemi-
cal structure characterization of the compounds was carried
out through a combination of 1H NMR, 13C NMR (Bruker
AMX 400 spectrometer) and elemental analysis (Carlo-Erba
EA1112 analyzer). 1H NMR spectra were recorded using
deuterated chloroform (CDCl3) as solvent. Tetramethylsilane
(TMS) was used as an internal standard. The transition
temperatures and associated enthalpy values were determined
using a differential scanning calorimeter (DSC; Perkin-Elmer,
Model Pyris 1D) which was operated at a scanning rate of
5 1C min�1 both on heating and cooling cycles. The apparatus
was calibrated using indium (156.6 1C) as a standard. The
textural observations of the mesophase were carried out using
polarizing light microscopy (Olympus BX51) provided with a
heating stage (Mettler FP82HT) and a central processor
(Mettler FP90). X-Ray diffraction studies (XRD) were carried
out on unoriented samples using Cu-Ka (l = 1.54 A) radia-
tion from a Rigaku Ultrax 18 rotating anode generator
(5.4 kW) monochromated with a graphite crystal. The samples
were held in sealed Lindemann capillary tubes (0.7 mm
diameter) and the diffraction patterns were collected on a
two-dimensional Marresearch image plate.
Synthesis of trimers
Rufigallol 2, 1,5-dihydroxy-2,3,6,7-tetraalkoxy-9,10-anthra-
quinone 3, hexaalkoxytriphenylene 4, monohydroxypenta-
alkoxytriphenylene 5 and o-bromo-substituted triphenylene
6 were prepared as reported by us previously.9 All the trimers
were prepared following same method which involves alkyla-
tion of 1,5-dihydroxy-2,3,6,7-tetraalkoxy-9,10-anthraquinone
3 with terminal bromo-substituted triphenylene 6 using micro-
wave dielectric heating. A typical procedure for the synthesis
of a representative example 7a10 is given below. The suffix
number in the series 7a and 7b, represents the number of
carbon atoms in the peripheral chains attached with central
anthraquinone moiety (R in the structure 7, Scheme 1).
A mixture of compound 6a (n = 9) (300 mg, 0.30 mmol),
3 (R= C10H21) (43 mg, 0.05 mmol) and Cs2CO3 (200 mg, 0.61
mmol) in NMP (0.5 mL) was irradiated in a microwave oven
for 30 s. The vial was removed from the oven and left to stand
for about 1 min and again irradiated for 30 s. This process was
repeated for 20 times until the reaction was complete (TLC
monitoring). The cooled reaction mixture was then poured
into an excess of distilled water and extracted with chloroform.
The organic extract was dried over anhydrous sodium sulfate,
concentrated and the product was purified by repeated column
chromatography over silica gel (eluent: 4% ethyl acetate in
hexane). Solvent was then removed in rotary evaporator. The
residue was then dissolved in dichloromethane and the result-
ing solution was added to cold methanol to afford 7a10
(34 mg, 25%). 1H NMR (400 MHz, CDCl3): d 7.83 (s, 12 H),
7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz,
4 H), 4.06 (t, J=6.2Hz, 8 H), 1.94 (m, 32H), 1.77 (q, J=7.5Hz,
4 H), 0.8–1.6 (m, 190 H). 13C NMR (100 MHz, CDCl3):
d 181.2, 157.5, 153.9, 149.1, 147, 132.7, 123.7, 107.6, 107.1,
77.3, 77, 76.7, 75.9, 74.7, 74.1, 69.8, 69.2, 31.9, 31.7, 30.4, 29.5,
29.4, 26.1, 25.9, 22.7, 21.3, 18.5, 15.9, 14.0. Elemental analysis:
Calc. for C174H276O20, C 77.75, H 10.35. Found: C 77.32,
H 10.53%. All other compounds give satisfactory spectral and
elemental analysis data in accordance with their chemical
structure. Selected data for compound 7a6: 1H NMR: d 7.83
(s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J =
6.4 Hz, 4 H), 4.06 (t, J = 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77
(q, J = 7.5 Hz, 4 H), 0.8–1.6 (m, 158 H). Elemental analysis:
Calc. for C158H244O20, C 77.03, H 9.98. Found: C 76.63,
H 9.98%. 7a7: 1H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23
(t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz, 4 H), 4.06 (t, J =
6.5 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J= 7.8 Hz, 4 H), 0.8–1.6
(m, 166 H). Elemental analysis: Calc. for C162H252O20, C
77.22, H 10.08; Found C 76.91, H 10.04%. 7a8: 1H NMR:
d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14
(t, J = 6.5 Hz, 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H),
1.78 (q, J = 6.9 Hz, 4 H), 0.8–1.6 (m, 174 H). Elemental
analysis: Calc. for C166H260O20, C 77.40, H 10.17. Found: C
77.13, H 9.82%. 7a100: 1H NMR: d 7.83 (s, 12 H), 7.61
(s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.5 Hz,
4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J =
6.9 Hz, 4 H), 0.8–1.6 (m, 190 H). Elemental analysis: Calc. for
C174H276O20, C 77.75, H 10.35. Found: C 77.32, H 10.89%.
7a14: 1H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J=6.5 Hz,
24 H), 4.14 (t, J= 6.3 Hz, 4 H), 4.06 (t, J= 5.6 Hz, 8 H), 1.94
(m, 32 H), 1.77 (q, J = 7.8 Hz, 4 H), 0.8–1.6 (m, 222 H).
Elemental analysis: Calc. for C190H308O20, C 78.35, H 10.66.
Found: C 77.96, H 10.71%. 7b6: 1H NMR: d 7.83 (s, 12 H),
7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.15 (t, J = 6.4 Hz,
4 H), 4.06 (t, J = 6.4 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J =
7.8 Hz, 4 H), 0.8–1.6 (m, 150 H). Elemental analysis: Calc. for
C154H236O20, C 76.83, H 9.88. Found: C 76.37, H 9.89%. 7b7:1H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz,
24 H), 4.14 (t, J = 6.8 Hz, 4 H), 4.06 (t, J = 6.3 Hz, 8 H),
1.94 (m, 32 H), 1.78 (q, J = 7.4 Hz, 4 H), 0.8–1.6 (m, 158 H).
Elemental analysis: Calc. for C158H244O20, C 77.03, H 9.98.
Found: C 76.62, H 10.36%. 7b10: 1H NMR: d 7.83 (s, 12 H),
7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.3 Hz,
4 H), 4.06 (t, J = 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77 (q, J =
7.8 Hz, 4 H), 0.8–1.6 (m, 182 H). Elemental analysis: Calc. for
C170H268O20, C 77.58, H 10.26. Found: C 77.31, H 10.23%.
7b100: 1H NMR: d 7.84 (s, 12H, Ar–H), 7.59 (s, 2 H), 4.23
(t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.3 Hz, 4 H), 4.06 (t, J =
6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77 (q, J= 7.8 Hz, 4 H), 0.8–1.6
(m, 182 H). Elemental analysis: Calc. for C170H268O20, C 77.58,
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 112–118 | 113
H 10.26. Found: C 77.14, H 10.00%. 7b12: 1H NMR: d 7.84
(s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.3 Hz, 24 H), 4.14 (t, J =
6.3 Hz, 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H), 1.77
(q, J = 7.8 Hz, 4 H), 0.8–1.6 (m, 190 H). Elemental analysis:
Calc. for C178H284O20, C 77.91, H 10.43. Found: C 77.78,
H 10.30%. 7b14: 1H NMR: d 7.83 (s, 12 H), 7.59
(s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz,
4 H), 4.06 (t, J = 6.3 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J =
7.6 Hz, 4 H), 0.8–1.6 (m, 198 H). Elemental analysis: Calc. for
C186H300O20, C 78.21, H 10.59. Found: C 78.16, H 10.53%.
Results and discussion
Synthesis
The synthesis of the novel symmetrical trimers was achieved as
shown in Scheme 1. The unequal reactivity of the six phenolic
groups of rufigallol 2, two of which are less reactive by virtue
of being intramolecularly hydrogen bonded to the adjacent
quinone carbonyls, was exploited. Etherification of rufigallol 2
under mild conditions produced 1,5-dihydroxy-2,3,6,7-tetra-
alkoxy-9,10-anthraquinone 3 without alkylating the hydrogen
bonded C-1 and C-5 positions. These tetraalkoxy derivatives
were further alkylated by o-bromo-substituted triphenylenes
with the help of microwave dielectric heating as shown in
the Scheme 1, under mild basic conditions to furnish the
symmetrical trimers within 10 min, which is simple, efficient,
rapid and economic. All attempts to etherify the intramolecu-
larly hydrogen bonded C-1 and C-5 positions with bulky
o-bromo-substituted triphenylene failed under classical
thermal heating conditions even by using strong basic condi-
tions and prolonged reaction times (24 h). For instance,
heating the same reaction mixture in DMF at 100 1C for
48 h or heating a mixture of 3 and 6 in DMF and NaOH or
K2CO3 for 48 h did not furnish any product.
Thermal behavior
The thermal behavior of all the compounds was investigated
by polarizing optical microscopy (POM) and differential scan-
ning calorimetry (DSC). In the case of materials which were
mesomorphic, classical textures of discotic columnar meso-
phases appeared upon cooling from the isotropic liquid as
shown in Fig. 1. These textures are similar to the known
textures for Colh phases. All the trimers contain two identical
triphenylenes substituted with five hexyloxy peripheral chains
linked to the central anthraquinone moiety through a
12- (7a series) or a 10- (7b series) methylene spacer. In both
the series the peripheral alkyl chain lengths around the
anthraquinone core varies from hexyloxy to tetradecyloxy.
The transition temperature and associated enthalpy data
obtained from the heating and cooling cycles of DSC are
collected in Table 1. The peak temperatures are given in 1C
and the numbers in parentheses indicate the transition en-
thalpy (DH) in J g�1. The compound 7a0, without any
peripheral alkyl chains (OR = H) around the central core of
the trimer, does not exhibit any liquid crystalline property. It
melts from crystalline solid state to isotropic liquid state at
Scheme 1 Synthetic route of triphenylene–anthraquinone trimers. 7a Series: OR = H (7a0); R = n-C6H13 (7a6); R = n-C7H15 (7a7); R =
n-C8H17 (7a8); R = n-C10H21 (7a10); R = 3,7-dimethyloctyl (7a100); R = n-C14H29 (7a14); 7b Series: R = n-C6H13 (7b6); R = n-C7H15 (7b7);
R = n-C10H21 (7b10); R = 3,7-dimethyloctyl (7a100); R = n-C12H25 (7a12); R = n-C14H29 (7a14).
114 | New J. Chem., 2009, 33, 112–118 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
39.7 1C on heating and on cooling it crystallizes slowly over a
period of time at room temperature. This could be because the
absence of alkyl chains around the core does not provide the
space filling effect of alkyl chains which is crucial for exhibiting
mesophase behavior in discotic liquid crystals. The highest
homologue of the series 7a14 also does not display any liquid
crystalline property, it passes from crystalline solid state to
isotropic liquid state at 47 1C on heating and on cooling the
isotropic liquid crystallizes at 18.4 1C. This could be because
the longer alkyl chains around the central anthraquinone core
may hinder the self-assembly of molecules. All other members
of the 7a series 7a6, 7a7, 7a8, 7a10 and 7a100 display enantio-
tropic mesophase behavior. In their DSC thermograms, they
display a soft solid to mesophase transition followed by
mesophase to isotropic transition on heating. Upon cooling
they show only isotropic to mesophase transition and the
mesophase remains stable down to room temperature or
partially solidified at low temperature. As a typical example
the DSC thermogram of compound 7a6 is shown in Fig. 2. On
increasing the alkyl chain length around the anthraquinone
core the mesophase to isotropic transition temperatures of the
trimers decrease as shown in the Fig. 3. This could be because
the longer alkyl chains introduce more intracolumnar disorder
and hence core–core unstacking becomes easier.
In series 7b only two trimers 7b6 and 7b7 were found to
display enantiotropic liquid crystalline properties. Compound
7b100 shows monotropic phase behavior. Other trimers 7b10,
7b12 and 7b14 of the series do not exhibit any liquid crystalline
property. They show only crystalline to isotropic and isotropic
to crystalline transitions on heating and cooling, respectively.
This is not surprising as the spacer connecting the donor with
Fig. 1 Optical micrograph of 7a6 at 80 1C on cooling from the
isotropic liquid (crossed polarizer, magnification � 200)
Table 1 Phase transition temperatures (peak, 1C) and associated enthalpy changes (J g�1 in parentheses) of novel symmetrical trimers
Compounda First heating scan First cooling scan
7a6 ss 59.1 (1.6) Colh 104.1(6.0) I I 99.3 (6.4) Colh7a7 ss 37 (1.9) g0 67.4 (1.5) Colh 89.6 (2.4) I I 81.4 (2.4) Colh 6.4 (0.9) ss7a8 ss 47.3 (8.6) Colh 83.0 (2.5) I I 72.1 (3.1) Colh7a10 ss 51.2 (8.6) Colh 59.1 (0.9) I I 53 (2.6) Colh 32.6 (0.9) ss7a100 ss 45.6 (10.6) Colh 69 (2.3) I I 57 (2.6) Colh7a14 Cr 47 (34.2) I I 18.4 (23.0) Cr7b6 ss 41.5 (9.6) Colh 69.3 (1.2) I I 59.7 (1.4) Colh7b7 ss 45 (20.4) Colh 65.8 (2.6) I I 58.6 (2.8) Colh7b10 Cr 47(2.4) Cr0 63 (31.1) I I 31.4 (1.0) Cr0 21.4(0.4) Cr7b100 Cr 70.7 (36.5) I I 45.4 (6.9) Colh7b12 Cr 44.4 (18.1) I I 8.6 (11.2) Cr7b14 Cr 60.1 (33.1) I I 29.7 (28.4) Cr
a See Scheme 1 for chemical structures. ss: semisolid; Cr: crystal; Colh: hexagonal columnar phase; I: isotropic phase.
Fig. 2 DSC thermogram of the trimer 7a6 on heating and cooling
cycles (scan rate 10 1C min�1).
Fig. 3 Variation of phase transition temperatures of 7a6–7a10
with number of carbon atoms in the peripheral alkyl chains of
anthraquinone.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 112–118 | 115
the acceptor is short, and so long peripheral substitution
around the central core can disturb their packing. The absence
of a mesophase in compounds 7a14, 7b10, 7b12 and 7b14
clearly indicates that, when the peripheral chain lengths of the
central core are either equal to or longer than the spacer
length, then these symmetrical trimers do not exhibit any
liquid crystalline property. Shorter alkyl chains around the
central core stabilize the mesophase in these discotic trimers. If
we compare the mesophase stability between compound 7a10
and 7a100 having the same mass unit around the central core,
the compound 7a100 shows a wider mesophase range of
23.4 1C compared to 7.9 1C of compound 7a10. Similarly on
comparing 7b10 and 7b100 we find that compound 7b10 does
not exhibit any liquid crystalline property but compound
7b100 displays a monotropic phase behavior. The above
trimers contain the same mass units around the central core
but the alkyl chain lengths around the central core are
different. Both 7a100 and 7b100 contain shorter chain lengths
i.e. 3,7-dimethyloctyl as compared to 7a10 and 7b10 with
longer decyl chains.
X-Ray diffraction studies
In order to reveal the mesophase structure and hence the
supramolecular organization of these compounds, X-ray dif-
fraction experiments were carried out using unoriented sam-
ples. X-Ray diffraction patterns for all the trimers were
recorded in the columnar phase 10 1C below the clearing
temperature while cooling from the isotropic phase. The
X-ray diffraction patterns of the mesophase exhibited by all
the samples belonging to both the series is supportive of a
discotic hexagonal columnar arrangement. As a typical exam-
ple, the X-ray diffraction pattern of compound 7a6 and its
one-dimensional intensity vs. theta (y) graph derived from the
pattern are shown in the Fig. 4. Qualitatively all the com-
pounds show similar X-ray diffraction patterns. As can be seen
from the figure, in the small angle region, two sharp peaks, one
very strong and one weak reflection are seen whose d-spacings
are in the ratio of 1 : 1/O3, consistent with a two-dimensional
hexagonal lattice. In the wide-angle region two diffuse reflec-
tions are seen. The broad one centered at 4.62 A corresponds
to the liquid-like order of the aliphatic chains. The reflection at
higher y value and well separated from the previous one is due
to the stacking of the molecular cores one on the top of the
other. The diffuse nature of this peak implies that the stacking
of the discs within each column is correlated over short
distances only. The average stacking distance (core–core
separation) was found to be 3.66 A and falls in the range
observed for a number of materials exhibiting a discotic
columnar phase. The discotic molecules stack one on top of
the other to form the columns and these columns in turn
arrange themselves on a two-dimensional hexagonal lattice for
both the series of compounds. The intercolumnar distances, a,
calculated using the relation a = d10/cos301, where d10 is the
spacing corresponding to the strong peak in the small angle
region, for all the compounds, are listed in Table 2. In both
the series it is evident that as alkyl chain lengths increase
the diameter of the cylindrical columns formed by the
discotic molecules also increases, as shown in Fig. 5. The
Fig. 4 X-Ray diffraction pattern of the trimer 7a6 at 85 1C and its
intensity vs. y profile.
Table 2 Values of d-spacings, and of inter- (dinter) and intracolumnar(dintra) distances (A) of the trimers derived from their diffractionpatterns
Compound d-Spacing/A dinter/A dintra/A
7a6 17.71 20.45 3.587a7 17.80 20.56 3.657a8 18.15 20.96 3.667a10 18.59 21.47 3.667a100 18.13 20.93 3.737b6 17.33 20.01 3.667b7 17.43 20.13 3.65H6TP 19.5 22.52 3.56H6AQ 18.19 21.0 3.6
Fig. 5 Variation of d-spacing value with respect to side chain length.
116 | New J. Chem., 2009, 33, 112–118 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
intercolumnar distances varies from 20.5–21.5 A, whereas the
intracolumnar distance is constant at around 3.7 A, which is
usually observed for discotic columnar mesophases. In these
unoriented samples, we do not observe any additional small
angle peak for the formation of a superlattice arising from the
ideal top-on-top stacking of the trimer molecules which could
lead to the formation of columnar double cables. Therefore, it
was concluded that the triphenylene and anthraquinone sub-
units arrange themselves statistically to form a columnar
hexagonal phase. The intercolumnar distance for hexahexyl-
oxytriphenylene (H6TP) and hexahexyloxyanthraquinone
(H6AQ) is 22.52 A,10 and 21.0 A,11 respectively, but the
intercolumnar distance of the symmetrical trimer 7a6 is
20.45 A, which is less than the corresponding monomers. This
minor shrinkage of the intercolumnar distance in the trimer is
expected upon covalent linking the two molecules. On com-
paring the X-ray diffraction results of 7a6 with 7b6 and 7a7
with 7b7 (Table 2), it is evident that the intercolumnar distance
is decreasing with decreasing spacer length. This is due to
shortening of hexagonal lattice with decreasing the length of
spacer linking the discotic moieties. As expected, the inter-
columnar distance of 7a10 is larger than that of 7a100, since
7a10 contains longer alkyl chains around the central anthra-
quinone core than 7a100, although they contain the same mass
units around the anthraquinone core. However, the intra-
columnar distance of 7a10 is less than 7a100 because of the
steric effect exerted by the branched alkyl chains around the
central core of 7a100, which will hinder the discotic cores
coming closer in columns.
Absorption spectra
As the trimers contain both electron donor and acceptor
moieties, it is expected that they may show charge transfer
absorption. However, the UV-vis spectrum of the trimer 7a10
(Fig. 6) does not show any additional absorption band as
compared to the separate hexaalkoxytriphenylene 4 and hexa-
alkoxyanthraquinone (RF6C4) and is essentially a sum of
donor and acceptor units. The colour of the trimer 7a10 also
almost matches with the colour of the acceptor. This implies
that there is no or very weak charge transfer interaction
between donor and acceptor units. Similar behaviour has
previously been reported for other non-liquid crystalline as
well as liquid crystalline donor–acceptor dimers.9a,12
Conclusions
In conclusion, we have synthesized two series of novel symme-
trical liquid crystalline trimers based on anthraquinone and
triphenylene moieties using microwave irradiation. The etheri-
fication of H-bonded hydroxyl groups of tetraalkoxyanthra-
quinones with bulky o-bromo-substituted triphenylenes failed
to produce the desired triads under classical reaction condi-
tions. The mesophase behavior of the symmetrical trimers was
studied by polarizing optical microscopy and differential
scanning calorimetry and they exhibit a columnar mesophase
over a wide range of temperature. Hexagonal columnar struc-
ture of the mesophase of these donor–acceptor–donor triads
was established by X-ray diffraction studies. Longer spacer
length, smaller peripheral alkyl chain length and branching in
peripheral alkyl chains of the anthraquinone favor liquid
crystalline property in these symmetrical trimers.
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118 | New J. Chem., 2009, 33, 112–118 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Synthesis, crystal structures and luminescence properties of lanthanide
oxalatophosphonates with a three-dimensional framework structurew
Yanyu Zhu, Zhengang Sun,* Yan Zhao, Jing Zhang, Xin Lu, Na Zhang,
Lei Liu and Fei Tong
Received (in Montpellier, France) 20th August 2008, Accepted 3rd October 2008
First published as an Advance Article on the web 14th November 2008
DOI: 10.1039/b814400a
Six new three-dimensional (3D) lanthanide oxalatophosphonates, [Ln(HL)(C2O4)0.5(H2O)2]�H2O
(Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6); H3L = H2O3PCH(OH)CO2H), have been
synthesized under hydrothermal conditions and structurally characterized by single-crystal X-ray
diffraction as well as by infrared spectroscopy, elemental analysis and thermogravimetric analysis.
Compounds 1–6 are isomorphous and they exhibit a complex three-dimensional (3D) open-
framework structure with a one-dimensional channel system along the c-axis. The interconnection
of the lanthanide(III) ions by phosphonate ligands results in a lanthanide phosphonate layer, and
these layers are further bridged by oxalate anions to form a 3D open-framework. Compound 6
shows strong red luminescence in the solid state at room temperature.
Introduction
Metal phosphonates as a class of inorganic–organic hybrid
materials have attracted a great deal of research interest as a
result of their ability to form interesting structures with
potential applications as catalysts, ion exchangers, sorbents,
meso-/microporous materials, or intercalation chemistry.1–5
Usually, the metal phosphonates adopt layered or pillared
layered structures, with the organic groups filling in between
the inorganic layers.6–10 Other structural types have also been
observed in some phosphonates, among which the open-
framework and porous structures are of particular inter-
est.11–16 The strategy of attaching functional groups such as
amine, hydroxyl and carboxylate groups to the phosphonic
acid has proven to be effective for the isolation of a variety
of metal phosphonates with open-framework and micro-
porosity.17–21 Based on 2-hydroxyphosphonoacetic acid, proline-
N-methylphosphonic acid and DL-(a-aminoethyl)phosphonic
acid, a series of metal phosphonates with two-dimensional
(2D) layer and three-dimensional (3D) open-framework struc-
tures have also been isolated in our laboratory.22
Recently, many research activities have focused on the
synthesis of inorganic–organic hybrid compounds by incor-
porating organic ligands in the structures of metal phospho-
nates.23–26 The direct use of two types of ligands in the
preparation, such as a phosphonic acid and a carboxylic acid,
has been found to be another effective method for the
exploration of hybrid open-frameworks. Among these studies,
the oxalate moiety, C2O42�, was found to be a good candidate
and has been successfully incorporated into phosphonate
frameworks with transition metals and main group ele-
ments.27–30 Although some progress has been made in the
construction of metal oxalatophosphonates as mentioned
above, less progress has been achieved in the synthesis of
lanthanide oxalatophosphonates.31–33 Lanthanide phospho-
nates normally have low solubility in water and other organic
solvents, hence introducing a second ligand such as C2O42�
into the lanthanide phosphonate system can improve the
solubility and crystallinity of the lanthanide phosphonate. In
addition, the coordination of two types of ligands with the
lanthanide ion may reduce or eliminate water molecules from
the coordination sphere of the lanthanide(III) ion, hence
increasing the luminescent intensity and lifetime of the
materials.34 In this paper, we selected 2-hydroxyphosphono-
acetic acid (H3L) as the phosphonate ligands and oxalate
as the second metal linker. Hydrothermal reactions of the
above two ligands with lanthanide(III) chlorides afforded six
new lanthanide oxalatophosphonate hybrids with 3D open-
framework structures, namely, [Ln(HL)(C2O4)0.5(H2O)2]�H2O
(Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6); H3L =
H2O3PCH(OH)CO2H). The luminescent property of com-
pound 6 has also been studied.
Results and discussion
Synthesis
By using 2-hydroxyphosphonoacetic acid as the phosphonate
ligand and oxalate as the second metal linker, six new lantha-
nide(III) oxalatophosphonates have been synthesized under
hydrothermal conditions. The compounds 1–6 were obtained
as a pure phase materials by adjusting the synthetic conditions.
Institute of Chemistry for Functionalized Materials, Faculty ofChemistry and Chemical Engineering, Liaoning Normal University,Dalian, 116029, P. R. China. E-mail: [email protected];Fax: +86 411 82156858w Electronic supplementary information (ESI) available: Fig. S1:Simulated XRD pattern of compound 1 and experimental powderXRD patterns of compounds 1–6. Fig. S2: Experimental powder XRDpattern of compound 1 and of dehydrated samples after calcination at150 and 180 1C. Table S1: Selected bond lengths (A) for compounds1–6. Table S2: Selected bond angles (1) for compounds 1–6. CCDCreference numbers 670477–670481 (1–5) and 686602 (6). For ESIand crystallographic data in CIF or other electronic format seeDOI: 10.1039/b814400a
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 119–124 | 119
PAPER www.rsc.org/njc | New Journal of Chemistry
The molar ratio of the starting materials and the pH of the
reaction mixture play an important role in the formation of
these six compounds. NaOH was employed as the inorganic
base to adjust the pH of the reaction mixture. It was found
that pure phases of compounds 1–6 can be obtained with good
yields when the molar ratio of LnCl3�6H2O, H3L, H2C2O4�2H2O, NaOH, H2O and the pH are 1 : 4 : 4 : 4 : 888 and
1.5–2.5. In addition, the reaction temperature was very
important for the formation of suitable single crystals for
X-ray diffraction. The compounds 1–6 were obtained at
120–140 1C under hydrothermal conditions. The powder
XRD patterns of compounds 1–6 and the simulated XRD
patterns of compound 1 are shown in the supplementary
material (Fig. S1, ESIw). The diffraction peaks on the patterns
correspond well in position, confirming these six compounds
are isomorphous, and showing their phase purity. The differ-
ences in reflection intensities are probably due to preferred
orientation in the powder samples.
Description of the crystal structures
Compounds 1–6 are isomorphous and feature three-dimen-
sional open frameworks, hence only the structure of 3 will be
discussed in detail as a representation. The ORTEP diagram
for compound 3 is shown in Fig. 1. Crystallographic data and
structural refinements for compounds 1–6 are summarized in
Table 1.
As shown in Fig. 1, the Pr(III) ion is nine-coordinated by two
phosphonate oxygen atoms, two carboxylate oxygen atoms,
and one hydroxyl oxygen atoms from three HL2� anions, two
oxygen atoms from one oxalate anion as well as two aqua
ligands. The Pr–O distances range from 2.372(3) to 2.573(3) A,
which are comparable to those reported for other praseo-
dymium(III) phosphonates.23,33 The asymmetric unit contains
half of an oxalate ion which lies about an inversion centre.
The oxalate anion is bidentate, and it chelates with
two different Pr(III) ions by using its four carboxylate
oxygen atoms. Each oxalate anion forms two Pr–O–C–C–O
five-membered chelating rings. The pentadentate HL2� ligand
is bidentate with Pr1 and Pr1D and monodentate with Pr1B.
Each HL2� anion chelates with Pr1D ion by using its one
carboxylate oxygen atom (O6) and one hydroxyl oxygen
atom (O4), and one carboxylate oxygen atom (O5) and one
phosphonate oxygen atom (O2) chelate with Pr1 ion.
One phosphonate oxygen atom (O3) is unidentate, whereas
the remaining one (O1) is protonated and noncoordinated.
Such configuration is favorable because of the formation of
stable six-atom rings (P–O–Pr–O–C–C) and five-atom rings
(O–Pr–O–C–C). It is noted that the Ln–O (hydroxyl oxygen)
distances are longer than the other Ln–O distances in com-
pounds 1–6, attributed to the presence of the hydroxyl proton
(Table S1, ESIw).The HL2� anion acts as a bridging ligand to link Pr(III) ions
into a 1D chain of {Pr(HL)}+ along the b axis (Fig. 2(a)).
The dihedral angle between two chelating rings sharing a
common Pr(III) ion is 74.61(10)1. These chains are cross-linked
by bridging HL2� anions to form a praseodymium phosphonate
layer in the bc plane (Fig. 2(b)), the layers are interconnected
by sharing Pr(III) ions into a pillared-layered architecture with
the oxalate groups acting as pillars (Fig. 3). The result of
connections in this manner is the formation of a 1D channel
system along the c axis (Fig. 4(a)). The channel is formed by
21-atom rings composed of five Pr(III) ions, three HL2� anions
and two oxalate anions (Fig. 4(b)). The dimensions of the
channels are estimated to be 11.2 A (Pr1a–P1e) � 10.2 A
(Pr1–C3c) based on the structural data. The oxygen atoms
from coordinated water molecules are oriented toward the
channel center, and lattice water molecules are located inside
the channels. The structure of 3 can be viewed as the praseo-
dymium phosphonate layer being connected via oxalate anions
to form a complex 3D open-framework structure.
Fig. 1 ORTEP representation of a selected unit of compound 3. The
thermal ellipsoids are drawn at the 30% probability level. All H atoms
and lattice water molecules are omitted for clarity: Pr(1)–O(3)B,
2.372(3) A; Pr(1)–O(2), 2.481(3) A; Pr(1)–O(7), 2.493(3) A;
Pr(1)–O(6)A, 2.522(3) A; Pr(1)–O(5), 2.559(3) A; Pr(1)–O(9), 2.537(4)
A; Pr(1)–O(8)C, 2.571(3) A; Pr(1)–O(10), 2.542(4) A; Pr(1)–O(4)A,
2.573(3) A. Symmetry codes: A: �x + 2, y + 1/2, �z + 3/2; B: �x +
2, �y,�z+2; C:�x+ 1,�y, �z+ 1; D: �x+ 2, y� 1/2,�z+3/2.
Fig. 2 (a) 1D chain {Pr(HL)}+ and (b) A 2D praseodymium(III)
phosphonate layer in compound 3.
120 | New J. Chem., 2009, 33, 119–124 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
IR spectra
The IR spectra of the six compounds have many similar
features corresponding to the common groups, thus only the
spectrum of compound 3 will be discussed (Fig. 5). The
IR spectrum for compound 3 was recorded in the region
4000–400 cm�1. The broad band in the range 3550–3000 cm�1
corresponds to the O–H stretching vibrations of water mole-
cules, hydroxyl groups and phosphonate groups. There are
two strong bands centered at 1650 and 1575 cm�1, which are
assigned to the asymmetrical and symmetrical stretching
vibrations of C–O groups when present as COO� moieties.35
Strong bands between 1200 and 900 cm�1 are due to stretching
vibrations of the tetrahedral CPO3 groups, as expected.36
Additional intense and sharp bands at low energy (617, 572
and 430 cm�1 etc) are found. These bands are probably due to
bending vibrations of the tetrahedral CPO3 groups.
Thermal properties
Except for the final weight loss temperature and total weight
losses, the TGA curves of compounds 1–6 are very similar,
with three main continuous weight losses. Herein, we use
compound 1 as an example to illuminate the weight losses in
detail. As shown in Fig. 6, the first step corresponds to the loss
Table 1 Crystal data and structure refinements for compounds 1–6
1 2 3 4 5 6
Empirical formula C3H9O11PLa C3H9O11PCe C3H9O11PPr C3H9O11PNd C3H9O11PSm C3H9O11PEuM 390.98 392.19 392.98 396.31 402.42 404.03Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic MonoclinicSpace group P21/c P21/c P21/c P21/c P21/c P21/ca/A 7.1991(6) 7.2260(7) 7.2300(7) 7.2326(6) 7.2351(6) 7.2293(9)b/A 13.3838(11) 13.2918(13) 13.2239(13) 13.1558(11) 13.0550(10) 13.0429(16)c/A 10.2926(8) 10.2745(10) 10.2535(10) 10.2337(8) 10.1999(8) 10.1980(13)b/1 98.8980(10) 99.4930(10) 99.8690(10) 100.1070(10) 100.4270(10) 100.541(2)V/A3 979.77(14) 973.32(16) 965.82(16) 958.63(14) 947.51(13) 945.4(2)Z 4 4 4 4 4 4Dc/g cm�3 2.651 2.676 2.703 2.746 2.821 2.839m/mm�1 4.576 4.894 5.263 5.636 6.420 6.858GOF on F2 1.017 1.063 1.074 1.039 1.090 1.099R1 [I 4 2s(I)]a 0.0210 0.0239 0.0278 0.0220 0.0206 0.0243wR2 [I 4 2s(I)]a 0.0547 0.0526 0.0726 0.0543 0.0512 0.0589R1 (All data)a 0.0233 0.0296 0.0318 0.0242 0.0226 0.0255wR2 (All data)a 0.0560 0.0555 0.0753 0.0557 0.0523 0.0595
a R1 =P
(||Fo| � |Fc|)/P
|Fo|; wR2 = [P
w(|Fo| � |Fc|)2/P
wFo2]1/2.
Fig. 3 A ball-and-stick and polyhedral view of compound 3 along the
b axis.
Fig. 4 (a) View of the framework for compound 3 along the c-axis showing the voids in the structure. (b) A 21-atom rings in compound 3.
All H atoms and lattice water molecules are omitted for clarity. Symmetry codes: a: �x+ 2, y � 1/2, �z+ 3/2; b: x, �y � 1/2, z � 1/2; c: �x+ 1,
y � 1/2, �z + 1/2; d: �x + 1, �y, �z + 1; e: x � 1, y, z � 1.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 119–124 | 121
of one lattice water molecule and two aqua ligands. The
weight loss started at 50 1C and was completed at 145 1C.
The observed weight loss of 14.0% is close to the calculated
value (13.8%). The second step between 345 and 430 1C can be
attributed to decomposition of oxalate and phosphonate units.
The third step corresponds to the further decomposition of the
phosphonate group. The observed total weight loss at 735 1C
is about 41.5%, and the final products are not identified.
However, we suspect they are mainly LaPO4. The total weight
loss of 41.5% is close to the calculated value (40.2%) if the
final product is assumed to be LaPO4. The observed total
weight losses of compounds 2–6 are 41.4, 39.0, 37.0, 38.6,
40.3%, respectively. Considering the thermal stability of the
compounds, X-ray powder diffraction studies were performed
for the as-synthesized compound 1 and the samples calcined at
150 and 180 1C. The XRD patterns for the calcined samples fit
well with that of the as-synthesized samples, indicating that the
structure of these six compounds can be kept after dehydra-
tion process (Fig. S2, ESIw).
Photoluminescent properties
It is well-known that the lanthanides, especially europium and
terbium, can absorb ultraviolet radiation efficiently through an
allowed electronic transition to convert to the excited state5D4, and these excited states are deactivated to the multiplet7FJ states radiatively via emission of visible radiation as
luminescence. The solid-state luminescence property of com-
pound 6 was investigated at room temperature. Compound 6
emits red light upon excitation at 396 nm, and its luminescence
spectrum is depicted in Fig. 7. These emission bands arise from5D0 - 7FJ (J = 1, 2 and 4) transitions, typical of Eu(III)
ions.34,37 The 5D0 -7F1 transition (593 nm) corresponds to a
magnetic dipole transition, and the intensity of this emission
for 6 is medium-strong. The most intense emission in
the luminescent spectrum is the 5D0 - 7F2 transitions at
617 nm, which are the so-called hypersensitive transitions
and are responsible for the brilliant-red emission of compound
6.38 The emission spectrum of 6 shows a weak emission band
at 695 nm, which can be attributed to the 5D0 - 7F4
transition. The results indicate that compound 6 is a good
candidate as a red-light luminescent material.
Conclusions
By using 2-hydroxyphosphonoacetic acid as the phosphonate
ligand and oxalate as the second metal linker, six new
lanthanide(III) oxalatophosphonates with a general formula
[Ln(HL)(C2O4)0.5(H2O)2]�H2O (Ln = La (1), Ce (2), Pr (3),
Nd (4), Sm (5), Eu (6); H3L = H2O3PCH(OH)CO2H) have
been synthesized and structurally characterized. Compounds
1–6 are isomorphous and the structure of these compounds
features a 3D open-framework with a one-dimensional
channel system along the c-axis. The interconnection of the
lanthanide(III) ions by phosphonate ligands results in a lantha-
nide phosphonate layer, and these layers are further bridged
by oxalate anions to form 3D open-frameworks. Compound 6
is a new example of luminescent rare-earth oxalatophospho-
nates characterized by a significant red luminescence. The
results of our study indicate that by introduction of oxalate
Fig. 5 IR spectra of compounds 1–6.
Fig. 6 TGA curves of compounds 1–6. Fig. 7 Solid-state emission spectrum of compound 6 at room
temperature.
122 | New J. Chem., 2009, 33, 119–124 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
as the second ligand, we can obtain lanthanide oxalatophos-
phonates with well characterized crystal structures as well as
strong luminescence.
Experimental
Materials
2-Hydroxylphosphonoacetric acid (H3L) solution was
obtained from Taihe Chemical Factory (48.0 wt%). The
lanthanide(III) chlorides were prepared by the dissolving
corresponding lanthanide oxides (General Research Institute
for Nonferrous Metals, 99.99%) in hydrochloric acid followed
by recrystallization and drying. All other chemicals were used
as received without further purification.
Physical measurements
Elemental analyses (carbon and hydrogen) were performed
using a PE-2400 elemental analyzer. La, Ce, Pr, Nd, Sm, Eu
and P were determined by using an inductively coupled plasma
(ICP) atomic absorption spectrometer. IR spectra were
recorded on a Bruker AXS TENSOR-27 FT-IR spectrometer
with KBr pellets in the range 4000–400 cm�1. The X-ray
powder diffraction data were collected on a Bruker AXS D8
Advance diffractometer using Cu-Ka radiation (l=1.5418 A)
in the 2y range of 9–601 with a step size of 0.021. The
luminescence analysis was performed on a JASCO FP-6500
spectrofluorimeter (solid). TG analysis was performed on a
Perkin–Elmer Pyris Diamond TG–DTA thermal analysis
system in static air with a heating rate of 10 K min�1 from
50 to 800 1C.
Synthesis
[La(HL)(C2O4)0.5(H2O)2]�H2O (1). A mixture of LaCl3�6H2O (0.18 g, 0.50 mmol), H3L (0.50 ml, 2.00 mmol),
H2C2O4�2H2O (0.25 g, 2.00 mmol), and NaOH (0.08 g,
2.00 mmol) was dissolved in 8 mL distilled water. The resulting
solution was stirred for about 1 h at room temperature, sealed
in a 20 mL Teflon-lined stainless steel autoclave, and heated at
140 1C for 4 days under autogenous pressure. After the
mixture was cooled slowly to room temperature, colorless
block crystals were obtained in ca. 40.0% yield based on La.
C3H9O11PLa (390.98): calc.: C 9.21, H 2.30, P 7.93, La 35.53;
found: C 9.28, H 2.22, P 7.85, La 35.45%. IR (KBr) data: 3540
(br), 1644 (m), 1581 (s), 1432 (w), 1373 (w), 1309 (w), 1209 (s),
1178 (w), 1070 (s), 935 (m), 781 (w), 719 (w), 619 (w), 580 (w),
526 (w) cm�1.
[Ce(HL)(C2O4)0.5(H2O)2]�H2O (2). The procedure was the
same as that for 1 except that LaCl3�6H2O was replaced by
CeCl3�7H2O (0.19 g, 0.50 mmol). Yield: 81.0% (based on Ce).
C3H9O11PCe (392.19): calc.: C 9.18, H 2.29, P 7.90, Ce, 35.73;
found: C 9.11, H 2.21, P 7.95, Ce 35.65%. IR (KBr) data: 3465
(br), 2221 (w), 1648 (m), 1583 (s), 1425 (w), 1373 (w), 1311 (w),
1213 (s), 1074 (s), 937 (w), 781 (w), 721 (w), 615 (w), 588 (w),
524 (w) cm�1.
[Pr(HL)(C2O4)0.5(H2O)2]�H2O (3). The procedure was the
same as that for 1 except that LaCl3�6H2O was replaced by
PrCl3�6H2O (0.18 g, 0.50 mmol). Yield: 76.0% (based on Pr).
C3H9O11PPr (392.98): calc.: C 9.16, H 2.29, P 7.89, Pr 35.86;
found: C 9.23, H 2.20, P 7.96, Pr 35.94%. IR (KBr) data: 3473
(br), 2915 (w), 1650 (m), 1575 (s), 1432 (m), 1371 (m), 1363
(m), 1317 (m), 1214 (s), 1064 (s), 927 (m), 831 (w), 777 (w), 696
(w), 617 (w), 572 (w), 516 (w) cm�1.
[Nd(HL)(C2O4)0.5(H2O)2]�H2O (4). The procedure was the
same as that for 1 except that LaCl3�6H2O was replaced by
NdCl3�6H2O (0.18 g, 0.50 mmol). Yield: 55.0% (based on Nd).
C3H9O11PNd (396.31): calc.: C 9.08, H 2.27, P 7.82, Nd 36.40;
found: C 9.15, H 2.35, P 7.91, Nd 36.49%. IR (KBr) data:
3484 (br), 2915 (w), 1652 (s), 1577 (s), 1432 (m), 1369 (m), 1319
(m), 1209 (s), 1064 (s), 968 (w), 931 (m), 835 (w), 786 (w), 781
(w), 694 (w), 619 (m), 580 (m), 520 (m) cm�1.
[Sm(HL)(C2O4)0.5(H2O)2]�H2O (5). A mixture of SmCl3�6H2O (0.19 g, 0.50 mmol), H3L (0.50 ml, 2.00 mmol),
H2C2O4�2H2O (0.25 g, 2.00 mmol), and NaOH (0.08 g,
2.00 mmol) in 8 mL distilled water was sealed in an autoclave
equipped with a 20 mL Teflon liner, and then heated at 120 1C
for 4 days. After the mixture was cooled slowly to room
temperature, pale yellow block crystals were obtained in ca.
86.0% yield based on Sm. C3H9O11PSm (402.42): calc.: C 8.95,
H 2.25, P 7.69, Sm 37.36; found: C 9.03, H 2.33, P 7.63, Sm
37.28%. IR (KBr) data: 3477 (br), 3290 (br), 2925 (w), 1660
(s), 1575 (s), 1433 (m), 1366 (m), 1318 (m), 1212 (s), 1072 (s),
930 (m), 783 (w), 704 (w), 617 (m), 524 (m) cm�1.
[Eu(HL)(C2O4)0.5(H2O)2]�H2O (6). The procedure was the
same as that for 5 except that SmCl3�6H2O was replaced by
EuCl3�6H2O (0.19 g, 0.50 mmol). Yield: 45.0% (based on Eu).
C3H9O11PEu (404.03): calc.: C 8.92, H 2.24, P 7.67, Eu 37.61;
found: C 8.98, H 2.31, P 7.58, Eu 37.69%. IR (KBr) data: 3475
(br), 3292 (br), 2920 (w), 1670 (s), 1579 (s), 1435 (m), 1361 (m),
1317 (m), 1217 (s), 1180 (m), 1070 (s), 974 (w), 921 (m), 783
(w), 707 (w), 621 (m), 580 (w), 526 (w), 482 (m) cm�1.
Crystallographic determinations
Data collections for compounds 1–6 were performed on the
Bruker Smart APEX II X-diffractometer equipped with
graphite-monochromated Mo-Ka radiation (l = 0.71073 A)
at 293 � 2 K. An empirical absorption correction was applied
using the SADABS program. All structures were solved by
direct methods and refined by full-matrix least squares fitting
on F2 by SHELXS-97.39 All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms of organic ligands were
generated geometrically with fixed isotropic thermal para-
meters, and included in the structure factor calculations.
Acknowledgements
This research was supported by grants from the Natural
Science Foundation of Liaoning Province of China
(20062140).
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124 | New J. Chem., 2009, 33, 119–124 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
The annular tautomerism of the curcuminoid NH-pyrazolesw
Pilar Cornago,*aPilar Cabildo,
aRosa M. Claramunt,
aLatifa Bouissane,
a
Elena Pinilla,bM. Rosario Torres
band Jose Elguero
c
Received (in Montpellier, France) 16th July 2008, Accepted 10th October 2008
First published as an Advance Article on the web 2nd December 2008
DOI: 10.1039/b812018h
The structures of four NH-pyrazoles, (E)-3,5-bis[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-1H-
pyrazole (3), (E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-methyl-1H-pyrazole (4),
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-4,5(3)-dimethyl-1H-pyrazole (5) and (E)-3(5)-
[b-(3,4-dimethoxyphenyl)-ethenyl]-4-methyl-5(3)-phenyl-1H-pyrazole (8), have been determined by
X-ray crystallography. Compounds that have a phenol residue crystallize forming sheets that are
stabilized by a complex pattern of hydrogen bonds between a unique tautomer (4), or by a 2 : 1
mixture of both tautomers (5) (these tautomers being identical in the case of 3). Pyrazole 8, which
lacks OH groups, crystallizes in cyclic dimers that are stabilized by N–H� � �N hydrogen bonds.
The tautomerism in solution and in the solid state was determined by 13C and 15N CPMAS NMR
spectroscopy. For compounds 4, 5 and 8, the solid state results agree with those observed by
crystallography; the most abundant tautomer in solution coincides with the tautomer present in
the solid state (4 and 8) or with the most abundant tautomer in the crystal (5).
Introduction
Turmeric is a spice derived from the rhizomes of Curcuma
longa, which is a member of the ginger family.1 The bright
yellow color of turmeric comes mainly from polyphenolic
pigments known as curcuminoids. Curcumin (1) (Scheme 1)
is the principal curcuminoid found in turmeric, and is gen-
erally considered to be its most active constituent. In addition
to its use as a spice and a pigment, turmeric has been used in
India for medicinal purposes for centuries. More recently,
evidence that 1 may have anti-inflammatory and anti-cancer
activities has renewed scientific interest in its potential to
prevent and treat disease. 1 is also an effective scavenger of
reactive oxygen and nitrogen species in vitro. In addition to its
direct antioxidant activity, 1 has been found to inhibit PLA2,
COX-2 and 5-LOX activity in cultured cells. It has also been
found to inhibit NF-kB-dependent gene transcription, and to
inhibit the induction of COX-2 and iNOS in cell culture and
animal studies.2 1 has been found to induce cell cycle arrest
and apoptosis in a variety of cancer cell lines grown in
cultures. The ability of 1 to induce apoptosis in cultured
cancer cells has generated scientific interest in its potential to
prevent some types of cancer. Oral administration of 1 has
been found to inhibit the development of chemically-induced
cancer in animal models of oral, stomach, liver and colon
cancer.
We have devoted a series of papers to the annular tauto-
merism of NH-pyrazoles 2 (2a vs. 2b),3,4 and decided to study
those derived from 1 and related b-diketones.Pyrazole 3, which is derived from 1, has been prepared many
times since 1991.5–11 It has been described as a pale yellow
solid that melts at 211–2145 or 2157 1C.
The activity of the curcuminoid pyrazoles covers domains
such as anti-inflammatory (5-lipooxygenase and cyclooxygen-
ase inhibitors)5,8 and anti-tumoral (anti-angiogenic)6–8 agents,
and drugs for the treatment of Alzheimer’s disease (AD;
potent g-secretase inhibitors, potent ligands for fibrillar
Ab42 aggregates, tau aggregation inhibitors and depolymeriz-
ing agents for tau aggregates).10,11 Particularly promising for
treating reduced cognitive functions is 4,40-[(1-phenyl-1H-
pyrazole-3,5-diyl)di-(1E)-2,1-ethenediyl]bis(2-methoxyphenol)
(CNB-001), the product obtained by reacting 1 with phenyl-
hydrazine.12 In the last of these applications, curcumin-
derived pyrazoles were synthesized in order to minimize
the metal chelation properties of 1. The reduced rotational
freedom and the absence of stereoisomers were anticipated
to enhance the inhibition of g-secretase. Accordingly, the
replacement of the 1,3-dicarbonyl moiety by isosteric hetero-
cycles, such as pyrazoles, turned these compounds into very
interesting candidates for AD research.
Scheme 1 The structure of curcumin (1) and the tautomerism of
pyrazoles 2.
aDepartamento de Quımica Organica y Bio-Organica, Facultad deCiencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain.E-mail: [email protected]; Fax: +34 913988372;Tel: +34 913987323
bDepartamento de Quımica Inorganica I, Facultad de CienciasQuımicas, Universidad Complutense de Madrid (UCM), 28040Madrid, Spain
c Instituto de Quımica Medica, CSIC, Juan de la Cierva 3, E-28006Madrid, Spainw CCDC reference numbers 690489–690492. For crystallographic datain CIF or other electronic format see DOI: 10.1039/b812018h
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 125
PAPER www.rsc.org/njc | New Journal of Chemistry
The aim of this paper is to determine and discuss the
structure, tautomerism and possible proton transfer in the
solid state (SSPT) of six NH-pyrazoles by using a combination
of X-ray crystallography and 13C/15N NMR spectroscopy.
The nomenclature used in the text and in the experimental is
not in accordance with IUPAC rules. For all of the com-
pounds with phenolic hydroxyl groups, 3–6, the phenol system
has the highest priority; however, using IUPAC nomenclature
here would be at the expense of comparability and clearness.
For instance, compound 4 would be 2-methoxy-4-[(E)-2-
(5-methyl-1H-pyrazol-3-yl)vinyl]phenol under IUPAC rules,
rather than (E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)ethenyl]-
5(3)-methyl-1H-pyrazole. In order to prioritize comparability
over correct nomenclature, we have named all of the com-
pounds as pyrazole derivatives.
Results and discussion
Synthesis
All of the compounds discussed in this work (Scheme 2) are
reported in the experimental section. They were prepared by
the reaction of hydrazine with the corresponding b-diketone,the most common method of synthesizing pyrazoles,13 which
in the case of 3 was 1.14
X-Ray structure determination
The structures of pyrazoles 3 (derived from 1), 4, 5 and 8 have
been determined by X-ray crystallography.
Concerning tautomerism, in the case of 3, tautomers 3a and
3b are identical. In the case of 4, the only tautomer present
is 3-(3-methoxy)-4-hydroxy-styryl-5-methyl-1H-pyrazole (4a).
In the case of 5, there is a 2 : 1 mixture of 3-(3-methoxy)-4-
hydroxy-styryl-4,5-dimethyl-1H-pyrazole (5a) and 3,4-di-
methyl-5-(3-methoxy)-4-hydroxy-styryl-1H-pyrazole (5b). In
the case of 8, the only observed tautomer is 3-phenyl-4-
methyl-5-(3-methoxy)-4-hydroxy-styryl-1H-pyrazole (8b). The
main data are collected in Table 1 and Table 2. A charac-
teristic feature of the geometry of NH-pyrazoles is that the
angle centered at N1 (the atom bearing the NH proton) is
always larger than that centered at N2, about 112 and 1041,
respectively.15
Crystals of sufficient quality for X-ray diffraction analysis
were obtained for compounds 3 (1 : 1 H2O/EtOH), 4 (1 : 1 : 1
CH2Cl2/hexane/EtOH), 5 (1 : 1 : 1 CH2Cl2/hexane/EtOH) and
8 (1 : 1 : 1 CH2Cl2/hexane/EtOH) from their respective solvent
mixtures. Table 1 shows selected bond lengths and angles for
each of these compounds, and Table 2 shows the distances and
angles of the intermolecular hydrogen bonds.
One crystallographically-independent molecule was identi-
fied in the structural determination of 3, where the pyrazole
and phenyl rings were co-planar, with bond distances and
angles within normal ranges (Fig. 1). The intermolecular
hydrogen bonds led to layers parallel to (1 0 1), as shown in
Fig. 2.
Scheme 2 The structures of the NH-pyrazoles.
Table 1 The bond lengths (A) and angles (1) for compounds 3, 4, 8and the three crystallographically-independent molecules of 5
3 4 5(1) 5(2) 5(3) 8
N1–N2 1.354(3) 1.365(3) 1.349(4) 1.352(4) 1.359(3) 1.351(3)N2–C3 1.347(4) 1.339(3) 1.341(5) 1.348(5) 1.349(5) 1.339(4)C3–C4 1.399(4) 1.398(4) 1.388(6) 1.410(5) 1.401(6) 1.415(4)C4–C5 1.373(4) 1.369(3) 1.381(6) 1.366(5) 1.374(6) 1.379(4)C5–N1 1.353(4) 1.340(3) 1.332(6) 1.346(5) 1.331(5) 1.360(4)C3–C6 1.445(4) 1.453(3) — 1.463(5) 1.450(6) 1.377(3)C5–C6 — — 1.446(7) — — 1.444(4)C6–C7 1.327(4) 1.325(3) 1.309(1) 1.310(6) 1.304(4) 1.333(4)C7–C8 1.467(4) 1.472(3) 1.460(1) 1.457(5) 1.475(6) 1.460(4)C3–C15 — — 1.484(6) — — —C5–C15 1.450(4) 1.484(2) — 1.490(5) 1.509(6) —C15–C16 1.322(4) — — — — —C16–C17 1.463(4) — — — — —C10–O2 1.376(4) 1.367(3) 1.359(6) 1.367(4) 1.372(5) 1.372(3)O2–C14 1.433(4) 1.419(3) 1.424(6) 1.430(5) 1.442(5) 1.416(4)C11–O1 1.368(4) 1.369(3) 1.372(5) 1.361(5) 1.363(5) 1.371(3)C15–O1 — — — — — 1.418(4)C19–O4 1.366(4) — — — — —O4–C23 1.416(4) — — — — —C20–O3 1.382(4) — — — — —N2–N1–C5 112.2(3) 112.7(2) 112.2(4) 111.8(3) 111.6(3) 112.4(2)N1–N2–C3 105.3(2) 104.4(2) 104.4(3) 105.2(3) 104.7(3) 105.3(2)
Table 2 The bond lengths (A) and angles (1) for the hydrogen bondsin compounds 3, 4, 5 and 8
Compound D–H� � �A dD–H dH� � �A dD� � �A +D–H� � �A
3 O3–H3� � �O4 1.10 1.98 2.647(4) 115.1N1–H1B� � �O3a 1.06 1.93 2.864(4) 144.7O1–H1A� � �N2b 1.17 1.79 2.811(4) 142.7O3–H3� � �O1c 1.10 2.26 2.825(4) 108.7
4 O1–H1A� � �N2d 0.99 1.86 2.832(3) 167.5N1–H1B� � �O2e 1.07 2.17 2.962(3) 128.6
5 O13–H113� � �N21 1.16 1.81 2.782(5) 137.3N12–H12� � �N23 1.10 1.82 2.914(5) 175.6O11–H111� � �O13f 0.92 2.03 2.813(4) 141.3O12–H112� � �N22g 1.14 1.57 2.673(4) 159.4N11–H11� � �O11g 1.08 2.01 2.951(5) 144.3N13–H13� � �O12i 1.02 1.93 2.853(4) 148.6
8 N1–H1� � �N2j 0.90(4) 2.07(4) 2.872(3) 147(4)
Symmetry transformations used to generate equivalent atoms: a �x+
2, y � 12, �z + 1
2.b �x + 1, y + 1
2, z +32.
c x + 1, y, z � 1. d �x + 1,
�y + 2, �z + 1. e x, �y + 32, z � 1
2.f �x + 4, y � 1
2, �z + 32.
g �x +
1, y � 12, �z + 1
2.h �x + 4, y + 1
2, �z + 32.
i �x + 1, y + 12, �z +
12.
j �x + 2, �y, �z + 1.
126 | New J. Chem., 2009, 33, 125–135 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Fig. 3 shows an ORTEP representation of the asymmetric
unit of compound 4, a non-planar molecule with a dihedral
angle of 19.0(1)1 between the pyrazole and phenyl rings.
Dimers (O1–H1A–N2) linked by hydrogen bonds
(N1–H1B–O2) led to layers parallel to (1 0 0), as shown in
Fig. 4.
The asymmetric unit of compound 5 is presented in Fig. 5.
The crystal consists of three crystallographically-independent,
almost planar molecules, held together by hydrogen bonds
that form a trimer, which, through additional hydrogen
bonding, forms layers parallel to (–1 0 3), as shown in Fig. 6.
Fig. 7 shows the non-planar molecule of compound 8, with
a dihedral angle of 15.7(1)1 between the pyrazole and
the phenyl ring at the 3-position, and 36.5(1)1 between the
pyrazole and the phenyl ring of the styryl group at the
5-position. Molecules of 8 are centrosymmetrically linked by
hydrogen bonds (Table 2), giving rise to dimers, and these
species are within van der Waals distances (Fig. 8).
The cyclic N–H� � �N hydrogen-bonded motifs (cyclamers) of
NH-pyrazoles have been studied on several occasions.4d,16,17
These motifs are characteristic of NH-pyrazoles lacking sub-
stituents that bear hydrogen bonding functional groups, such
as –OH or –CO2H. These groups, as well as solvent molecules
like H2O and ROH, participate in the hydrogen bonding
network that determines the secondary structure of the crys-
tals, destroying the (N–H� � �N)n hydrogen bonds.18–20 In three
of the compounds described in the present paper, those
bearing phenol groups (3, 4 and 5) form several hydrogen
bonds involving the OH group: 3 (O–H� � �N, N–H� � �O,
O–H� � �O), 4 (O–H� � �N, N–H� � �O) and 5 (O–H� � �N,
N–H� � �O, O–H� � �O, N–H� � �N; present as two molecules of
tautomer 5a and one molecule of tautomer 5b). In the case of
8, which lacks phenol groups, the compound crystallizes as a
dimer. This kind of cyclamer is characteristic of NH-pyrazoles
that are substituted with phenyl groups at the 3- and 5-posi-
tions,16 to which compound 8 is clearly related.
Fig. 1 The X-ray molecular structure of compound 3 (ORTEP plot,
35% probability for the ellipsoids).
Fig. 2 The view along the a axis of 3, showing the formation of layers
due the intermolecular hydrogen bonds.
Fig. 3 The X-ray molecular structure of compound 4 (ORTEP plot,
35% probability for the ellipsoids).
Fig. 4 The view along the b axis of 4, showing the formation of layers
due the intermolecular hydrogen bonds.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 127
NMR study
We have reported the 1H, 13C and 15N NMR results concerning
compounds 3–8 in Table 3, Table 4 and Table 5, respectively.
These data have been collected with the aim of determining the
tautomeric equilibrium constants by simple integration.
Although it has been pointed out that only 1H NMR signal
intensities are reliable for the determination of populations, in
our experience, 13C and 15N signals can also been used in
connection with signals related by tautomerism, i.e. carbon or
nitrogen atoms linked to the same substituents.3c The assign-
ments of the signals were based on standard 2D experiments,
on the values of coupling constants (auto-consistency) and by
comparison with other NH-pyrazoles where tautomerization
is blocked.21
We have illustrated with one example the kind of spectra
that we obtained (Fig. 9). The spectrum corresponds to
compound 5 in HMPA-d18, concentration 0.10 M and tem-
perature 268 K (Table 4). The region of the methyl groups
shows two narrow signals corresponding to the most abundant
tautomer, and two broad signals corresponding to the less
abundant one, as expected by simple consideration of the
energy profile.
For compounds whose structure had not been determined
by crystallography, we relied on CPMAS NMR results: 6b and
7b were the only tautomers present in the solid state
(see Table 4 and Table 5). We are aware that solid state
NMR and single crystal X-ray diffraction do not show exactly
the same properties, for instance, static vs. dynamic disorder.3b
To avoid further complications, we used fine powders for
Fig. 5 The X-ray molecular structure of compound 5 (ORTEP plot, 40% probability for the ellipsoids).
Fig. 6 The view along the a axis of 5, showing the formation of layers
due the intermolecular hydrogen bonds.
Fig. 7 The X-ray molecular structure of compound 8 (ORTEP plot,
35% probability for the ellipsoids).
Fig. 8 The view along the a axis of 8, showing the formation of
dimers.
128 | New J. Chem., 2009, 33, 125–135 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Table
3The
1H
NMR
chem
icalshifts
(d)and
1H–1H
couplingconstants
ofcompounds3–8(J/H
z)in
DMSO-d
6andHMPA-d
18solutionsa
Compound
R1
R2
R3
Solvent
Conc./M
T/K
NH
R2
H3
H4
H6
OMe
OR
3H7
H8
R1
Tautomerism
3*
HH
DMSO
0.12
300
12.80
6.61(H
)6.76
6.93
7.13
3.82
9.17(H
)7.03
6.91
—Average
4CH
3H
HDMSO
0.07
300
12.40
6.20(H
)6.74
6.91
7.12
3.81
9.15(H
)6.95
6.88
2.19(M
e)Average
HMPA
0.07
300
13.26
6.11(H
)6.85/7.16
3.80
10.26(H
)6.85/7.16
2.23(M
e)B50%
a
HMPA
0.07
300
13.20
6.11(H
)6.85/7.16
3.80
10.24(H
)6.85/7.16
2.15(M
e)B50%
b
HMPA
0.10
276
13.34
6.19(H
)6.85
6.85
7.06
3.80
10.42(H
)7.20
6.87
2.25(M
e)B50%
a
HMPA
0.10
276
13.27
6.11(H
)6.85
6.85
7.06
3.80
10.34(H
)6.92
6.83
2.14(M
e)B50%
b
5CH
3CH
3H
DMSO
0.07
300
12.29
2.03(M
e)6.75
6.91
7.13
3.83
9.08(H
)6.95
6.86
2.10(M
e)Average
HMPA
0.10
300
13.16
2.04(M
e)6.87
6.92
6.97
3.80
10.28(H
)7.21
6.82
2.04(M
e)35%
a
HMPA
0.10
300
13.10
2.04(M
e)6.87
6.92
6.97
3.80
10.20(H
)7.21
6.82
2.07(M
e)65%
b
HMPA
0.10
268
13.25
2.05(M
e)6.87
6.96
7.00
3.81
10.44(H
)7.25
6.88
2.05(M
e)35%
a
HMPA
0.10
268
13.20
2.05(M
e)6.87
6.96
7.00
3.81
10.38(H
)7.25
6.88
2.07(M
e)65%
b
6C6H
5H
HDMSO
0.11
300
12.96
6.88(H
)6.78
6.96
7.15
3.84
9.10(H
)7.10
6.95
7.80(o)
36%
a
7.43(m
)7.31(p)
DMSO
0.11
300
13.18
6.88(H
)6.78
6.96
7.15
3.84
9.21(H
)7.10
6.95
7.80(o)
64%
b
7.43(m
)7.31(p)
7C6H
5H
CH
3DMSO
0.06
300
13.00
6.87(H
)6.96
7.06
7.19
3.83
3.78(M
e)7.14
7.03
7.80(o)
40%
a
7.43(m
)7.32(p)
DMSO
0.06
300
13.21
6.87(H
)6.96
7.06
7.19
3.83
3.78(M
e)7.14
7.03
7.80(o)
60%
b
7.43(m
)7.32(p)
8C6H
5CH
3CH
3DMSO
0.05
300
12.94
2.29(M
e)6.95
7.07
7.25
3.84
3.77(M
e)7.14
7.06
7.65(o)
Richin
b
7.45(m
)7.34(p)
HMPA
0.06
268
13.94
2.34(M
e)7.09
7.09
7.25
3.88
3.84(M
e)7.45
7.13
7.70(o)
b
7.45(m
)7.31(p)
aThecouplingconstants
were,
onaverage:
3JH3–H4=
8.0
Hz,
4JH4–H6=
2.0
Hz(notalwaysobserved)and
3JH7–H8trans=
16.5
Hz.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 129
Table 4 The 13C NMR chemical shifts (d) and 1H–13C coupling constants (J/Hz) in DMSO-d6 and HMPA-d18 solutions, and under CPMASconditionsa
Compound R1 R2 R3 Solvent Conc./M T/KCa Cb Cc R2 C1 C2 C3
TautomerismC4 C5 C6 C7 C8 OCH3 R1
3 * H H DMSO 0.12 300 151.0 99.3 142.0 — (H) 147.9 146.8 115.6 No tautomerism120.1 128.4 109.5 129.8 112.9 (C8) 55.6
118.4 (C80)CPMAS — 300 150.2 95.5 142.8 — (H) 147.4 145.1 114.5 No tautomerism
N.o.b 127.1 106.3 129.9 111.9 53.5
56.5
4 CH3 H H DMSO 0.36 300 149.6 101.3 140.5 — (H) 147.9 146.6 115.7 Average
119.9 128.6 109.5 129.0 117.4 55.6 11.6 (Me)
HMPA 0.10 276 150.9 100.0 142.4 — (H) 148.7 148.6 115.7 B50% a
119.4 128.4 110.5 128.7 113.2 55.9 10.8 (Me-5)
138.4 101.6 148.9 — (H) 148.7 146.9 115.7 B50% b
119.6 128.4 110.5 129.4 119.3 55.9 13.9 (Me-3)
CPMAS — 300 151.5 101.1 142.4 — (H) 148.8 143.3 115.3 a
120.5 129.9 113.2 129.9 113.2 55.9 9.9 (Me-5)
115.3
5 CH3 CH3 H DMSO 0.07 300 141.6 110.4 141.6 8.1 (Me) 147.9 146.6 115.6 Average
119.8 128.8 109.6 127.9 114.9 55.7 10.6
HMPA 0.08 300 147.5 109.9 135.7 8.4 (Me) 149.0 148.7 116.1 35% a
119.6 129.0 111.5 127.7 118.7 56.3 11.9 (br)
HMPA 0.08 300 138.3 109.9 145.8 8.4 (Me) 149.0 148.7 116.1 65% b
119.6 129.0 111.5 128.4 112.7 56.3 11.9 (br)HMPA 0.10 268 147.5 110.0 135.7 8.8 (br, Me) 148.8 148.6 115.8 35% a
119.5 128.8 110.7 127.6 118.5 55.9 9.1 (br)HMPA 0.10 268 138.3 109.9 145.8 8.4 (Me) 148.8 148.6 115.8 65% b
119.5 128.8 110.7 128.3 112.4 55.9 12.1CPMAS — 300 145.9 110.2 138.6 9.8 (Me) 148.8 146.6 121.8 66% a
123.4 130.9 105.5 128.9 117.0 55.3 11.2 (br)137.5 112.0 146.6 9.8 (Me) 148.8 146.6 121.8 34% b
123.4 130.9 105.5 128.9 119.0 55.3 11.2 (br)
6 C6H5 H H DMSO 0.11 300 151.4 100.4 140.3 — (H) 147.9 146.6 115.3 36% a
122.1 128.1 109.5 130.1 118.4 55.5 132.0 (i)125.0 (o)128.7 (m)127.5 (p)
DMSO 0.11 300 142.6 99.5 151.0 — (H) 147.9 147.1 115.6 64% b
120.2 128.1 109.5 130.1 112.7 55.6 133.6 (i)125.1 (o)128.7 (m)127.5 (p)
6b C6H5 H H CPMAS — 300 144.0 103.5 152.6 — (H) 148.3 116.0116.0 129.0 112.3 129.0 113.5 54.0 133.2 (i)
126.4 (o)129.0 (m)129.0 (p)
7 C6H5 H CH3 DMSO 0.11 300 151.3 99.2 142.8 — (H) 149.0 149.0 111.9 40% a
119.4 129.4 108.9 128.9 113.6 55.51 (C1) 133.7 (i)55.45 (C2) 125.0 (o)
128.6 (m)127.4 (p)
DMSO 0.11 300 142.4 99.8 150.9 — (H) 149.0 149.0 111.9 60% b
119.9 129.4 108.9 129.7 113.6 55.51 (C1) 133.7 (i)55.45 (C2) 125.0 (o)
128.6 (m)127.4 (p)
130 | New J. Chem., 2009, 33, 125–135 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
CPMAS NMR, obtained by grinding the same batch of
crystals that we used for X-ray crystallography.
Percentages of tautomers and equilibrium constants
Although some exceptions are known, the assumption of the
identical nature of the most stable tautomer in solution and
the tautomer present in the crystal is one of the most basic
tenets in tautomerism.3b,3c,17b The results in Table 6 confirm
this principle for compounds 4, 5 and 8, and allow us
to conclude that in the solid state, 6 should crystallize as
6b and 7 as 7b, or at least in cyclamers where 6b and 7b are
predominant.
Compound 5 exists in the solid state as a 66% 5a/34% 5b
mixture and in HMPA as a 35% 5a/65% 5b mixture, thus
being an exception to the rule of similarity between solution
and solid state. However, the difference in energy at 300 K
between the two situations is only of 3.2 kJ mol�1.
Conclusions
The structure, tautomerism and absence of SSPT have been
determined for six NH-pyrazoles by a combination of X-ray
crystallography and 13C/15N NMR spectroscopy. Two of the
conditions required to observe SSPT in NH-pyrazoles are the
identity (or, at least, strong similarity) of the substituents at
the 3- and 5-positions, and the formation of cyclic structures,
cyclamers, linked by N–H� � �N hydrogen bonds. Compound 3
has the same substituent at both positions (tautomer 3a is
identical to tautomer 3b), but crystallizes in a complex
network of hydrogen bonds involving the OH groups. Com-
pound 8 crystallizes as a dimer, but with only one tautomer
present (8a). Thus, none of the compounds of Table 6 display
SSPT. Finally, compound 5 is the only known example of an
NH-pyrazole that crystallizes as a 2 : 1 mixture of two
tautomers (there are examples of 2 : 2 and 3 : 1 mixtures,
but in cyclic tetramers17b,22).
Experimental
The melting points of pyrazoles 3–8 were determined by
differential scanning calorimetry (DSC) on a Seiko DSC
220C connected to a Model SSC5200H Disk Station; for the
other compounds, a hot stage microscope was used. Thermo-
grams (sample size 0.003–0.0010 g) were recorded at a scan-
ning rate of 2.0 1C min�1. Thin-layer chromatography
(TLC) was performed using Merck silica gel (60 F254) and
compounds were detected with a 254 nm UV lamp. Silica gel
(60–320 mesh) was employed for routine column chromato-
graphy separations. Elemental analyses for carbon, hydrogen
and nitrogen were carried out by the Microanalytical Service
of the Universidad Complutense of Madrid on a Perkin-Elmer
240 analyzer.
Table 4 (continued )
Compound R1 R2 R3 Solvent Conc./M T/KCa Cb Cc R2 C1 C2 C3
TautomerismC4 C5 C6 C7 C8 OCH3 R1
7b C6H5 H CH3 CPMAS — 300 143.1 96.3 149.8 — (H) 148.8 148.8 110.6120.9 129.1 108.0 129.1 110.6 53.5 (C1*) 132.1 (i)
56.1 (C2*) 125.2 (o)129.1 (m)126.2 (p)
8 C6H5 CH3 CH3 DMSO 0.31 300 141.7 110.7 147.1 9.4 (Me) 149.1 148.8 111.9 Aver.119.9 130.0 109.1 128.4 114.5 55.6 (C1) 133.2 (i) Rich in b
55.5 (C2) 127.1 (o)128.5 (m)127.3 (p)
HMPA 0.06 268 139.7 110.4 149.5 10.1 (Me) 149.8 149.3 112.1 b
120.2 130.9 109.1 128.8 113.2 55.9 (C1) 135.9 (i)55.9 (C2) 127.2 (o)
128.6 (m)126.9 (p)
CPMAS — 300 140.7 112.5 148.8 9.2 (Me) 148.8 148.8 112.5 b
124.7 130.2 110.7 130.2 117.1 54.7 134.6 (i)128.5 (o)130.2 (m)126.7 (p)
a The 1J coupling constants are not reported; their average values are: pyrazole C4–Hb = 175 Hz; phenyl CH = 159 Hz except C4–H and
C6–H = 156 Hz; olefin C–H = 155 Hz; OCH3 = 144 Hz; C–Me substituents: 126.5 Hz. The other couplings (Hz) are: 2J = 2.2 (C1), 2J = 4.5
(C7), 2J = 5.9 (Cb–Me4); 3J = 8.4 (C1), 3J = 7.3 (C2), 3J = 5.8 (C4), 3J = 6.8 (C5), 3J = 6.0 (C6), 3J = 4.5 (C7), 3J = 2.4 (Cb–H).b Not observed.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 131
General procedure for the preparation of pyrazole derivatives
(3–8)
Compounds 3–8 were prepared by reacting the corresponding
b-diketones23 (1 mmol) with hydrazine hydrate 98% (1.5 mmol)
in acetic acid (5 mL). After heating at reflux for 2 h, the
reaction mixture was poured into water, and the precipitate
filtered off, washed with water and dried. The solid was
purified by column chromatography using ethyl acetate as
the eluent.
(E)-3,5-Bis[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-1H-
pyrazole (3)
3 was prepared from purified commercially available 1. The
compound was obtained as a colourless solid after recrystalli-
zation from H2O/EtOH (1 g, 2.74 mmol, 63%). Mp: 217.1 1C,
lit.: 211–214 1C5 or 215 1C.8 Anal. calc. for C21H20N2O4
(364.14): C, 69.22; H, 5.53; N, 7.69; found: C, 68.79; H,
5.53; N, 7.70%.
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-methyl-
1H-pyrazole (4)
4 was prepared from (E)-6-(4-hydroxy-3-methoxyphenyl)hex-
5-ene-2,4-dione.23 The compound was obtained as a colourless
solid after recrystallization from CH2Cl2/hexane/EtOH
(251 mg, 1.1 mmol, 85%). Mp: 141.6 1C. Anal. calc. for
C13H14N2O2 (230.11): C, 67.26; H, 6.44; N, 12.11; found: C,
67.81; H, 6.13; N, 12.17%.
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-4,5(3)-
dimethyl-1H-pyrazole (5)
5 was prepared from (E)-6-(4-hydroxy-3-methoxyphenyl)-3-
methylhex-5-ene-2,4-dione.23 The compound was obtained as
a colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (180 mg, 0.73 mmol, 61%). Mp: 176.1 1C. Anal. calc.
for C14H16N2O2 (244.12): C, 68.46; H, 6.61; N, 11.35; found:
C, 68.83; H, 6.60; N, 11.47%.Table
5The
15N
NMR
chem
icalshifts
(d)in
DMSO-d
6andHMPA-d
18solutions,andunder
CPMASconditions
Compound
R1
R2
R3
Solvent
Conc./M
T/K
N–H
–N=
%a
%b
PTa
3*
HH
CPMAS
—300
�180.8
�100.6
50
50
No
4CH
3H
HHMPA
0.10
276
�180.5
N.o.b
B50
B50
No
�173.6
4a
CH
3H
HCPMAS
—300
�177.7
�100.9
100
0No
5CH
3CH
3H
HMPA
0.08
300
�185.6
(major)
N.o.
30
70
No
�175.9
CPMAS
—300
�187.8
�111.2
66
34
No
�172.0
(major)
�103.6
(major)
6b
C6H
5H
HCPMAS
—300
–181.5
�105.3
0100
No
8b
C6H
5CH
3CH
3HMPA
0.06
268
–182.2
N.o.
0100
No
CPMAS
—300
–181.3
�98.7
0100
No
aProtontransfer
bNotobserved
Fig. 9 The methyl group region of the 13C NMR spectrum of 5.
132 | New J. Chem., 2009, 33, 125–135 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-phenyl-
1H-pyrazole (6)
6 was prepared from (E)-5-(4-hydroxy-3-methoxyphenyl)-1-
phenylpent-4-ene-1,3-dione.23 The compound was obtained as
a colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (228 mg, 0.78 mmol, 77%). Mp: 142.9 1C. Anal. calc.
for C18H16N2O2 (292.12): C, 73.95; H, 5.54; N, 10.11; found:
C, 73.95; H, 5.54; N, 10.11%.
(E)-3(5)-[b-(3,4-dimethoxyphenyl)-ethenyl]-5(3)-phenyl-1H-
pyrazole (7)
7 was prepared from (E)-5-(3,4-dimethoxyphenyl)-1-phenyl-
pent-4-ene-1,3-dione.23 The compound was obtained as a
colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (196 mg, 1.27 mmol, 51%). Mp: 173.4 1C. Anal. calc.
for C19H18N2O2 (306.37): C, 74.48; H, 5.92; N, 9.14; found: C,
74.21; H, 5.82; N, 9.16%.
(E)-3(5)-[b-(3,4-dimethoxyphenyl)-ethenyl]-4-methyl-5(3)-
phenyl-1H-pyrazole (8)
8 was prepared from (E)-5-(3,4-dimethoxyphenyl)-2-methyl-1-
phenylpent-4-ene-1,3-dione.23 The compound was obtained as
a colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (170 mg, 0.53 mmol, 58%). Mp: 182.0 1C. Anal. calc.
for C20H20N2O2 (320.39): C, 74.97; H, 6.29; N, 8.74; found: C,
74.28; H, 6.14; N, 8.77%.
X-Ray data collection and structure refinement (compounds 3, 4,
5 and 8)
Data collection for all of the compounds was carried out at
room temperature on a Bruker Smart CCD diffractometer
Table 6 The tautomeric composition of 3–8 (Sty: Ar–CHQCH–)a
Compound Tautomers X-Ray CPMAS DMSO HMPA
3 a, b: 3,5-BisSty 3a = 3b 3a = 3b 3a = 3b No PTb N. M.4 a: 3-Sty-5-Me 4a 4a Average rich in 4a B50% 4a
b: 3-Me-5-Sty B50% 4b
5 a: 3-Sty-5-Me 66% 5a 66% 5a Average rich in 5b 35% 5a
b: 3-Me-5-Sty 34% 5b 34% 5b 65% 5b
6 a: 3-Sty-5-Ph N. M. 6b 36% 6a N. M.b: 3-Ph-5-Sty 64% 6b
7 a: 3-Sty-5-Ph N. M. 7b 40% 7a N. M.b: 3-Ph-5-Sty 60% 7b
8 a: 3-Sty-5-Ph 8b 8b Average rich in 8b 8b
b: 3-Ph-5-Sty
a N. M. means not measured. b Proton transfer
Table 7 The crystal and structure refinement data for compounds 3, 4, 5 and 8
Crystal data 3 4 5 8
Empirical formula C21H20N2O4 C13H14N2O2 C14H16N2O2 C20H20N2O2
Formula weight 364.39 230.26 244.29 320.38Crystal system Monoclinic Orthorhombic Monoclinic OrthorhombicSpace group P2(1)/c Pbca P2(1)/c PbcaUnit cell dimensions a/A 8.2394(10) 13.2563(15) 8.519(2) 13.2363(13)
b/A 14.0198(17) 7.6962(9) 12.964(4) 8.2769(8)c/A 16.306(2) 22.855(3) 34.615(10) 30.673(3)b (1) 101.060(3) — 94.607(7) —
Volume/A3 1848.7(4) 2331.7(5) 3810.6(19) 3360.4(6)Z 4 8 12 8Density (calculated)/Mg m�3 1.309 1.312 1.277 1.267Absorption coefficient/mm�1 0.092 0.090 0.087 0.083Scan technique o and j o and j o and j o and jF(000) 768 976 1560 1360Range for data collection (1) 1.93 to 25.00 1.78 to 27.00 1.18 to 25.00 1.33 to 25.00Index ranges �9, �16, �18 to 9, 16, 19 �13, �9, �29 to 16, 9, 29 �9, �15, �41 to 10, 15, 41 �15, �9, �36 to 10, 9, 32Reflections collected 13 998 19 397 28 784 16 484Independent reflections 3244 2541 6720 2954Observed reflections [I 4 2s(I)] 1418 1248 2855 1655Rint 0.1198 0.0889 0.0905 0.0708Completeness to y (%) 99.6 100.0 100.0 99.9Data/restraints/parameters 3244/0/245 2541/0/156 6720/2/497 2954/0/224Goodness-of-fit on F2 0.912 1.034 0.984 1.074R1a 0.0539 0.0508 0.0769 0.0507wR2b (all data) 0.1808 0.1768 0.2486 0.1848Largest differential peak andhole/eA�3
0.232 and �0.278 0.214 and �0.247 0.950 and �0.377 0.193 and �0.192
a R1 =P
||Fo| � |Fc||/P
|Fo|.b wR2 =
P[w(Fo
2 � Fc2)2]/
P[w(Fo
2).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 133
using graphite-monochromated Mo-Ka radiation (l =
0.71073 A) operating at 50 kV and 30 mA. In all cases, the
data were collected over a hemisphere of the reciprocal space
by the combination of three exposure sets. Each frame ex-
posure time was either 10 or 20 s, covering 0.31 in o. The cellparameters were determined and refined by a least-squares fit
of all reflections collected. The first 100 frames were re-
collected at the end of the data collection to monitor crystal
decay, and no appreciable decay was observed. A summary of
the fundamental crystal and refinement data is given in
Table 7. The structures of all the compounds were solved by
direct methods and conventional Fourier synthesis, and re-
fined by full matrix least-squares on F2 (SHELXL-97).24 All
non-hydrogen atoms were refined anisotropically.
In all cases, the hydrogen atoms were calculated, included
and refined as riding on their respective carbon-bonded atom
with a common anisotropic displacement. The rest of the
hydrogen atoms, i.e. those bonded to nitrogen or oxygen
atoms, were located in a Fourier difference synthesis, and in
all cases were included and refined as riding on their respective
bonded atoms for 3, 4 and 5, while for 8, its coordinates were
refined and the thermal factors kept constant. The longer O–H
bond distances in some of the hydroxyl groups are due to the
formation of hydrogen bonds.25
The largest peaks and holes in the final difference map were
0.232 and �0.278, 0.214 and �0.247, 0.950 and �0.377, and0.193 and �0.192 eA�3 for 3, 4, 5 and 8, respectively. The final
R1 and wR2 values were 0.0539 and 0.1808, 0.0508 and 0.1768,
0.0769 and 0.2486, and 0.0507 and 0.1848 for 3, 4, 5 and 8,
respectively.
NMR spectroscopy
Solution NMR spectra. Solution NMR spectra were re-
corded on a Bruker DRX 400 (9.4 T; 400.13 MHz for 1H,
100.62 MHz for 13C and 40.56 MHz for 15N) spectrometer
fitted with a 5 mm inverse detection H–X probe and equipped
with a z-gradient coil at 300 K. 1H and 13C NMR chemical
shifts (d) are referenced to Me4Si; for15N NMR, nitromethane
(0.00) was used as an external standard. Typical parameters
for the 1H NMR spectra were: a spectral width of 5787 Hz, a
pulse width of 7.5 ms, an attenuation level of 0 dB and a
resolution of 0.34 Hz per point. Typical parameters for the 13C
NMR spectra were: a spectral width of 21 kHz, a pulse width
of 10.6 ms, an attenuation level of �6 dB, a relaxation delay of
2 s and a resolution of 0.63 Hz per point; WALTZ-16 was used
for broadband proton decoupling and the FIDs were multi-
plied by an exponential weighting (lb = 1 Hz) before Fourier
transformation. 2D inverse proton detected heteronuclear
shift correlation spectra, gs-HMQC (1H–13C) and gs-HMBC
(1H–13C), were acquired and processed using standard Bruker
NMR software. Typical parameters for these spectra were:
a spectral width of 5787 Hz for 1H and 20.5 kHz for 13C, a
1024 � 256 data set, number of scans = 2 (gs-HMQC) or 4
(gs-HMBC), a relaxation delay of 1 s, and a delay for the
evolution of 13C–1H coupling constants of 3 ms (gs-HMQC)
or 60 ms (gs-HMBC). The FIDs were processed using zero
filling in the F1 domain, and a sine-bell window function in
both dimensions was applied prior to Fourier transformation.
In the gs-HMQC experiments, GARP modulation of 13C was
used for decoupling. 15N NMR spectra were acquired using
2D inverse proton detected heteronuclear shift correlation
spectroscopy. Typical parameters for the gs-HMQC
(1H–15N) spectra were: a spectral width of 5787 Hz for 1H
and 12.5 kHz for 15N, a 1024 � 256 data set, number of
scans = 4, a relaxation delay of 1 s and a 7 ms delay for the
evolution of the 15N–1H coupling. The FIDs were processed
using zero filling in the F1 domain, and a sine-bell window
function in both dimensions was applied prior to Fourier
transformation. A Bruker BVT 3000 temperature unit was
used to control the temperature of the cooling gas stream and
an exchanger was used to achieve low temperatures.
Solid state. Solid state 13C (100.73MHz) and 15N (40.60MHz)
CPMAS NMR spectra were recorded on a Bruker WB 400
spectrometer at 300 K using a 4 mm DVT probe head.
Samples were carefully packed in 4 mm diameter cylindrical
zirconia rotors with Kel-F caps. Operating conditions in-
volved 90 3.2 ms 1H pulses and a decoupling field strength of
78.1 kHz in a TPPM sequence. The non-quaternary suppres-
sion (NQS) technique to observe only the quaternary carbon
atoms was employed. 13C spectra were initially referenced
to a glycine sample and then the chemical shifts were recalcu-
lated to Me4Si (for the carbonyl atom, dglycine = 176.1).
Similarly, 15N spectra were initially referenced to 15NH4Cl
and then recalculated to nitromethane, using the relationship:
d 15Nnitromethane = d 15NNH4Cl� 338.1. Typical acquisition
parameters for the 13C CPMAS were: a spectral width of
40 kHz, a recycle delay of 15–75 s, an acquisition time of
30 ms, a contact time of 2 ms and a spin rate of 12 kHz.
Typical parameters for the 15N CPMAS were: a spectral width
of 40 kHz, a recycle delay of 15–75 s, an acquisition time of 35
ms, a contact time of 7–8 ms and spin rate of 6 kHz.
Acknowledgements
This work has been financed by the Spanish MEC (CTQ2006-
02586 and CTQ2007-62113).
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 125–135 | 135
Neutral 5-nitrotetrazoles: easy initiation with low pollutionw
Thomas M. Klapotke,* Carles Miro Sabate and Jorg Stierstorfer
Received (in Durham. UK) 21st July 2008, Accepted 8th September 2008
First published as an Advance Article on the web 24th October 2008
DOI: 10.1039/b812529e
5-Nitro-2H-tetrazole (1), 1-methyl-5-nitrotetrazole (2) and 2-methyl-5-nitrotetrazole (3) were
synthesized starting from the corresponding 5-amino-substituted tetrazoles in good yields and
purities. The compounds were fully characterized by analytical and spectroscopic methods and
their solid state structures were determined by low temperature X-ray diffraction techniques. Due
to the potential of tetrazoles as energetic materials an extensive computational study (CBS-4M)
was performed in order to estimate the energies of formation (DfU1) of the molecules, which are
highly endothermic (1, 2527 kJ kg�1; 2, 2253 kJ kg�1 and 3, 2006 kJ kg�1). The EXPLO5
software was used to calculated the corresponding detonation velocities (Ddet) and detonation
pressures (pdet) (1, Ddet = 9457 m s�1 and pdet = 390 kbar; 2, Ddet = 8085 m s�1 and
pdet = 257 kbar and 3, Ddet = 8109 m s�1 and pdet = 262 kbar) by combining the DfU1 values
of the materials with the (X-ray calculated) densities and molecular formulas, giving performances
comparable to commonly used secondary explosives (e.g., RDX). Lastly, all three neutral
compounds can be easily initiated by impact (o2 J) and with high detonation velocities and
excellent combined oxygen and nitrogen contents offer a more powerful and environmentally
friendly alternative to commonly used primary explosives in initiating devices.
Introduction
In the continuous search for novel green energetic materials1
with high nitrogen but low carbon content,2,3 several groups
around the world are currently investigating HEDMs (High
Energy Dense Materials) based on tetrazoles.4 These energetic
materials have variable application such as in low-smoke
producing pyrotechnic compositions,5 gas generators,6 pro-
pellants,7 high explosives8 and primers in primer charges
(PC).9 Tetrazole derivatives,10,11 tetrazolate12,13 and tetra-
zolium14,15 salts are of special interest. One of the most
promising class of molecules in this regard are 5-substituted
tetrazoles16 (Fig. 1) due to the fact that their properties can be
controlled by selection of the substituent at the carbon atom.
While electron donating groups (EDGs) such as NH217 or
OH18 yield rather stable compounds, electron withdrawing
groups (EWGs) such as NO219 and CN20 destabilize the ring
system and increase the sensitivity of the materials. Also
protonation/alkylation of the tetrazole ring is directed by the
electronegativity of the substituent. While EWGs direct the
protonation/alkylation to the nitrogen atom labelled as N2 of
the tetrazole ring (see crystal structure labels),21 EDGs favor
substitution at N1.22 However, there are other factors that
contribute to the explosivity of tetrazoles. For example, the
high sensitivity of 5-azidotetrazole (C)23 and 5-nitriminotetra-
zole (D)24,25 is better explained due to the energetic nature of
the azide and nitramine groups rather than based on the
electronic influence of these groups on the ring system.
The combination of a tetrazole ring with energetic groups
containing oxygen such as nitro groups (R–NO2),26 nitrate
esters (R–O–NO2)27 or nitramines (R2N–NO2)
28 is of parti-
cular interest. Energetic materials based on tetrazoles show the
desirable compromise in properties with high nitrogen con-
tents on the one hand, and surprising kinetic and thermal
stabilities due to aromaticity on the other.
The interesting energetic properties of tetrazole-based
energetic materials have been mainly investigated in view of
the properties of such compounds for use as propellants and/
or secondary explosives1,29 and it has only been until recent
times that metal salts with 5-substituted tetrazole ligands have
been studied as prospective primary explosives.30,31 Primary
explosives are characterized by easy initiation when submitted
Fig. 1 Structural formulas of neutral 5-substituted tetrazoles.
Prof. Dr. Thomas M. Klapotke, Energetic Materials Research,Department of Chemistry and Biochemistry, University of Munich(LMU), Butenandtstr. 5-13, D-81377 Munich, Germany.E-mail: [email protected]; Fax: +49 89 2180 77492w CCDC reference numbers 689202 (1), 689201 (2) and 689203 (3). Forcrystallographic data in CIF or other electronic format see DOI:10.1039/b812529e
136 | New J. Chem., 2009, 33, 136–147 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
to heat or shock and have the ability to transmit the detona-
tion to less sensitive (secondary) explosives. For these reasons,
they are used in initiating devices. Typical detonation
velocities for this class of compounds are in the range
3500–5500 m s�1, much lower than those of secondary
explosives (5500–9000 m s�1).32 Commonly used primary
explosives are based on lead (e.g., lead azide or styphnate)
with the accompanying environmental impact and thus, recent
efforts have focused on the development of more environmen-
tally friendly metal-based alternatives.30,31
In this work we would like to present the syntheses, full
analytical, spectroscopic and structural characterization of
neutral 5-nitrotetrazoles. In addition, the energetic properties
of the compounds were assessed revealing easy initiation by
impact and detonation velocities, which are almost twice as
high as those of commonly used primary explosives.5
Results and discussion
Syntheses
5-Nitro-2H-tetrazole (1) was prepared starting from 5-amino-
1H-tetrazole (5-At) by a modified literature procedure accord-
ing to Scheme 1.33 5-At was diazotized according to a
previously published procedure in our group34 to yield ammo-
nium 5-nitrotetrazolate. ‘‘In situ’’ formation of the potassium
salt by reaction with potassium hydroxide in ethanol and
subsequent treatment with diluted hydrochloric acid and
extraction with ether yields the desired compound. The solvent
needs to be removed using vacuum since the product (1)
absorbs water on time and the compound needs to be stored
under nitrogen. On the other hand, methylation of sodium
5-aminotetrazolate using dimethyl sulfate22 yields a separable
mixture of the two (1-methyl and 2-methyl) isomers.35
Both compounds can be treated similarly and diazotization
with two equivalents of sodium nitrite in the presence of a
non-nucleophilic acid (e.g., sulfuric acid) yields 1-methyl-5-
nitrotetrazole (2) and 2-methyl-5-nitrotetrazole (3) as crystal-
line compounds. Similar reactions are also found in the
literature by using N2O5.36
2 and 3 are extracted from the
reaction mixture using CH2Cl2. The selection of the acid for
the diazotation process is of utmost importance since it affects
the yield of the nitro-compound. For example using hydro-
chloric acid 1- or 2-methyl-5-chlorotetrazoles are obtained as
the main product.
Lastly, 1 is readily soluble in most common solvents such as
ether, THF, MeCN, acetone, water, DMSO and DMF
whereas 2 and 3 show also good solubility in MeOH, EtOH,
acetone, MeCN, ethyl acetate, THF, CH2Cl2 and DMSO
and DMF.
NMR spectroscopy
All three neutral 5-nitrotetrazoles were characterized by ana-
lytical and spectroscopic methods. The elemental analysis of 1
was omitted due to the risk of explosion found in similar
compounds with a high sensitivity30 on the one hand and to
the hygroscopicity of the material on the other. The 1H NMR
spectra of 1–3 measured in DMSO-d6 show two signals
corresponding to the ring proton (1, broad, d = 6.29 ppm)
and to the methyl group protons (2, d = 3.68 ppm and 3,
d = 4.50 ppm). The electron withdrawing character of the
–NO2 group shifts the proton resonances to low field in
comparison to 5-amino-1H-tetrazole and 1-methyl- and
2-methyl-5-amino-1H-tetrazole (i.e., –NH2 group).37 Table 1
contains summarized the 13C and 15N NMR chemical shifts
and the 15N–1H coupling constants for all three compounds.
The proton coupled as well as the proton decoupled 15N NMR
spectra (with full NOE) were also recorded. As already
observed in the 1H NMR spectra, the methyl group resonance
(in this case carbon resonance) of the 1-methyl isomer (2, d =
33.1 ppm) is shifted to higher field in comparison with that of
the 2-methyl isomer (3, d = 41.9 ppm). Similarly, the ring
carbon atom signal is also to be found at higher field for
2 (d = 157.6 ppm) than for 3 (d = 166.4 ppm). This carbon
atom shows the lowest field resonance for 1 (d = 168.4 ppm),
which is in keeping with salts containing the 5-nitrotetrazolate
anion.30,34
Scheme 1 Syntheses of neutral 5-nitrotetrazoles: a = ref. 34;
b = (i) KOH, (ii) HCl (2 M); (c) (i) NaOH, (ii) Me2SO4; d = 2 eq.
NaNO2, H2SO4.
Table 1 15N and 13C NMR resonances of compounds 1–3 with protonation (1, PIS) and methylation (2 and 3, MIS) induced shiftsa and couplingconstantsb
Compound N1 N2 N3 N4 N5 C1 C2
1 �69.6 [�3.4] 19.6 [5.2] 19.6 [5.2] �69.6 [�3.4] �29.8 [�4.5] 168.4 —2 �155.7 [�89.5] �0.7 [�15.1] 6.7 [7.7] �54.8 [11.4] �37.6 [�12.3] 157.6 33.1
2J(N–H) = 2.1 3J(N�H) = 1.83 �97.9 [�31.7] �76.6 [�91.0] 5.3 [9.1] �55.1 [11.1] �33.5 [�8.2] 166.4 41.9
3J(N–H) = 1.7 2J(N–H) = 2.1 3J(N�H) = 1.7NaNTc �66.2 14.4 14.4 �66.2 �25.3 169.2 —
a PIS and MIS values are shown in square [] brackets and given in ppm. b Coupling constants (J) are given in Hz. c NaNT = Sodium
5-nitrotetrazolate (see ref. 30).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 136–147 | 137
The quadrupolar moment of the 14N nucleus results in
signals at approximately +14 (N2/3), �24 (NO2) and �66(N1/4) in the 14N NMR spectrum of compound 1, which are
broad (n1/2 B 300 Hz, B60 Hz and B320 Hz, respectively).
The 15N NMR spectra show comparable resonances to those
observed in the 14N NMR spectra but much sharper (Fig. 2).
The proton induced shifts (PIS, 1) and methyl induced shifts
(MIS, 2 and 3)37 are useful for identifying the protonation/
alkylation site as well as assigning the resonances of the
nitrogen atoms and are also tabulated in Table 1. Comparison
of the resonances observed for the 5-nitrotetrazolate anion in
sodium 5-nitrotetrazolate with those of the compounds in this
study shows unexpected shifts. The nitrogen atoms labelled as
N2 and N3, which are equivalent due to fast exchange in the
NMR in solution of 1, show the largest (positive) PIS value,
indicative of protonation taking place on these two nitrogen
atoms as observed (in the solid state) in the crystal structure of
the compound (see X-ray discussion). The remainder of the
PIS values are small in value and negative. The MIS effect in
compounds 2 and 3 is much more unexpected and the methyl-
ated nitrogen atoms (N1 for 2 and N2 for 3) show the largest
(negative) MIS values (B�90 ppm for both). The next nitrogen
atom close to the methyl group (i.e., at two bonds) feels the
effect of the alkyl group much more weakly (MIS = �31.7 ppmfor N1 in 3) but can still be used to assign the resonances of
this atom. Lastly, the fast exchange of the proton in 1 results in
broadening of the resonance corresponding to the protonated
nitrogen atom, whereas 2 and 3 show coupling constants to the
methyl groups, which are slightly larger for the nitrogen atoms
directly attached to the methyl group (2J(N�H) = 2.1 Hz)
than for those at three bonds of the methyl group protons
(3J(N�H) = 1.7–1.8 Hz).
Molecular structures
Suitable single crystals of 1 and 2 were picked from the
crystallization mixture and mounted in Kel-F oil and trans-
ferred to the N2 stream of an Oxford Xcalibur3 diffractometer
with a Spellman generator (voltage 50 kV, current 40 mA) and
a KappaCCD detector. The data collections were performed
using the CrysAlis CCD software,38 the data reduction with
the CrysAlis RED software.39 The data for compound 3 were
collected on a Nonius Kappa CCD diffractometer under an N2
stream as well. Data collection and reduction was done by the
Bruker ‘‘Collect’’ and the ‘‘HKL Denzo and Scalepack’’
software.40 The structures were solved with SIR-92 (2, 3),41
and SHELXS-97 (1),42 refined with SHELXL-9743 and finally
checked using the PLATON software.44 The non-hydrogen
atoms were refined anisotropically and the hydrogen atoms
were located and freely refined. The absorptions of 1 and 2
were corrected by a SCALE3 ABSPACK multi-scan
method.45 All relevant data and parameters of the X-ray
measurements and refinements are given in Table 2.46
One of the two crystallographically independent formula
units found in the crystal structure of compound 1 is repre-
sented in Fig. 3. Protonation of the NT� anion occurs at N3,
Fig. 2 15N NMR spectra of compounds 1–3.
Table 2 Crystallographic data and refinements
1 2 3
Formula CHN5O2 C2H3N5O2 C2H3N5O2
Mr/g mol�1 115.07 129.09 129.09Crystal system Monoclinic Monoclinic MonoclinicSpace group P21 (No. 4) P21/n (No. 14) P21/c (No. 14)Color/habit Colorless plates Colorless rods Colorless rodsSize/mm 0.03 � 0.18 �
0.270.04 � 0.08 � 0.10 0.03 � 0.18 �
0.27a/A 5.3358(4) 10.0578(4) 6.331(1)b/A 9.4799(7) 9.7055(4) 4.993(1)c/A 8.3190(8) 16.5331(6) 16.388(3)b/1 106.989(9) 101.701(4) 97.13(3)V/A3 402.44(6) 1580.36(11) 514.0(2)Z 4 12 4Dc/g cm�3 1.899 1.628 1.668m/mm�1 0.174 0.143 0.146F(000) 232 792 264lMoKa/A 0.71073 0.71073 0.71073T/K 123 200 200y Range/1 4.0, 32.5 3.9, 25.0 3.2, 26.0Data set �7: 7; �14: 14;
�12:12�11: 10; �11: 11;�19: 15
�7: 7; �6: 6;�20: 19
Reflectionscollected
5975 7250 3454
Independentreflections
1452 2766 1003
Rint 0.059 0.064 0.037Observedreflections
742 1139 862
No. parameters 153 258 94R1 (obs) 0.0274 0.0664 0.0364wR2 (all data) 0.0497 0.2102 0.0946GooF 0.83 0.91 1.08Dr/e A�3 �0.23, 0.21 �0.27, 0.85 �0.22, 0.14CCDC 689202 689201 689203
Fig. 3 Formula unit of 1 with the labelling scheme. Hydrogen atoms
shown as spheres of arbitrary radius and thermal displacements set at
50% probability.
138 | New J. Chem., 2009, 33, 136–147 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
which is in contrast with 5-amino-46 or 5-azidotetrazole.23 In
Table 3 there are summarized the angles and distances of the
two 5-nitrotetrazolate rings, which, within the limits of error,
are not significantly different. The main difference is observed
in the twist of the nitro groups in respect to the tetrazole rings.
Whereas in one of the two molecules the nitro group is almost
coplanar to the ring (O4–N10–C1–N6 = �178.2(3)1), in the
other, this is significantly deviated (O2–N5–C1–N1 =
�164.9(3)1). So, one of the formula units is similar to metal
NT salts, which show small torsion angles between 2 and 51,30
whereas the other one is more similar to NT salts with
nitrogen-rich bases (0–101).34 A plausible explanation for this
could be that in NT salts, there is a negative charge, which is
delocalized all around the tetrazole ring and over the nitro
group, making them virtually coplanar. Proof for this is the
relatively longer C1–N1 distances (B1.445(4) A) in 1. There-
fore one would expect larger torsion angles due to the lack of
delocalization in both formula units. The smaller torsion angle
for one of the two units can be explained by hydrogen-bonding
effects (see discussion below).
Regardless of the expected planarity of 1 the presence of a
proton surrounded by many electronegative atoms forces the
compound to form hydrogen bonds, which prohibits layering.
These hydrogen bonds are formed by the protonated nitrogen
atom (N2 or N7) as the donor atom and either tetrazole ring
nitrogen atoms or, in one instance with one of the nitro groups
oxygen atoms (O3). A report of hydrogen-bridges is given in
Table 4. The interaction between N7 and O3 (N7� � �O3i =
3.015(4) A; symmetry code: (i) �x, 0.5 + y, �z) ‘‘fixes’’ thenitro group in such a way that it is coplanar to the tetrazole
ring and forms the C1,1(6) motifs represented in Fig. 4
(at the primary level) (Table 5). Similarly, the dimer
pairs formed by two crystallographically related rings
Table 3 Selected bond lengths [A] and angles [1] for compounds 1–3
1 (A) 1 (B) 2 (A) 2 (B) 2 (C) 3
O1–N5 1.229(3) 1.227(3) 1.208(6) 1.194(6) 1.196(5) 1.223(2)O2–N5 1.221(3) 1.215(3) 1.191(6) 1.202(5) 1.185(5) 1.222(2)N5–C1 1.440(4) 1.450(4) 1.450(7) 1.481(7) 1.438(6) 1.445(2)N1–C1 1.319(4) 1.310(4) 1.326(6) 1.316(6) 1.342(6) 1.321(2)N1–N2 1.323(4) 1.319(4) 1.336(6) 1.345(5) 1.354(6) 1.319(2)N2–N3 1.318(3) 1.322(3) 1.297(6) 1.317(6) 1.325(6) 1.329(2)N3–N4 1.324(4) 1.318(3) 1.356(7) 1.363(6) 1.317(7) 1.317(2)N4–C1 1.333(4) 1.336(4) 1.303(6) 1.291(6) 1.295(6) 1.331(2)N1(2)–C2 1.461(6) 1.478(7) 1.487(6) 1.461(2)
O2–N5–O1 125.5(3) 126.0(3) 127.6(6) 127.2(5) 125.6(5) 125.1(1)O1–N5–C1 117.9(3) 117.2(3) 115.8(5) 117.2(5) 117.4(5) 117.4(1)O2–N5–C1 116.6(3) 116.7(3) 116.6(5) 115.7(5) 117.0(5) 117.5(1)N1–C1–N5 123.2(3) 122.3(3) 125.9(5) 123.2(5) 124.8(4) 121.9(1)C1–N1–N2 100.1(3) 99.0(3) 106.8(4) 106.5(4) 107.3(4) 99.9(1)N3–N2–N1 114.7(3) 115.4(3) 106.6(5) 106.2(4) 104.9(4) 114.3(1)N2–N3–N4 105.7(2) 105.5(2) 111.4(5) 110.8(4) 111.5(5) 106.1(1)N3–N4–C1 105.0(2) 104.3(3) 103.6(5) 103.5(4) 106.6(5) 104.6(1)N4–C1–N5 122.1(3) 121.9(3) 122.5(5) 123.5(5) 125.4(5) 123.0(1)N1–C1–N4 114.5(3) 115.8(3) 111.6(5) 113.1(5) 109.7(5) 115.1(1)C1–N1–C2 106.8(4) 131.9(5) 131.4(5)N1–N2–C2 123.6(1)N2–N1–C2 121.1(5) 121.5(5) 121.3(5)N3–N2–C2 122.1(1)
Table 4 Geometry for selected hydrogen bonds in the structure of 1
D–H� � �A D–H (A) H� � �A (A) D� � �A (A) D–H� � �A (1)
1
N2–H1� � �N4 0.97(4) 1.88(4) 2.837(4) 171.(3)N7–H2� � �O3a 0.85(4) 2.22(4) 3.015(4) 158.(3)N7–H2� � �N3b 0.85(4) 2.53(4) 3.057(4) 121.(3)
a Symmetry codes for 1: �x, 0.5 + y, �z. b 1 � x, 0.5 + y, 1 � z.
Fig. 4 View of the unit cell of 1 along the a-axis showing the graph-
sets in the structure (dotted lines). Symmetry codes: (ii) 1 � x, 0.5 + y,
1 � z; (iii) 1 + x, y, 1 + z; (iv) 1 � x, �0.5 + y, 1 � z; (v) 2 � x, 0.5 +
y, 1 � z; (vi) 1 � x, 0.5 + y, �z; (vii) x, 1 + y, z; (viii) 1 + x, y, z.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 136–147 | 139
(N7� � �N3ii = 3.057(4) A; symmetry code: (ii) 1 � x, 0.5 + y,
1 � z) yield a C1,1(4) graph-set. Lastly, the third hydrogen
bond found in the structure forms only finite patterns of the
type D1,1(2) at the primary level, which combine with the
other two hydrogen bonds yielding larger dimeric interactions
with the label D3,3(X) (X = 7, 9) at the secondary level. This
results in a highly efficient packing as can be deduced from the
high density of the compound (1.899 g cm�3).
The unit cell of 2, which crystallizes in the monoclinic space
group P21/c contains twelve molecules. For better clearness
only one molecule of the asymmetric unit is shown in Fig. 5.
Since hydrogen bonds are not present in the structures
of 2 and 3, the densities (2: 1.628, 3: 1.668 g cm�3) are
significantly lower than that observed for 1 (1.899 g cm�3).
3, (in Fig. 6), crystallizes monoclinic in the space group P21/c
with four molecules in the unit cell. The molecular geometry
of 2 as well as of 3 is particularly comparable to that of
1 and other 5-substituted tetrazoles. All C–N and N–N bond
lengths lie between single and double bonds, whereby the
shortest distance (1.30–1.33 A) is observed between the
nitrogen atoms N2 and N3. In both cases the NO2
group is co-planar with the tetrazole ring, which confirms
previously published assumptions.47 The distances between
the atoms C1 and N5 are between 1.43 and 1.48 A, which
are in the range of typical C–N single bonds. The same trend
can be found for the N1–C2 and N2–C2 bond lengths
(1.46–1.49 A).
Thermal and energetic properties
In order to assess the thermal and energetic properties of
neutral 5-nitrotetrazoles 1–3 the thermal stability (decomposi-
tion points from DSC measurements), as well as the sensitivi-
ties to friction, impact, electrostatic discharge and thermal
shock of all three compounds were experimentally assessed
(Tables 6 and 7) using standard BAM tests.50–55 In addition,
for all three CHNO compounds the constant volume energies
Table 5 Graph-set matrix for medium to strong hydrogen bonds inthe crystal structure of 1. First level motifs on-diagonal and secondlevel graph sets off-diagonal
H-Bond N2–H1� � �N4 N7–H2� � �O3a N7–H2� � �N3b
N2–H1� � �N4 D1,1(2)N7–H2� � �O3a D3,3(9) C1,1(6)N7–H2� � �N3b D3,3(7) C1,1(4)
a Symmetry codes for 1: �x, 0.5 + y, �z. b 1 � x, 0.5 + y, 1 � z.
Fig. 5 Formula unit of 2 with the labelling scheme. Hydrogen atoms
shown as spheres of arbitrary radius and thermal displacements set at
30% probability.
Fig. 6 Formula unit of 3 with the labelling scheme. Hydrogen atoms
shown as spheres of arbitrary radius and thermal displacements set at
50% probability.
Table 6 Physico-chemical properties, initial safety data and predictedperformance of compounds 1–3
1 2 3
Formula CHN5O2 C2H3N5O2 C2H3N5O2
Molecular mass/g mol�1
115.05 129.08 129.08
Impact sensitivitya/J o 1 2 1Friction sensitivityb/N o 5 82 40Electrical dischargec/J — 0.50 0.20N (%)d 60.9 54.3 54.3N + O (%)e 88.6 79.0 79.0O (%)f �7.0 �43.4 �43.4Thermal shockg
Deflagration Combustion CombustionCombustion Very good Good GoodSmokeless + + +DSCh/1C 98 (mp), 130
(decomp.)45 (mp), 155(decomp.)
75 (mp), 150(decomp.)
Densityi/g cm�3 1.899 1.628 1.668DfHm1
j/kJ mol�1 281 278 247DfU1
k/kJ kg�1 +2527 +2253 +2006
Calculated values using EXPLO5
�DEUm1l/J g�1 �5744 �5588 �5368
TEm/K 4804 4226 4071
pn/kbar 390 257 262Do/m s�1 9457 8085 8109Gas vol.p/L kg�1 779 766 763
a BAMmethods, see ref. 50–55. b BAMmethods, see ref. 50–55. c OZM
electric spark tester, see ref. 57–59. d Nitrogen content. e Nitrogen +
oxygen content. f Oxygen balance.60 g Fast heating behavior. h Decom-
position temperature from DSC (b = 5 1C). i Estimated from X-ray
diffraction. j Calculated molar enthalpy of formation. k Energy of
formation. l Energy of explosion, EXPLO5 V5.02. m Explosion tempera-
ture. n Detonation pressure. o Detonation velocity. p Assuming only
gaseous products.
140 | New J. Chem., 2009, 33, 136–147 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
of combustion were calculated using quantum chemical
methods (see Computational Methods section). Initially, we
measured experimentally the combustion data for 3 using
oxygen bomb calorimetry, however the high sensitivity of
the compound did not allow reproducible values to be ob-
tained. The material explodes rather than burning in the
aerobic conditions of the measurements leading to erroneous
values. The heats and energies of formation of 1–3 were back-
calculated from the combustion data and subsequently used in
conjunction with the molecular formula and density (from
X-ray) to predict the performance (detonation pressure and
velocity) for each compound using the EXPLO5 computer
code.61
Fig. 7 shows typical DSC thermographs of compounds
1–3. Slow heating in a DSC apparatus (b = 5 1C min�1) of
samples of B1.5 mg of each energetic material gives rapid
decomposition at temperatures above 130 1C for all three
compounds. All three materials show highly exothermic
decompositions following to endothermic peaks at 98 (1), 45 (2)
and 75 (3) 1C corresponding to the melting of the compounds.
The difference in area between endothermic and exothermic
peaks gives a feeling for the energy released upon decomposi-
tion. For all 1–3 the decomposition releases much more energy
than that required for melting. Particularly, compound 1
shows only a small melting endotherm followed by highly
energetic decomposition. It is interesting to note the effect
of the substituent in the tetrazole ring in the melting and
decomposition points. The presence of the ring proton in 1
results in a higher melting point than for 2 and 3 due to the
possibility of forming classical hydrogen bonds in 1, however,
the compound is much more sensitive (i.e., less stable) and
decomposes at lower temperatures. The substitution pattern of
the methyl group in 2 and 3 also accounts for the lower
melting point of 2 in comparison to 3 due to the formation
of a less effective packing, as suggested by the lower crystal
density of 2 (1.628 g cm�3) in comparison to 3 (1.668 g cm�3).
Furthermore, the presence of the methyl group results in
an increase (20–25 K) of the decomposition temperatures
(B150 1C) as observed for methylated 5-aminotetrazoles.37
Further studies on the decomposition of 3 can be found in
literature.48 In addition to DSC analysis, the response to thermal
shock of 1–3was tested by placing a small sample (B0.5–1.0 mg)
of compound in the flame. This resulted in an vigorous reaction
(deflagration) in the case of 1 and normal burning in the case of
2 and 3, in all cases smokeless. By comparison with typical
primary explosives such as lead azide or styphnate, which both
explode in the flame, the compounds studied here are less
sensitive to thermal shock and show a similar response to
classical secondary explosives such as TNT or RDX.
Data collected for initial safety testing of compounds 1–3
are summarized in Table 6. The impact and friction sensiti-
vities as well as the electrostatic sensitivity were determined.49
The impact sensitivity tests were carried out according to
STANAG 448950 modified according to instruction51 using a
BAM (Bundesanstalt fur Materialforschung)52 drophammer.53
The friction sensitivity tests were carried out according to
STANAG 448754 modified according to instruction55 using
the BAM friction tester. Compound 1 is very sensitive towards
impact (o1 J) and extremely friction sensitive (o5 N). 2 and 3
are also very sensitive towards impact (2, 2 J and 3, 1 J) but
less sensitive towards friction (2, 82 N and 3, 40 N). Grinding
of the compounds in a mortar results in rattling and (in some
instances) a loud explosion. According to the ‘‘UN Recom-
mendations on the transport of dangerous goods’’,56
compounds 1–3 are classified as ‘‘very sensitive’’ regarding
the impact sensitivity values. The compounds in this study
are significantly more sensitive to friction and impact than
nitrogen-rich salts of 5-nitro-2H-tetrazole34 and the impact
sensitivity approaches that of alkali metal salts of 5-nitro-2H-
tetrazole.30 Comparison of the energetic compounds of the
materials in this study with those of commonly used high
explosives are useful to assess the potential of the materials
described here. All three materials have impact sensitivity
values, which are comparable to lead azide (2.5–4.0 J, pure
product). As for the friction sensitivity, 1 has a value between
that of the primary explosives lead azide (0.1–1.0 N, pure
product) and tetrazene (7 N), whereas 2 and 3 have similar
sensitivity to the secondary explosive PETN (60 N).5 In
addition, the sensitivity towards electrostatic discharge of 2
and 3 was tested using an electric spark tester ESD 2010EN
(OZM Research) operating with the ‘‘Winspark 1.15 software
package’’.57 Due to the hygroscopicity of compound 1, this
compound was omitted from this study. The electrical spark
sensitivities of microcrystalline materials (5–100 mm)58 were
determined to be 0.50 � 0.05 (2) and 0.20 (3) � 0.04 J. These
values can be compared to those of commonly used secondary
Table 7 Comparison of energetic properties of compounds 1–3 withRDX
1 2 3 RDX
Density/g cm�3 r 1.899 1.630 1.670 1.820Oxygen balance (%) O �7.0 �43.4 �43.4 �21.6Energy of formation/kJ kg�1 DfU +2527 +2253 +2006 +67Heat of detonation/kJ kg�1 Qv �5744 �5588 �5368 �5902Detonation temperature/K Tex. 4804 4226 4071 3986Detonation pressure/kbar P 390 257 262 299Detonation velocity/m s�1 D 9457 8085 8109 8796Volume of detonation gases/L kg�1 V0 779 766 763 932
Fig. 7 DSC thermographs of 5-nitrotetrazoles 1–3 at a heating rate
b = 5 1C min�1.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 136–147 | 141
explosives, e.g. RDX (0.15 J), PETN (0.19) and TNT (0.57).
However, the ESD sensitivities determined are higher
than those of modern insensitive explosives such as TATB
(1,3,5-triamino-2,4,6-trinitrobenzene).59 Lastly, the high
sensitivities of 1–3 can be attributed not only to the high
endothermicity of the materials (see discussion below) but also
to the only slightly negative oxygen balance, in particular in
the case of compound 1.
In addition to safety considerations, performance of
HEDMs is of utmost importance. Using the molecular for-
mula, density (from X-ray) and energy of formation, the
EXPLO5 computer code61 can be used to calculate the deto-
nation velocity and pressure of CHNO-based explosive
materials. The program is based on the chemical equilibrium,
steady-state model of detonation. It uses the Becker–
Kistiakowsky–Wilson’s equation of state (BKW EOS) for
gaseous detonation products and Cowan–Fickett’s equation
of state for solid carbon.61,62 The calculation of the equili-
brium composition of the detonation products is done by
applying modified White, Johnson and Dantzig’s free energy
minimization technique. The program is designed to enable
the calculation of detonation parameters at the CJ point. The
BKW equation in the following form was used with the
BKWN set of parameters (a, b, k, y) as stated below the
equations and Xi being the mol fraction of ith gaseous
product, ki is the molar covolume of the ith gaseous pro-
duct.40,41 The results of the EXPLO5 calculations for neutral
5-nitrotetrazoles 1–3 are presented in Tables 6 and 7, with the
corresponding values for commonly used RDX for compari-
son purposes.
pV/RT = 1 + xebxx = (kP
Xiki)/[V (T + y)]a; a = 0.5,
b = 0.176, k = 14.71, y = 6620.
Further physico-chemical properties of all three compounds
are tabulated in Table 7. Compounds 1–3 have high nitrogen
contents in the range between B50 and 60%, excellent com-
bined oxygen and nitrogen balances in the range between
B80 and 90% and slightly negative oxygen balances approxi-
mately in the range between that of dinitroglycol (C2H4N2O6,
O = �0.0%) and that of nitromethane (CH3NO2, O =
�39.3%). As expected, the densities, calculated from the
X-ray measurements, are lower in the case of the methylated
derivatives 2 and 3 (B1.65 g cm�3) but still comparable to
TNT (1.654 g cm�3), while 1 has an exceptionally high density
of 1.899 g cm�3 comparable to b-HMX (1.900 g cm�3).5 The
energies of formation of 1–3 were back-calculated from the
energies of combustion on the basis of their combustion
equations (see below), Hess’s Law, the known standard heats
of formation for water and carbon dioxide and a correction
for change in gas volume during combustion. No corrections
for the non-ideal formation of nitric acid (typically B5% of
the nitrogen content reacts to form HNO3) were made.
As pointed out above, all three compounds are highly en-
dothermic with energies of formation above +2000 kJ kg�1.
1 has the most positive value of all at +2527 kJ kg�1 and all
three compounds show similar endothermicities to nitrogen-
rich salts with the 5,50-azotetrazolate anion ([N4C–N =
N–CN4]2�).12,63
1: CHN5O2 (s) + 0.25 O2 (g) - CO2 (g) + 0.5 H2O (l)
+ 2.5 N2 (g) (1)
2, 3: C2H3N5O2 (s) + 1.75 O2 (g) - 2 CO2 (g) + 1.5
H2O (l) + 2.5 N2 (g) (2)
The methylated derivatives 2 and 3 have calculated detonation
velocities of B8100 m s�1, higher than TNT (6900 m s�1),
lower than RDX (8800 m s�1) and similar to 5,50-azotetrazole
salts,12,63 regardless of the high sensitivity of the compounds.
On the other hand, 1 although being very sensitive to impact
and friction and thus classifying as a primary explosive has an
astonishingly high calculated detonation velocity of 9457 m s�1,
which is comparable to some of the highest performing
secondary explosives known to date such as HMX (octogen,
9100 m s�1), CL-20 and octanitrocubane (B10 000 m s�1)5
and also higher than the primary explosive 5-azido-1H-tetra-
zole regardless of the lower endothermicity of the –NO2 group
in comparison to the –N3 substituent.21 Here it is necessary to
mention that the previous study of Koldobskii and coworkers
on compound 1, reports a experimental density value of
1.73 g cm�3,33 which is much lower than our calculated value
of 1.899 g cm�3 and therefore affects strongly the detonation
parameters. The detonation pressures have accordingly high
values (390 kbar for 1 and B260 kbar for 2 and 3), which are
comparable to HMX (octogen) (pdet. = 384 kbar) and RDX
(hexogen) (pdet. = 299 kbar) respectively.5
Decomposition gases
Using the calculated heats of formation, the calculated density
(from X-ray) and the molecular formula the ICT code64 was
used to predict the heats of explosion as well as the decom-
position gases formed upon explosion/decomposition of com-
pounds 1–3. Table 8 contains tabulated results of these
calculations together with the predicted values for two com-
monly used high explosives, namely lead azide (primary
Table 8 Predicted decomposition gases and heats of explosion of compounds 1–3 and comparison with commonly used high explosives (using theICT code)
Compoundab CO2 H2O N2 CO H2 NH3 CH4 HCN C Pb DHexc
1 276.61 75.54 607.47 17.11 0.05 1.34 — — 21.40 — 16212 100.72 185.39 533.13 17.25 0.47 11.16 0.80 0.44 150.35 — 15583 100.45 186.28 533.22 16.21 0.43 11.06 0.66 0.43 150.97 — 1512Pb(N3)2 — — 288.56 — — — — — — 711.44 391RDXd 292.09 232.40 373.83 22.90 0.21 5.26 0.16 0.30 72.28 — 1592
a The amount of gases formed at 298 K is given in g kg�1 (i.e., grams of gas per kilogram of energetic compound). b —, the decomposition product
was not predicted by the code. c Heat of explosion in cal g�1. d Measured at a density of 1.76 g cm�3.
142 | New J. Chem., 2009, 33, 136–147 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
explosive) and RDX (secondary explosive), for comparative
purposes.
As expected from the high nitrogen content of the materials
molecular nitrogen is predicted to be the major product of the
decomposition of compounds 1–3 (B500–600 g kg�1). By
comparison, the decomposition of RDX is expected to pro-
duce much lower amounts of environmentally-friendly nitro-
gen (374 g kg�1), which is however still the main expected
product followed by the formation of carbon dioxide (292 g
kg�1). In keeping with the logic that RDX derives its energy
from both oxidation of the carbon backbone and the forma-
tion of nitrogen. The second main product predicted upon
decomposition of 1 is also carbon dioxide (277 g kg�1), which
is anticipated to form in larger amounts than for compounds 2
and 3 (B100 g kg�1) fitting with the better oxygen balance of
1. 2 and 3 are nevertheless expected to generate larger amounts
of water than 1 (B185 vs. 75 g kg�1). Apart from carbon soot,
which is predicted to form in relatively large amounts for 2 and
3 (B150 g kg�1), the rest of the decomposition gases (CO, H2,
NH3, CH4 and HCN) are foreseen to form in marginally low
quantities (o20 g kg�1). The amount of highly toxic gases
(i.e., CO and HCN) expected from the explosion of 1–3 are
then comparable to those formed upon explosion of RDX and
in contrast with the large amounts of highly toxic lead powder
predicted for the explosion of lead azide (711 g kg�1). Lastly,
the heats of explosion have all values above 1500 cal g�1, is
larger for the more energetic compound 1, are comparable to
the secondary explosive RDX and much larger than the
primary explosive lead azide (391 cal g�1).
Computational methods. Due to the high sensitivity of all
compounds studied here, bomb calorimetric measurements
could only be performed with small amounts of the materials
and doubtful combustion data was obtained. Therefore we
decided to estimate the thermodynamic data by quantum
chemical methods. All calculations were carried out using
the Gaussian G03W (revision B.03) program package.65 The
enthalpies (H) and free energies (G) were calculated using the
complete basis set (CBS) method described by Petersson and
coworkers in order to obtain very accurate values. The CBS
models use the known asymptotic convergence of pair natural
orbital expressions to extrapolate from calculations using a
finite basis set to the estimated complete basis set limit. CBS-4
begins with a HF/3-21G(d) geometry optimization; the zero
point energy is computed at the same level. It then uses a large
basis set SCF calculation as a base energy, and a MP2/
6-31+G calculation with a CBS extrapolation to correct
the energy through second order. A MP4(SDQ)/6-31+(d,p)
calculation is used to approximate higher order contributions.
In this study we applied the modified CBS-4M method
(M referring to the use of minimal population localization)
which is a re-parametrized version of the original CBS-4
method and also includes some additional empirical correc-
tions.66,67 The enthalpies of the gas-phase species M were
computed according to the atomization energy method
(eqn (3)) (Tables 9–12).68
DfH1(g, M, 298) = H(Molecule, 298) �P
H1(Atoms, 298)
+P
DfH1(Atoms, 298) (3)
From the gas-phase enthalpies of formation DfH1(g) the
enthalpies of the solid state were calculated using the enthal-
pies of sublimation by the equation:
DfH1(s) = DfH1(g) � (DsubH) (4)
For a solid compound the enthalpy of sublimation (DsubH) can
be approximated on the basis of TROUTON’s rule 72 if the
melting temperature (Tm in K) is known:
DsubH [J mol�1] = 188 Tm [K] (5)
With the known enthalpies of formation of carbon
dioxide (DfH1298(CO2(g)) = �393.8 kJ mol�1) and water
(DfH1298(H2O(g)) = �241.9 kJ mol�1) the enthalpies of
formation of 1–3 can now be calculated. From these values,
the energy of formation (DfU1298) can easily be obtained from
the combustion eqns (1)–(3) according to eqn (6) with Dnbeing the change of moles of the gaseous components
(Dn: 1 = �3.25; 2, 3 = 2.75) in eqns (7) and (8).
DUm = DHm � DnRT (6)
1: C (s) + 0.5 H2 (g) + 2.5 N2 (g) + O2 (g)
- CHN5O2 (s) (7)
2, 3: 2 C (s) + 1.5 H2 (g) + 2.5 N2 (g) + O2 (g)
- C2H3N5O2 (s) (8)
Table 9 CBS-4M results
Pt. Gp. �H298/a.u. �G298/a.u. NIMAG
5-Nitro-1H-tetrazole Cs 462.190261 462.227578 05-Nitro-2H-tetrazole Cs 462.195276 462.232789 01-Methyl-5-nitrotetrazole Cs 501.427898 501.468919 02-Methyl-5-nitrotetrazole Cs 501.437871 501.479892 0H 0.500991 0.514005C 37.786156 37.803062N 54.522462 54.539858O 74.991202 75.008515
Table 10 Literature values for atomic DH1f298/kcal mol�1
ref. 69 NIST70
H 52.6 52.1C 170.2 171.3N 113.5 113.0O 60.0 59.6
Table 11 Enthalpies of the gas-phase species M
M M DfH1(g)/kcal mol�1
5-Nitro-1H-tetrazole CHN5O2 +87.15-Nitro-2H-tetrazole CHN5O2 +84.01-Methyl-5-nitrotetrazole C2H3N5O2 +80.72-Methyl-5-nitrotetrazole C2H3N5O2 +74.5
Table 12 Enthalpies of sublimation of compounds 1–371
Tm/K DHsub/kcal mol�1
1 374 16.82 318 14.33 348 15.6
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 136–147 | 143
As can be seen from Table 13 compounds 1–3 are formed
strongly endothermically (1: 281, 2: 278, 3: 247 kJ mol�1).
These values are slightly higher than that of 5-amino-1H-
tetrazole (DfH1(s) = 208 kJ mol�1) and in the same range
observed for 5-nitriminotetrazole (264 kJ mol�1) and
1-methyl-5-nitriminotetrazole (260 kJ mol�1). The enthalpy
of formation of energetic materials are governed by the
molecular structure of the compound. Therefore, heterocycles
with a higher nitrogen content (e.g. imidazole (DfH1(s) = 58.6
kJ mol�1),72 1,2,4-triazole (DfH1(s) = 109.3 kJ mol�1),73 1H-
1,2,3,4-tetrazole (DfH1(s) = 237.4 kJ mol�1))74 show trends in
increasing heats of formation.
Experimental
CAUTION! The 5-nitrotetrazoles described here are energetic
compounds, which are sensitive towards heat, impact, friction
and electrostatic discharge. Although we experienced no diffi-
culties in the synthesis of these materials, proper protective
measures (safety glasses, face shield, leather coat, earthened
equipment and shoes, Kevlars gloves and ear plugs) should be
used when undertaking work involving 1–3 on small and in
particular on larger scales.
General method
All reagents and solvents were used as received (Sigma-
Aldrich, Fluka, Acros Organics) unless stated otherwise.
Melting points were measured with a Linseis PT10 DSC75
and checked with a Buchi Melting Point B-450 apparatus
(uncorrected). DSC measurements were performed at a heat-
ing rate of 5 1C min�1 in closed aluminum sample pans with a
1 mm hole in the top for gas release under a nitrogen flow of
20 mL min�1 with an empty identical aluminum sample pan as
a reference. NMR spectra were recorded with a Jeol Eclipse
270, Jeol EX 400 or a Jeol Eclipse 400 instrument. All chemical
shifts are quoted in ppm relative to TMS (1H, 13C) and
MeNO2 (14N, 15N). Infrared (IR) spectra were recorded using
a Perkin-Elmer Spektrum One FT-IR instrument.76 Transmit-
tance values are qualitatively described as ‘‘very strong’’ (vs),
‘‘strong’’ (s), ‘‘medium’’ (m) and ‘‘weak’’ (w). Raman spectra
were measured using a Perkin-Elmer Spektrum 2000R NIR
FT-Raman instrument equipped with a Nd:YAG laser
(1064 nm). The intensities are reported as percentages of the
most intense peak and are given in parentheses. Elemental
analyses were performed with a Netsch Simultaneous Thermal
Analyzer STA 429.
Synthesis of 5-nitro-2H-tetrazole (1)
Anhydrous ammonium 5-nitrotetrazolate (0.44 g, 3.32 mmol)
and potassium hydroxide (0.19 g, 3.32 mmol) were dissolved in
3.7 mL water. The solution was stirred at reflux until no more
ammonia gas was evolved. At this point, the reaction mixture
was cooled by means of an ice-bath and cold B25% sulfuric
acid (2 mL) was added dropwise using a plastic syringe. The
solution was then extracted with ether (4 � 6 mL) and the
ether extracts were combined and washed to remove the excess
of acid with water (6 mL). The organic phase was then dried
with magnesium sulfate and filtered and the solvent was
stripped under high vacuum (B10�3 mbar) yielding the pure
product as a slightly yellow semicrystalline solid (0.27 g, 72%),
which was carefully (!!) scratched out using a plastic spatula
and analyzed. DSC (5 1C min�1, 1C): 98 (mp), 4130 (de-
comp.); IR ~n/cm�1 (KBr, rel. int.): 3443 (s), 2013 (w), 1629
(m), 1565 (vs), 1443 (m), 1401 (m), 1320 (s), 1262 (vw), 1192
(w), 1103 (w), 1047 (m), 1022 (m), 840 (s), 666 (w), 534 (vw);
Raman ~n/cm�1 (rel. int.): 3316 (2), 3261 (2), 1572 (14), 1492
(9), 1446 (100), 1433 (90), 1396 (15), 1358 (7), 1317 (13), 1200
(13), 1186 (14), 1142 (30), 1094 (42), 1069 (13), 1043 (11), 1027
(26), 837 (22), 775 (13), 736 (4), 592 (3), 532 (11), 444 (22), 256
(17), 240 (16), 154 (6); 1H NMR (DMSO-d6, 400.18 MHz, 25
1C, TMS) d/ppm: 6.29 (1H, NH); 13C{1H} NMR (DMSO-d6,
100.63 MHz, 25 1C, TMS) d/ppm: 168.4 (1C, C–NO2);14N
NMR (DMSO-d6, 40.55 MHz, 25 1C, MeNO2) d/ppm: +14
(2 N, n1/2 B300 Hz, N2/3), �24 (1 N, n1/2 B60 Hz, NO2), �66(2 N, n1/2 B320 Hz, N1/4); 15N NMR (DMSO-d6, 40.55 MHz,
25 1C, MeNO2) d/ppm: +19.6 (2 N, s, N2/N3), �29.8 (1 N, s,
NO2),�69.6 (2 N, s, N1/4);m/z (FAB�, xenon, 6 keV,m-NBA
matrix): 113.9 (100, CN5O2�); EA (CHN5O2, 115.07): calc. C
10.44, H 0.88, N 60.87; found: not determinable due to high
sensitivity; BAM drophammer: o1 J, friction tester: o5 N,
flame: deflagration.
Synthesis of 1-methyl-5-nitrotetrazole (2)
A suspension of 1-methyl-5-aminotetrazole (2.00 g, 20 mmol)
in 1 M sulfuric acid (10 mL) and 30 mL of water was added at
0 1C to 30 mL water containing sodium nitrite (2.76 g,
40 mmol). After stirring at room temperature for 12 h and
filtration of the precipitated bis(1-methyltetrazolyl)triazene,
the solvent was evaporated. Dry acetone (80 mL) was added
to this and the precipitated Na2SO4 was removed by filtration.
After evaporating the acetone the crude product was recrys-
tallized from a small amount of ethanol (1.52 g, yield 59%);
DSC (5 1C min�1, 1C): 45 1C (mp), 155 1C (decomp.); IR
(KBr, cm�1): ~n = 3038 (w), 2860 (w), 1550 (vs), 1481 (s), 1467
(m), 1408 (s), 1364 (s), 1328 (vs), 1280 (w), 1209 (m), 1073 (m),
1025 (w), 846 (s), 720 (s), 535 (w), 430 (m); Raman (1064 nm,
200 mW, 25 1C, cm�1): ~n = 3054 )2), 2978 (6), 2964 (6), 1530
(20), 1508 (9), 1469 (100), 1463 (44), 1447 (44), 1425 (15), 1412
(11), 1329 (24), 1261 (10), 1208 (13), 1103 (11), 1085 (23), 1028
(21), 923 (7), 779 (2), 740 (2), 709 (3), 679 (4); 1H NMR ([d6]-
DMSO, 25 1C, ppm) d: 3.68 (s, 3H, CH3);13C NMR ([d6]-
DMSO, 25 1C, ppm) d: 157.6 (CN4), 33.1 (CH3);14N NMR
(DMSO-d6, 40.55 MHz, 25 1C, MeNO2) d/ppm: �37 (1 N,
n1/2 B60 Hz, NO2),15N NMR ([d6]-DMSO, 25 1C) d = 4. 5
(N3), �14.1 (N6), �18.29 (N2, t, 3JNH = 1.9 Hz), �71.15(N4), �157.16 (N5), �168.38 (N1, d, 2JNH = 2.2 Hz), –289.13
(N7, 1JNH = 102.7 Hz), �329.66 (N8, 1JNH = 69.4 Hz); m/z
(DEI+): 130 (19) [M +H]+, 129 (65) [M]+, 100 (1), 83 (8), 55
Table 13 Solid state enthalpies (DfH1) and energies of formation(DfU1)
DfH1(s)/kcalmol�1
DfH1(s)/kJmol�1 Dn
DfU1(s)/kcalmol�1
M/gmol�1
DfU1(s)/kJkg�1
1 +67.2 +281.4 �4 +69.5 115.07 +2527.12 +66.5 +278.4 �5 +69.5 129.08 +2252.83 +58.9 +246.6 �5 +61.9 129.08 +2006.4
144 | New J. Chem., 2009, 33, 136–147 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(15), 54 (17), 53 (100), 46 (38), 43 (28), 40 (7), 39 (5), 28 (45), 18
(8), 15 (4); EA (C2H3N5O2, 129.08): calcd.: C 18.61, H 2.34, N
54.26; found: C 18.39, H 2.28, N 52.80; BAM drophammer:
2 J; friction tester: 82 N, ESD: 0.50� 0.05 J, flame: combustion.
Synthesis of 2-methyl-5-nitrotetrazole (3)
To 20 mL of an aqueous sodium nitrite (2.76 g, 0.04 mol)
solution, a solution of 2-methyl-5-aminotetrazole (2.00 g, 0.02 mol)
in 20 mL 1N sulfuric acid was added at 0 1C. The reaction
mixture was stirred for 8 h and the precipitated bis(2-methyl-
tetrazolyl)triazene precipitated was removed by filtration.
Afterwards the product was extracted three times with 20 mL
of CH2Cl2. The organic phases were combined, dried over
MgSO4 and evaporated. The crude product was recrystallized
from acetone yielding single crystals suitable for XRD ana-
lysis. (1.68 g, yield 65%); DSC (5 1C min�1, 1C): 75 1C (mp),
150 1C (decomp.); IR (KBr, cm�1): ~n = 3022 (m), 1610 (m),
1565 (s), 1510 (m), 1468 (m), 1412 (s), 1285 (s), 1160 (m), 1001
(w), 880 (m), 788 (m), 750 (m), 670 (w), 610 (w), 530 (w);
Raman (1064 nm, 200 mW, 25 1C, cm�1): ~n= 3052 (12), 2967
(60), 1555 (28), 1486 (40), 1468 (26), 1418 (100), 1369 (11),
1335 (8), 1322 (14), 1287 (12), 1209 (30), 1075 (12), 1043 (40),
1026 (44), 841 (16), 776 (17), 715 (46), 547 (10), 436 (30), 378
(18), 307 (16), 218 (16); 1H NMR ([d6]-DMSO, 25 1C, ppm) d:4.50 (s, 3H, CH3);
13C NMR ([d6]-DMSO, 25 1C, ppm) d:166.4 (CN4), 41.9 (CH3);
14N NMR (DMSO-d6, 40.55 MHz,
25 1C, MeNO2) d/ppm: �34 (1 N, n1/2 B50 Hz, NO2);15N
NMR ([d6]-DMSO, 25 1C) d = 5.3 (N3), �33.5 (N5), �55.1(N4), �76.6 (N2, 2JNH = 2.1 Hz), –97.9 (N1, 3JNH = 1.7 Hz);
m/z (DEI+): 130 (2) [M+H]+, 129 (2) [M]+, 115 (1) [M+H
� CH 3]+, 101 (15), 58 (89), 43 (100) [HN3]
+, 42 (6), 28 (3)
[N2]+, 18 (29); EA (C2H3N5O2, 129.08): calcd.: C 18.61,
H 2.34, N 54.26; found: C 18.88, H 2.35, N 52.99; BAM
drophammer: 1 J; friction tester: 40 N, ESD: 0.20 � 0.04 J,
flame: combustion.
Conclusions
From this combined experimental and theoretical study the
following conclusions can be drawn:
Convenient procedures for the synthesis of three highly
energetic neutral 5-nitrotetrazoles (1–3) are presented, which
allow the materials to be obtained at low cost using facile
routes, good yields and excellent purities. The full characteri-
zation of the compounds by analytical and spectroscopic
methods is described in detail. In addition we determined the
molecular structure of the compounds in the solid state by
X-ray diffraction methods. The energetic properties of the
compounds were assessed by means of standard tests and
quantum chemical calculations (CBS-4M). 1–3 are calculated
to be strongly endothermic with heats of formation between
247 and 282 kJ mol�1. The compounds show highly exother-
mic decomposition peaks (DSC) and are easily initiated by
impact. Furthermore, 1–3 have high performances (EXPLO5
code) comparable to commonly used secondary explosives
regardless of their ease of initiation and 1 classifies as a
primary explosive in regard to its impact and friction sensitivity
values and still has a calculated detonation velocity, which is
almost twice as large as that of common primary explosives
(e.g., lead azide) and puts it first in the list of high performing
primers. Unfortunately, 1 absorbs water, which limits its
application. Furthermore 1–3 are thermally too unstable for
use as conventional high explosives. The predicted products
(ICT code) formed upon explosion of 1–3 are expected to be
less harmful than those expected from the decomposition of
commonly used high explosives, which suggest their potential
(2 and 3) as environmentally friendly alternatives with high
performance and low initiation barriers (by impact) for use in
energetic applications (e.g., as ingredients for energetic fillers
in high explosive compositions).
Acknowledgements
Financial support of this work by the Ludwig-Maximilian
University of Munich (LMU), the Fonds der Chemischen
Industrie (FCI), the European Research Office (ERO) of the
U.S. Army Research Laboratory (ARL) under contract nos.
N-62558-05-C-0027, 9939-AN-01 and W911NF-07-1-0569
and the Bundeswehr Research Institute for Materials, Explo-
sives, Fuels and Lubricants (WIWEB) under contract nos.
E/E210/4D004/X5143 and E/E210/7D002/4F088 is gratefully
acknowledged. The authors are indebted to and thank
Dr Betsy Rice and Dr Gary Chen for many helpful discussions
and support of our work. We also acknowledge Mr. Stefan
Huber for help with the sensitivity tests. The authors acknowl-
edge collaborations with Dr M. Krupka (OZM Research,
Czech Republic) in the development of new testing and
evaluation methods for energetic materials and with
Dr M. Sucesca (Brodarski Institute, Croatia) in the develop-
ment of new computational codes to predict the detonation
parameters of high-nitrogen explosives.
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Probing multivalency for the inhibition of an enzyme: glycogen
phosphorylase as a case studyw
Samy Cecioni,a Oana-Andreea Argintaru,a Tibor Docsa,b Pal Gergely,b
Jean-Pierre Pralyaand Sebastien Vidal*
a
Received (in Montpellier, France) 22nd July 2008, Accepted 21st August 2008
First published as an Advance Article on the web 23rd October 2008
DOI: 10.1039/b812540f
Glycogen phosphorylase is involved in the hepatic glucose production and appears an emerging
biological target for the treatment of type 2 diabetes. Two distinct trivalent inhibitors of GP were
synthesized either through Cu(I)-assisted 1,3-dipolar cycloaddition or through formation of a tris-
oxadiazole derivative. A biological study of the inhibiting properties of these trivalent inhibitors
of GP have shown that the valency of the molecules influences slightly the inhibition of the
enzyme whereas the presence of a spacer arm between the core and the pharmacophore moieties
does not. The possible modes of binding of these multivalent inhibitors to the enzyme are
discussed.
Introduction
Glycogen phosphorylase and diabetes
Diabetus mellitus affects about 3% of the world population
and up to 6% for the adult population of developed countries.
Diabetes, one of the major causes of death worldwide, is
characterized by elevated glycaemia causing heart and kidney
failures as well as visual impairment problems.1 Type 2
diabetes is non-insulino-dependent and arises from insulin
signalling inefficiency resulting in insufficient or even late
insulin secretion. A series of biological targets have been
identified for anti-diabetic therapy2 such as peroxisome
proliferator-activated receptors a/g (PPARs a/g),3 glucagon-
like peptide-1 (GLP-1),4 dipeptidyl peptidase IV (DPP-IV)5 or
protein tyrosine phosphatase 1B (PTP 1B).6 Glycogen phos-
phorylase (GP) has recently appeared as an enzyme of interest
for the treatment of type 2 diabetes.7 This enzyme catalyses
glycogen depolymerisation to release glucose-1-phosphate
according to the schematic equation:
(Glucose)n - (Glucose)n�1 + Glucose-1-phosphate
The inhibition of GP is expected to slow down glycogenolysis
and to lower the production of glucose from the liver therefore
allowing for a better control over hyperglycaemia. GP has
been extensively studied and crystallographic data analyses are
displaying a large number of sites for the inhibition of this
enzyme.8 A series of GP inhibitors have been described pre-
viously with various heterocyclic structures9 but our work10 is
focusing on carbohydrate-based inhibitors of GP7b,c,f which
are capable of binding selectively at the catalytic site of GP.
These glycomimetic approaches are based on structural modi-
fications at the molecular level for improving the binding to
the enzyme and therefore affording valuable GP inhibitors.
Multivalency and inhibition of enzymes
Another approach for the inhibition of GP could take advan-
tage of multivalency. This strategy may provide additional
opportunities in the field of drug discovery for the design of
potent enzyme inhibitors particularly by reaching higher
affinities and probably better selectivities. A few examples of
multivalent inhibition of an enzyme are reported in the
literature where multimeric species of a specific drug are
capable of improving the inhibition in comparison to the
monomeric molecule.11 The binding of one ligand subunit
from the multivalent molecule to the enzyme generates an
increase in local concentration of ligands, thus creating an
apparent cooperativity causing an enhancement in inhibition.
Dimeric inhibitors of influenza virus neuraminidase have been
developed by MacDonald et al.12 and displayed up to a
100-fold increase in inhibition along with improved pharmaco-
kinetic properties. In an additional study of the same
group,13 a set of trimeric and tetrameric inhibitors displayed
improved antiviral activities and long-lasting protective activ-
ities against influenza virus. More recently, the group of
J. Gervay-Hague has described the synthesis of a series of
trivalent zanamivir derivatives via click chemistry although no
biological activity has been reported yet.14 Inhibition of
acetylcholinesterase by dimeric molecules resulted in up to
3000-fold increases in potency and selectivity compared to
the monomeric inhibitor.15 Glycosidases inhibition16 with
tethered dimeric azasugars was investigated and the molecules
displayed interesting inhibitions of these enzymes but more
aUniversite de Lyon, Lyon, Universite Lyon 1, Villeurbanne, CNRS,UMR5246, Institut de Chimie et Biochimie Moleculaires etSupramoleculaires, Laboratoire de Chimie Organique2 - Glycochimie, 43 Boulevard du 11 Novembre 1918, F-69622Villeurbanne, France. E-mail: [email protected];Fax: +33 472 448 349; Tel: +33 472 448 349
bCell Biology and Signalling Research Group of the HungarianAcademy of Sciences, Department of Medical Chemistry, ResearchCentre for Molecular Medicine, University of Debrecen, Nagyerdeikrt. 98, Debrecen, H-4032, Hungary. E-mail: [email protected];Fax: +36 52 412 566; Tel: +36 52 412 345
w Electronic supplementary information (ESI) available: Determina-tion of Ki values and detailed atom numbering of molecules. See DOI:10.1039/b812540f
148 | New J. Chem., 2009, 33, 148–156 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
importantly a selectivity for two enzymes out of the seven
tested.16a However, tetravalent 1-azafagomine inhibitors dis-
played no improved inhibition compared to the monovalent
structure but rather a strong decrease in activity.16b Finally,
bivalent inhibitors of tetrameric b-tryptase constructed on a
cyclodextrin scaffold have shown increased inhibitions for this
enzyme.17
Inspired by the above mentioned results for the multivalent
neuraminidase inhibition and by the fact that a multimeric
enzyme offers additional possibilities for improved inhibition
through multivalency, we have designed synthetic routes to
trivalent carbohydrate-based GP inhibitors. A single case of a
dimeric inhibitor of GP has been reported with a bis(5-
chloroindole-2-carboxamide) derivative inhibiting human liver
GPa (HLGPa) with an IC50 value of 6 nM compared to 12.5 mMfor the parent monovalent inhibitor (2000-fold increase).18
This result highlights a productive and cooperative binding
of both ends of the bivalent inhibitor to two binding sites. The
co-crystallization of HLGPa with the divalent inhibitor
demonstrated that a single molecule of inhibitor was capable
of interacting with each monomeric unit of GP by linking the
two binding sites across the interface of GP homodimeric
structure. This result encouraged us to further investigate this
approach for the design of multivalent inhibitors of GP.
A closer look at the modes of binding of multivalent
inhibitors to an enzyme reveals several possibilities as depicted
in Fig. 1. A dimeric enzyme such as GP can interact with two
monomeric molecules of inhibitor in a 1:1 complex (2:2 at the
molecular level) providing a reference IC50mono value for
monovalent inhibitors. When considering the same inhibitor
repeated three times on a molecular scaffold, four main
possible cases can then be envisaged. The inhibition of a
trivalent inhibitor must be divided by three in order to
consider the contribution of each residue in its comparison
to a monovalent inhibitor. If a 1:1 complex is formed in
solution, a simple statistical effect can be invoked if no positive
effect is observed and the IC50 value observed will be similar to
1/3 IC50mono (Fig. 1, Case 1). Nevertheless, the IC50 measured
can be improved with a lower value in comparison to 1/3
IC50mo (Fig. 1, Case 2). If each binding site of the enzyme is
occupied by a ligand of the multivalent inhibitor, the forma-
tion of 3:1 complexes would afford aggregates of proteins. If
the size of the aggregates remains small enough to maintain a
good solubility of the complex, the IC50 observed will be
similar to 1/3 IC50mono (Fig. 1, Case 3). Nevertheless, if the
size of the multivalent inhibitor-enzyme clusters becomes large
enough to cause their precipitation, the quantity of enzyme
present in the solution will diminish and therefore the IC50
value measured will be lower than 1/3 IC50mono (Fig. 1, Case
4). In this case, the IC50 value measured will be a ‘‘virtual’’
value because of the lower quantity of the enzyme available in
solution.
Results and discussion
Synthesis of trivalent inhibitors
We have recently reported the preparation of 3-C-glycosyl-
5-aryl-1,2,4-oxadiazoles which displayed good inhibition
towards GP.10b In this context, we synthesized an alkyne-
terminated 3-C-glycosylated 1,2,4-oxadiazole which could then
be involved in a 1,3-dipolar cycloaddition with a tris-azido-
functionalized derivative to obtain a multivalent GP inhibitor
candidate. A more condensed trimeric inhibitor was also
prepared by direct coupling of an amidoxime with a tris-acyl
chloride and subsequent dehydrative cyclization to the corres-
ponding trivalent C-glycosylated oxadiazole. These inhibitors
were designed in order to determine the influence of a spacer
arm between the core and the pharmocophore ligands on the
inhibition of the enzyme.
Synthesis of the trivalent inhibitor with a spacer arm
The perbenzoylated glucosyl cyanide 119 was reacted with
hydroxylamine hydrochloride in pyridine to afford the desired
amidoxime 2 (Scheme 1). In our previous work,10b the crude
product obtained was rather difficult to purify by silica gel
column chromatography. The amidoxime 2 could be obtained
pure without chromatography simply by diluting the crude
product in ethyl acetate and then washing the organic layer
with 1 M aqueous HCl to remove pyridine and excess of
hydroxylamine, followed by saturated aqueous NaHCO3 and
brine. This simple chromatography-free purification process
afforded the expected amidoxime 2 in 99% yield and high
purity. The formation of the O-acyl-amidoxime 3 was
achieved with 4-pentynoic acid in the presence of EDCI/HOBt
as coupling agents.
We previously observed that reactions times lasting from a
few hours to a few days were required for the thermal
cyclodehydration of O-acyl-amidoximes. In order to optimize
both time and yield, we performed this reaction under TBAF
catalysis20 and/or microwaves activation21 (Table 1). We
observed that the use of TBAF catalysis at room temperature
provided the cyclic oxadiazole 4 within 1 day (entry 1) while
thermal activation combined with TBAF catalysis drastically
shortened the reaction time to 10 minutes (entry 2). NoFig. 1 Possible modes of binding for a mono- and trivalent inhibitors
with a dimeric enzyme.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 148–156 | 149
reaction or decomposition of the starting material was ob-
served when applying microwaves activation without TBAF
catalysis (entries 3 and 4). Nevertheless, the association of
TBAF catalysis and microwaves activation performed on a
short timescale (entry 5 and 6) provided a result comparable to
that observed under conventional heating (entry 2). These
results underline the beneficial influence of TBAF catalysis.
The alkyne-terminated oxadiazole 4 was then engaged in a
Huisgen’s Cu(I)-catalyzed 1,3-dipolar cycloaddition22 reaction
under microwaves activation with benzyl azide to afford the
desired 1,4-disubstituted 1,2,3-triazole 6 in excellent yield.
Debenzoylation of compounds 4 and 6 afforded two hydro-
xylated GP inhibitor candidates 5 and 7. Similarly, the reac-
tion of 1,3,5-tris(azidomethyl)benzene23 with the alkyne
derivative 4 under microwaves activation and Cu(I) catalysis
afforded the cycloadduct 8. The saponification of the benzoate
esters provided the fully hydroxylated macromolecule 9.
Synthesis of the trivalent inhibitor without spacer arm
We next prepared a more condensed trifunctional macro-
molecule were the C-glucosyl-oxadiazole moiety was directly
attached to a benzene ring (Scheme 2). Condensation of
amidoxime 2 with 1,3,5-benzenetricarbonyl trichloride af-
forded the corresponding triester 10 in 73% yield. At first,
compound 10 was subjected to cyclodehydration under
thermal conditions (reflux in 1,4-dioxane). The product obtained
was not the expected tris-oxadiazole 13 but the bis-oxadiazole
11 with one unreacted O-acyl amidoxime moiety as evidenced
by mass spectrometry (m/z = 2035.4 [M + H]+). Interest-
ingly, molecular ions could be observed neither for compound
13 nor the mono-oxadiazole intermediate. Saponification of
the ester groups of 11 resulted in the concomitant cleavage of
the O-acyl amidoxime function and afforded the benzoic acid
derivative 12 whose structure was clearly demonstrated by
mass spectrometry (m/z= 581 [M �H]�) and NMR analyses.
The triple thermal cyclodehydration of 10 was then performed
under microwaves activation and TBAF catalysis for
40 minutes. The tris-oxadiazole derivative 13 was isolated in
72% yield as the only product of the reaction highlighting
again the positive influence of TBAF catalysis and microwaves
activation for this cyclodehydration process. Deprotection
under Zemplen conditions afforded the expected hydroxylated
trivalent GP inhibitor candidate 14.
Inhibition of glycogen phosphorylase
The inhibition of GP was determined, as previously repor-
ted,10b for the three monovalent C-glycosylated oxadiazoles
(5, 7 and 1510b) and the two trivalent derivatives 9 and 14
(Fig. 2, Table 2). The enzymatic assays were performed at two
concentrations and most molecules displayed poor inhibition
properties at a concentration of 625 mM and moderate to good
inhibition at higher concentration (2.5 mM). In addition,
Ki values could be estimated only for trivalent derivatives 9
and 14 (see ESIw).The alkyne-terminated C-glycosylated oxadiazole derivative
5 displayed no inhibition at 625 mM and poor activity at
Scheme 1 Reagents and conditions: (a) NH2OH�HCl, C5H5N, 50 1C, 5 h, 99%; (b) HCRC(CH2)2CO2H, EDCI, HOBt, CH2Cl2/DMF (9:1),�8 1Cthen r.t., 16 h, 67%; (c) PhMe, TBAF 10 mol%, mW (150 1C, 200 W, 5 min), 97%; (d) NaOMe, MeOH then Amberlite IR-120 (H+ form);
(e) PhCH2N3, CuI, Et3N, mW (110 1C, 150 W, 15 min), 88%; (f) C6H3(CH2N3)3, CuI, Et3N, mW (110 1C, 150 W, 15 min), 98%.
Table 1 Cyclodehydration of O-acyl-amidoxime 3 to the 1,2,4-oxadiazole 4 in toluene
Entry Catalyst T/1C Microwave condition Time Yield (%)
1 10% TBAF 25 None 24 h 992 10% TBAF 110 None 10 min 973 None 150 100 W 1 h No reaction4 None 175 200 W 2 h Decomposition5 10% TBAF 150 200 W 5 min 976 10% TBAF 150 200 W 30 min 66
150 | New J. Chem., 2009, 33, 148–156 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
2.5 mM. The inhibition properties disappeared completely
when a spacer arm was added such as in the structure of 7.
Interestingly, the trivalent analogue 9 of the non-active deri-
vative 7 was now inhibiting GP with values of 30% at 625 mMand 56% at 2.5 mM. The valency of the molecule is therefore
responsible for an increase in inhibition from 0 to 56% when
comparing 7 and 9 at 2.5 mM. The C-glycosylated oxadiazole
derivative 15 bearing a phenyl group on the 5-position of the
oxadiazole ring displayed 10% inhibition at 625 mM.10b The
inhibition was again increased to 35% at 625 mM for trivalent
analogue 14. We anticipated that the distance between the core
and the carbohydrate moiety would influence for the binding
to the enzyme. Nevertheless, this was not the case based on the
inhibition measured for 9 and 14.
The increase of valency from monovalent to trivalent species
is responsible for an increase in inhibition of GP. The inhibi-
tion per residue for trivalent molecules is always similar the
Scheme 2 Reagents and conditions: (a) C6H3(COCl)3, 1,4-dioxane, r.t., 24 h, 73%; (b) 1,4-dioxane, 100 1C, 4 days; (c) NaOMe, MeOH then
Amberlite IR-120 (H+ form); (d) PhMe, TBAF 30 mol%, mW (150 1C, 200 W, 40 min), 72%.
Fig. 2 Structure of monovalent and trivalent GP inhibitors tested.
Table 2 Inhibition of GP observed for monovalent and trivalentinhibitors at two concentrations
Inhibition (%)
Inhibitor Valency At 625 mM At 2.5 mM Ki/mM
5 1 0 22 � 4 n.d.a
7 1 0 0 n.d.a
15 1 10 n.d.a n.d.a
9 3 30 � 5 56 � 5 480 � 45b
14 3 35 � 5 62 � 5 535 � 50b
a n.d. = not determined. b Estimated.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 148–156 | 151
corresponding monovalent analogue in accordance with the
statistical effect model proposed (Fig. 1, Case 1). The 3:1
complex non soluble mode of binding (Fig. 1, Case 4) can be
ruled out for these trivalent inhibitors of GP to the dimeric
enzyme since no precipitate was observed under the concen-
trations of trivalent inhibitors and enzyme used for the
inhibition studies. The inhibition observed for the trivalent
species was never better than 1/3 of the inhibition (in %)
observed for the corresponding monovalent molecules. In
conclusion, two modes of binding are possible with either
1:1 or 3:1 complexes (Fig. 1, Case 1 or Case 3, respectively)
resulting in an observed inhibition close to 1/3 of the inhibition
for the parent monovalent inhibitor.
In the present study, the expected binding sites of these
glucose-based multivalent inhibitors are the catalytic site of
GP homodimer which are separated from each other by a long
distance and pointing into opposite directions.8d The structure
of the trivalent inhibitors tested did not permit such an intra-
molecular interaction with both catalytic sites on the same
GP dimer, but rather an interaction with two independent
GP dimers. In comparison, the bis(5-chloroindole-2-carboxamide)
derivative is binding simultaneously at each indole binding site
near the interface between the monomeric units of the GP
dimer.17 The linker is composed of 12 atoms between two
indole aromatic units which are therefore available for inter-
acting with the binding site of each monomer of GP.
The designed trivalent molecules could also bind to the enzyme
on a different site. The large aromatic appendage present in the
aglycon, composed of oxadiazole, phenyl and triazole rings,
might interact with the surface of the protein through hydro-
phobic interactions. The stability of the inhibitor-protein com-
plex would therefore be lower than complex involving an internal
binding site such as the catalytic site. The observed inhibitions
would therefore be weak as currently observed in the present
study. Nevertheless, we do not possess any experimental data
confirming or denying such a mode of interaction.
Conclusions
In conclusion, we have designed two kinds of multivalent
inhibitors of GP based on the acylation of an amidoxime
intermediate followed by thermal dehydrative cyclization to
the corresponding oxadiazole. The introduction of an alkyne
residue at the 5-position of the oxadiazole ring allowed the
coupling to a trivalent azido-functionalized benzene ring
leading to an extended trivalent inhibitor candidate. The
enzyme inhibition assays revealed poor to moderate inhibitory
effect of these analogues. But, more important was the fact
that multivalent inhibitors were always superior to their
monovalent counterparts. This study provides one of the few
examples of multivalent inhibition for an enzyme, even though
the inhibitions observed remain modest.
Experimental
General methods
Thin-layer chromatography (TLC) was carried out on aluminum
sheets coated with silica gel 60 F254 (Merck). TLC plates
were inspected by UV light (l = 254 nm) and developed by
treatment with a mixture of 10% H2SO4 in EtOH/H2O
(1:1 v/v) followed by heating. Silica gel column chromato-
graphy was performed with Gedurans silica gel Si 60 (40–63 mm)
purchased from Merck (Darmstadt, Germany). Reactions
under microwave activation were performed on a CEM
Discover system. HRMS (LSIMS) mass spectra were recorded
in the positive mode using a Thermo Finnigan Mat 95 XL
spectrometer. MS (ESI) mass spectra were recorded in the
positive mode using a Thermo Finnigan LCQ spectrometer.1H and 13C NMR spectra were recorded at 23 1C using Bruker
Advance DRX300 or DRX500 spectrometers with the residual
solvent as the internal standard. The following abbreviations
are used to explain the observed multiplicities: s, singlet; d,
doublet; dd, doublet of doublet; ddd, doublet of doublet of
doublet; t, triplet; td, triplet of doublet; q, quadruplet; m,
multiplet; br, broad; p, pseudo. Structure elucidation was
deduced from 1D and 2D NMR spectroscopy which allowed,
in most cases, complete signal assignments based on COSY,
HSQC, and HMBC correlations. NMR solvents were
purchased from Euriso-Top (Saint Aubin, France). Atom
numbering of the molecules is presented in the ESI.w
Syntheses
1,3,5-Tris(azidomethyl)benzene. A solution of 1,3,5-tris(bro-
momethyl)benzene (3.07 g, 8.6 mmol) and sodium azide
(3.36 g, 51.6 mmol) in DMF (100 mL) was stirred at 65 1C
for 24 hours. The solution was cooled to room temperature
then poured into water (400 mL). The aqueous layer was
extracted with Et2O (3 � 250 mL). The combined organic
layers were washed with water (2 � 400 mL) and brine
(300 mL). The organic layer was dried (Na2SO4), filtered
and evaporated with extreme care (water-bath at room tem-
perature, reduced pressure and Plexiglas shield) to afford 1,3,5-
tris(azidomethyl)benzene (2.05 g, 98%) as a colorless oil. Rf =
0.83 (PE/EtOAc, 8:2). 1H NMR (300 MHz, CDCl3) d = 4.39
(s, 6H, CH2N3), 7.25 (s, 3H, H-ar).
C-(2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl)-formami-
doxime (2). A solution of 2,3,4,6-tetra-O-benzoyl-b-D-gluco-pyranosyl cyanide 1 (3.00 g, 4.96 mmol) and hydroxylamine
hydrochloride (0.86 g, 12.4 mmol) in pyridine (10 mL) was
stirred at 50 1C for 5 hours. The mixture was diluted with
EtOAc (250 mL) and washed with 100 mL portions of water,
1 M HCl, saturated NaHCO3, water and brine successively.
The organic layer was dried (MgSO4), filtered and evaporated
to obtain the pure amidoxime 2 (3.24 g, 99%) as a white foam.
Rf = 0.48 (PE/EtOAc, 1:1). 1H NMR (300 MHz, CDCl3)
d 4.21 (ddd, 1H, J = 9.7 Hz, J = 5.1 Hz, J = 2.7 Hz, H-5),
4.31 (d, 1H, J = 9.8 Hz, H-1), 4.47 (dd, 1H, J = 5.1 Hz, J =
12.4 Hz, H-6a), 4.62 (dd, 1H, J= 2.7 Hz, J= 12.4 Hz, H-6b),
4.76 (bs, 2H, NH2), 5.69 (t, 1H, J = 9.8 Hz, H-2), 5.73 (t, 1H,
J = 9.8 Hz, H-4), 5.96 (t, 1H, J = 9.8 Hz, H-3), 7.24–7.43
(m, 10H, H-ar), 7.47–7.57 (m, 2H, H-ar), 7.81–8.04 (m, 8H, H-ar).
O-(Pent-40-ynoyl)-3-C-(2,3,4,6-tetra-O-benzoyl-b-D-gluco-pyranosyl)-formamidoxime (3). A solution of 4-pentynoic acid
(27 mg, 0.27 mmol) in CH2Cl2/DMF (4 mL, 9:1) was cooled to
�8 1C before addition of 1-hydroxybenzotriazole (HOBt)
152 | New J. Chem., 2009, 33, 148–156 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(36.5 mg, 0.27 mmol), 1-(3-dimethylaminopropyl)-3-ethyl-
carbodiimide hydrochloride (EDCI) (52 mg, 0.27 mmol) and
amidoxime 2 (146 mg, 0.23 mmol). The mixture was kept at
�8 1C for 30 minutes then stirred at room temperature for
16 hours. The solvents were evaporated off and the crude
product was purified by flash silica gel column chromato-
graphy (PE then PE/EtOAc, 1:1) to afford theO-acylamidoxime
3 (110 mg, 67%) as a white foam. Rf = 0.53 (PE/EtOAc, 1:1).
[a]D = �2.9 (c = 1.00/CH2Cl2).1H NMR (300 MHz, CDCl3)
d 1.94 (t, 1H, J= 2.5 Hz, H-50), 2.40–2.63 (m, 4H, H-20 H-30),
4.31 (ddd, 1H, J= 2.7 Hz, J= 5.1 Hz, J= 9.8 Hz, H-5), 4.54
(d, 1H, J = 9.8 Hz, H-1), 4.53–4.59 (m, 1H, H-6a), 4.67
(dd, 1H, J = 2.7 Hz, J = 9.5 Hz, H-6b), 5.36 (s, 2H, NH2),
5.76 (t, 1H, J = 9.8 Hz, H-4), 5.80 (t, 1H, J = 9.8 Hz, H-2),
6.01 (t, 1H, J = 9.8 Hz, H-3), 7.25–7.57 (m, 12H, H-ar),
7.83–8.07 (m, 8H, H-ar). 13C NMR (75 MHz, CDCl3) d 14.3
(C-30), 32.1 (C-20), 63.0 (C-6), 69.2 (C-4), 69.3 (C-50), 70.0
(C-2), 73.7 (C-3), 75.6 (C-1), 76.7 (C-5), 82.5 (C-40), 128.40,
128.45, 128.5 (3s, 8C, CH-ar), 128.77, 128.82, 129.4 (3s, 4C,
CIV-ar), 129.8, 129.9, 130.00, 130.04 (4s, 8C, CH-ar), 133.4,
133.5, 133.7 (3s, 4C, CH-ar), 153.7 (NQCR–NH2), 165.3,
165.6, 165.7, 166.3 (4s, 4C, COPh), 169.0 (C-10). ESI-MS
(positive mode) m/z: 719.2 [M + H]+, 741.3 [M + Na]+,
786.9 [M + HCOOH + Na]+, 1436.9 [2M + H]+, 1458.9
[2M + Na]+, 1504.5 [2M + HCOOH + Na]+. HR-ESI-MS
(positive mode) m/z: calcd. for C40H34N2O11 [M + H]+
719.2241, found 719.2244.
5-(But-100-yn-400-yl)-3-C-(20,30,40,60-tetra-O-benzoyl-b-D-gluco-pyranosyl)-1,2,4-oxadiazole (4). In a CEM Discover 5 mL vial
was introduced a solution of O-acylamidoxime 3 (369 mg,
0.5 mmol) and TBAF (50 mL, 50 mmol, 1 M in THF) in toluene
(5 mL). The reaction vial was heated at 150 1C for 5 min upon
microwave irradiation (200 W). The solvent was evaporated
and the residue purified by flash silica gel column chromato-
graphy (PE then PE/EtOAc, 1:1) to afford the oxadiazole 4
(348 mg, 97%) as a white foam. Rf = 0.65 (PE/EtOAc, 7:3).
[a]D =+8.3 (c= 1.12/CH2Cl2).1H NMR (300 MHz, CDCl3)
d 1.84 (t, 1H, J= 2.6 Hz, H-100), 2.65 (td, 2H, J= 2.6 Hz, J=
7.5 Hz, H-300), 3.10 (t, 2H, J = 7.5 Hz, H-400), 4.33 (ddd, 1H,
J = 3.4 Hz, J = 5.1 Hz, J = 9.8 Hz, H-50), 4.53 (dd, 1H, J =
5.2 Hz, J = 12.4 Hz, H-60a), 4.65 (dd, 1H, J = 3.0 Hz, J =
12.4 Hz, H-60b), 5.09 (d, 1H, J = 9.5 Hz, H-10), 5.82 (t, 1H,
J= 9.5 Hz, H-40), 6.00 (m, 2H, H-20 H-30), 7.29–7.58 (m, 12 H,
H-ar), 7.81–8.02 (m, 8H, H-ar). 13C NMR (75 MHz, CDCl3) d16.0 (C-300), 26.2 (C-400), 63.3 (C-60), 69.4 (C-40), 70.2 (C-100),
70.6 (C-20), 72.4 (C-10), 74.1 (C-3 0), 77.0 (C-50), 80.8 (C-200),
128.3 (s, 2C, CH-ar), 128.4 (s, 4C, CH-ar), 128.5 (s, 2C, CH-
ar), 128.7, 128.7, 128.8, 129.5 (4s, 4C, CIV-ar), 129.7, 129.8,
129.8, 129.9 (4s, 8C, CH-ar), 133.2, 133.3, 133.4, 133.5 (4s, 4C,
CH-ar), 164.6, 165.2, 165.8, 166.3 (s, 4C, COPh), 166.2 (C-3),
179.0 (C-5). ESI-MS (positive mode) m/z: 701.1 [M + H]+,
723.2 [M + Na]+, 1400.9 [2M + H]+, 1422.9 [2M + Na]+.
HR-ESI-MS (positive mode) m/z: calcd. for C40H32N2O10Na
[M + Na]+ 723.1955, found 723.1954.
3-C-(b-D-Glucopyranosyl)-5-(but-100-yn-400-yl)-1,2,4-oxadiazole (5).
A solution of benzoylated oxadiazole 4 (261 mg, 0.37 mmol)
and NaOMe (5 mg, 0.09 mmol) in CH2Cl2/MeOH (5 mL, 2:3)
was stirred at room temperature for 4 hours. The solution
was neutralized with a cation exchange resin (Amberlite IR-120,
H+ form) and the resin washed with MeOH (3 � 5 mL).
The filtrate was evaporated off and the residue was dissolved in
MeOH then precipitated with CH2Cl2. The resulting solid was
washed with CH2Cl2 (2 � 5 mL) and dried under vacuum
to afford the hydroxylated oxadiazole 5 (103 mg, 98%) as a
white foam. Rf = 0.26 (CH2Cl2/MeOH, 9:1). [a]D = +9.6
(c = 0.51/H2O).1H NMR (300 MHz, CD3OD) d 2.36 (t, 1H,
J = 2.6 Hz, H-100), 2.73 (td, 2H, J = 2.6 Hz, J = 7.3 Hz, H-300),
3.18 (t, 2H, J= 7.3 Hz, H-400), 3.42–3.53 (m, 3H, H-30 H-40 H-50),
3.65–3.73 (m, 2H, H-20 H-60a), 3.87 (dd, 1H, Jo1.0 Hz, J= 12.0
Hz, H-60b), 4.44 (d, 1H, J = 9.7 Hz, H-10). 13C NMR (75 MHz,
CD3OD) d 16.6 (C-300), 27.1 (C-400), 62.8 (C-60), 71.2 (C-40), 71.3
(C-100), 73.3 (C-20), 74.8 (C-10), 79.2 (C-30), 82.3 (C-200), 82.6 (C-50),
169.2 (C-3), 180.5 (C-5). ESI-MS (positive mode) m/z: 285.0
[M + H]+, 307.1 [M + Na]+, 590.9 [2M + Na]+. HR-ESI-MS
(positive mode) m/z: calcd. for C12H16N2O6Na [M + Na]+
307.0906, found 307.0907.
5-[200-(10 0 0-Benzyl-10 0 0,20 0 0,30 0 0-triazol-40 0 0-yl)ethyl]-3-C-
(20,30,40,60-tetra-O-benzoyl-b-D-glucopyranosyl)-1,2,4-oxa-diazole (6). In a CEM Discover 5 mL vial was introduced a
solution of benzyl azide (110 mg, 0.828 mmol), alkyne 4
(193 mg, 0.276 mmol), copper iodide (26 mg, 0.138 mmol)
and DIPEA (240 mL, 1.38 mmol) in toluene (5 mL). The
solution was sonicated for 1 min then heated at 110 1C for 15
min upon microwave irradiation (150 W). The solvent was
evaporated off and the residue purified by flash silica gel
column chromatography (PE/EtOAc, 1:1) to afford the cyclo-
adduct 6 (202 mg, 88%) as a colorless oil. Rf = 0.24
(PE/EtOAc, 1:1). [a]D = +1.4 (c = 1.02/CH2Cl2).1H NMR
(500 MHz, CDCl3) d 3.22 (bs, 2H, H-200), 3.28 (bs, 2H, H-100),
4.37 (ddd, 1H, J=3.0 Hz, J= 5.3 Hz, J= 9.7 Hz, H-50), 4.56
(dd, 1H, J = 5.3 Hz, J = 12.4 Hz, H-60a), 4.68 (dd, 1H, J =
3.0 Hz, J = 12.4 Hz, H-60b), 5.10 (d, 1H, J = 9.7 Hz, H-10),
5.48 (s, 2H, NCH2Ph), 5.86 (t, 1H, J = 9.7 Hz, H-40), 5.97
(t, 1H, J = 9.7 Hz, H-20), 6.06 (t, 1H, J = 9.7 Hz, H-30),
7.24–7.56 (m, 18H, H-50 0 0 H-ar), 7.80–8.03 (m, 8H, H-ar). 13C
NMR (125 MHz, CDCl3) d 21.8 (C-200), 26.6 (C-100), 53.6
(NCH2Ph), 62.9 (C-60), 68.1 (C-40), 69.8 (C-20), 71.7 (C-10),
73.4 (C-30), 76.5 (C-50), 122.2 (C-50 0 0), 127.8, 127.9, 128.0,
128.4, 128.5, 128.9, 129.7, 129.8 (8s, 25C, CH-ar), 133.4, 133.6,
133.8, 133.9 (4s, 4C, CIV-ar), 134.7 (CIV-ar), 145.3 (C-40 0 0),
164.7, 165.0, 165.6, 165.3 (4s, 4C, COPh), 165.6 (C-3), 180.1
(C-5). ESI-MS (positive mode) m/z: 834.1 [M + H]+, 856.1
[M+Na]+, 1666.4 [2M+H]+. HR-ESI-MS (positive mode)
m/z: calcd. for C47H40N5O10 [M + H]+ 834.2775, found
834.2781.
5-[200-(10 0 0-Benzyl-10 0 0,20 0 0,30 0 0-triazol-40 0 0-yl)-ethyl]-3-C-(b-D-glucopyranosyl)-1,2,4-oxadiazole (7). A solution of benzoy-
lated cycloadduct 6 (128 mg, 0.153 mmol) and NaOMe
(5 mg, 0.09 mmol) in CH2Cl2/MeOH (5.5 mL, 10:1) was
stirred at room temperature for 4 hours. The solution was
neutralized with a cation exchange resin (Amberlite IR-120,
H+ form) and resin washed with MeOH (3 � 5 mL). The
filtrate was evaporated off and the residue purified by
flash silica gel column chromatography (CH2Cl2 then
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 148–156 | 153
CH2Cl2/MeOH, 8:2 then EtOAc/MeOH, 8:2) to afford the
hydroxylated cycloadduct 7 (63 mg, 98%) as a white foam.
Rf = 0.68 (EtOAc/MeOH, 4:1). [a]D = +5.5 (c = 0.95/
MeOH). 1H NMR (300 MHz, CD3OD) d 3.18–3.23 (m, 2H,
H-200), 3.24–3.36 (m, 2H, H-100), 3.44–3.52 (m, 3H, H-30 H-40
H-50), 3.68–3.74 (m, 2H, H-20 H-60a), 3.88 (dd, 1H, Jo1.0 Hz,
J = 11.4 Hz, H-60b), 4.44 (d, 1H, J = 9.7 Hz, H-10), 5.55
(s, 2H, NCH2Ph), 7.28–7.38 (m, 5H, H-ar), 7.79 (s, 1H, H-50 0 0).13C NMR (75 MHz, CD3OD) d 23.3 (C-200), 27.2 (C-100), 54.9
(NCH2Ph), 62.8 (C-60), 71.3, 79.2, 82.6 (3s, 3C, C-30 C-40
C-50), 73.4 (C-2 0), 74.9 (C-10), 123.9 (C-50 0 0), 129.1, 129.5,
130.0 (3s, 5C, CH-ar), 136.8 (CIV-ar), 146.9 (C-40 0 0), 169.2
(C-3), 180.9 (C-5). ESI-MS (positive mode) m/z: 418.1 [M +
H]+, 440.1 [M + Na]+, 856.6 [2M + Na]+. HR-ESI-MS
(positive mode) m/z: calcd. for C19H23N5NaO6 [M + Na]+
440.1546, found 440.1549.
1,3,5-Tris-40-200-[30 0 0-C-(20 0 0 0
,30 0 0 0
,40 0 0 0
,60 0 0 0
-tetra-O-benzoyl-b-D-glucopyranosyl)-1 0 0 0,2 0 0 0,4 0 0 0-oxadiazol-5 0 0 0-yl]-ethyl-1 0,20,3 0-
triazol-1 0-ylmethylbenzene (8). In a CEM Discover 5 mL vial
was introduced a solution of 1,3,5-tris(azidomethyl)benzene
(POTENTIALLY EXPLOSIVE, 4.9 mg, 20 mmol), alkyne 4
(63 mg, 90 mmol), copper iodide (1.9 mg, 10 mmol) and DIPEA
(17 mL, 100 mmol) in toluene (6 mL). The solution was
sonicated for 1 min then heated at 110 1C for 15 min upon
microwave irradiation (150 W). The solvent was evaporated
off and the residue purified by flash silica gel column chromato-
graphy (PE/EtOAc, 1:1 then EtOAc) to afford the tris-
cycloadduct 8 (46 mg, 98%) as a colorless oil. Rf = 0.67
(EtOAc). 1H NMR (300 MHz, CDCl3) d 3.10–3.32 (m, 12H,
H-100 H-200), 4.34–4.40 (m, 3H, H-50 0 0 0
), 4.51 (dd, 3H, J = 5.1
Hz, J= 12.4 Hz, H-60 0 0 0
a), 4.66 (dd, 3H, J= 2.7 Hz, J= 12.4
Hz, H-60 0 0 0
b), 5.12 (d, 3H, J = 9.4 Hz, H-10 0 0 0
), 5.31 (s, 6H,
NCH2C6H3), 5.87 (t, 3H, J= 9.4 Hz, H-40 0 0 0
), 5.97 (t, 3H, J=
9.4 Hz, H-20 0 0 0
), 6.05 (t, 3H, J = 9.4 Hz, H-30 0 0 0
), 6.93 (s, 3H,
H-2 H-4 H-6), 7.23–7.50 (m, 36H, H-ar), 7.74–8.00 (m, 24H,
H-ar). 13C NMR (75 MHz, CDCl3) d 22.5 (s, 3C, C-100), 26.6
(s, 3C, C-200), 53.1 (NCH2C6H3), 63.3 (s, 3C, C-60 0 0 0
), 69.3
(s, 3C, C-40 0 0 0
), 70.7 (s, 3C, C-20 0 0 0
), 72.3 (s, 3C, C-10 0 0 0
), 74.1
(s, 3C, C-30 0 0 0
), 77.0 (s, 3C, C-50 0 0 0
), 122.2 (s, 3C, C-50), 127.0
(s, 3C, C-2, C-4, C-6), 128.39, 128.43, 128.5 (3s, 24C, CH-ar),
128.69, 128.71, 128.8, 129.5 (4s, 12C, CIV-ar), 129.7, 129.78,
129.82, 129.9 (4s, 24C, CH-ar), 133.2, 133.4, 133.6 (3s, 12C,
CH-ar), 137.0 (s, 3C, C-1, C-3, C-5), 145.6 (s, 3C, C-40), 164.9,
165.2, 165.8, 166.2 (4s, 12C, COPh), 166.4 (s, 3C, C-30 0 0),
180.0 (s, 3C, C-50 0 0). ESI-MS (positive mode) m/z: 1173.5
[M + 2H]2+.
1,3,5-Tris-40-200-[30 0 0-C-(b-D-glucopyranosyl)-10 0 0,20 0 0,40 0 0-oxa-diazol-50 0 0-yl]ethyl-10,20,30-triazol-10-ylmethylbenzene (9). A
solution of benzoylated tris-cycloadduct 8 (114 mg, 49 mmol)
and NaOMe (5 mg, 92 mmol) in CH2Cl2/MeOH (5.5 mL, 10:1)
was stirred at room temperature for 6 hours. The solution was
neutralized with a cation exchange resin (Amberlite IR-120,
H+ form) and resin washed with MeOH (3 � 5 mL). The
filtrate was evaporated off and the residue was dissolved in
MeOH then precipitated with PE. The resulting solid was
washed with PE (5 � 5 mL), dissolved into pure water and
freeze-dried to afford the hydroxylated tris-cycloadduct 9
(45 mg, 84%) as a white foam. 1H NMR (300 MHz, D2O) d3.02–3.19 (m, 6H, H-100), 3.20–3.30 (m, 6H, H-200), 3.51–3.86
(m, 18H, H-20 0 0 0
H-30 0 0 0
H-40 0 0 0
H-50 0 0 0
H-60 0 0 0
a H-60 0 0 0
b), 4.54
(d, 3H, J = 8.8 Hz, H-10 0 0 0
), 5.39 (s, 6H, NCH2C6H3), 6.98
(s, 3H, H-2 H-4 H-6), 7.73 (s, 3H, H-50). 13C NMR (125 MHz,
D2O) d 22.0 (s, 3C, C-100), 26.3 (s, 3C, C-200), 53.4 (s, 3C,
NCH2C6H3), 61.1 (s, 3C, C-60 0 0 0
), 72.1 (s, 3C, C-20 0 0 0
), 73.2
(s, 3C, C-10 0 0 0
), 69.6, 77.1, 80.6 (3s, 9C, C-30 0 0 0
C-40 0 0 0
C-50 0 0 0
),
124.2 (s, 3C, C-50), 127.3 (s, 3C, C-2 C-4 C-6), 137.2 (s, 3C, C-1
C-3 C-5), 146.5 (s, 3C, C-40), 167.5 (s, 3C, C-30 0 0), 181.0 (s, 3C,
C-50 0 0). ESI-MS (positive mode) m/z: 1118.2 [M + Na]+.
HR-ESI-MS (positive mode) m/z: calcd. for C45H57N15NaO18
[M + Na]+ 1118.3904, found 1118.3918.
N,N0,N00-1,3,5-Tris(benzoyloxy)-C-(20,30,40,60-tetra-O-benzoyl-
b-D-glucopyranosyl)tricarboximidamide (10). A solution of
1,3,5-benzenetricarbonyl trichloride (102 mg, 0.38 mmol) and
amidoxime 2 (794 mg, 1.24 mmol) in 1,4-dioxane (15 mL) was
stirred at room temperature for 24 hours. The solvent was then
evaporated off and the mixture was diluted with EtOAc (150mL).
The organic layer was washed by 100 mL portions of saturated
NaHCO3, water and brine successively. The organic layer was
dried (MgSO4), filtered and evaporated. The crude product was
purified by flash silica gel column chromatography (EtOAc) to
afford the O-acylamidoxime 10 (571 mg, 73%) as a white foam.
Rf = 0.75 (PE/EtOAc, 3:7). [a]D = �48.6 (c = 1/CH2Cl2).1H
NMR (300 MHz, CDCl3) d 4.23–4.33 (m, 3H, H-50), 4.49–4.57
(m, 6H, H-10 H-60a), 4.58–4.65 (m, 3H, H-60b), 5.46 (bs, 6H,
NH2), 5.70 (t, 3H, J = 9.6 Hz, H-20), 5.76 (t, 3H, J = 9.6 Hz,
H-40), 5.98 (t, 3H, J = 9.6 Hz, H-30), 7.22–7.58 (m, 36H, H-ar),
7.80–8.04 (m, 24H, H-ar), 8.52 (s, 3H, H-2 H-4 H-6). 13C NMR
(75 MHz, CDCl3) d 62.9 (C-60), 69.0 (C-40), 70.0 (C-20), 73.5
(C-30), 75.6 (C-10), 76.8 (C-50), 128.3, 128.4, 128.5, 128.7, 129.3,
129.7, 129.8, 129.90, 129.94, 130.2 (10s, 20C, CH-ar), 133.3,
133.4, 133.6, 134.1 (4s, 4C, C-ar), 154.5 (H2NCQNO), 161.5
(NOCQO), 165.2, 165.58, 165.63, 166.1 (4s, 4C, COPh). LSIMS
(positive mode, thioglycerol) m/z: 2071.6 [M + H]+. HR-ESI-
MS (positive mode) m/z: calcd. for C114H91N6O33 [M + H]+
2071.5627, found 2071.5651.
3,5-Bis[30-C-(b-D-glucopyranosyl)-10,20,40-oxadiazol-50-yl]-benzoic acid (12). A solution of tris-O-acylamidoxime 10
(532 mg, 256 mmol) in 1,4-dioxane (12 mL) was stirred at
100 1C for 4 days. The reaction was then cooled to room
temperature and the solvent evaporated off. The crude pro-
duct 11 was used without further purification. A solution of
crude 11 (239 mg) and NaOMe (10 mg) in CH2Cl2/MeOH
(5 mL, 1:1) was stirred at room temperature for 5 hours. The
solvent was evaporated off and the crude mixture was purified
by flash reverse-phase silica gel chromatography (H2O then
H2O/MeOH 7:3) to afford the benzoic acid derivative 12
(95 mg, 58% over two steps) as a white foam. Rf = 0.20
(EtOAc/MeOH 1:1). [a]D = +7.1 (c = 0.41/MeOH). 1H
NMR (300 MHz, CDCl3) d 3.62–3.76 (m, 3H, H-300, H-400,
H-500), 3.81–3.89 (m, 2H, H-200, H-600a), 3.99 (m, 1H, H-600b),
4.75 (m, 1H, H-100), 8.77 (s, 2H, H-ar), 8.87 (s, 1H, H-ar). 13C
NMR (75 MHz, CDCl3) d 61.2 (C-600), 69.7, 77.1, 80.8 (3s, 3C,
C-300, C-400, C-500), 72.1 (C-200), 73.4 (C-100), 124.7 (s, 2C,
CIV-ar), 126.9 (CIV-ar), 129.8 (CH-ar), 133.0 (s, 2C, CH-ar),
154 | New J. Chem., 2009, 33, 148–156 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
139.5 (CO2H), 168.4 (C-30), 175.8 (C-50). ESI-MS (negative
mode) m/z: 581 [M � H]�. HR-ESI-MS (negative mode) m/z:
calcd for C23H25N4O14 [M � H]� 581.1367, found 581.1369.
1,3,5-Tris[30-C-(200,300,400,600-tetra-O-benzoyl-b-D-glucopyra-nosyl)-10,20,40-oxadiazol-50-yl]benzene (13). In a CEMDiscover
5 mL vial was introduced a solution of O-acylamidoxime
10 (454 mg, 0.22 mmol) and TBAF (70 mL, 70 mmol, 1 M in
THF) in toluene (5 mL). The reaction vial was heated
at 150 1C for 40 min upon microwave irradiation (200 W).
The solvent was evaporated and the residue purified by
flash silica gel column chromatography (PE then PE/EtOAc,
1:1) to afford the trivalent oxadiazole 13 (317 mg, 72%) as a
white foam. Rf = 0.79 (PE/EtOAc, 1:1). [a]D = �35.1 (c =
1.00/CH2Cl2).1H NMR (300 MHz, CDCl3) d 4.41 (ddd, 3H,
J = 3.1 Hz, J = 5.1 Hz, J = 9.5 Hz, H-500), 4.59 (dd, 3H,
J = 5.2 Hz, J = 12.5 Hz, H-600a), 4.71 (dd, 3H, J = 2.9 Hz,
J = 12.5 Hz, H-600b), 5.22 (d, 3H, J = 9.5 Hz, H-100), 5.91
(t, 3H, J = 9.7 Hz, H-400), 6.04–6.15 (m, 6H, H-200 H-300),
7.26–7.52 (m, 36H, H-ar), 7.82–8.02 (m, 24H, H-ar), 8.96
(s, 3H, H-2). 13C NMR (75 MHz, CDCl3) d 63.3 (s, 3C,
C-600), 69.4 (s, 3C, C-400), 70.8 (s, 3C, C-200), 72.6 (s, 3C, C-100),
74.1 (s, 3C, C-300), 77.4 (s, 3C, C-500), 126.2 (s, 3C, C-1 C-3
C-5), 128.5, 128.5, 128.6 (3s, 24C, CH-ar), 129.9, 130.0
(2s, 24C, CH-ar), 131.3 (s, 3C, C-2 C-4 C-6), 133.3, 133.4,
133.6, 133.6 (4s, 12C, CH-ar), 164.9, 165.2, 165.9, 166.3
(4s, 12C, COPh), 167.6 (s, 3C, C-30), 174.1 (s, 3C, C-50).
ESI-MS (positive mode) m/z: 2039.6 [M + Na]+.
1,3,5-Tris[30-C-b-D-glucopyranosyl)-10,20,40-oxadiazol-50-yl]-benzene (14). A solution of benzoylated tris-oxadiazole 13 (296
mg, 0.15 mmol) and NaOMe (15 mg, 0.3 mmol) in CH2Cl2/
MeOH (8 mL, 3:5) was stirred at room temperature for 3
hours. The solution was neutralized with a cation exchange
resin (Amberlite IR-120, H+ form) and the resin washed with
MeOH (3 � 5 mL). The filtrate was evaporated off and the
residue was dissolved in MeOH then precipitated with
CH2Cl2. The resulting solid was washed with CH2Cl2 (2 �5 mL) and dried under vacuum to afford the hydroxylated tris-
oxadiazole 14 (114 mg, 99%) as a white foam. Rf = 0.63
(CH2Cl2/MeOH, 9:1). [a]D = +10.6 (c = 1.00/H2O). 1H
NMR (300 MHz, D2O) d 3.61–3.84 (m, 15H, H-200 H-300
H-400 H-500 H-600a), 3.97 (d, 3H, J = 11.9 Hz, H-600b), 4.67
(d, 3H, J = 9.4 Hz, H-100), 8.74 (s, 3H, H-2 H-4 H-6). 13C
NMR (75 MHz, D2O) d 59.0 (s, 3C, C-600), 71.0 (s, 3C, C-100),
67.4, 69.9, 74.9, 78.6 (4s, 12C, C-200 C-300 C-400 C-500), 123.5
(s, 3C, C-1 C-3 C-5), 129.2 (s, 3C, C-2 C-4 C-6), 166.5 (s, 3C,
C-30), 172.0 (s, 3C, C-50). ESI-MS (negative mode) m/z:
812.9 [M + HCO2�]�. ESI-MS (positive mode) m/z: 791.7
[M + Na]+. HR-ESI-MS (positive mode) m/z: calcd. for
C30H36N6NaO18 [M + Na]+ 791.1984, found 791.1981.
Glycogen phosphorylase inhibition measurements
Glycogen phosphorylase b was prepared from rabbit skeletal
muscle according to the method of Fischer and Krebs,24 using
dithiothreitol instead of L-cysteine, and recrystallized at least
three times before use. Kinetic experiments were performed in
the direction of glycogen synthesis as described previously.25
Kinetic data for the inhibition of rabbit skeletal muscle
glycogen phosphorylase were collected using different concen-
trations of a-D-glucose-1-phosphate (2–20 mM), constant
concentrations of glycogen (1% w/v) and AMP (1 mM), and
various concentrations of inhibitors. Inhibitors were dissolved
in dimethyl sulfoxide (DMSO) and diluted in the assay buffer
(50 mM triethanolamine, 1 mM EDTA and 1 mM dithio-
threitol) so that the DMSO concentration in the assay should
be lower than 5%. The enzymatic activities were presented in
the form of double-reciprocal plots (Lineweaver–Burk) apply-
ing a nonlinear data analysis program. The inhibitor constants
(Ki) were determined by Dixon plots, by replotting the
slopes from the Lineweaver–Burk plots against the inhibitor
concentrations.26,27 The means of standard errors for all
calculated kinetic parameters averaged to less than 10%.
Ki values for compounds 9 and 14 were also estimated and
found to be 490 � 45 mM and 535 � 50 mM, respectively.
The poor solubility of inhibitors 5, 7 and 15 limited the
concentrations used in the kinetic studies. The inhibition of
glycogen phosphorylase was therefore determined at 625 mMand 2.5 mM concentrations of these inhibitors and given in
Table 2.
Acknowledgements
The authors wish to thank Universite Claude Bernard Lyon 1
and CNRS for financial support. A stipend to S. C. and
financial support from Region Rhone-Alpes )Cluster de
Recherche Chimie* are gratefully acknowledged. CNRS is
also thanked for additional funding through )Programme
Interdisciplinaire: Chimie pour le Developpement Durable*.
This work was also supported by grants from the Hungarian
Science Research Fund (OTKA K60620) and the Hungarian
Ministry of Health (ETT 083/2006).
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156 | New J. Chem., 2009, 33, 148–156 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
The formation of silver nanofibres by liquid/liquid interfacial reactions:
mechanistic aspects
Kun Luo and Robert A. W. Dryfe*
Received (in Montpellier, France) 9th June 2008, Accepted 22nd August 2008
First published as an Advance Article on the web 23rd October 2008
DOI: 10.1039/b809654f
The liquid/liquid interfacial reaction (LLIR) between silver nitrate in aqueous solution and
ferrocene in organic solution has been investigated: the resultant silver deposit is found to contain
long, well-defined nanometre scale fibres, together with thin silver nanowire networks. In situ
optical microscopy and ex situ scanning electron microscopy indicate that the 1D growth of the
interfacial deposits is due to recrystallisation of the structure formed initially. Geometric factors
are found to exert a larger effect on the 1D growth of silver by LLIRs compared to the
electrochemical mechanism previously suggested by Scholz et al.
1. Introduction
Nanostructures (i.e. structures with at least one dimension in
the range of 1 to 100 nm) have attracted increasing attention
because of their unusual chemical and physical properties.
There has been particular interest in methods of forming
one dimensional (1D) nanostructures, including nanowires,
because such structures provide a better model system for
investigating the dependence of electronic transport, optical
and mechanical properties on size confinement and dimen-
sionality.1 Strategies for achieving 1D growth have been
summarized by Xia et al.,2 these include: (i) use of the
intrinsically anisotropic crystallographic structure of a solid;3
(ii) introduction of a liquid/solid interface to reduce the
symmetry of a seed;4 or use of supersaturation control to
modify the growth habit of a seed;5 (iii) use of various
templates with 1D morphologies to direct the formation of
nanostructures6–9 (iv) assembly of zero dimensional nano-
structures (i.e. nanoparticles);10 (v) use of appropriate capping
reagent(s) to kinetically control the growth rates of various
facets of a seed.11,12 Another interface, the liquid/liquid (L/L)
interface, can also be used to limit the growth of materials, as
in (ii) above, or to assemble the symmetry of nanoparticles
(NPs), as in (iv) above, where liquid/liquid interfacial reactions
(LLIRs) are involved.
Metal NPs can be grown at the L/L interface either electro-
chemically, by applying a voltage across the L/L interface
when sufficient electrolytes are present in each phase,13 or by
spontaneous chemical reaction where the electron exchange
between redox couples present in the oil and water phases is
normally accompanied with biphasic ion exchange. Using the
former approach, gold NPs,14 platinum NPs15 and pyrrole
oligomers16 have been prepared electrochemically at the inter-
face between immiscible electrolyte solutions. The second
approach, using spontaneous deposition, can be traced back
to Faraday’s formation of colloidal gold at the water/carbon
disulfide boundary. In this case, particles can either be formed,
or pre-formed particles can be assembled,17 at the L/L inter-
face. A surprising variation in particle morphology has been
reported at the L/L interface. Most interfacial deposits appear
to consist of spherical NPs, which assemble to form films, or
aggregate into larger structures if no stabilising ligands are
present.18,19 The intrinsic difficulty in studying the larger-scale
structure is in finding an appropriate microscopic technique to
probe particle morphology in situ. Recent studies have des-
cribed the preparation of well-defined metal and metal oxide
NPs at the toluene/water interface, with X-ray scattering being
used to study the nanometre-scale assembly of Au NPs into an
ordered interfacial film.20,21 Silver deposition by LLIR, the
focus of this manuscript, has been described in a number of
previous reports. Silver assembly (as opposed to formation) in
the presence of surfactants at the water/dichloromethane
interface produces a ‘‘metal liquid-like film’’,22 whose struc-
ture has been described as micron-scale flocs of silver NPs.23,24
Assembly of silver NPs at an aqueous/chloroform interface in
the presence of thiol species has also been described.25 Other
reports have suggested that more unusual structures are ob-
served for Ag assembly and/or deposition at the L/L interface.
Agitation of aqueous silver hydrosols, during their assembly at
the water/toluene interface, has been reported to form
‘‘2D networks of uniform diameter nanowires’’.26 The forma-
tion of silver deposits, by interfacial reduction with an organic
phase electron donor, gives rise to intergrown ‘‘whisker’’
structures, although in this case the geometry is not uniform.27
The latter article noted that a transition between 1D and 2D
growth could be tuned according to the experimental condi-
tions of the spontaneous LLIR. By choosing appropriate
organic solvents and concentrations of the reagents in the
two phases, either silver whiskers (with radii from about 50 nm
to 50 microns) or ultrathin Ag films were observed. Herein, we
present further investigations into the spontaneous LLIR
between Fc in various organic solvents and aqueous AgNO3
solutions, where long and well-defined Ag nanofibres were
found under appropriate reaction conditions. The morpholo-
gical evolution and reaction mechanism are also discussed,
based on the micrographic observations.
School of Chemistry, University of Manchester, Oxford Road,Manchester, UK M13 9PL. E-mail: [email protected];Fax: +44 (0)161 275 4734
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 157–163 | 157
PAPER www.rsc.org/njc | New Journal of Chemistry
2. Experimental
Silver nitrate (AgNO3, BDH Chemicals, GPR), ferrocene
(Fc, 99%, Alfa Aesar), 1,2-dichoroethane (DCE, Rathburn,
HPLC), nitrobenzene (NB, 99%, Sigma) and toluene
(99%, Fisher Scientific) were used directly without further
treatment. Typically, 3.3 mM of silver nitrate solution was
prepared with deionised water from an Elga ‘‘Purelab Ultra’’
(Elga, Marlow, UK) system. Ferrocene was dissolved in DCE,
or other organic solvents, as the organic phase for the inter-
facial reactions. The aqueous solution of AgNO3 and one of
the organic Fc solutions were placed together in a glass tube
with dimensions 75 mm (height) � 25 mm (diameter), follow-
ing the sequence that the higher density phase was added prior
to the light one. The mixture was then kept still at ambient
temperature. The interfacial deposit was collected after 48 h of
reaction, and transferred onto glass slides and dried in air. It
was then washed with acetone and deionised water separately,
and dried at ambient temperature before further analysis.
Copper grids with holey carbon films (S147-4, Agar Scientific)
were employed to collect samples for analysis via transmission
electron microscopy (TEM) and high resolution transmission
microscopy (HRTEM). The samples were rinsed with both
acetone and deionised water, and were dried in air in order to
remove the remained contaminants.
In situ optical microscopy was performed by a Leica DMIL
optical microscope fitted with a Sony CCD-IRIS camera on
an anti-vibration system (Active vibration isolation system
TS-200, HWL Scientific Instruments GmbH). The X-ray
diffraction (XRD) analysis was carried out using an Oxford
Diffraction System (Xcalibur 2, Mo-Ka = 0.7093 A), and XL
30 FEG Philips and ESEM XL30 Philips electron microscopes
were employed at 15 kV for scanning electron microscopy
(SEM). TEM and HRTEM were performed with a Tecnai F30
FEG-TEM system operating at 300 kV.
3. Results
The deposition of Ag resulting from the LLIR between
AgNO3 in water and Fc in organic solvent can be written as:27
Fc(o) + Ag+(w) + X�(w) - Fc+(o) + X�(o) + Ag(s) (1)
where the subscripts ‘‘s’’, ‘‘w’’, and ‘‘o’’ in the reactions
represent interfacial, aqueous and organic phases, respectively,
and the anion X� is added to balance the charge since no Fc+
transfer to the aqueous phase was believed to occur (in the
experiments reported herein, X� is nitrate). The reaction was
monitored in situ by an optical microscope placed on the active
anti-vibration system. As shown in Fig. 1(a), at the beginning
of the reaction (ca. 1 min), only separate particles were
observed at the L/L interface. Many particles were rapidly
generated, and started aggregating, after about five minutes of
contact between the two phases (Fig. 1(b)). After 10 min,
fractal-like aggregates appeared at the interface, as illustrated
by Fig. 1(c), and the fluidity at the interface became obstructed
after 25 min of reaction, owing to the appearance of large Ag
agglomerates (see Fig. 1(d)). After 24 h of reaction (Fig. 1(e)),
the L/L interface became somewhat solidified, and a grey
coloured deposit was seen. The interfacial deposits became a
bit denser compared to Fig. 1(e) when the reaction time was
extended to 48 h (shown in Fig. 1(f)), but no visible fibre-like
deposit was found under the optical microscopy. The process
was also investigated ex situ by SEM, and the morphological
evolution of the Ag deposit is illustrated by Fig. 2, although an
important point to note here is that the extraction and drying
of the sample could induce changes in morphology. The
interfacial deposit seen after twenty five minutes of reaction
appeared as micron-scale ‘‘flakes’’ with a few nuclei on the
surface as displayed in Fig. 2(a), indicative of a possible
destruction of an originally compact 2D interfacial layer
during the sample collection. After 1 h of the reaction, some
1D Ag deposits can be differentiated from others (see
Fig. 2(b)). After 4 h of reaction (Fig. 2(c)), some of the
‘‘microflakes’’ are found with holes and irregular edges in
the background and co-exist with the 1D Ag nanostructures,
which are not seen at shorter or longer reaction times. After 48
h, long Ag nano-scale fibres are observed, as illustrated in
Fig. 2(d), together with some short 1D nanostructures and
‘‘microflakes’’. The inset shows that the nanofibre is rather
smooth and well-defined at a larger magnification. The Ag
nanofibres shown in Fig. 2(d) are measured and give an
average diameter of 171 � 4 nm (N = 13) with a mean aspect
ratio of ca. 174, where the largest aspect ratio from the other
micrographs is observed to be ca. 450. Fig. 2(e) further reveals
that the growth of the nanofibres originates from defects, such
as independent nuclei or the edges of the ‘‘microflakes’’ etc.
TEM and HRTEM micrographs offer the means of observa-
tion under higher magnification. Fig. 3(a) suggests that some
of the ‘‘microflakes’’ observed under SEM are actually com-
posed of networks of thinner 1D nanostructures, termed
‘‘nanowires’’ in the following text, with an average diameter
of 14.8 � 3.7 nm (N = 163), where the distribution of the
diameter values visible in Fig. 3(a) is shown in Fig. 3(b).
Fig. 3(a) also illustrates the evolution from the 2D film to
1D nanostructures, where a few branches of nanowires are
observed to extend from a piece of film higlighted by the circle
in the figure. The triangular highlights in Fig. 3(c) suggest that
Fig. 1 Optical micrographs recorded during the formation of Ag
interfacial deposits by LLIR: (a) at ca. 1 min, (b) at 5 min, (c) at
25 min, (d) at 1 h, (e) at 24 h, (f) at 48 h. The length of the scale bars in
the figure is 50 microns.
158 | New J. Chem., 2009, 33, 157–163 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
the growth of the nanowires originates from the triangular
nuclei, and the 1D extension from the nuclei is ‘‘welded’’ on
meeting other wires as shown by the appearance of lattice
fringes under TEM (circular highlight). The HRTEM image in
Fig. 3(d) indicates that the wires are nanocrystalline. From the
micrographs presented in Fig. 2 and 3, one can summarize that
the microflakes (the 2D growth owing to the presence of the
L/L interface) are formed in the early stages of the LLIR, a
process followed by 1D growth at the active sites of the
interfacial layer after a long-term LLIR, such as the edge of
the layer or the tips of triangular nuclei. The intermediate
stage (holey microflakes with irregular edges displayed in
Fig. 2(c)) at 4 h of the LLIR, suggests the appearance of a
parallel process which might be either the dissolution of the
as-formed microflakes; alternatively the secondary aggrega-
tion or growth of the nuclei may occur, to form thin nanowire
networks shown in Fig. 3(a). Considering that complete
microflakes and nanofibres are seen in the SEM micrographs
at 48 h of the LLIR, and the nanowire networks can only be
seen under TEM, the visible networks in Fig. 3(c) would
appear to arise from the dissolution of the as-formed 2D
layers. The LLIR process is therefore viewed as involving:
(i) formation of Ag nuclei at the L/L interface; (ii) agglomera-
tion of the as-prepared Ag nuclei to form 2D flakes due to the
constraint of the L/L interface; (iii) dissolution of some of the
initial Ag nuclei while secondary nucleation or growth occurs
elsewhere. Some of the larger 2D structures can even be
dissolved if the nuclei are depleted; (iv) the structural defects,
including the tips of the triangular nuclei, independent nuclei
and the edges of the microflakes, offer active sites for new
nucleation, leading to 1D growth. The diameter of the 1D
nanostructures is normally dependant on the size of the
protuberance of the defects, for example larger nuclei for the
nanofibres, compared to the corner of the smaller triangular
nuclei for the nanowires.
Different organic solvents, such as NB and toluene, were
used instead of DCE in the LLIR process. A thin and
Fig. 2 SEM micrographs of the Ag interfacial deposits collected at different times during the LLIR process: (a) at 25 min, (b) at 1 h, (c) at 4 h,
(d) at 48 h, the inset shows the diameter of the nanowire is around 100–200 nm; (e) at 48 h, 1D growth stems from the defects of the interfacial deposit.
Fig. 3 TEM and HRTEM micrographs of the Ag interfacial deposit
of the LLIR reaction between 3.3 mM AgNO3 aqueous solution and
5 mM Fc in DCE at 48 h: (a) nanowire networks in the deposit, the
highlighted part shows the 1D growth from a piece of a 2D thin film,
(b) distribution of the diameter of the nanowires, (c) the connection of
the nanowires, the parts highlighted with ‘‘&’’ indicate that nanowires
protrude from portions that were originally nanoparticulate. The
other parts highlighted with ‘‘J’’ denote the ‘‘welding’’ positions of
the nanowires; (d) HRTEM image of the nanowires, which indicates
the nanowires are composed of crystalline silver.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 157–163 | 159
continuous film was observed at the NB/water interface in a
Teflon container after 24 h of LLIR between 3.3 mM AgNO3
solution and 1 mM Fc in NB (see Fig. 4(a)), in accordance
with the results described by Scholz and Hasse.27 In contrast, a
radial pattern gradually appeared after a period of time in a
glass container (see Fig. 4(b)), in possible association with
random vibrations. The pattern was quite stable over time,
and exhibited a ‘‘self-recovery’’ capability from external dis-
ruption of the interface. If the LLIR was forced to stop ‘‘half
way’’ by the depletion of the silver salt, a ring-like thin film
extending from the surface of the glass tube with some
irregular deposit in the centre was seen, indicative of the
adhesion of Ag nuclei on the hydrophilic surface of glass (as
shown in Fig. 4(c)). Fig. 4(d) shows that no pattern appeared if
the LLIR was carried out on an active anti-vibration table for
48 h. Hence, the pattern shown in Fig. 4(b) can be interpreted
in terms of: (i) the adsorption of the initial Ag nuclei on the
surface of glass tube; (ii) growth of the Ag deposit to form a
ring-like interfacial deposit layer as shown in Fig. 4(c); (iii) this
process continues and consequently the interfacial layer is able
to cover the whole L/L interface; (iv) vibrations cause standing
waves to form at the L/L interface, and the interfacial layer is
then easily folded since its outer edge is ‘‘pinned’’ to the
surface of the glass container. However, when the Ag nuclei
are adjacent to the Teflon surface, no adsorption occurs, and
the Ag layer formed by the LLIR ‘‘floats’’ on the L/L inter-
face, hence no such standing waves are set up. Consequently
no radial pattern appeared after 48 h of reaction.
The microstructure of the interfacial deposits in water/NB
and water/toluene was observed under SEM. Fig. 5(a) shows
that the interfacial deposit collected from the NB/water inter-
face displays an analogous microstructure to that in Fig. 2(d).
Long and well-defined nanofibres and other short 1D nano-
structures are observed with the presence of ‘‘microflakes’’.
In contrast, no 1D growth is seen after the LLIR between
3.3 mM AgNO3 solution and 5 mM Fc in toluene, but only
smoother ‘‘microflakes’’ are shown in Fig. 5(b) under SEM.
The X-ray diffraction patterns of the Ag interfacial deposits
formed by the LLIRs between 3.3 mM AgNO3 solution and
5 mM Fc in DCE, NB and toluene are presented in Fig. 6.
Reflections assigned to Ag (111), (200), (220), (311), (222)
planes are marked in the plot (Fm3m, a= 4.08 A, JCPDF No.
02-1167). The crystallite size is estimated from the broadening
of X-ray diffraction peaks by Scherrer’s equation:28
Bcrystallite = kl/(L cos y) (2)
where l is the wavelength of the X-ray, y is the Bragg angle,
L is the average crystallite size measured in a direction
perpendicular to the surface of the specimen, and k is a
constant taken to be 0.9. The crystallite size calculated from
the (111) reflection of the interfacial deposit of DCE/water
system is 2.2 nm, which is the same as that in the toluene/water
system. The crystallite size for the interfacial deposit from the
NB/water system is 3.1 nm. Other polar and nonpolar organic
solvents, such as 1,2-dichlorobenzene and silicone oil (data not
shown), were also employed to perform the LLIR with the
same concentrations of reactants, and the morphology of the
interfacial deposits also follows the same trend, in that polar
organic solvents favour the formation of 1D Ag deposits at
L/L interfaces.
The effect of varying the concentrations of the reagents was
investigated. As shown in Fig. 7(a) and (b), a lower concentra-
tion of AgNO3 solutions was employed to react with 5 mM Fc
in DCE. The 0.33 mM AgNO3 (c+Ag/cFc = 0.066) exhibited a
tendency to 1D growth, while the 0.07 mM AgNO3 solution
(c+Ag/cFc = 0.014) basically formed Ag aggregates. If the
concentration of Fc was varied, as illustrated in Fig. 7(c) and
(d), 1D growth could be seen but was not fully developed
in the case of 3.3 mM AgNO3 solution reacted with 0.5 mM
(c+Ag/cFc = 6.6) and with 0.1 mMFc in DCE (c+Ag/cFc = 33).
The influence of the organic solvent on the resultant composi-
tion of the aqueous phase was also investigated via the visible
absorbance of the aqueous phase (Fig. 8). The toluene/water
system shows the highest transfer of Fc+ to water, whereas the
NB/water displays the weakest spectral response. The transfer is
also found to be proportional to the concentration of Fc
employed in the DCE solutions (data not shown).
4. Discussion
Scholz and Hasse27 have proposed an electrochemical mecha-
nism for the deposition of silver via LLIR, where the reaction
occurs at the L/L interface (see eqn (1), above). In the
treatment of Scholz et al., the nuclei at the L/L interface were
viewed as disc-shaped microelectrodes, where the current (i) to
the equivalent disc-shaped silver/electrolyte interface was
described by:
idisc ¼ nFAdiscca4Da
prð3Þ
where n is the number of electrons transferred, F is the
Faraday constant, Adisc is the surface area of the disc, ca and
Fig. 4 The Ag film obtained by interfacial reaction between 3.3 mM
AgNO3 aqueous solution and 1 mM Fc in NB (after reaction for 24 h):
(a) in Teflon container, (b) in glass container, (c) stopped half-way
owing to the depletion of AgNO3 in glass container, (d) the LLIR in a
glass container on an active anti-vibration table.
160 | New J. Chem., 2009, 33, 157–163 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Da the bulk concentration and diffusion coefficient of
species a, respectively, and r is the radius of the disc. When
the same crystal is growing in a 1D mode, a cylinder electrode
was used by Scholz and Hasse to approximate the current flow
across the silver/liquid interface:
icyl ¼ nFAcylca2Da
r ln tð4Þ
where t = Dat/r2, and t is the time. Acyl and r are the surface
area and radius of the cylinder, respectively. Since the oxida-
tive process (oxidation of Fc) should balance the reductive one
(reduction of Ag+) at all times, Scholz and Hasse assumed the
1D Ag structure must protrude into the organic phase for the
above-named fluxes to balance under conditions of excess
silver ion, since equating (3) and (4) leads to:
Acyl
Adisc¼
cAgþðwÞcFcðoÞ
2DAgþ
DFc
ln tp
ð5Þ
Fig. 5 SEM micrographs of the Ag interfacial deposits at different LLIR systems: (a) 3.3 mM AgNO3 aqueous solution with 5 mM Fc in NB,
(b) 3.3 mM AgNO3 aqueous solution with 5 mM Fc in toluene.
Fig. 6 X-Ray diffraction patterns of the Ag interfacial deposits by the
LLIR between 3.3 mM AgNO3 aqueous solution and 5 mM Fc in (a)
DCE, (b) NB and (c) toluene.
Fig. 7 SEM micrographs of the Ag interfacial deposits as a function of reagent concentration: (a) 0.33 mM AgNO3 aqueous solution with 5 mM
Fc in DCE, (b) 0.07 mM AgNO3 aqueous solution with 5 mM Fc in DCE, (c) 3.3 mM AgNO3 aqueous solution with 0.5 mM Fc in DCE,
(d) 3.3 mM AgNO3 aqueous solution with 0.1 mM Fc in DCE.
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where DAg+ and DFc are the diffusion coefficients of Ag+ in
the aqueous phase and Fc in the organic phase, respectively.
Eqn (5) indicates that the higher concentration ratio of Ag+ to
Fc increases the ratio of Acyl to Adisc and favours 1D growth,whereas the converse case should lead to 2D films. Note that
the Ag+ reduction can occur at a site distant from Fc
oxidation, if the electrical conductivity of the deposit is
sufficient.
The data presented in Fig. 7 act as experimental tests of
eqn (5): from inspection of the deposits, it is clear that the
initial concentration ratio of the LLIR is not the sole factor
controlling deposit morphology (cf. eqn (5)), and the concen-
tration of AgNO3 itself actually exerts a large effect on the
final deposit. Combined with the observation (in Fig. 3) that
no 1D Ag nanostructures were found in the first 25 min of the
LLIR, which also suggests that a secondary crystallisation step
is involved in the 1D growth, this leads to the conclusion that
the actual mechanism is more complicated than the simple
electrochemical process suggests. However, the experiments
on the effect of organic solvents demonstrate that the use of
non-polar solvents suppressed the formation of 1D structures.
The morphological evolution seen here suggests that 2D thin
films are formed initially at the L/L interface, followed with a
transformation from 2D to 1D growth, in the case of more
polar organic solvents.
The spontaneous LLIR between Fc in the organic phase and
Ag+ in the aqueous solution initially generates Ag nuclei. An
associated transfer of Fc+ from the organic phases (i.e. DCE,
NB or toluene) to water, or of nitrate in the reverse direction,
must occur to preserve electroneutrality. The visible absor-
bance band (see Fig. 8) centred on 620 nm is attributed to Fc+,
on the basis of a previous report,29 but the extent of transfer is
a function of the polarity of the solvent: the least polar solvent
(toluene) is least able to solvate the Fc+ nitrate ion pair, hence
in the toluene case, transfer of Fc+ to the aqueous phase
predominates.
This observation, combined with the change to 2D morpho-
logy on using the less polar solvent, leads to the following
mechanism being postulated for the 1D growth mode. Ag
nuclei are initially generated by the spontaneous LLIR, and
form a 2D interfacial layer because of the constraint of the L/L
interface. After that, a transformation from 2D layers to 1D
nanostructures occurs as a higher flux of reactants to
the deposit can be sustained by radial diffusion.30 Con-
sequently, parts of the 2D structures appear to dissolve,
accompanied with the emergence of 1D nanostructures. The
1D growth is observed to occur at active sites with high
surface energy, such as independent nuclei, the edges of 2D
structures or the corner of the small triangular crystals,
which show surprisingly well-defined long nanofibres without
any branches. Nanowires from the Ag triangular crystals
can even connect to form nanowire networks. The evolution
of the 1D process is, however, suppressed in less polar
solvents since it requires the (unfavourable) formation of a
ferrocenium nitrate ion pair in the organic phase, by transfer
of the nitrate, or the transfer of the ferrocenium to the aqueous
phase. The latter process is more favourable, but the extent of
transfer depends on the distance from the interface where the
ferrocenium ion is formed. In the case of a 2D Ag deposit,
the ferrocenium ion is formed adjacent to the interface
and is readily transferred. By contrast, if 1D growth occurs,
the ferrocenium ion may be formed some distance from the
aqueous phase (a distance determined by the length of
the structure). We therefore suggest that the driving force
behind the morphological change observed in the deposit is the
solvation of the ions formed by the LLIR.
5. Conclusions
The liquid/liquid interfacial reaction (LLIR) between silver
nitrate in aqueous solution and ferrocene in various organic
solvents has been investigated: long and well-defined silver
nanofibres and thin nanowire networks were obtained in more
polar media. In situ optical microscopy and ex situ scanning
electron microscopy indicate that the 1D growth of the inter-
facial deposits is due to directed recrystallization, where geo-
metric factors associated with the flux to the growing deposit,
and energetic factors, associated with the solvation of the ions
generated, play an important role.
Acknowledgements
The authors thank the financial support from the UK
Engineering & Physical Science Research Council (EPSRC,
grant EP/C509773/1).
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The role of nucleophilic catalysis in chemistry and stereochemistry of
ribonucleoside H-phosphonate condensationwMichal Sobkowski,*
aJacek Stawinski
band Adam Kraszewski
a
Received (in Montpellier, France) 24th July 2008, Accepted 10th September 2008
First published as an Advance Article on the web 29th October 2008
DOI: 10.1039/b812780h
The efficiency and stereoselectivity of condensation of ribonucleoside 30-H-phosphonates with alcohols were
investigated as a function of amines used for the reaction. It was found that irrespective of the presence or absence
of nucleophilic catalysts, the Dynamic Kinetic Asymmetric Transformation (DYKAT) was the major factor
responsible for the stereoselective formation of the DP(SP) isomers of the H-phosphonate diesters, and a
mechanistic rationalization of this observation was proposed. In addition, studies on the reactions carried out in
the presence of various bases led to the conclusion that certain sterically hindered pyridines, e.g. 2,6-lutidine, may
act as nucleophilic catalysts in the condensation of ribonucleoside 30-H-phosphonates with alcohols.
Introduction
P-Chiral oligonucleotide analogues (e.g. phosphorothioates,2
phosphoramidates,3 methylphosphonates,4 or boranophos-
phates5) having defined configuration at the phosphorus atom
find diverse applications in investigations of nucleic acid inter-
actions with other biologically important molecules, for exam-
ple proteins, RNA, and DNA.6 Such P-chiral oligonucleotides
may also be considered as potential drugs for nucleic acid-based
therapies,7 that could permit a more precise tuning of oligo-
nucleotide interactions with the biological targets than is possible
with the currently used pools of P-diastereomers. This should
also relieve problems of potential variation of therapeutic and
toxic effects resulting from different ratios of P-diastereomers
produced in various batches of oligonucleotide drugs.
There are several strategies to stereocontrolled synthesis of
P-chiral oligonucleotides.8 One of them, stereoselective (or more
precisely, diastereoselective) condensation of ribonucleosideH-phos-
phonates,9 attracted our attention due to its simplicity and high
efficiency. It makes use of commercially available H-phosphonate
synthons which are condensed with nucleosides under standard
reaction conditions commonly used for the synthesis of H-phos-
phonate diesters to provide DP diastereomersz as major products.
Recently, we have proposed a Dynamic Kinetic Asymmetric
Transformation (DYKAT) as a possible mechanism for the
stereoselectivity observed in these reactions.1 According to this
model, diastereomers of nucleoside H-phosphonic–pivalic
mixed anhydrides 2 exist in a rapid equilibrium, and one of
them, namely the LP(SP) diastereomer, is significantly more
reactive towards nucleosides (or alcohols) than the other one
(Fig. 1 and Chart 1). To simplify mechanistic considerations,
in our earlier studies the role of nucleophilic and base catalysis
by the amines was consciously neglected. However, since the
participation of nucleophilic catalysis in condensation of
H-phosphonates is a well-established phenomenon,11–15 it
was important to examine and to assess its impact on the
asymmetric induction in the reactions investigated. In this
paper we present studies on the role of nucleophilic catalysis
in the chemistry and stereochemistry of condensation of
ribonucleoside H-phosphonates with alcohols.
Results and discussion
In routine condensations of nucleoside H-phosphonates
pyridine or quinoline (either neat or diluted with non-basic
solvent) is used as a basic component of the reaction mixture.
Both of these weakly basic heterocyclic amines (pKa 5.2 and
4.9, respectively) secure fast and quantitative formation
of H-phosphonate diesters due to their ability to act as
nucleophilic catalysts.11,12 In contrast to this, in the presence
of more powerful nucleophilic catalysts, e.g. NMI or DMAP,ynucleoside H-phosphonates are prone to P-acylation that
compromises the diester formation.12 Also strongly basic
tertiary amines (e.g. TEA, pKa 11.0) are usually avoided since
these can promote undesired base-catalysed bis-acylation of
H-phosphonate monoesters,13,15 while in the presence of less
basic tertiary amines (e.g. DMA, pKa 5.1) the condensations
a Institute of Bioorganic Chemistry, Polish Academy of Sciences,Noskowskiego 12/14, 61-704 Poznan, Poland.E-mail: [email protected]; Fax: +48 61 8520 532;Tel: +48 61 852 8503
bDepartment of Organic Chemistry, Arrhenius Laboratory, StockholmUniversity, S-106 91 Stockholm, Sweden
w Stereochemistry of internucleotide bond formation by the H-phos-phonate method. Part 4.1
z For the compounds presented in this paper the DP descriptor refersto a structure in which the P–H bond is directed to the right in theFischer projection, and in the LP one, to the left. The full DP/LP
notation is described in ref. 10.
y Abbreviations: DABCO, 1,4-diazabicyclo[2.2.2]octane; DIPEA, di-isopropylethylamine; DMAP, 4-(N,N-dimethylamino)pyridine; DMA,N,N-dimethylaniline; DTBP, 2,6-di-tert-butylpyridine; EDIPP,4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine; HMTA, hexamethylene-tetramine; Lut, 2,6-lutidine; MPO, 4-methoxypyridine N-oxide; NMI,N-methylimidazole; PvCl, pivaloyl chloride; Py, pyridine; TEA,triethylamine.
164 | New J. Chem., 2009, 33, 164–170 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
are effective but sluggish (at least 10 times slower than those
for pyridine), presumably due to lack of nucleophilic cata-
lysis.12 Thus, it was somewhat surprising that 2,6-lutidine
(pKa 6.7), which is usually considered as poorly nucleophilic
base,16,17 promoted condensations of ribonucleoside H-phos-
phonates with similar efficiency as pyridine or quinoline.1
Moreover, the stereochemistry of the reactions performed in
the presence of 2,6-lutidine was the same as that with pyridine.
The above called into question the commonly accepted
non-nucleophilic character of 2,6-lutidine and prompted us
to consider the involvement of nucleophilic catalysis as an
additional process in the DYKAT mechanism (Fig. 1).
Since the involvement of P–N+ adducts of type 3 (Fig. 1) in
ribonucleoside H-phosphonate diester formation has to be
crucial for the rate of condensation as well as for stereo-
chemical outcome of the reaction (Fig. 2), we undertook
investigations to pinpoint the cases in which amines acted
solely as base catalysts or as base and nucleophilic catalysts
during H-phosphonate condensations. To this end, the reac-
tions of H-phosphonate 1 with ethanol were carried out in the
presence of selected tertiary amines, various pyridine deriva-
tives, and strong nucleophilic catalysts. The obtained data
(Table 1) showed that irrespective of significant differences in
the yields and stereoselectivity observed for different amines,
the same DP(SP) diastereomer of diester 4 was always formed
as the main product. In the light of our earlier studies,1,18 these
results might suggest that in the absence of nucleophilic
catalysts, the previously described DYKAT mechanism oper-
ated at the level of the mixed anhydride 2 (Fig. 2, Path B),
while in the nucleophile-catalyzed reactions, an analogous
DYKAT took place at the level of adducts of type 3 (Fig. 2,
Path A2).zAdditionally, these experiments confirmed the earlier find-
ings11–15 that neither powerful nucleophilic catalysts nor
strongly basic tertiary amines could promote quantitative
condensations of H-phosphonates with alcohols. However,
in contrast to the literature data,11–15 there was no (or very
little) side product formation, and the 31P NMR spectra of the
reaction mixtures revealed only presence of the expected
diester 4 and unreacted monoester 1 (Fig. 3). This lack of
by-product formation was tentatively attributed to low
Fig. 1 Putative routes of the reaction during stereoselective condensation of ribonucleoside H-phosphonate monoester 1 with alcohols and
nucleosides according to the DYKAT mechanism in the absence (curved arrows) and in the presence (central pathways) of a nucleophilic catalyst.
Chart 1
z Involving a rapid 3-DP " 3-LP equilibrium in which the morereactive diastereomer 3-DP was esterified preferentially.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 164–170 | 165
concentration of the amines in the reaction mixtures (0.3 M or
ca. 2.5%).
In order to find sources for the incomplete condensations
that have been carried out in the presence of the amines
examined herein, the reactivity of pivaloyl chloride towards
nucleosides was investigated in separate experiments. It was
found that TEA and pyridine derivatives when used alone did
not promote significant acylation of nucleosides, however, in
the presence of strong nucleophilic amines (e.g. DMAP) or
TEA–pyridine mixtures, pivaloyl chloride was rapidly con-
sumed in the acylation of 50-OH or N3-H functions of
uridine.41 These side reactions could compete with the forma-
tion of the mixed anhydride 2 and, at least partly, could
be responsible for incomplete condensations. However,
H-phosphonate condensations were also not quantitative in
the presence of tertiary aliphatic amines alone (Table 1, entries
25–27), i.e. under the conditions in which the acylation of
nucleoside components was negligible.41 This issue was
addressed in additional experiments, which indicated that
the mixed anhydride 2 might undergo deacylation by pivalic
Fig. 2 Possible stereochemistry of esterification of the more reactive LP(SP) diastereomer of ribonucleoside H-phosphonic—pivalic mixed
anhydride 2 in the presence (Path A) and absence (Path B) of nucleophilic catalysts.
Table 1 Diastereomeric excess (de) of the DP(SP) diastereomer of the H-phosphonate diester 4b (Fig. 1, B = Ura) formed in the presence ofvarious amines
Entry Amine pKa (H2O)a pKa (DMSO) pKa (ACN) pKHBb dec,d (DP) Yield of diester (%)d
Strong nucleophilic catalysts1 MPO 2.119 3.520 12.421 62% 272 HMTAe 5.2 1.922 57% 663 NMI 7.0 14.323 2.724 60% 844 DABCOe 8.7 8.925 18.326 2.622 53% 425 DMAP 9.7 7.927 17.728 2.829 53% 85
Heteroaromatic amines6 Pyrazine 0.7 1.229 39% 557 Pyrimidine 1.2 1.429 39% 708 Tetramethylpyrazine 3.6 59% 1009 Quinoline 4.9 12.028 1.929 63% 10010 1,10-Phenanthrolinee 4.9 66% 10011 2,6-Di-tert-butyl-pyridine 5.030 1.031 47% 7012 Pyridine 5.2 3.227 12.528 1.929 62% 10013 2-Picoline 5.9 4.027 13.932 2.029 69% 10014 4-Picoline 6.0 3.827 14.532 2.129 68% 10015 Neocuproinee 6.2 64% 10016 2,5-Lutidine 6.4 68% 10017 3,4-Lutidine 6.5 4.327 14.732 2.229 63% 10018 2,6-Lutidine 6.7 4.427 14.432 2.129 70% 10019 2,4-Lutidine 6.7 4.527 15.032 70% 10020 2,4,6-Collidine 7.5 15.028 2.329 68% 10021 EDIPP (7.6)f 52% 9222 (�)-Nicotine 8.0 65% 10023 (�)-Nicotine 8.0 64% 100
Tertiary amines24 DMA 5.1 2.533 11.428 0.534 56% 10025 N-Methylmorpholine 7.4 15.635 1.722 70% 9126 TEA 11.0 9.036 18.828 2.022 75% 7427 DIPEA 11.4 1.122 71% 89
a Aqueous pKa data, unless otherwise indicated, are taken from ref. 37. b Hydrogen bonding basicity. pKHB = logK(formation of HB complex); larger
values correspond to greater basicity.38 c One should note that the difference between de values, for instance de 52% and de 75%, corresponds to
over two-fold increase of the stereoselectivity measured as a ratio of diastereomers (i.e. B3 : 1 vs. B7 : 1, respectively). d Determined via
integration of the corresponding 31P NMR signals. e For structure, see Chart 1. f Estimated, assuming an additive and similar methyl and ethyl
groups effect on the pKa39 and a linear correlation between a,a0-steric hindrance and pKa
40 of substituted pyridines.
166 | New J. Chem., 2009, 33, 164–170 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
acid with regeneration of the starting H-phosphonate mono-
ester 1 and formation of pivalic anhydride (a poor activator of
H-phosphonates42). The rate of deacylation was found to
correlate well with the ability of an amine conjugated acid to
form hydrogen bonds (quantified as a pKHB value8) rather
than with the amine basicity expressed by pKa. A plausible
rationale, which could account for the obtained results in-
volved an increased contribution of general acid catalysis
during decomposition of the mixed anhydride 2 by amines
having high pKHB (Fig. 4).43
Thus, it can be tentatively concluded that pivaloyl chloride
promoted coupling of H-phosphonates with alcohols in the
presence of strongly nucleophilic amines, and/or those of high
H-bonding basicity, did not go to completion due to con-
sumption of the condensing agent (PvCl) in the acylation
of nucleosides or due to formation of unreactive pivalic
anhydride via a partial deacylation of the mixed anhydride 2.
In contrast, pyridine and most of its derivatives investigated
secured quantitative condensations (with an exception of
pyridine derivatives bearing branched substituents in both
a positions)** despite significant differences in their pKa
(3.6–8.0) and considerably high pKHB values (1.9–2.3).
Although it might be argued that the high pKHB of pyridines
should be associated with high catalytic activity of their
conjugate acids which should lead to deacylation of the mixed
anhydride 2 (Fig. 4), apparently it was not the case in the
reactions discussed. A plausible explanation of the excellent
yields obtained for the most of the pyridines examined could
be the participation of nucleophilic catalysis, i.e. the involve-
ment of intermediate phosphonopyridinium adducts of type 3
(Fig. 2) which, as monofunctional entities, should undergo a
nucleophilic attack at the phosphorus centre only. While this is
readily understandable in the case of pyridine derivatives with
unhindered endocyclic nitrogen atoms (i.e. having at least one
a position unsubstituted), the question might arise, whether
this could hold also for a,a0-dimethylpyridines?
Although 2,6-lutidine and its derivatives are usually con-
sidered as poor nucleophiles,16,17 they can act as nucleophiles
under mild conditions undergoing, for instance, N-alkylation
with alkyl halides,44 alkyl iodonium triflate45 or radical
cations,46 or N-sulfonation with triflic anhydride.47 Notably,
in phosphorus chemistry the lack of nucleophilic properties of
2,6-lutidine was observed for P(V) compounds, e.g. for phos-
phoroiodidates,16 while whether nucleophilic catalysis by this
base may operate for H-phosphonates, remains to be deter-
mined. Since P(V) and P(III) compounds differ significantly in
electrophilicity,48 and the steric hindrance around the phos-
phorus atom in H-phosphonates is clearly lower than that
in P(V) compounds, significant differences in their reactivity
towards hindered pyridine derivatives cannot be excluded.
To get a better insight into this problem, condensations of
H-phosphonate 1 were performed in the presence of EDIPP
(a peralkylated 2,6-diisopropylpyridine derivative, pKa
B7.6)49 and DTBP (2,6-di-tert-butylpyridine, pKa 5.0) for
which the nucleophilicity might be safely excluded on steric
grounds. The yields of H-phosphonate diester 4 obtained in
these reactions (92 and 70%) were similar to those found for
trialkyl amines, while low stereoselectivity (de ca. 50%) was
similar to that observed for tertiary aniline derivatives
(e.g. DMA, de 56%). In contrast, all the other pyridine
derivatives, including a,a0-dimethylpyridines, differed only
slightly in stereoselectivity and invariably gave quantitative
condensations of H-phosphonate 1. Thus, it seems reasonable
to assume that the main route for H-phosphonate diester
formation in the presence of 2,6-lutidine derivatives could still
involve the nucleophilic catalysis (preventing in this way
deacylation of the mixed anhydride 2, and in consequence,
the yield deterioration), and that only bulky alkyl substituents
in a,a0 positions were able to suppress the nucleophilic proper-
ties of pyridine.
In additional experiments the condensations of uridine
H-phosphonate 1 with ethanol performed in the presence of
mixtures of 2,6-lutidine with more nucleophilic amines
(pyridine, NMI, DMAP, MPO) were investigated (Fig. 5). In
neither case were any specific effects due to the nucleophilic
amine noted, and the yields and stereoselectivity of the con-
densations were proportional to the weighted average of the
values obtained for each amine used separately. This lent
support to the aforementioned assumption that the same
mechanism (i.e. nucleophilic catalysis) was operating for 2,6-
lutidine and for other amines of known nucleophilic character.
Fig. 331P NMR spectra of the reaction of H-phosphonate 1 with
ethanol (3 equiv.) promoted by PvCl (1.5 equiv.) in DCM containing
3 equiv. of 2,6-lutidine or TEA. The minor signal (ca. 1.5%) at�3.2 ppmin the upper spectrum is in the region of P-acylated compounds.
Fig. 4 A possible participation of general acid catalysis in deacyla-
tion of the mixed anhydride 2 by pivalic acid.
8 The pKHB measures the relative strength of the acceptor in hydro-gen-bonded complex formation with a reference acid (H-bondingbasicity). pKa and pKHB may be unrelated.38
** Two heteroaromatic amines, pyrazine and pyrimidine, were appar-ently too weakly basic (pKa 0.7 and 1.2, respectively) to be efficientpromoters of the condensations investigated since a significant detri-tylation was observed during the course of reactions, even in thepresence of 6 equiv. of an amine (c E 5%). These amines were thusexcluded from further investigations.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 164–170 | 167
Kinetic quenching experiments
To probe the involvement of nucleophilic catalysis in the
DYKAT mechanism, kinetic quenching experiments for
various amines were carried out using large excess of methanol.
Under such reaction conditions we expected to observe
significant changes in the ratio of diastereomers (with a
possible reversal of stereoselectivity1) of the produced
H-phosphonate diester 4a as a result of substantial increase
in the rate of esterification of the reactive intermediates (mixed
anhydride 2 and amine adduct 3). Indeed, a remarkable
decrease in stereoselectivity was observed for the reactions
involving pyridine or 2,6-lutidine as bases (Table 2).
Such results can be interpreted as a partial change of the
DYKAT into the Dynamic Thermodynamic Resolution
(DYTR) mechanism of the asymmetric induction due to
acceleration of the esterification at high concentration of
MeOH.1 In contrast, in the presence of the poorly nucleophilic
amines, the stereoselectivity under the kinetic quenching
conditions decreased only slightly.
Thus, it seems that the nucleophilic catalysis (Table 2,
entries 1 & 2) speeded up the esterification of intermediates 3
more efficiently than their epimerization, while for the base
catalysed reactions (entries 3–6 & 9) or in the presence of
highly basic amines (e.g. TEA, pKa 11.0; entries 7 & 8), the rate
of epimerization was always significantly higher than that of
esterification, even in the presence of large excess of an
alcohol. Interestingly, it seems that the behaviour of a given
amine in a kinetic quenching experiment might be exploited as
a marker of its nucleophilic properties towards H-phospho-
nates, according to the following rule of thumb: the higher the
stereoselectivity of ribonucleoside H-phosphonate conden-
sation in neat methanol, the lower the nucleophilicity of the
amine used for the reaction.
Conclusions
In the previous paper in this series we reported that stereo-
selectivity in condensations of ribonucleoside H-phosphonates
1 with alcohols originated from the Dynamic Kinetic Asym-
metric Transformation (DYKAT).1 The data presented in this
paper confirmed this conclusion and suggested that the equili-
brium between the diastereomers of nucleoside H-phosphonic—
pivalic mixed anhydride (2-DP " 2-LP) was significant
for the stereochemical outcome of the reaction only in the
absence of nucleophilic catalysis. In the presence of nucleo-
philic amines, however, the DYKAT mechanism was
governed most likely by the 3-DP " 3-LP equilibrium between
the putative P–N+ intermediates. In most instances this path
was also essential for quantitative yield of the condensation.
Pyridine derivatives (excluding those with a large steric
hindrance around the nitrogen atom) secured practically
quantitative yields of the condensations along with reasonable
high stereoselectivity (de 60–70%). Noteworthy, pyridine
derivatives with methyl groups in the a positions (e.g. 2,6-
lutidine) also provided fast, clean and highly stereoselective
condensations, and thus indicated that the esterification of
H-phosphonate monoesters in the presence of these bases
might proceed with the intermediacy of the P–N+ adducts
of type 3 (i.e. involving nucleophilic catalysis; Fig. 1 and 2). To
the best of our knowledge this would be the first documented
example of manifestation of nucleophilic properties of
2,6-dimethylpyridines in SN2(P) reactions.
For practical purposes, among investigated bases, 2,6-luti-
dine was found to be the amine of choice (quantitative yield of
condensations, high stereoselectivity, and easy availability)
Fig. 5 Diastereomeric excess (solid bars) of the DP(SP) diastereomer
of H-phosphonate diester 4b formed in the presence of mixtures of
amines, and the total yield of diester 4b (a sum of diastereomers, open
bars). Reaction conditions: 0.05 mmol of 1 (B = Ura) + EtOH
(3 equiv.) + amines (the number of molar equivalents specified on the
x axis) + PvCl (1.5 equiv.) in DCM (0.5 mL).
Table 2 Comparison of the yield and the ratio of diastereomers of the methyl uridine H-phosphonate diester 4a (Fig. 1) formed under standardand kinetic quenching conditions
Entry Amine
‘‘Standard’’ 3 equiv. of MeOH 3 equiv.of amine [1] = 100 mM
‘‘Kinetic quenching’’ 2500 equiv. of MeOH,30 equiv. of amine [1] = 10 mM
de (DP)a Yield of diester (%)a de (DP)
a Yield of diester (%)a
1 Pyridine 63 100 �10b 1002 2,6-Lutidine 68 100 12 1003 EDIPP 47 100 66 1004 DMA 56 96 42 1005 TEA 69 73 51 936 Proton sponge 49 95 45 957 Pyridine + TEA 1:1c 62 89 60 888 2,6-Lutidine + TEA 1:1c 68 80 61 919 DMA + TEA 1:1c 60 84 58 94
a Determined via integration of the corresponding 31P NMR signals. b Advantage of the LP diastereomer. c 3 + 3 equiv. or 15 + 15 equiv.
168 | New J. Chem., 2009, 33, 164–170 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
and is advised to be used in stereoselective ribonucleoside
30-H-phosphonate diesters formation.
Experimental section
Methods and materials
31P NMR spectra were recorded at 121 MHz on a Varian
Unity BB VT spectrometer. 31P NMR experiments were
carried out in 5 mm tubes using 0.5 mL of the reaction
mixture and the spectra were referenced to 2% H3PO4 in
D2O (external standard). The quantities of phosphorus-
containing compounds were determined via integration of
the corresponding 31P NMR signals. Diastereomeric excess
was calculated with accuracy of �1.5 percentage points
(an average of 3 measurements).
Commercial (Sigma-Aldrich, Alfa Aesar, Merck, POCh-
Poland) reagents and were used as purchased unless otherwise
noted. Ethanol was distilled over magnesium. Dichloro-
methane and pyridine were refluxed over P2O5, distilled, and
stored over 4 A molecular sieves until they contained below
20 ppm of water (Karl Fischer coulometric titration, Metrohm
684 KF coulometer). Anhydrous triethylamine (TEA) was
distilled and kept over CaH2. Commercial p-methoxypyridine
N-oxide (MPO) hydrate was rendered anhydrous by co-
evaporation with dry acetonitrile (1�) and dry toluene (2�).Other liquid amines were refluxed for 1 hour with 2,4,6-
triisopropylbenzenesulfonyl chloride (TPS-Cl) and distilled
under reduced pressure. 4-Ethyl-2,6-diisopropyl-3,5-dimethyl-
pyridine (EDIPP)49 was a gift from Prof. A. T. Balaban,
Texas A&M University. Uridine H-phosphonate 150 was
obtained according to the published method. Racemization
of S-(�)-nicotine was done according to ref. 51. Immediately
prior to all reactions, H-phosphonate 1 was rendered anhy-
drous by dissolving in toluene (3 mL/0.05 mmol) and evapora-
tion of this solvent under reduced pressure. After drying under
vacuum (15 min, 0.5 Torr), the flask was filled with air, dried
up by passing through Sicapent (Merck).
General procedure for condensation ofH-phosphonates of type 1
with alcohols
Nucleoside H-phosphonate 1 (0.05 mmol) was dissolved in
0.5 mL of DCM and amine (3 equiv.) and EtOH or MeOH
(3 equiv.) were added, followed by PvCl (1.5 equiv.). The
reaction mixture was transferred to an NMR tube and the 31P
NMR spectra were recorded within 1 hour.
Kinetic quenching experiments
Nucleoside H-phosphonate 1 (0.05 mmol) was dissolved in
DCM (0.3–0.5 mL), and TEA (0.2 equiv.) and PvCl
(1.2 equiv.) were added successively. The formation of the
mixed anhydride 2 was confirmed by 31P NMR spectroscopy
(dP 1.47 & 1.56) and the reaction mixture was utilized within
one hour (no degradation products were found within that
period).
The solution (0.3 mL) of the intermediate 2 (0.5 mmol;
generated as described above) was added dropwise by a
syringe to a septum-sealed flask containing vigorously stirred
methanol (5 mL) and an amine (2.4% v/v or w/v). After ca.
30 s toluene (15 mL) was added and the mixture was evapo-
rated almost to dryness under vacuum at temperature o40 1C
(such procedure was obligatory for strongly basic tertiary
amines in order to avoid transesterification52 of the product).
The oily residue was dissolved in DCM (0.5 mL) and analyzed
by 31P NMR spectroscopy.
Acknowledgements
The financial support from the Polish Ministry of Science and
Higher Education is gratefully acknowledged.
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170 | New J. Chem., 2009, 33, 164–170 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Two polyaminophenolic fluorescent chemosensors for H+
and Zn(II).
Spectroscopic behaviour of free ligands and of their dinuclear Zn(II)
complexesw
Gianluca Ambrosi,aCristina Battelli,
aMauro Formica,
aVieri Fusi,*
aLuca Giorgi,
a
Eleonora Macedi,aMauro Micheloni,*
aRoberto Pontellini
aand Luca Prodi
b
Received (in Durham, UK) 17th June 2008, Accepted 18th September 2008
First published as an Advance Article on the web 31st October 2008
DOI: 10.1039/b810228g
The UV-Vis and fluorescence optical properties of the two polyamino-phenolic ligands
3,30-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2 0-dihydroxybiphenyl (L1) and 2,6-bis{[bis-
(2-aminoethyl)amino]methyl}phenol (L2) were investigated in aqueous solution at different pH
values as well as in the presence of Zn(II) metal ion. Both ligands show two diethylenetriamine
units separated by the 1,10-bis(2-phenol) (BPH) or the phenol (PH) for L1 and L2, respectively.
Both ligands are fluorescence-emitting systems in all fields of pH examined, with L1 showing a
higher fluorescence emission than L2. In particular, the emission of fluorescence mainly depends
on the protonation state of the phenolic functions and thus on pH. The highest emitting species
is H3L3+ for both systems, where the BPH is monodeprotonated (in L1) and the PH is in the
phenolate form (in L2). On the contrary, when BPH and PH are in their neutral form both
ligands show the lowest fluorescence, since H-bonds occurring between the phenol and the closest
tertiary amine functions decrease fluorescence. The Zn(II)-dinuclear species are also fluorescent
in the pH range where they exist; the highest emitting species being [Zn2(H�2L1)]2+ and
[Zn2(H�1L2)]3+ which are present in a wide range of pH including the physiological one.
Fluorescence experiments carried out at physiological pH highlighted that, in the case of L1, the
presence of Zn(II) ion in solution produces a simultaneous change in lem with a drop in
fluorescence due to the formation of the [Zn2(H�2L1)]2+ species, while, in the case of L2, it gives
rise to a strong CHEF effect (a twenty-fold enhancement was observed) due to the formation of
the [Zn2(H�1L2)]3+ species. These results, supported by potentiometric, 1H and 13C NMR
experiments, are of value for the design of new efficient fluorescent chemosensors for both H+
and Zn(II) ions.
Introduction
The development of chemosensors is in continuous expansion
due to their usefulness in many fields; they have a wide range
of applications, such as environmental monitoring, process
control, food and beverage analysis, medical diagnosis and
others.1–8 Due to their use in many disciplines, they are very
attractive for chemists, biologists, physicists and material
scientists. For example, in biochemistry, clinical and medical
sciences, and cell biology, freely mobile sensor molecules are
employed extensively in microscopy, offering the possibility of
performing real-space measurements.9,10
Among the different chemosensors, the fluorescence-based
ones present many advantages: fluorescence measurements are
usually very sensitive, low-cost, easily performed and versatile,
offering submicrometer spatial resolution and submillisecond
temporal resolution.11–19 The versatility of fluorescence-based
sensors originates also from the wide number of parameters
that can be tuned in order to optimize the convenient signal. In
most cases, changes in luminescence intensity represent the
most directly detectable response to target recognition; more
recently, however, other properties such as excited-state life-
time and fluorescence anisotropy have also been preferred as
diagnostic parameters, since they are less affected by environ-
mental and experimental conditions.
Phenol and poly-phenols show well known optical proper-
ties which mainly depend on their protonation degree;20,21 in
our lab, several polyamino-phenolic ligands of different topol-
ogies have been synthesized. In this study, we wanted to
extend our knowledge to the spectroscopic properties of two
of them to identify their possible applications as chemosensors
for suitable guests. In this case, we focused our attention on
the two previously synthesized amino-phenolic ligands L1 and
L2 (Chart 1). They were chosen for several reasons: they have
similar topology; they both show two diethylenetriamine
(dien) units separated by a phenolic aromatic spacer, the
1,10-bis(2-phenol) group (BPH) and the phenol for L1 and
a Institute of Chemical Sciences, University of Urbino,P.za Rinascimento 6, I-61029 Urbino, Italy
bDepartment of Chemistry, University of Bologna, Via Selmi 2,Bologna, Italy. E-mail: [email protected]
w Electronic supplementary information (ESI) available: Fig. S1:Location of acidic hydrogen atoms in the protonated species of L2.See DOI: 10.1039/b810228g
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 171–180 | 171
PAPER www.rsc.org/njc | New Journal of Chemistry
L2, respectively; in addition, they easily form dinuclear species
with transition metal ions. The molecular skeleton of both
ligands affords the formation of preorganized dinuclear
Zn(II) species where the two Zn(II) ions can cooperate in
binding guests; in particular, it has been demonstrated that
in some dinuclear species such as the [Zn2(H�2L1)]2+ and
[Zn2(H�1L2)]3+ ones, the two zinc ions show, in both systems,
an equal coordination environment, are displaced at fixed
different distances and are able to add guests to saturate the
coordination requirement of the two zinc ions (see Scheme 1).
Although zinc is an essential metal ion in human life and
plays a fundamental role in many biological functions, for
example in the alkaline phosphatase or carbonic anhydrase
enzymes,22 excess zinc can be very harmful, as it can lead to
many health problems.23 For this reason, easy recognition of
the zinc ion is key mainly and as a result many fluorescent
molecular sensors have been developed in recent years, also to
allow its in vivo mapping.24
In this work, we have studied the NMR, UV-Vis and
fluorescence properties of the free ligands as well as of their
zinc complexes in aqueous solution. The aim has been to
detect if the optical properties of these systems are affected
by pH as well as by the presence of Zn(II) in solution.
Experimental
Synthesis
Ligand 3,30-bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2 0-di-
hydroxybiphenyl (L1) and 2,6-bis{[bis-(2-aminoethyl)amino]-
methyl}phenol (L2) were prepared as previously described.25
EMF measurements
Equilibrium constants for protonation and complexation
reactions with L2 were determined by pH-metric measure-
ments (pH = �log[H+]) in 0.15 M NaCl at 298.1 � 0.1 K,
using the fully automatic equipment that has already been
described; the EMF data were acquired with the PASAT
computer program.26 The combined glass electrode was cali-
brated as a hydrogen concentration probe by titrating known
amounts of HCl with CO2-free NaOH solutions and determin-
ing the equivalent point by Gran’s method,27 which gives the
standard potential E1 and the ionic product of water (pKw =
13.73(1) at 298.1 K in 0.15 M NaCl, Kw = [H+][OH�]). At
least three potentiometric titrations were performed for each
system in the pH range 2–11, using different molar ratios of
Zn(II)/L2 ranging from 1:1 to 2:1. All titrations were treated
either as single sets or as separate entities, for each system; no
significant variations were found in the values of the deter-
mined constants. The HYPERQUAD computer program was
used to process the potentiometric data.28
Spectroscopic experiments
1H and 13C NMR spectra were recorded on a Bruker Avance
200 instrument, operating at 200.13 and 50.33 MHz, respec-
tively, and equipped with a variable temperature controller.
The temperature of the NMR probe was calibrated using
1,2-ethanediol as calibration sample. For the spectra recorded
in D2O, the peak positions are reported with respect to HOD
(4.75 ppm) for 1H NMR spectra, while dioxane was used as
reference standard in 13C NMR spectra (d = 67.4 ppm).
Fluorescence spectra were recorded at 298 K with a Varian
Cary Eclipse spectrofluorimeter. UV absorption spectra were
recorded at 298 K with a Varian Cary-100 spectrophotometer
equipped with a temperature control unit.
The fluorescence quantum yields (Ff) of the highest fluores-
cent species were calculated as reported in ref. 29 using
2-aminopyridine as standard reference.
Results and discussion
Solution studies
Ligands L1 and L2 as well as the Zn(II)/L systems were studied
by fluorescence spectroscopy in aqueous solution at different
pH values to investigate the fluorescence properties of both
ligands and how these are affected by protonation and the
presence of Zn(II) ion. 1H and 13C NMR experiments on the
free L1 as well as those reported for the Zn(II)/L1 system25a
aided in understanding the role played by both protonation
and Zn(II). The fluorescence quantum yields (Ff) of the highest
fluorescent species are reported in Table 1.
Similar 1H NMR studies carried out on L2 and Zn(II)/L2
system are reported in refs. 30 and 31, respectively. Moreover,
further studies on the UV-Vis absorption properties of both
L and Zn(II)/L systems were performed in aqueous solution
in addition to those already reported.25,30,31
Chart 1 Ligands together with labels for the NMR resonances.
Scheme 1 Coordination scheme for Zn(II) in the [Zn2(H�2L1)]2+ and
[Zn2(H�1L2)]3+ complexes.
Table 1 Fluorescence quantum yield (Ff) of the main fluorescentspecies in 0.15 mol dm�3 NaCl at 298.1 K
Ff
H3L13+ 0.34
H3L23+ 0.01
[Zn2H�2L1]2+ 0.24
[Zn2H�1L2]3+ 0.08
172 | New J. Chem., 2009, 33, 171–180 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
L1 and L2 in aqueous solution at different pH values
Basicity. The basicity of L1 in 0.15 mol dm�3 NaCl aqueous
solution at 298.1 K was potentiometrically studied and the
results obtained reported in ref. 25a; the protonation constants
of ligand L2 were determined under these ionic conditions and
the stepwise basicity constants of L2 are reported in Table 2.
The basicity of L2 is similar to that previously reported using
NMe4Cl as ionic medium thus the discussion can be outlined
in the same way.30
Fluorescence of L1 at different pH values. Emission spectra
performed at different pH values gave information on the
interaction between the dien and the 2,20-biphenol (BPH) units
and on the behavior of the ligand in its excited states.
As reported in the literature, BPH shows emission of
fluorescence depending on the degree to which it is deproto-
nated;20 in particular, it shows the most intense fluorescence in
its monodeprotonated form and the least intense in its neutral
one (more than six times lower), while the dianionic form,
although fluorescent, is obtainable only at very high pH values
(pH 4 15).20,32
The fluorescence spectra of L1 (lexc = 287 nm) recorded in
aqueous solution in the pH range 2–12 are reported in Fig. 1;
the trend of the fluorescence emission intensity (E) vs. pH
(lexc = 287 nm) is reported in Fig. 2(a) together with the
maximum absorption (� � �) and the emission (---) wavelength
trend. Fig. 2(b) reports the trend of the absorption titration at
l = 308 nm (K) together with the distribution curves for the
species of L1 (—) as a function of pH.
Excitation of L1 acid solution at pH 2 (lexc = 287 nm) gives
rise to a fluorescence emission band of very low intensity
(lem = 403 nm) attributed to the BPH fluorophore. The
intensity of the fluorescence emission of the compound is
highly dependent on the protonation state of the ligand
(see Fig. 1 and 2(a)); however the shape and the lem of the
spectra are substantially pH-independent. In this pH range,
the free BPH group shows a similar fluorescent behavior
produced by the monoanionic excited state of BPH.20,32
Taking into account that the fluorescence of L1 is due to the
BPH fluorophore, this suggests that also in L1 the changes in
fluorescence emission reflect only the ground states acid–base
equilibrium.33 For this reason, no indication of the excited
state proton transfer reaction was found and, as reported for
free BPH, the fluorescence is due to the monoanionic excited
state of BPH in L1.
In the fluorescence spectra, the emission remains substan-
tially very low and constant (Fig. 2(a)) at acidic pH values
(2 r pH r 5) while it starts increasing at pH 5 in concomi-
tance with the appearance of the H3L13+ species in solution,
reaching a maximum intensity at pH 7.4–8.4 with the complete
formation of the H3L13+ species. A small decrease can be
Table 2 Basicity and equilibrium constants for the complexationreactions of L2 with Zn(II) ion determined in 0.15 mol dm�3 NaCl at298.1 K
Reaction logK
L + H+ = HL+ 10.04(1)a
HL+ + H+ = H2L2+ 9.87(1)
H2L2+ + H+ = H3L
3+ 9.12(1)H3L
3+ + H+ = H4L4+ 7.59(1)
H4L4+ + H+ = H5L
5+ 2.50(3)Zn2+ + L + 2H+ = ZnH2L
4+ 28.42(1)Zn2+ + L + H+ = ZnHL3+ 23.82(2)Zn2+ + L = ZnL2+ 14.67(2)Zn2+ + L = Zn(H�1L)
+ + H+ 5.05(2)2Zn2+ + L = Zn2(H�1L)
3+ + H+ 17.17(1)2Zn2+ + L + H2O = Zn2(H�1L)OH2+ + 2H+ 8.34(3)2Zn2+ + L + 2H2O = Zn2(H�1L)(OH)2
+ + 3H+ �1.63(3)Zn2(H�1L)
3+ + OH� = Zn2(H�1L)OH2+ 4.90Zn2(H�1L)OH2+ + OH� = Zn2(H�1L)(OH)2
+ 3.76
a Values in parentheses are the standard deviations on the last
significant figure.
Fig. 1 Fluorescence spectra of L1 at different pH values.
Fig. 2 Fluorescent emission titration (lexc = 287 nm, lem = 403 nm)
(E), absorption wavelength trend (� � �), and emission wavelength trend
(---) (a); absorption titration at l = 308 nm (K) and distribution
curves of the species (—) (b) as function of pH in aqueous solution:
[L1] = 5.0 � 10�5 M, I = 0.15 M NaCl, T = 298.1 K.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 171–180 | 173
observed in the alkaline range up to pH 10.5 at which the less
protonated species appear in solution; on the contrary, when
the pH is increased to 11 emission rises again, reaching
maximum intensity at pH 12 with the presence in solution of
the monoanionic H�1L1� species.
Bearing in mind the previous studies on BPH,20,32 the trend
of the emission intensity in the range of pH 2–8 can be easily
explained by the deprotonation of the neutral BPH unit to
form its monoanionic species that occurs with the formation of
the H3L13+ species. In other words, in the protonated species
H5L15+ and H4L1
4+, BPH is present in its neutral form while
in the H3L13+ species it has lost one of the acidic protons
forming the highest emitting species (F = 0.34, Table 1).
These results are in agreement with those already obtained by
UV-Vis absorption studies which revealed that the deproto-
nation of one of the hydroxyl functions of BPH occurred in
the pH range involving the passage from H4L14+ to H3L1
3+
species.25a This was highlighted, as reported in Fig. 2(b), by
the change in absorption at 308 nm which increases when the
monoanionic form of BPH is present in solution and is further
underlined by the variation in the trend of the maximum of the
absorption wavelength (Fig. 2(a)) as a function of pH; both
figures highlight that the changes take place in the field of pH
where the H3L13+ species forms. Although the absorption and
emission wavelength maxima as well as the absorption at
308 nm remain constant, increasing the pH to form lesser
protonated species than H3L13+, there is a small decrease
(about 25% at pH 10) in fluorescence intensity occurring with
the formation of the H2L12+, HL1
+ and neutral L1 species
(Fig. 2(a)). This trend could be explained by the formation of a
H-bond network involving BPH and the closer nitrogen
atoms. In fact, as reported for free BPH,20,32 the formation
of an intramolecular H-bond interaction occurring between
the two oxygen atoms of BPH in stabilizing the hydrogen
atom in the monoanionic species gives the greatest fluores-
cence intensity, while, on the contrary, the formation of
intermolecular H-bonds with H-accepting molecules, such as
water, gives rise to a very fast nonradiating process through-
out the H-bond, thus leading to a decrease in the fluorescence
(this occurs for example in the neutral form of excited BPH).
In addition, it has been demonstrated that in the presence of
strong proton-accepting molecules such as triethylamine
(TEA), the formation of H-bonding between TEA and a
hydrogen atom of BPH once again leads to a decrease in
fluorescence.20b In our case, it is presumable that similar
H-bonding between the BPH oxygen and the closer nitrogen
atoms of the dien units is formed, thus decreasing fluorescence;
however, the formation of this type of H-bond cannot be the
favourite situation since only a slight drop in fluorescence was
observed. Moreover, two different H-bonds could be sug-
gested in the case of L1: via OH� � �N as well as via O�� � �HN+;
in other words, in the H2L12+, HL1
+ and L1 species, a partial
stabilization of the acidic hydrogen atom of the monoanionic
BPH unit could also take place with the closer N atom
(c in Scheme 2), but also a partial ammonium character of
the closer N atom could give rise to the same quenching
H-bond effect with the BPH unit (b in Scheme 2). In any case,
the form (a) shown in Scheme 2 is the favoured form and it is
the only one present in the H3L13+ as well as in the H�1L1
�
species where the highest fluorescence is reached. In addition,
the absence of fluorescence changes even at highly alkaline pH
values once again demonstrates that the full deprotonation of
BPH in L1 is not reachable under our experimental conditions.
L11H and
13C NMR studies at different pH values. In order
to obtain further structural information about the distribution
of acidic protons in the protonated species of L1, 1H and 13C
NMR spectra were recorded over the pH range of the
Scheme 2 Possible H-bond interactions for the neutral L1 species.
Fig. 3 Experimental NMR chemical shifts in aqueous solution of L1
as a function of pH: 1H NMR (a); 13C NMR (b).
174 | New J. Chem., 2009, 33, 171–180 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
potentiometric, UV-Vis and fluorescence measurements.1H–1H and 1H–13C NMR 2D correlation experiments were
performed to assign all the signals. The trends for the chemical
shift of the 1H and 13C NMR resonances are reported in
Fig. 3(a) and (b). The 1H NMR spectrum recorded at pH 12,
where the H�1L1� species is prevalent in solution, exhibits two
triplets at 2.67 and 2.85 ppm corresponding to the resonance
of the hydrogen atoms H2 and H1, respectively, one singlet at
3.76 ppm due to the hydrogen atoms H3, one triplet at
6.91 ppm for the resonances of H6 and two doublets at 7.31 and
7.42 ppm for H5 and H7, respectively. This spectral feature
indicates a C2v symmetry mediated on the NMR time-scale
which is preserved throughout the pH range investigated. In
agreement with this symmetry, the 13C NMR spectrum
recorded at the same pH value shows only nine signals at d37.7 (C1), 53.0 (C3), 55.0 (C2), 117.8 (C6), 126.6 (C4), 129.7
(C8), 130.5 (C5), 130.6 (C7) and 158.0 (C9). At lower pH,
where the species L1, HL1+, H2L1
2+ and H3L13+ are form-
ing (pH= 11–7), the main shift is exhibited by the protons H1
which show a marked downfield shift, suggesting that the four
protonation steps take place mainly on the primary amine
functions. This hypothesis is confirmed by the trend of the 13C
NMR resonances which mainly shows an upfield shift in the
signal of the carbon atom C2, in agreement with the b-effect ofthe protonation of the polyamines.34 However, in this pH
range, slight shifts in other 1H NMR resonances could be seen:
for example, the resonance of H7 first moves downfield up to
pH 9 then decreases with the formation of the H3L13+ species,
while H3 moves upfield; this suggests little changes in charge
density on both the tertiary amine groups and BPH unit
occurring in this pH range that can be correlated with the
formation of H-bonding involving the BPH oxygen and the
closer nitrogen atoms in the L1, HL1+ and H2L12+ species, in
agreement with the fluorescence experiments reported above.
In the pH range 4–6 the H4L4+ species is prevalent and, as
demonstrated both by UV and fluorescence experiments, the
fifth protonation step occurs at the BPH group. This was also
confirmed in the NMR experiments by the downfield shift of
the H6 signal in the para position to the phenolic oxygens and
by the upfield shift of the H7 protons in the 1H NMR spectra,
as well as by the accompanying upfield shift of C4, C8 and C9
and downfield shift of C6 in the 13C NMR spectra. The strong
upfield shift exhibited by the signal of H7 could be related not
only to a protonation process of the BPH unit but also to a
change in the angle between the two aromatic rings that
probably is affected by the protonation degree of L1 leading
the formation of a new H-bond network involving the neutral
BPH and the unprotonated tertiary amine functions, as
depicted in Fig. 4 for the H4L14+ species; this almost entirely
quenches the fluorescence (see above). The protonation step
giving the H5L5+ species, occurring below pH 4, basically
causes a downfield shift of protons H2 and H3 together with
an upfield shift in the signals of the carbon atoms C1 and C4,
suggesting that it takes place on the tertiary amine groups.
Once again the H7 and H5 resonances, both of which shift
downfield, are perturbed by this protonation step, highlighting
the formation of a H-bond network with the closer amine
functions on the BPH unit different from the previous one; this
Fig. 4 Location of acidic hydrogen atoms in the protonated species
of L1.
Fig. 5 Fluorescence emission titration (lex = 280 nm) (E), absorp-
tion wavelength trend (� � �), and emission wavelength trend (---) (a);
absorption titration at l = 290 nm (K) and distribution curves of the
species (—) (b); of L2 as function of pH in aqueous solution: [L2] =
5.0 � 10�5 M, I = 0.15 M NaCl, T = 298.1 K.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 171–180 | 175
affects the chemical shift, modifying the electron density of the
neutral BPH unit as well as the angle between the two
aromatic rings.
A protonation scheme arising from NMR experiments is
summarized in Fig. 4.
Fluorescence of L2 at different pH values. The same fluores-
cence experiments were carried out on the ligand L2
and compared to the previous UV-Vis and NMR studies
performed in aqueous solution at different pH values.30 The
trend in fluorescence emission intensity (E) versus pH (lexc =280 nm) is reported in Fig. 5(a) together with the maximum
absorption (� � �) and emission (---) wavelength trends. Fig. 5(b)
reports the trend for the absorption titration at l = 290 nm
(K) together with the distribution curves of the species of L2
(—) as a function of pH obtained by potentiometry.
The acidic solutions of L2 up to pH 6 are barely fluorescent,
as also reported for the free neutral phenol (PH), while
fluorescence increases with the formation of the H3L23+
species, reaching maximum emission at pH 8 together with
the maximum presence in solution of the H3L23+ species; at
higher pH values, the emission drops, reaching a plateau at pH
higher than 11 with the formation of the neutral L2 species.
The fluorescence of ligand L2, which is lower compared to that
of L1 (see Table 1), is highly dependent on the protonation
state of the ligand as seen before for L1. The acidic proton
distribution in the several protonated species of L2 obtained
by UV-Vis, potentiometry and NMR studies was previously
reported and the scheme is reported in Fig. S1 of the ESI;w the
most fluorescent H3L23+ species is the one in which the phenol
is deprotonated (i.e. phenolate) and the four acidic protons are
located on the primary amine functions; this is the same
situation found for the H3L13+ species where there are no
H-bond interactions with the closest amine functions, thus
affording the highest emission quantum yield also in the
H3L23+ species. It should be noted that in the free PH, the
anion presents a much lower fluorescence intensity than the
neutral species.21 In this case the opposite behaviour was
observed; this could be explained (see also below) by a
decrease in the solvation via H-bond network of the phenolate
oxygen atom by the water molecules in the H3L23+ species in
comparison with the free PH anion.21a In other words, the
presence of the two protonated dien units linked to the PH
group modifies the accessibility of the solvent molecules to the
phenolate oxygen atom decreasing its quenching effect and
thus increasing the emissive relaxation decay of the PH anion.
As reported, an acidic proton redistribution was observed in
the less protonated species involving at least a tertiary amine
function that becomes protonated. This ammonium group,
found mainly in the neutral L2 species, is stabilized viaH-bond
with the close phenolate oxygen atom (see Fig. S1, ESIw). Forthis reason, as for ligand L1, the formation of H-bonding with
the amine function leads to a decrease in its fluorescence.
This H-bond interaction, which is also monitorable through
the UV-Vis spectra (see Fig. 5(b)), is also highlighted by the
change in the maximum of the absorption and emission
wavelengths (Fig. 5(a)) as a function of pH. lmax and lemshifted in different directions, increasing the Stokes shift when
the phenol becomes phenolate (pH Z 5, lmax and lem shift
towards lower and higher energies, respectively), while an
opposite trend was observed at higher pH values (lmax and
lem shift towards higher and lower energies, respectively) with
the formation of the neutral zwitterionic L2 species in which a
strong H-bond between the closest tertiary ammonium and
phenolate groups was suggested. Taking into account the
trend and shift in both lmax and lem, it can be suggested that
the fluorescence is yielded by light emission decay from the
phenolate excited state of all L2 species to different ground
states, characterized by the formation of strong intramolecular
H-bonds.
In conclusion, although L1 is a much more efficient fluores-
cent system than L2 (Table 1), both ligands show fluorescence
emission depending on the protonation state of the aromatic
functions. In particular, the highest emitting species are due to
the monodeprotonated form of BPH of L1 as well as to the
phenolate species of PH of L2, both of which are achieved in
the H3L3+ species; on the contrary, the neutral BPH and PH
species are very low fluorescence emitters. The presence of the
closer tertiary amine function affects the emission quantum
yield in some species by forming intramolecular H-bonding
with the close phenol oxygen atom of both systems. The
H-bonding induces a nonradiative relaxation process of
the excited species, yielding a decrease in the fluorescence in
both ligands. This H-bonding is weaker in L1 via OH� � �N as
well as O�� � �HN+, and for this reason only a relatively low
efficiency of fluorescence quenching could be observed, while it
takes place strongly via O�� � �HN+ in L2 giving an almost
total quenching of the fluorescence of L2. Taking into account
these results, both ligands behave as chemosensors of H+ in
that they are able to change their optical absorption and
fluorescence properties as a function of pH.
Coordination of Zn(II)
The coordination behaviour of both systems towards Zn(II)
was potentiometrically studied and the results obtained are
reported in ref. 25 and 31; as for basicity, the Zn(II)/L2 system
had been studied in NMe4Cl ionic medium,31 thus we per-
formed new potentiometric measurements to obtain the stabi-
lity constants for the Zn(II)/L2 system under the same
experimental conditions as the Zn(II)/L1 system (0.15 mol dm�3
NaCl aqueous solution at 298.1 K). The potentiometrically
determined stability constants for the equilibrium reactions of
L2 with Zn(II) are reported in Table 2. The species formed as
well as the values of the stability constants evaluated are
similar to those previously reported and thus the discussion
can be outlined in the same way. The main difference found
was the formation of the [Zn2(H�1L2)(OH)2]+ species in this
ionic medium which was not previously detected. The addition
of the second OH� anion to [Zn2(H�1L2)OH]2+ is quite high
(logK = 3.76) suggesting that it is probably bound in a bridge
disposition between the Zn(II) ions. The distribution diagrams
for the Zn(II)-complexed species for both 2Zn(II)/L systems are
reported in Fig. 6 for L1 and in Fig. 8 for L2 as a function of
pH. However, the results previously discussed can be summar-
ized in this way: (i) the dinuclear species are prevalent in
solution and the only species existing at pH higher than 7 is a
L/Zn(II) with a 1:2 molar ratio; (ii) the most prevalent species
176 | New J. Chem., 2009, 33, 171–180 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
are [Zn2(H�2L1)]2+ and [Zn2(H�1L2)]
3+ for L1 and L2,
respectively; (iii) these dinuclear species have similar molecular
skeletons indicating a preorganized dinuclear Zn(II) species in
which the two Zn(II), similarly coordinated, can cooperate in
binding suitable guests (see Scheme 1).
Fluorescence and UV-Vis of the 2Zn(II)/L1 system at differ-
ent pH values. Emission and absorption spectra were per-
formed at different pH values using Zn(II)/L1 at a 2 to 1
molar ratio. The trend in fluorescence emission intensity (E)
versus pH (lexc = 283 nm) is reported in Fig. 6(a) together
with the maximum absorption (� � �) and emission (---) wave-
length trends. Fig. 6(b) reports the trend for the absorption
titration at l = 295 nm (K) together with the distribution
curves for the species of the 2Zn(II)/L1 system (—) as a
function of pH. Moreover, fluorescence titration was carried
out by adding increasing amounts of Zn(II) to a HEPES buffer
(pH = 7.4) solution of L1 and the spectra are reported in
Fig. 7. The fluorescence quantum yield of the highly emitting
species is reported in Table 1.
The UV-Vis absorption spectra of solutions containing
2Zn(II)/L1 recorded at different pH values were discussed
previously;25a they showed spectral profiles indicating the
deprotonation of BPH and simultaneous coordination of the
Zn(II) ions; in these new experiments, some further aspects can
be discussed. The absorption lmax shifts toward lower energy
when monitored from acidic (free ligand) to basic pH values
(Zn(II)-complexes); up to the presence in solution of the Zn(II)-
mononuclear species it moves from 280 to 305 nm, while the
appearance in solution of the dinuclear species, at approxi-
mately pH 6, gives rise to a change in the lmax which shifts
from 305 nm in the presence of the mononuclear [Zn(HL1)]3+
species to 298 nm with the complete formation of the more
stable [Zn2(H�2L1)]2+ species at pH = 7.4. This lmax is
preserved also at higher pH values where only dinuclear
Zn(II)-complexed species are present in solution. The shift in
lmax observed from the mono- to the di-nuclear species can be
ascribed to the full deprotonation of BPH which loses both
acidic hydrogen atoms in the Zn(II)-dinuclear species, afford-
ing the bi-negative form of BPH; this result is in agreement
with the studies previously reported for the Zn(II)-dinuclear
species of L1. The changes in absorption from the mono-
negative BPH to the bi-negative species are also visible in
Fig. 6(b), where a change in absorptivity can also be observed
when the dinuclear species appear in solution. These changes
are in agreement with a change in the protonation degree of
BPH and thus to its full deprotonation and simultaneous
coordination of each Zn(II) ion by one phenolate oxygen
atom of the BPH unit as already reported. The fluorescence
experiments gave rise to analogous results, with fluorescence
increasing at values starting from acidic pH and reaching
maximum intensity in the field of pH 7.4–8.4 with the maxi-
mum presence in solution of the [Zn2(H�2L1)]2+ species, then
decreasing at higher pH values and reaching a plateau at pH
4 11 with the presence in solution of the di-hydroxylated
[Zn2(H�2L1)(OH)2] species (Fig. 6). It is interesting to note
that, unlike the free L1, the lem changes (lexc = 283 nm) by
changing the pH, and as in the absorption experiments
the change occurs at the pH values where there is the forma-
tion of the Zn(II)-dinuclear species. Specifically, lem shifts from
403 nm (free ligand) to 379 nm with the formation of the
[Zn2(H�2L1)]2+ species, while remaining constant in the other
dinuclear species. Once again, this trend can be related to the
full deprotonation of BPH, as retrieved in the crystal structure
of the [Zn2(H�2L1)(H2O)2]2+ previously reported, which
produces changes in the ground as well as in the excited state
of BPH. Moreover, the formation of the hydroxylated
[Zn2(H�2L1)OH]+ and [Zn2(H�2L1)(OH)2] species produces
a drop in fluorescence emission without changing the lem(Fig. 6(a)); this is due to an increase in electron density
Fig. 6 Fluorescence emission titration (lex = 283 nm) (E), absorp-
tion wavelength trend (� � �), and emission wavelength trend (---) (a);
absorption titration at l = 295 nm (K) and distribution curves of the
species (–) (b); as a function of pH in aqueous solution: [L1] = 5.0 �10�5 M, [Zn(II)] = 10�4 M, I = 0.15 M NaCl, T = 298.1 K.
Fig. 7 Fluorescence spectra of the Zn(II)/L1 system in aqueous buffer
(HEPES, 5 � 10�2 M) solution at pH = 7.4, obtained by adding
several amounts of Zn(II) up to 2 equivalents with respect to [L1] =
5.0 � 10�5 M.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 171–180 | 177
of the BPH unit by coordinating the OH� species which,
as reported in similar cases, increases a thermal relaxation
negatively affecting emission decay mechanisms.20b The
change in lem occurring with the formation of the dinuclear
[Zn2(H�2L1)]2+ is well highlighted by titrating a buffer
(pH = 7.4) solution of L1, adding increasing amounts of
Zn(II) up to 2 equivalents (Fig. 7); as shown in the figure, the
lem shifts toward higher energy by adding Zn(II) but,
at the same time, the fluorescence of the new species
formed decreases by about 30% and thus none chelation-
enhanced fluorescence (CHEF) effects were observed for
this system.
Fluorescence and UV-Vis of the 2Zn(II)/L2 system at different
pH values. Analogous fluorescence and absorption experi-
ments were performed at different pH values using Zn(II)/L2
at a 2 to 1 molar ratio; the results are reported in Fig. 8.
UV-Vis absorption spectra of solutions containing 2Zn(II)/
L2 at different pH values show, as previously reported,
spectral profiles due to the deprotonated form of PH. How-
ever, also in this case, some further aspects can be discussed.
Observing the lmax of the spectra from acidic to alkaline pH
values (Fig. 8(a)), a shift in the lmax from 273 (free ligand) to
286 nm (complexed ligand) occurs at pH 4 5 with the
appearance in solution of the [Zn2(H�1L2)]3+ species, in
agreement with the deprotonation of PH as previously demon-
strated. The value of lmax 286 nm is enough preserved also at
higher pH values where only a little decrease is shown with the
appearance in solution of the dihydroxylated species (lmax =
282 at pH = 12). On the contrary, in the 6–8 pH range, where
the [Zn2(H�1L2)]3+ species is prevalent in solution, a slight
increase in absorption with respect to the free ligand can
be observed, while a marked increase is visible at higher
pH values with the formation of the hydroxylated
[Zn2(H�1L2)OH]2+ species (see Fig. 8). This finding could
be explained by a different disposition of L2 in forming the
Zn–O–Zn cluster system (O is the phenolate oxygen atom) in
the [Zn2(H�1L2)]3+ and [Zn2(H�1L2)OH]2+ species. In fact,
while it was demonstrated that the hydroxylated
[Zn2(H�1L2)OH]2+ species shows the OH� displaced in a
bridged disposition between the two Zn(II) ions,30 on the
contrary, a coordination environment without secondary brid-
ging ligands could be hypothesized in the [Zn2(H�1L2)]3+
species. In the latter, the fifth coordination site of each Zn(II)
ion could be saturated by a water molecule or by a chloride
anion of the ionic medium. This may be the reason for the
increase in absorption of the [Zn2(H�1L2)OH]2+ with respect
to the [Zn2(H�1L2)]3+ species.
Analysis of the fluorescence experiments gives additional
information; examining the maximum of lem (lexc = 275 nm)
from acidic to alkaline field of pH, a shift of the lem is
observable (see Fig. 8) at pH 4 5; lem moves from 354 nm,
typical of the free ligand, reaching a constant value (308 nm) at
pH 6, with the full formation of the [Zn2(H�1L2)]3+ species.
This change in lem is coupled with an increase in fluorescence,
which shows its highest emission in the range of the
[Zn2(H�1L2)]3+ species. These changes are in agreement with
the simultaneous deprotonation of the phenolic oxygen atom
due to the Zn(II) complex formation and its bridging coordi-
nation between the two Zn(II) ions, as phenolate. At pH4 9, a
further change in the lem can be highlighted, since it shifts
from 308 to 325 nm in concomitance with the appearance of
the [Zn2(H�1L2)OH]2+ species in solution; this occurs without
observing any significant change in fluorescence intensity. This
result may be related, as above, to a different disposition of
the secondary ligands in the two complexed [Zn2(H�1L2)]3+
and [Zn2(H�1L2)OH]2+ species that could be responsible
of the different lem in the dinuclear [Zn2(H�1L2)]3+ and
[Zn2(H�1L2)OH]2+ species. As previously discussed for
the [Zn2(H�2L1)(OH)2] species, the increase in the total
electron density of the complex in the dihydroxylated
[Zn2(H�1L2)(OH)2]+ species affects fluorescence at higher
pH values.
The Zn(II)-L2 dinuclear complexes showed very interesting
fluorescent properties; in fact, although free L2 exhibits emit-
ting species in the same range of pH of the Zn(II)-dinuclear
one, the fluorescence intensity of the latter is higher, giving a
strong CHEF effect. This effect, occurring to L2 in the
presence of Zn(II), is highlighted in Fig. 9, which reports the
fluorescence spectra of L2 obtained by adding several amounts
of Zn(II) in aqueous buffer pH = 7.4 solution. At this pH
value, the species formed in the presence of Zn(II) is the
[Zn2(H�1L2)]3+ species. As can be observed in Fig. 9, the free
ligand shows low fluorescence emission with a lem centered
at 347 nm; by adding Zn(II), the emission increases and lemshifts toward higher energy. The spectra preserve the same
profile when adding up to 2 equivalents of Zn(II), reaching a
constant emission and lem of 308 nm, in concomitance
with the complete formation of the [Zn2(H�1L2)]3+ species.
Fig. 8 Fluorescence emission titration (lex = 279 nm) (E), absorp-
tion wavelength trend (� � �), and emission wavelength trend (---) (a);
absorption titration at l = 287 nm (K) and distribution curves of the
species (—) (b); as a function of pH in aqueous solution: [L2] = 5.0 �10�5 M, [Zn(II)] = 1.0 � 10�4 M, I = 0.15 M NaCl, T = 298.1 K.
178 | New J. Chem., 2009, 33, 171–180 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
(see Fig. 8(b)). At this pH the emission quantum yield is more
than twenty-fold higher for the [Zn2(H�1L2)]3+ species than
for the free ligand; furthermore, a similar CHEF effect was
also found in other fields of pH such as 8 and 10, at which the
dinuclear species are formed, thus highlighting the sensing role
of L2 towards Zn(II) in aqueous solution in a biologically
important range of pH. For this reason, L2 can be considered
a potential chemosensor for Zn(II).
Conclusions
The studies highlighted that the intensity of the fluorescence of
both ligands depends on the protonation state of the phenolic
functions, and in the case of L2, the lem is also affected by
protonation while this does not occur for L1. For this beha-
vior, both ligands are suitable chemosensors of H+ in that
they are able to change their optical absorption and fluores-
cence properties as function of pH.
For both systems the most fluorescent species is the same:
H3L3+ in which the BPH unit of L1 is in its mono-deproto-
nated form, while PH is present as phenolate form in L2; on
the contrary, when BPH and PH are in their neutral form both
ligands show the lowest fluorescence. While these results are in
agreement with those found for free BPH (the more fluores-
cent species is the monoanionic species of BPH), this finding is
opposite to that for free PH where the neutral species is the
most fluorescent. This can be explained by a lower solvation of
the phenolate oxygen atom in the H3L23+ species which limits
the quenching effect occurring via H-bond with the water
molecules. The presence of the tertiary amine function close
to the phenol oxygen affects the emission quantum yield of
those species in which the formation of intramolecular
H-bonds is possible, highlighting that the formation of
H-bonds has a quenching effect to the fluorescence in these
systems.
The Zn(II)-dinuclear species are fluorescent in the field of
pH where they exist; the highest emitting species are the
[Zn2(H�2L1)]2+ and the [Zn2(H�1L2)]
3+ species, respectively;
they are prevalent in a wide range of pH including the
physiological one. In the [Zn2H�2L1]2+, the presence of the
dianionic form of BPH produces a blue shift of lem in the
fluorescence experiments, in comparison with the free ligand.
The interaction with guests such as OH� perturbs the emission
but not the absorption of the dinuclear species.
In the [Zn2(H�1L2)]3+ species a slight blue shift in lem can
also be observed, as well as, a decrease in fluorescence brought
about by the addition of an anionic guest such as OH�.
The main result retrieved is that both L1 and L2 sense the
Zn(II) in aqueous solution at physiological pH 7.4 by fluores-
cence; at this pH the [Zn2(H�2L1)]2+ and [Zn2(H�1L2)]
3+
species are prevalent in solution. The [Zn2(H�2L1)]2+ species
shows a simultaneous change in the lem with a drop in
fluorescence, but real and efficient sensing was obtained by
using ligand L2 which, in the presence of two equivalents of
Zn(II), gives rise to a strong CHEF effect (a twenty-fold
increase) with the formation of the [Zn2(H�1L2)]3+ species;
in this case, a similar CHEF effect was also found in other
fields of pH such as 8 and 10, highlighting the sensing role of
L2 towards Zn(II) in aqueous solution in a biologically im-
portant range of pH.
Concluding, both systems behave as chemosensors for both
H+ and Zn(II) and their investigation has given much useful
information for the design of more efficient systems. More-
over, taking into account that both [Zn2(H�2L1)]2+ and
[Zn2(H�1L2)]3+ dinuclear species show the highest fluores-
cence intensity and that they are the most suitable hosting
species for guests, they are a very interesting platform for the
sensing of guest species.
Acknowledgements
The authors thank the Italian Ministero dell’Istruzione
dell’Universita e della Ricerca (MIUR), PRIN2007 for finan-
cial support.
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30 N. Ceccanti, M. Formica, V. Fusi, L. Giorgi, M. Micheloni,R. Pardini, R. Pontellini and M. R. Tine, Inorg. Chim. Acta,2001, 321, 153.
31 P. Dapporto, M. Formica, V. Fusi, L. Giorgi, M. Micheloni,P. Paoli, R. Pontellini and P. Rossi, Inorg. Chem., 2001, 40, 6186.
32 (a) H. Pal and T. N. Das, J. Phys. Chem., 2003, 107, 5876;(b) M. Jonsson, J. Lind and G. Merenyi, J. Phys. Chem., 2002,106, 4758; (c) M. Jonsson, J. Lind and G. Merenyi, J. Phys. Chem.,2003, 107, 5878.
33 (a) A. Testa, J. Photochem. Photobiol. A: Chem., 1992, 64, 73;(b) G. Wenska, B. Skalski, Z. Gdaniec, R. W. Adamiak,J. Matulic-Adamic and L. Beigelman, J. Photochem. Photobiol.A: Chem., 2000, 133, 169–176.
34 (a) J. C. Batchelor, J. H. Prestegard, R. J. Cushley and S. R. Lipsy,J. Am. Chem. Soc., 1973, 95, 6558; (b) A. R. Quirt, J. R. Lyerla,I. R. Peat, J. S. Cohen, W. R. Reynold and M. F. Freedman,J. Am. Chem. Soc., 1974, 96, 570; (c) J. C. Batchelor, J. Am. Chem.Soc., 1975, 97, 3410.
180 | New J. Chem., 2009, 33, 171–180 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Dynamic covalent self-assembled macrocycles prepared from 2-formyl-
aryl-boronic acids and 1,2-amino alcoholsw
Ewan Galbraith, Andrew M. Kelly, John S. Fossey, Gabriele Kociok-Kohn,
Matthew G. Davidson, Steven D. Bull* and Tony D. James*
Received (in Durham, UK) 2nd September 2008, Accepted 18th September 2008
First published as an Advance Article on the web 31st October 2008
DOI: 10.1039/b815138e
Reaction of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self
assembly to quantitatively afford tetracyclic macrocyclic Schiff base boracycles containing
bridging boron–oxygen–boron functionality.
Introduction
The development of boronic acid based saccharide sensors
that rely on the dynamic covalent interaction of boronic acids
with diols has been widely investigated.1–9 Boronic ester
formation with diols has also been used for the construction
of discrete macrocycles and cages.10 The reversible nature
of boronic acid complexation with diols makes this type of
interaction highly suitable for the reversible self-assembly of
multicomponent systems. With these types of reversible
systems any errors that occur during the assembly process may
be corrected because equilibration of the reactive species
results in formation of a thermodynamically favoured
product. A number of boracycles have been prepared
that employ a combination of facile imine formation and
boronic acid esterification to afford multicomponent macro-
cycles.11–24 For example, Severin has prepared a series
of self assembled macrocycles/cages by combining 3- or 4-for-
myl-phenyl-boronic acids with bis or tris primary amines
and pentaerythritol (tetraol).25,26 Nitschke has also prepared
a macrocycle derived from pentaerythritol, 2-formyl-phenyl-
boronic acid and para-diaminobenzene, as well as a cage
compound arising from self assembly of cyclotricatechylene,
meta-xylylenediamine and 2-formyl-phenyl-boronic acid.27
Farfan has prepared boracycles from boric acid, 4-diethyla-
mino salicylaldehyde and (R)-phenylglycinol 6d. This
complex was formed in two steps involving reaction of
4-diethylamino salicylaldehyde and (R)-6d to produce an
imine, followed by reflux with boric acid in toluene under
Dean–Stark conditions for 18 h to produce the observed
complex.28
We now report herein that simple room temperature mixing
of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results
in dynamic covalent self assembly to afford stable tetracyclic
macrocyclic Schiff base complexes that contain a rigid brid-
ging boron–oxygen–boron functionality.
Results and discussion
We have recently reported the development of versatile three-
component derivatization protocols for determining the
enantiomeric excess of chiral primary amines, diols or
diamines.29–35 For the case of amines, this approach involves
derivatization of a chiral amine 1 with 2-formyl-phenyl-
boronic acid 2 and enantiopure BINOL (S)-3 in CDCl3 to
quantitatively afford a mixture of diastereoisomeric imino-
boronate esters (S,S)-4 and (S,R)-5. The diastereoisomeric
ratio of (S,S)-4:(S,R)-5 is then determined by 1H NMR
spectroscopic analysis, and since no kinetic resolution occurs
this value is an accurate reflection of the enantiomeric excess
of the parent amine (Scheme 1).
We reasoned that this type of three-component derivatiza-
tion protocol might also be useful for analyzing the enantio-
purity of chiral 1,2-amino alcohols. Therefore, (S)-leucinol 6b
was treated with 2-formyl-phenyl-boronic acid 2 and (S)-
BINOL 3 in CDCl3 and its 1H NMR spectrum acquired after
ten minutes. The resultant 1H NMR spectra revealed the
presence of a complicated mixture of interconverting products
Scheme 1 Three-component protocol for determining the enantio-
meric purity of chiral amines by 1H NMR spectroscopic analysis.
Department of Chemistry, University of Bath, Bath, UK BA2 7AY.E-mail: [email protected]. E-mail: [email protected];Tel: +44 1225 383810w CCDC reference numbers 694358–694361 [(S,2R,4S)-7, 8a, 8f and8h]. For crystallographic data in CIF or other electronic format seeDOI: 10.1039/b815138e
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 181–185 | 181
PAPER www.rsc.org/njc | New Journal of Chemistry
that was clearly unsuited for carrying out ee determination.
However, on standing overnight, the crude reaction product
fractionally crystallised to afford the expected oxazolidine-
boronate ester (S,2R,4S)-7, whose structure was subsequently
confirmed by X-ray crystallographic analysis (Scheme 2).
In order to investigate this complexation reaction further, it
was decided to determine what products would be formed
when 2-formyl-phenyl-boronic acid 2 was individually reacted
with either (S)-BINOL 3 or (R)-valinol 6a. Two-component
mixing of 2-formyl-phenyl-boronic acid 2 with (S)-BINOL 3
in CDCl3 resulted in no reaction occurring. However, reaction
of 2 with (R)-valinol 6a at room temperature in chloroform
resulted in exclusive formation of a new boracycle (R,R)-8a in
quantitative yield (Scheme 3). The structure of symmetrical
boracycle (R,R)-8a was confirmed by X-ray crystallographic
analysis (Fig. 1), which revealed it to be the condensation
product of two equivalents of 2-formyl-phenyl-boronic acid
2 with two equivalents of (R)-valinol 6a, with concomitant
elimination of five molecules of water. This complexation
reaction results in formation of the densely packed central
core of boracycle (R,R)-8a which comprises two fused seven
membered rings formed from two tetrahedral sp3-boron
atoms, two imino alcohol fragments, and a central oxygen
atom that bridges both boron atoms. This architecture results
in its central fused bicyclic ring structure being further
appended by two five-membered rings formed from two
imino-boronate ester linkages that confer sp3 character on
the boron atoms. The scope and limitation of this four-
component condensation reaction was then investigated via
treatment of a series of five chiral amino alcohols 6b–f with
2-formyl-phenyl-boronic acid 2, which resulted in clean for-
mation of their respective boracycles 8b–f in 84–96% isolated
yield (Scheme 3).
The reversible nature of macrocycle formation of these
boracycles 8a–f was confirmed by adding one equivalent of
amino alcohol (S)-6a to macrocycle (S,S)-8b in chloroform.
Mass spectrometry indicated that this solution now contained
a mixture of three macrocycles, (S,S)-8a (M + H 431 m/z),
(S,S)-8b (M + H 445 m/z) and a mixed macrocycle derived
from (S)-6a and (S)-6b (M + H 417 m/z) in a statistical
1:1:2 ratio.
Norman and coworkers have previously reported the synth-
esis of achiral boracycle 8g derived from condensation of
2-aminophenol with 2-formyl-phenyl-boronic acid 2 in
ethanol at reflux.36 Attempts to repeat this condensation
reaction using our mild complexation conditions at room
temperature resulted in no reaction occurring. However,
heating 2-aminophenol 6g (or 4-methyl-2-aminophenol 6h)
with 2-formyl-phenyl-boronic acid 2 at reflux in 95:5 ethanol:
benzene under Dean–Stark conditions did result in quantita-
tive formation of the boracycles 8g (or 8h). Comparison of the
X-ray crystal structures of boracycle (S)-8a with that of
boracycle 8h (Fig. 2) revealed that whilst they belong to the
Scheme 2 Formation and X-ray crystal structure of boronic ester
(S,2R,4S)-7.
Scheme 3 Condensation of 2-formyl-phenylboronic acid 2 with chiral
amino alcohols 6a–f and achiral amino alcohols 6g, h affords four-
component boracycles 8a–h.
Fig. 1 Crystal structure of macrocycle 8a. (a) Viewed along the
boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.
182 | New J. Chem., 2009, 33, 181–185 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
same class of bridging boracycle, their three dimensional
architectures are very different. In the case of boracycle 8a,
the central bridging oxygen atom lies on the opposite side to
the other two oxygen atoms about the plane bisected by the
two boron atoms. This results in the alkyl side-chains of their
amino alcohol fragments adopting a conformation that creates
the walls of a potential binding cavity centred around its
bridging oxygen atom, with its aryl rings acting as buttressing
elements to contribute structural rigidity. Conversely, for the
case of macrocycle 8h, the presence of the more rigid amino-
phenol fragments results in the three oxygen atoms now being
presented on the same face of the plane bisected by the boron
atoms. This, in turn, results in the aryl rings of the boronic
acid fragment forming the walls of a cavity centred around the
bridging oxygen atom, with its aminophenol derived frag-
ments now adopting the role of buttressing substituents to
confer structural rigidity.
We have also varied the nature of the boronic acid template
used for supramolecular assembly, demonstrating that com-
plexation of 2-formyl-furanyl-boronic acid 9 with chiral
aminoalcohols 6a–e in chloroform quantitatively affords their
corresponding four-component boracycles 10a–e in 85–92%
isolated yield (Scheme 4). 11B NMR spectroscopic analysis of
these macrocycles reveals that the boron atoms of the furan
derived boracycles 10a–e (d 4.6–5.4 ppm) have more tetra-
hedral character than their corresponding phenyl derived
boracycles 8a–f (d 10.5–11.5 ppm). This increased tetrahedral
character may be a consequence of the need to incorporate a
more geometrically constrained five-membered furan ring into
these complexes. It may also explain why reaction of achiral
amino alcohols 6g–h with 2-formyl-furanyl-boronic acid 9 did
not result in clean formation of their corresponding four
component boracycles, which may be precluded by the oppos-
ing steric demands of incorporating tetrahedral sp3 boron
atoms and vicinal sp2 aryl carbon atoms into the central
boracyclic core of the macrocyclic ring system.
Conclusions
In conclusion, a range of covalent self-assembled macrocycles
8 and 10 containing bridging O–B–O–B–O have been prepared
and fully characterised. Their ease of preparation suggests that
this class of boracycle is well suited for the reversible self-
assembly of multicomponent systems, and we are currently
investigating the recognition properties of this structurally
diverse class of macrocycle.
Experimental
General synthetic methods
The solvents and reagents were reagent grade unless otherwise
stated and were purchased from Acros Organics, Alfa Aesar,
Fisher Scientific UK, Frontier Scientific Europe Ltd., TCI
Europe or Sigma-Aldrich Company Ltd., and were used
without further purification. Infra-red spectra were recorded
on a Perkin Elmer SpectrumRX spectrometer between 4400 cm�1
and 450 cm�1. Samples were evaporated from CHCl3 on
to a NaCl disc (film). Nuclear magnetic resonance spectra
were run in either chloroform-d. A Bruker AVANCE 300 was
used to acquire 1H-NMR spectra and recorded at 300 MHz,11B-NMR spectra at 100 MHz and 13C{1H} NMR spectra at
75 MHz. Chemical shifts (d) are expressed in parts per million
and are reported relative to the residual solvent peak or to
tetramethylsilane as an internal standard in 1H and 13C{1H}
NMR spectra. Boron trifluoride diethyl etherate was used as
an external standard in 11B NMR spectra. Mass spectra were
acquired with a micrOTOFQ electrospray time-of-flight
(ESI-TOF) mass spectrometer (Bruker Daltonik GmbH).
General procedure for the preparation of boracycles 8a-f and
10a–e
2-Formyl-phenyl-boronic acid 2 (60 mg, 0.4 mmol) or 3-formyl-
furanyl-2-boronic acid 9 (56 mg, 0.4 mmol) was stirred with a
chiral 1,2-amino alcohol 6a–f or 6a–e (0.4 mmol) in chloro-
form (5 mL) for 10 min. The solvent was then removed
under reduced pressure to afford boracycles 8a–f or 10a–e in
84–96% yield.
(R,R)-8a. Yellow oil (70 mg, 84%); [a]20D +22.0 (c 1.0,
CH2Cl2); vmax (film) 1628 (CQN); dH (300 MHz; CDCl3)
8.08 (2H, s, CHQN), 7.51 (2H, d, J 7.4, ArH), 7.35–7.27
(4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1, ArH), 4.26 (2H, dd,
J 12.2 and 1.3, CHAHB(O)), 3.98 (2H, dd, J 12.2 and 1.3,
CHAHB(O)), 3.13 (2H, m, CH(iPr)–N), 2.96–2.83 (2H, m,
CH(CH3)2), 1.02 (6H, d, J 6.8, C(CH3)(CH3)) and 0.88
(6H, d, J 6.8, C(CH3)(CH3)); dC (75 MHz; CDCl3) 167.3
(CQN), 136.8, 133.6, 129.4, 127.2, 127.0, 126.2, 76.0, 60.9,
27.0, 21.1 and 19.4; dB (100 MHz; CDCl3) 10.7; m/z LRMS
(ESI+) 418 [(M + H)+, 13%], 283.2 (100), 200.1 (2); HRMS
(ESI+) found 417.2531 ([M + H]+ C24H30B2N2O3 requires
417.2515).
(S,S)-8b. Yellow solid (79 mg, 89%); m.p. 206–210 1C (dec);
[a]20D �26.1 (c 1.0, CH2Cl2); vmax (film) 1628 (CQN);
dH (300 MHz; CDCl3) 8.16 (2H, s, CHQN), 7.51 (2H, d,
J 7.4, ArH), 7.36–7.27 (4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1,
Fig. 2 Crystal structure of macrocycle 8h. (a) Viewed along the
boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.
Scheme 4 Preparation of boracycles 10a–e.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 181–185 | 183
ArH), 4.35 (2H, dd, J 11.9 and 1.7, CHAHB(O)), 3.81–3.73
(4H, m, CHAHB(O) and CH–N), 2.16–2.06 (2H, m,
CHAHBC(N)), 2.02–1.92 (2H, m, CHAHBC(N)), 1.72–1.63
(2H, m, CH(CH3)2) and 0.90 (12H, app t, J 6.8, C(CH3)2);
dC (75 MHz; CDCl3) 166.9 (CQN), 136.9, 133.5, 133.1, 129.4,
127.2, 126.1, 66.7, 62.5, 40.4, 24.8, 23.0 and 22.9; dB (100 MHz;
CDCl3) 11.5; m/z LRMS (ESI+) 445 [(M + H)+, 14%], 412.4
(100), 292.2 (66), 227.2 (15); HRMS (ESI+) found 445.2873
([M+H]+ C26H34B2N2O3 requires 445.2828).
(R,R)-8c. Yellow oil (69 mg, 88%); [a]20D +14.7 (c 1.0,
CH2Cl2); vmax (film) 1628 (CQN); dH (300 MHz; CDCl3)
8.13 (2H, s, CHQN), 7.50 (2H, t, J 7.4, ArH), 7.3–7.26
(4H, m, ArH), 7.12–7.07 (2H, m, ArH), 4.33 (2H, dd, J 12.0 and
1.7, CHAHB(O)), 3.78 (2H, dd, J 12.0 and 1.7, CHAHB(O)),
3.51 (2H, m, CH(Et)–N), 2.20–2.09 (4H, m, CHAHBMe) and
0.93 (6H, t, J 7.6, CH3); dC (75 MHz; CDCl3) 167.3 (CQN),
136.9, 133.5, 133.3, 129.3, 127.2, 126.2, 70.7, 62.4, 24.8
and 11.5; dB (100 MHz; CDCl3) 11.2; m/z LRMS (CI+) 389
[(M + H)+, 6%], 188.2 (50), 106.0 (46), 72.0 (100); HRMS
(EI+) found 388.2126 (2 � 11B) (M+� C22H26B2N2O3 requires
388.2124).
(R,R)-8d. Yellow oil (88 mg, 91%); [a]20D +21.1 (c 1.0,
CH2Cl2); vmax (film) 1627 (CQN); dH (300 MHz; CDCl3)
7.66–7.63 (4H, m, CHQN and ArH), 7.43–7.30 (12H, m,
ArH), 7.20 (2H, br t, J 7.4, ArH), 7.09 (2H, dt, J 7.4 and
0.8, ArH), 5.25 (2H, m, CHAHB(O)), 4.65 (2H, dd, J 11.9 and
10.4, CH(Ph)-N), 3.95 (2H, m, CHAHB(O)); dC (75 MHz;
CDCl3) 166.1 (CQN), 137.0, 135.7, 133.9, 133.5, 132.3, 130.0,
129.9, 129.7, 129.5, 127.2, 126.8, 126.7, 71.4, and 69.1; dB (100
MHz; CDCl3) 11.3; m/z LRMS (ESI+) 485 [(M + H)+, 9%],
368.2 (10), 312.1 (100), 278.2 (16); HRMS (ESI+) found
485.2230 ([M + H]+ C30H26B2N2O3 requires 485.2202).
(R,R)-8e. Yellow solid (140 mg, 95%); m.p. 125–129 1C
(dec); [a]20D +19.4 (c 1.0, CH2Cl2); vmax (film) 1635 (CQN); dH(300 MHz; CDCl3) 8.25 (2H, s, CHQN), 7.64 (2H, d, J 7.0,
ArH), 7.48–7.14 (16H, m, ArH), 5.46 (2H, br d, J 9.8,
CHAHB(N)), 4.50–4.42 (2H, m, CH(Ph)(O)) and 4.03 (2H,
br d, J 9.8, CHAHB(N)); dC (75 MHz; CDCl3) 166.0, 137.0,
135.6, 133.9, 133.5, 132.3, 130.0, 129.9, 129.7, 129.4, 128.0,
127.3, 126.8, 71.3 and 65.8; dB (100 MHz; CDCl3) 10.5; m/z
LRMS (ESI+) 485 [(M + H)+, 100%], 312.1 (99); HRMS
(ESI+) found 485.2219 ([M + H]+C30H26B2N2O3 requires
485.2202).
(rac)-8f. Yellow solid (85 mg, 96%); m.p. 142–144 1C (dec);
vmax (film) 1625 (CQN); dH (300 MHz; CDCl3) 8.20 (2H, d, J
3.0, CHQN), 7.47 (2H, d, J 6.8, ArH), 7.35 (2H, d, J 7.4,
ArH), 7.28 (2H, app dt, J 7.5 and 1.1, ArH), 7.10 (2H, app dt,
J 7.5 and 1.1, ArH), 3.96–3.88 (2H, m, CH(N)), 3.79–3.70 (2H,
m, CH(O)), 2.26 (2H, br d, J 12.0, CHAHBC–O), 1.88–1.81
(4H, m, CHAHBC–O and CHAHBC–N), 1.71–1.66 (2H, m,
CHAHBC–N) and 1.50–1.12 (8H, m, 2�(CH2)2); dC (75 MHz;
CDCl3) 164.0 (CQN), 137.2, 133.2, 129.9, 129.1, 126.9, 126.3,
65.6, 36.3, 29.8, 27.3, 24.9 and 24.8; dB (100 MHz; CDCl3)
10.8; m/z LRMS (ESI+) 440 [(M + H)+, 100%], 290.2 (15);
HRMS (ESI+) found 441.2549 ([M + H]+ C26H30B2N2O3
requires 441.2515).
8g. 2-Aminophenol 6g (200 mg, 1.83 mmol) and 2-formyl-
phenylboronic acid 2 (275 mg, 1.83 mmol) were dissolved in
95:5 ethanol–benzene (25 mL) in a round bottom flask fitted
with a Dean–Stark condenser and stirred at reflux for 4 h. The
reaction mixture was cooled and the solvent removed under
reduced pressure. Washing with a little cold methanol afforded
8g as a yellow powder (709 mg, 90%): m.p. 182–183 1C (dec.)
(Lit. 180 1C (dec.)36); dH (300 MHz, CDCl3) 8.65 (s, 2H), 7.49
(2H, d, J= 7.5 Hz), 7.40–7.37 (2H, m, Ar), 7.29–7.12 (8H, m),
6.92 (4H, m); dC (75 MHz, CDCl3) d = 160.9, 155.5, 135.1,
134.2, 134.13, 133.1, 132.9, 131.5, 127.9, 118.7, 115.8, 113.7; dB(96.3 MHz, CDCl3) 9.6; m/z HRMS (ESI+) found 429.1571.
([M + H]+ C26H19B2N2O3 (M + H+) requires 429.1582).
8h. 2-Hydroxy-5-methylaniline 6h (123 mg, 1.0 mmol) and
2-formyl-phenyl-boronic acid 1 (150 mg, 1.0 mmol) were
dissolved in 95:5 ethanol–benzene (20 mL) in a round bottom
flask fitted with a Dean–Stark condenser and stirred at reflux
for 4 h. The reaction mixture was cooled and the solvent
removed under reduced pressure. Washing with a little cold
methanol afforded 8h as a orange powder (374 mg, 82%): m.p.
231–232 1C (dec.); dH (300 MHz, CDCl3) 8.64 (2H, s,
CHQN), 7.42 (2H, m, ArH), 7.36 (2H, s, ArH), 7.29–7.16
(6H, m, ArH), 7.11 (2H, d, J 8.4 ArH), 6.85 (2H, d, J 8.4), 2.35
(6H, s, CH3); dC (75 MHz, CDCl3) 158.24, 154.9, 148.8, 134.9,
134.1, 133.9, 132.9, 131.2, 128.2, 127.8, 115.3, 113.8, 21.5; dB(100 MHz, CDCl3) 8.9; m/z HRMS (ESI+) found 457.2011.
([M + H]+ C28H23B2N2O3 (M + H+) requires 457.1889).
(S,S)-10a.Dark brown solid (74 mg, 93%); m.p. 131–140 1C
(dec); [a]20D �36.8 (c 1.0, CH2Cl2); vmax (film) 1649 (CQN);
dH (300 MHz; CDCl3) 8.13 (2H, d, J 3.0 CHQN), 7.35 (2H, d,
J 1.9, ArH), 6.33 (2H, d, J 1.9, ArH), 4.39 (2H, dd, J 9.4 and
6.2, CHAHB(O)), 4.15 (2H, dd, J 9.4 and 4.0, CHAHB(O)),
3.90–3.84 (2H, m, CHQN), 2.28–2.17 (2H, m, CH(CH3)2) and
1.06 (12H, app dd, J 6.8 and 7.2, C(CH3)2); dC (75 MHz;
CDCl3) 157.2, 144.5, 132.6, 123.3, 110.2, 69.3, 63.5, 32.6, 20.0
and 17.4; dB (100 MHz; CDCl3) 4.7; m/z LRMS (ESI+) 397
[(M + H)+, 9%], 345.2 (100), 283.2 (36); HRMS (ESI+)
found 397.2122 ([M+H]+C20H26B2N2O5 requires 397.2100).
(S,S)-10b.Red oil (76 mg, 90%); [a]20D �34.0 (c 1.0, CH2Cl2);
vmax (film) 1649 (CQN); dH (300 MHz; CDCl3) 8.13 (2H, d, J
3.0, CHQN), 7.36 (2H, d, J 1.9, ArH), 6.32 (2H, d, J 1.9,
ArH), 4.39 (2H, dd, J 8.9 and 6.0, CHAHB(O)), 4.24–4.15
(2H, m, CH–N), 3.99 (2H, dd, J 8.9 and 7.4, CHAHB(O)),
1.77–1.65 (6H, m, CHAHBCH(CH3)2) and 1.00 (12H, app t, J
5.5, C(CH3)2); dC (75 MHz; CDCl3) 157.2, 144.7, 132.7, 122.8,
110.0, 71.9, 52.2, 32.6, 20.5, 8.9 and 8.1; dB (100 MHz; CDCl3)
4.6; m/z LRMS (ESI+) 425 [(M + H)+, 32%], 412.4 (27),
389.3 (35), 375.2 (100); HRMS (ESI+) found 425.2452
([M + H]+ C22H30B2N2O5 requires 425.2419).
(R,R)-10c. Red oil (134 mg, 91%); [a]20D +33.0 (c 1.0,
CH2Cl2); vmax (film) 1656 (CQN); dH (300 MHz; CDCl3)
8.13 (2H, s, CHQN), 7.34 (2H, d, J 1.9, ArH), 6.31 (2H, d,
J 1.9, ArH), 4.42–4.39 (2H, m, CHAHB(O)), 4.09–3.99 (4H, m,
CHAHB(O) and CH–N), 2.05–1.90 (4H, m, CH2Me) and 1.07
(6H, t, J 7.0, CH3); dC (75 MHz; CDCl3) 156.3, 144.5, 132.6,
123.3 110.2, 67.7, 65.7, 26.4 and 10.4; dB (100 MHz; CDCl3)
184 | New J. Chem., 2009, 33, 181–185 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
4.8; m/z LRMS (ESI+) 369 [(M+H)+, 65%], 288.2 (100),
201.1 (34); HRMS (ESI+) found 369.1791 ([M+H]+
C18H22B2N2O5 requires 369.1785).
(R,R)-10d. Red solid (79 mg, 85%); m.p. 115–118 1C (dec);
[a]20D +39.6 (c 1.0, CH2Cl2); vmax (film) 1657 (CQN); dH(300 MHz; CDCl3) 7.83 (2H, d, J 3.0, CHQN), 7.53–7.44
(10H, m, ArH), 7.42 (2H, d, J 1.9, ArH), 6.24 (2H, d, J 1.9,
ArH), 5.35–5.28 (2H, m, CH(Ph)–N) and 4.57–4.45 (4H, m,
CHAHB(O)); dC (75 MHz; CDCl3) 158.3, 144.9, 136.6, 131.4,
129.8, 129.60, 129.59, 129.55, 129.50, 124.6, 110.3, 71.3
and 70.4; dB (100 MHz; CDCl3) 5.4; m/z LRMS (ESI+) 465
[(M + H)+, 100%], 415.2 (33), 335.2 (36), 292.1 (32), 215.1 (10);
HRMS (ESI+) found 465.1833 ([M + H]+C26H22B2N2O5
requires 465.1787).
(R,R)-10e. Dark brown solid (85 mg, 92%); m.p. 124–126 1C
(dec); [a]20D +18.5 (c 1.0, CH2Cl2); vmax (film) 1662 (CQN); dH(300 MHz; CDCl3) 8.26 (2H, br s, CHQN), 7.56 (4H, br d,
ArH), 7.45 (2H, d, J 1.9, ArH), 7.39–7.26 (6H, m, ArH), 6.34
(2H, d, J 1.9, ArH), 5.56–5.51 (2H, m, CHAHB(N)) and
4.11–4.08 (4H, m, CHAHB(N)) and CH(Ph)(O)); dC(75 MHz; CDCl3) 157.7, 145.1, 142.1, 129.7, 128.8, 128.6,
128.1, 126.7, 124.5, 110.4, 76.2 and 63.7; dB (100 MHz; CDCl3)
5.0; m/z LRMS (ESI+) 465 [(M + H)+, 65%], 415.2 (100),
323.2 (83); HRMS (ESI+) found 465.1841 ([M + H]+
C26H22B2N2O5 requires 465.1787).
Acknowledgements
We would like to acknowledge the EPSRC, Royal Society, the
Leverhulme Trust, Beckman-Coulter and University of Bath
for funding.
References
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 181–185 | 185
N-Inversion in 2-azabicyclopentane derivatives: model simulations
for a laser controlled molecular switch
Bastian Klaumunzer* and Dominik Kroner
Received (in Montpellier, France) 17th July 2008, Accepted 18th September 2008
First published as an Advance Article on the web 5th November 2008
DOI: 10.1039/b812319e
We report model quantum simulations for the nitrogen inversion in 2-azabicyclo[1.1.1]pentane
derivates controlled by laser pulses proposing to use this class of molecules as molecular switches.
The derivatives trans-5-fluoro-2-methyl-2-azabicyclo[1.1.1]pentane and cis-5-fluoro-2-methyl-2-
azabicyclo[1.1.1]pentane are investigated by means of density functional theory and quantum
wave packet dynamics. The molecules have two stable, i.e. energetically well-separated,
conformers along the N-inversion coordinate. In 1D model simulations the transformation from
one conformer to the other is accomplished in the electronic ground state by using two
overlapping chirped linearly polarized IR laser pulses for the trans- and cis-isomer or alternatively
via an electronic excited state employing a pump-dump sequence of ultrashort UV laser pulses.
1. Introduction
Currently molecular switches are of interest in the field of
nanotechnology, e.g. for application in molecular electronics.1,2
In addition, they are also important in biology since
many biological functions are based on them, for instance,
allosteric regulation and vision. In general, theoretical and
experimental research on photo-switchable compounds has
mainly focused on cis-trans isomerization or photocyclic
reactions.3–5 Examples are chiroptical switches based on steri-
cally overcrowded alkenes,6 azobenzenes used as surface
mounted molecular switches7,8 or the laser controlled rever-
sible ring-opening of cyclohexadiene.9
Conformational transformations in molecules without
affecting the bond order have been, however, of rather less
interest for the design of molecular switches. The reason is
obvious since the barrier separating conformers is often in the
order of 1–10 kJ mol�1 making differentiation and, hence,
detection of the switchable molecular property, at room
temperature difficult if not impossible. Nevertheless, energy
barriers between conformers can be increased by sterically
demanding substituents making those molecules more attrac-
tive for controlled conformational switching. For instance,
Umeda et al. presented quantum simulations for the optical
isomerization of helical difluorobenzo[c]phenanthrene10 and
Hoki et al. performed quantum simulations for the change of
axial chiral 1,10-binaphthyl from its P- to M-form by laser
induced torsion around a single bond.11 Recently, we reported
a laser controlled axial chiral molecular switch, which allows
for the selective transformation between the achiral and either
the left- or right-handed form of an F-substituted styrene
derivative by torsion around a C–C single bond.12
A particular type of conformational change is the nitrogen
inversion (N-inversion).13,14 A nitrogen compound like
ammonia in a trigonal pyramid geometry (tertiary amine)
undergoes rapid nitrogen inversion. This interconversion is
very fast at room temperature because the energy barrier
(24.2 kJ mol�1) is relatively small.15 However, if the nitrogen
has sterically demanding substituents or is part of a rigid ring
system, it cannot easily invert around the lone electron pair
making the two conformers separable at room temperature.
Here we report quantum dynamical simulations of laser
controlled N-inversion of two 2-azabicycles. This class of
azabicyclic molecules has a particularly high inversion barrier
due the bicyclic effect, which has been of great experimental
and theoretical interest.13,16,17 We propose that derivatives of
5-X/Y-2-azabicyclo[1.1.1]pentane could serve as laser pulse
controlled molecular switches, which change according to
their conformation the size and direction of their dipole
moment mainly originating from an electronegative substitu-
ent X/Y, see Fig. 1. For a defined setup of the molecular switch
this system could be immobilized by chemi- or physisorption
on a surface via an adequate linking group R, see Fig. 1.
In this paper we investigate cis-5-fluoro-2-methyl-2-azabi-
cyclo[1.1.1]pentane (X = F, Y = H and R = CH3 in Fig. 1)
and trans-5-fluoro-2-methyl-2-azabicyclo[1.1.1]pentane (X =
H, Y = F and R = CH3 in Fig. 1). These molecules possess
two conformers of different dipole moments separated by a
high N-inversion barrier. In the following we will demonstrate
how these molecular systems can be switched via vibrational or
Fig. 1 Model for a laser controlled molecular switch: N-inversion of
5-X/Y-2-R-2-azabicyclo[1.1.1]pentane with X/Y being an electro-
negative substituent (here: cis X = F/Y = H and trans X = H/Y
= F) and R being e.g. a linker for a surface (here R = methyl).
Universitat Potsdam, Institut fur Chemie, Karl-Liebknecht-Str. 24-25,D-14476 Potsdam, Germany.E-mail: [email protected]
186 | New J. Chem., 2009, 33, 186–195 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
vibronic states. For these purposes control mechanisms
employing ultrafast laser pulses have been developed.
The remainder of the paper is organized as follows: The
model and the applied theoretical methods are explained in
section 2, the results of the quantum chemical and quantum
dynamical calculations including the laser control are pre-
sented in section 3. Section 4 provides a summary.
2. Model and methods
2.1 Quantum chemistry
The geometries of the two N-inversion conformers of both
isomers, namely the trans- and cis-isomer, were optimized with
density functional theory (DFT) employing the B3LYP18,19
functional and the ANO-L-DZ20 basis set as implemented in
the Molcas 6.4 program package.21 The obtained geometries
are denoted trans-Min1 and trans-Min2 for the trans-molecule
or cis-Min1 and cis-Min2 for the cis-molecule, see section
3.1 and Fig. 2 and 4. The transition states, called trans-TS
and cis-TS, were also calculated at the same level of theory.
To simulate the change of conformation the molecules are
assumed to be oriented with their N–C1-bond along the space
fixed z-axis, as shown in Fig. 2. Then, the N-inversion is
approximated by a partial rotation of the methyl group
around the y-axis while keeping the rest of the molecule fixed
in space. The angle a between the N–C1-bond and the x-axis is
used as reaction coordinate. In addition, for the trans-isomer
the free rotation of the methyl group around the N–C1-bond is
simulated by a rotation of the hydrogen atoms of the methyl
group around the N–C1-bond. Here the dihedral b, measured
between the H1–C1-bond and the x-axis, is used as reaction
coordinate, see Fig. 2. (In practice, first, the hydrogen atoms of
the methyl group are rotated clockwise around z-axis by b and
afterwards the whole methyl group is rotated around the
y-axis by a.)For the laser control via the ground state N-inversion states,
see section 3.3, the unrelaxed potential energy surface (PES) of
the electronic ground state along a is calculated by B3LYP/
ANO-L-DZ while keeping the rest of the geometrical para-
meters frozen to the minimum energy geometry trans-Min1 or
cis-Min1. For the trans-switch the calculations are also per-
formed along b obtaining a two-dimensional PES. Accord-
ingly, the permanent dipole moment along a is obtained on the
same level of theory as the PES.
For the control scenario using UV laser pulses for the
cis-isomer, see section 3.4, the first ten singlet electronic excited
states along a are calculated by time-dependent DFT
(TDDFT) with B3LYP and 6-31G(d,p) as implemented in
the GAUSSIAN0322 package. Transition dipole moments
between ground and any of the electronic excited states are
obtained on the same level of theory. As previously cis-Min1 is
used as reference geometry.
2.2 Model Hamiltonian
As the moment of inertia of the methyl group with respect to
the space fixed y-axis is about 100-times smaller than that of
the rest of the molecule, we assume the F-azabicyclo group
being fixed in space with only the methyl group moving,23 see
Fig. 2. To obtain the N-inversion eigenenergies eiv and eigen-
functions fiv of the ith electronic state the time-independent
Schrodinger equation
Himol(a)f
iv(a) = eivf
iv(a) (1)
is solved numerically. The molecular Hamiltonian Himol(a) is
given as
Hi
molðaÞ ¼ ��h2
2Iy
d2
da2þ ViðaÞ: ð2Þ
Vi(a) is the potential energy curve of the ith electronic state
with i = 0 for the electronic ground states and i 4 0 for
electronic excited states, cf. Fig. 5. Iy is the moment of inertia
for the rotation of the methyl group around the y-axis: Iy =PAmA�r2A. The distances rA of the atoms A with mass mA,
namely C1 and the hydrogens attached to it, are obtained from
the minimum energy geometry trans-Min1 or cis-Min1, see e.g.
Fig. 2. We obtain Iy = 247390.32 mea20 for the trans- and
Iy = 246484.74 mea20 for the cis-isomer. Note that, the N-in-
version is here modelled as a partial rotation of the methyl
group around the space-fixed y-axis while keeping the rest of
the molecule fixed in space, as described in section 2.1. Eqn (1)
is, then, solved by the Fourier Grid Hamiltonian method24
using N = 256 grid points in the IR-pulse case and N = 1024
points in the UV-pulse case, i.e. the coordinate a is
expressed as
ai = a0 + iDa, i = 0, . . ., N � 1, (3)
where a0 = 601 and Da = 0.70591 in the IR case (section 3.3)
and Da = 0.15641 (section 3.4) in the UV case.
Fig. 2 Optimized geometries of trans-5-fluoro-2-methyl-2-azabicyclo-
[1.1.1]pentane obtained from B3LYP/ANO-L-DZ: trans-Min1 is
the global minimum with angle a set to 90.01 in the space fixed
coordinate system. trans-Min2 is the optimized geometry of the second
N-inversion conformer at a E1891. trans-TS is the transition state
geometry at a E1651. trans-Min3 is the unrelaxed minimum along awith a E1931 using trans-Min1 as reference.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 186–195 | 187
2.3 Quantum dynamics
To describe the laser-driven quantum dynamics the time-
dependent Schrodinger equation is solved numerically:
i�h@
@tCða; tÞ ¼ Hða; tÞCða; tÞ: ð4Þ
for
Cða; tÞ ¼C0ða; tÞ
..
.
Ciða; tÞ
0
B@
1
CA; ð5Þ
with C0(a,t) being the wave function of the electronic ground
state and Ci(a,t) the wave function of the ith excited state. The
Hamilton operator H(a,t) is given by:
Hða; tÞ ¼H
00. . . H
0i
..
. . .. ..
.
Hi0
. . . Hii
0
B@
1
CA; ð6Þ
within the semiclassical dipole approximation:
Hii ¼ H
i
mol�^m!iiðaÞ � E
!ðtÞ; ð7Þ
Hij ¼ �^m!ijðaÞ � E
!ðtÞ; ð8Þ
where^m!iiðaÞ are the permanent dipole moments of the ith
electronic state and^m!ijðaÞ are the electronic transition dipole
moments. For the dynamical simulations we set the permanent
dipole moments of the ith excited state equal to that of the
electronic ground state ð^m!iiðaÞ ¼ ^m!00ðaÞÞ , the transition dipole
moments are set^m!0iðaÞ ¼ ^m!i0ðaÞ and the transition dipole
moments between all other electronic excited states are set
zero ðj^m!ij j ¼ 0Þ .The electric field ~E(t) of the laser pulses used here is
given by:
E!ðtÞ ¼ e
!j E
0cosðo � ðt� tcÞ þ ZÞsin2 pðt� tcÞ2fwhm
þ p2
� �
; ð9Þ
for |t � tc|r fwhm. Z is the time-independent phase and fwhm
the full width at half maximum (2fwhm equals the pulse
duration). The polarization vector ~ej = ~excos(j) + ~ezsin(j)with polarization angle j, where ~ex/z is the unit vector along
the x/z-axis. Hence, the laser is chosen to propagate in
y-direction. E0 is the electric field amplitude and tc the pulse
center, i.e. the time when the sin2 shape-function reaches its
maximum. The laser pulse frequency o can be linearly chirped
by _o ¼ do=dt :
oðtÞ ¼ o0 þ _o � ðt� tcÞ; ð10Þ
where o0 is the central frequency at t = tc. All quantum
dynamical propagations were performed with the wavepacket
program package25 using the second order splitting26 in grid
representation with a time step of 0.25 fs for the IR case
(section 3.3) and 0.025 fs for the UV case (section 3.4).
3. Results and discussion
3.1 Geometries and PESs
The geometry optimization of the trans-5-fluoro-2-methyl-2-
azabicyclo[1.1.1]pentane with B3LYP/ANO-L-DZ resulted in
two stable minima trans-Min1 and trans-Min2, shown in
Fig. 2, where trans-Min1 is the global minimum. In terms of
the angle a the two minima are at 901 (trans-Min1) and at
189.41 (trans-Min2) according to the space fixed coordinate
system. Thus, the transformation between them is achieved by
a rotation of the methyl group around the y-axis by about
1001. At the transition state trans-TS of the nitrogen inversion
the angle a E140.21. The molecule has CS-symmetry with
respect to the xz-plane in all conformations. The energy
difference between the transition state trans-TS and the abso-
lute minimum trans-Min1 is 6397.9 cm�1 corresponding to
76.5 kJ mol�1 which is more than three times higher than the
inversion barrier of ammonia (24.2 kJ mol�1).15 As one can see
from Fig. 2 the methyl group is rotated around the C1–N bond
by about 1801 while going from trans-Min1 to trans-Min2.
Therefore a two-dimensional PES (Fig. 3) along a and b was
calculated.
The PES shows three minima belonging to three different
molecular structures. We find minima at a = 901/b = 01
(trans-Min1), at a = 1901/b = 01 (trans-Min3) and at a =
1901/b = 1801 (trans-Min4), while the latter corresponds to
the unrelaxed geometry of trans-Min2. Additionally there
are three distinct maxima: trans-Max1 at a = 901/b = 1801,
trans-Max2 at a = 1501/b = 01, which belongs to the
unrelaxed geometry of trans-TS, and trans-Max3 at a =
1501/b = 1801. The energy differences between trans-Min1
and trans-Max1 and the barrier height between trans-Min4
and trans-Min3 are approximately of the same size, namely
1000 cm�1 (12 kJ mol�1). This barrier, resulting from the free
rotation of the methyl group around the C1–N bond, is, as
expected, of the same height as the rotational barrier of ethane
(12 kJ mol�1).27 The PES shows that the N-inversion should
not significantly be affected by the free rotation of the methyl
group, see Fig. 3. Yet, the methyl group used here represents
merely a placeholder for an arbitrary substituent R, for
instance, a linker to a surface. The free rotation of the methyl
Fig. 3 Unrelaxed potential energy surface along a and b for trans-5-
fluoro-2-methyl-2-azabicyclo[1.1.1]pentane (B3LYP/ANO-L-DZ).
trans-Min1 denotes the minimum energy geometry which was used
as reference geometry.
188 | New J. Chem., 2009, 33, 186–195 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
group around the C1–N bond is neglected in the following, i.e.
the unrelaxed PES only along a with trans-Min1 as reference
geometry is used for all dynamical simulations.
It should be noted, as an aside, that a normal mode analysis
of the relaxed minimum geometry trans-Min1 employing
B3LYP/6-31G(d,p) reveals three modes that should be con-
sidered important for the dynamical simulations: (i) The
rotation of the methyl group around the C1–N bond (b) at245 cm�1, (ii) the bending of the C1–N-bicylo-angle describing
the rotation of the methyl group around the y-axis at 251 cm�1
(a), and (iii) the torsion of the C1–N-bicylo-dihedral describ-
ing the rotation of the methyl group around the x-axis at
286 cm�1 (all frequencies scaled according to ref. 29). Hence, a
coupling of mode (ii), which characterizes our model reaction
coordinate a, to modes (i) and (iii) cannot completely be ruled
out for higher excited states, because their energies lie within
the range of the inversion excitation energies, see section 3.2.
Due to the unrelaxed geometry the inversion barrier is
approx. 1600 cm�1 higher compared to the relaxed one. To
get an idea whether the barrier can be crossed thermally
we calculated N-inversion rates according to the theory of
Eyring.28 The necessary thermodynamic quantities were ob-
tained with the GAUSSIAN03 program package employing
B3LYP/6-31G(d,p). At 298 K we obtain an inversion rate
from trans-Min1 to trans-Min2 of 2.20 s�1. So at room
temperature we find a rather small rate for spontaneous
N-inversion compared to ammonia (about 109 s�1 without
tunneling). As the backward reaction rate is also fairly small at
room temperature (3.54 s�1) the here investigated conformers
are considered thermally sufficiently stable to monitor the
change of the dipole moment, see discussion below. For a
more detailed discussion the reader is referred to ref. 23.
The geometry optimization of the cis-5-fluoro-2-methyl-2-
azabicyclo[1.1.1]pentane with B3LYP/ANO-L-DZ resulted in
two stable minima, denoted cis-Min1 and cis-Min2. The
corresponding structures are shown in Fig. 4. Cis-Min1 is
the global minimum, however, the energy difference between
the two minima is only 7 cm�1. In terms of the inversion angle
a the two minima are found at 901 (cis-Min1) by definition and
at 179.81 (cis-Min2), i.e. the transformation between them is
achieved by flipping the methyl group by about 901. As the
steric interactions of the X-substituent (X = F) with
the methyl group (R) is stronger than for the trans-isomer
(X = H), the change in a going from one conformer to the
other (E901) is smaller than for the trans-isomer (E1001).
At the transition state cis-TS of the nitrogen inversion
the angle a E164.71. The molecule has a mirror plane in the
xz-plane in all conformations. The energetic difference
between the transition state cis-TS and the absolute minimum
cis-Min1 is now 6358.6 cm�1 corresponding to 76.1 kJ mol�1.
Hence, the barrier height is similar to the one of the trans-
isomer (76.5 kJ mol�1).
For the cis-isomer we also observe that the methyl group is
rotated around the C1–N bond by about 1801 while going
from cis-Min1 to cis-Min2. As the coupling of the N-inversion
to the rotation of the methyl group is, as discussed above,
rather weak, only the one-dimensional PES along a starting
from cis-Min1 is considered. The unrelaxed electronic ground
state potential along a (B3LYP/ANO-L-DZ) is shown in
Fig. 5. The inversion barrier height is 8000 cm�1 and due to
the unrelaxed geometry approx. 1600 cm�1 higher than in the
relaxed case (cis-TS). As noted previously, due to the frozen
geometry the inversion angles at the top of the inversion
barrier (cis-Max2) and for cis-Min3 differ from those of the
optimized geometries, i.e. a(cis-Max2) E1481 and a(cis-Min3)
E1911. Here we can denote that the 1D cut of the potential
energy surface of the trans- and cis-isomer, Fig. 5, are quanti-
tatively similar, so that the curves overlap in the figure.
Fig. 4 Optimized geometries of cis-5-fluoro-2-methyl-2-azabicyclo-
[1.1.1]pentane obtained from B3LYP/ANO-L-DZ: cis-Min1 is the
global minimum with angle a set to 90.01 in the space fixed coordinate
system. cis-Min2 is the optimized geometry of the second N-inversion
conformer at a E1791. cis-TS is the transition state geometry
at a E1651. cis-Min3 is the unrelaxed minimum along a with aE1911 using cis-Min1 as reference.
Fig. 5 Potential energy surface of 5-fluoro-2-methyl-2-azabicyclo-
[1.1.1]pentane along a for the electronic ground state S0 (B3LYP/
ANO-L-DZ) (fitted from 33 single point calculations with a cubic
spline) and first three electronic excited states, S1 to S3 (TD-B3LYP/
6-31G(d,p)). Min1 denotes cis- and trans-Min1, Min3 cis- and trans-
Min1 and Max2 denotes cis- and trans-Max2, since the potentials for
the cis- and trans-isomers overlap on the scale of the picture.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 186–195 | 189
For the UV laser pulse control of the cis-isomer electronic
excited states were calculated as explained in section 2.1. The
first three excited states S1, S2 and S3 (TD-B3LYP/6-31G(d,p))
of the cis-isomer are depicted in Fig. 5. The shape of the
excited state potentials are similar to those of other aliphatic
tertiary amines calculated by Solling et al. with TD-B3LYP/
6-31++G(2df).30 We observe a vertical excitation energy
from S0 to S1 at a = 901 of approx. 7.2 eV (58071.9 cm�1).
Compared to the amines in ref. 30 the here computed excita-
tion energies are similar, so that we consider the level of theory
used for the calculation of the electronic excited states to be
sufficient for our needs, although Rydberg states might not be
described precisely due to the restrictions of the basis set used
here, i.e. the lack of diffuse functions. An orbital analysis
shows that the transitions are predominantly of n - p and
n - s character in accordance to the amines in ref. 30.
The topology of the excited states differ from the ground
state. Instead of two minima along a there is only one single
minimum. The topology of the S1 potential is suited well for
switching the molecule via this excited state since no barrier
has to be crossed on V1 by switching from one conformer to
the other, see section 3.4.
The components of the permanent dipole moment^m!00 along
a are shown in Fig. 6(a) for the trans-isomer. Because of the
Cs-symmetry in the xz-plane the permanent dipole moment
along y is zero at all a. The laser will, therefore, be chosen to
propagate in y-direction, see eqn (9). The major change in
m00x occurs in range of 150–2101, while m00z has its major change
in the range of 70–1501.
For the cis-isomer the components of the permanent dipole
moment,^m!00ðaÞ , and of the transition dipole moments from S0
to S1,^m!01ðaÞ , are plotted in Fig. 6(b) and (c). For reasons of
symmetry again m00y = 0 for all a. In contrast to the trans-
isomer the major change in m00x is in range of 70–1201, while for
m00z the major change occurs in the range of 120–2101 now. For
an efficient pump–dumpmechanism31,32 for both the trans- and
the cis-isomer the laser pulses will be polarized in accordance
to the regions of largest change in the dipole components, see
section 3.3. For the electronic transition to the S1 state of the
cis-isomer, UV laser pulses will be xz-polarized as well, as
transitions in y polarization are forbidden by symmetry.
3.2 Inversion eigenstates
The inversion eigenstates of the ground state were calculated
as described in section 2.2. There are 36 eigenstates (trans-
isomer)/35 eigenstates (cis-isomer) below the barrier whose
eigenfunctions f0v are localized in the left and 21 eigenstates
(both isomers) whose eigenfunctions f0v are localized in the
right potential well. All eigenfunctions f0v which satisfy
PK�1i=1
|f0v(ai)|
2Da Z 0.999 are called ‘‘left localized’’ eigenfunctions.
Correspondingly, an eigenfunction is called ‘‘right localized’’ ifPN
K+1|f0v(ai)|
2Da Z 0.999 is fulfilled, where aK is the grid
point defined by the maximum of the inversion barrier V0(aK)(trans-Max2/cis-Max2). All states in the left quantum well are
termed ‘‘L’’ and those in the right quantum well are termed
‘‘R’’. The associated wave functions f0v are denoted fuL with
f0L to f35L/f34L (trans/cis) for the left well and fuR with f0R to
f20R for the right well. (The superscript 0 is omitted for the
‘‘localized’’ eigenfunctions since the concept applies only for the
ground state.) In addition, there are two more eigenstates below
the barrier (both isomers) which are considered ‘‘delocalized’’
in these terms. Table 1 lists the two lowest N-inversion
eigenenergies e0v in each ground state minimum, their energy
difference De = e0v0 � e0v and the corresponding dipole matrix
elements hf0v0|m
00x/z|f
0vi = hmx/zi for trans- and cis-isomer.
3.3 Switching via ladder climbing
For the quantum dynamical simulations the system is
initially assumed to be in the inversion ground state 0L, i.e.
Fig. 6 x-, y- and z-component along a for the permanent dipole
moment ~m 00 (B3LYP/ANO-L-DZ) of (a) trans- and (b) cis-5-fluoro-2-
methyl-2-azabicyclo[1.1.1]pentane, and (c) the transition dipole
moments^m!01 to S1 (TD-B3LYP/6-31G(d,p)) for the cis-isomer.
Table 1 Selection of eigen-energies e0v in cm�1 of the electronicground state for the trans- and cis-isomer, energy differences De andtransition dipole matrix elements hmx/zi in Debye
Isomer
trans cis
f0L f1L f0R f1R f0L f1L f0R f1R
e0v 126.2 379.0 3397.2 3649.3 124.5 389.7 3383.9 3642.0De 252.8 252.1 265.2 258.1hmxi �0.0095 �0.029 �0.078 �0.019hmzi �0.044 �0.0082 0.013 0.051
190 | New J. Chem., 2009, 33, 186–195 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
C(t=0)= f0L. The goal of the laser control is, to transfer the
population to the R states. This is achieved, first, by climbing
up the vibrational ladder until the wave packet is above the
barrier. Then, a dump laser pulse will be used to induce a
downward ladder climbing in the right potential well to trap
the wave packet there. To achieve a most efficient ladder
climbing the laser pulses will be linearly chirped33–35 according
to eqn (10) to compensate for the anharmonicity of the
potential at higher energies.
Fig. 7(a)/(d) show the time evolution of the electric field of
the laser pulse sequences for switching the trans- (a) or cis-
isomer (d). The resulting time evolution of the expectation
value of the angle a and the population of the L (PL) and R
(PR) states are shown in Fig. 7(b)/(e) and (c)/(f) for trans (b, c)
or cis (e, f), respectively. The populations in the L and R states
and the population in all other states (PD) are calculated as
follows:
PLðtÞ ¼X35=34
u¼1jhCðtÞjfuLij
2; ð11Þ
PRðtÞ ¼X20
u¼1jhCðtÞjfuRij
2; ð12Þ
PD(t) = 1 � PL(t) � PR(t). (13)
3.3.1 Switching the trans-isomer. The electric field consists
of an overlapping pump–dump sequence, see Fig. 7(a), with
optimal parameters as given in Table 2. All pulse parameters
were tuned manually to obtain the best possible result. In
general, the laser parameters are chosen in accordance with the
molecular properties, i.e., transition dipole moment elements
and energy differences. This approach allows for a deeper
understanding and more flexible control of the underlying
switching mechanism. As initial guess we set the frequency
o0 of the pump/dump pulse to the transition frequency of
0L - 1L (252.8 cm�1)/1R - 0R (252.1 cm�1). Further fine
tuning then lead to a frequency close to a transition frequency
between higher R states (202.00 cm�1). Initially the polariza-
tion angles j were estimated by tanj ¼ hmzihmxi36 for the transition
between 0L and 1L (77.801) and 1R and 0R (15.801). Further
optimization of the pulse parameter resulted in almost the
same values for the pump (77.801) and dump pulse (15.951),
see Table 2. A non-overlapping sequence of pump and dump
pulse sequence was found less efficient. At first, the overall
pulse is more z-polarized and has a negative chirp; after
450–500 fs it changes its polarization towards x-direction
and the chirp becomes positive. One can see the change in
polarization direction as well as the frequency chirp more
clearly in the Husimi probability distributions in Fig. 8. The
Husimi distribution37 is obtained from:
PHðt; eÞ ¼Z
dt0Z
1
�hde0e�
ðt�t0Þ2k e�
kðe�e0Þ2�h PW ðt0; e0Þ ð14Þ
with PW being the Wigner probability distribution:38
PW ðt; eÞ ¼1
p
Z1
�1
dt0E?ðt� t0ÞEðtþ t0Þe�2it0e
�h : ð15Þ
where E is the x- or z-component of the electric field, and
k = 2s2 the parameter of the gaussian distribution with
s ¼ 4000�h=Eh , e the energy, and t the time.
From Fig. 7(b) one can see that once the propagation is
started the wave packet begins to oscillate in the left quantum
well until it crosses the barrier after 500 fs and is dumped into
the right quantum well (a = 1851). The final population is
spread over several R states such that the expectation value of
a still oscillates around 1851 as the mainly R-localized wave
packet evolves in time. Nevertheless, the switching of the
molecule was successful as at final time 92.5% of the popula-
tion has been transferred from the left potential well (a = 901)
to the right potential well (a = 1911). States 0R to 6R are the
most populated eigenstates after the laser pulse sequence. The
missing 7.5% of population remains in theD-states, i.e.mainly
above the barrier.
It should be noted that the mean peak intensity
(I = 0.5e0c|E0|2) of the IR pulse is rather high: I =
16.5 TW cm�2 due to the high N-inversion barrier and the
comparatively small change of the dipole moment components
along a. The high laser amplitudes could be decreased by using
longer pulses. But longer pulses could cause a decrease of
efficiency in transferring population from L to R for effects as
wave packet broadening. For very long times even intramole-
cular vibrational redistribution (IVR) cannot be neglected any
more. Therefore, we considered the cis-isomer in the next
Fig. 7 Laser pulse sequence for the N-inversion via IR ladder
climbing from trans-Min1 to trans-Min3 (a)–(c) and cis-Min1 to
cis-Min3 (d)–(f); for the laser pulse parameters see Table 2. Time
evolution of (a)/(d) the x- and z- component of the electric field, (b)/(e)
the expectation value of the inversion angle hai, and (c)/(f) the
population of the L, R and D-states according to eqns (11)–(13).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 186–195 | 191
section which has greater transition dipole matrix elements, cf.
Table 1, between the eigenstates and such should lead to a
decrease of the laser pulse intensities.
3.3.2 Switching the cis-isomer. For switching the cis-isomer
the electric field consists as in the previous case of an over-
lapping pump–dump sequence with optimal parameters as
given in Table 2. Again a non-overlapping sequence of pump
and dump pulse sequence was found less efficient. However,
now the pump pulse is more x-polarized while the dump pulse
is more z-polarized, according to the regions where major
changes in the dipole moment components occur, cf. Fig. 6
and discussion in section 3.1. Here the polarization angles
were initially determined as above for the 0L–1L transition as
j = �9.51 and for the 1R–0R transition as j = �69.61.Hence, the optimized polarization angle for the pump pulse
(�10.01) is in a good agreement with the calculated one, for
the dump pulse the optimized angle (�751) differs slightly.For getting the wave packet above the barrier a pump pulse
with a slight positive chirp was found beneficial. The second
pulse, then, has a notable positive chirp and dumps the wave
packet into the right potential well. The wave packet propaga-
tion shows almost the same behaviour as for the trans-isomer
concerning the expectation value of a and the population
dynamics, see Fig. 7(d–f). The pulse sequence is found with
90% PR at final time almost as efficient as what we achieved
for the trans-isomer. The population is mostly transferred to
the states 3R–9R. As expected the intensity of the laser pulse
(I = 11.5 TW cm�2) was lowered by 5 TW cm�2, however, it is
still high. For that reason a switching mechanism via the
electronic excited states will be investigated in the following
section.
3.4 Switching the cis-isomer via S1
For the transformation of the cis-isomer of the azabicycle via
the excited state S1 the initial state is the inversion ground state
0L as in the previous case. Now the wave packet is to be
excited to S1 employing a UV pump laser pulse, and after some
short time the wave packet is dumped into the right potential
well of the electronic ground state. The criterion for a success-
ful propagation is again that a large part of population is
transferred to the twenty R states below the central barrier of
the ground state potential. Higher states are omitted at this
point, see discussion below.
Fig. 9 shows (a) the electric field of the UV pump dump
pulse sequence, (b) the expectation value of angle a, (c) and the
population (P) of S0 (P(S0)), S1 (P(S1)) and of the R states (PR).
We obtain a sequence of pulses where the pump and dump
pulse do not overlap at all. The UV pulse sequence is polarized
in the xz-direction. The pulse parameters for the initial guess
were obtained in analogy to the procedure discussed above:
We set the frequency o0 to the energy difference V1–V0 at a =
901 for the pump pulse and at a = 1901 for the dump pulse.
From the transition dipole moments hf00Lj
^m!01jf170i and
hf170j
^m!01jf00Ri we computed the initial polarization angles
j of the pump pulse (�83.11) and of the dump pulse (7.41),
see 3.2. For the pump pulse we obtained j = �83.21 and for
the dump pulse j = 10.51 after further manual optimization.
During the control sequence the pump pulse transfers 99%
of the population from S0 to S1 (t = 360 fs), see Fig. 9(c). The
center of the wave packet then travels on S1 back and forth
until the dump pulse transfers 91.5% of the population back
to the ground state (t = 600 fs) where the wave packet is then
mostly trapped in the right potential well of the ground state
(89.5%), see Fig. 9(c). All the population transferred from S1to the R-states of S0 is found in the inversion states 14R to
17R; so the wave packet is still highly vibrationally excited and
it is therefore oscillating between a = 1631 and a = 1881, see
Fig. 9(b). The missing 2% of the ground state population
remains above the barrier (Max2). 8.5% of the electronically
excited population remains in S1.
The goal of reducing the laser pulse intensity is reached. The
intensity was brought down to 0.83 TW cm�2 for the pump
Table 2 Laser pulse parameters for the IR laser pulse sequences, depicted in Fig. 7(a) and (d), for the trans- and cis-isomer
Isomer Pulse type j (1) fwhm/fs tc/fs E 0/GV m�1 o0/cm�1 _o/cm�1 fs�1 Z/rad
trans Pump 77.80 640 640 16.5 243.25 �0.365 �3.25Dump 15.95 955 1060 16.5 202.00 0.178 0.125
cis Pump �10.00 400 400 8.0 252.25 0.036 �0.25Dump �75.00 550 650 11.5 220.25 0.180 0.75
Fig. 8 Husimi probability distributions of the (a) z- and (b) x-com-
ponent of the electric field of the IR switching pulse sequence for the
trans-isomer.
192 | New J. Chem., 2009, 33, 186–195 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
pulse and 2.3 TW cm�2 for the dump pulse. As the population
is transferred to high N-inversion states of S1, namely eigen-
states 67–72, whereas 70 is the most populated, the wave
packet is not in a compact form any more on the excited state
and hence it turned out to be very difficult to dump the
population effectively to the ground state. The transition
frequency of the pump pulse o0 = 58170 cm�1 is close to
the energy difference of the eigenenergies of the eigenstates f170
and f0L (58169.65 cm�1). Neither shortening or prolonging
the laser pulse durations nor lowering or increasing their
intensity increased the population of the R states.
Comparing the ladder climbing mechanism to the excited
state mechanism one can say that almost the same amount of
the population is transferred to the twenty R states below the
barrier. But in the ladder climbing case lower vibrational R
states have been populated, which leads to smaller oscillations
in a. In the UV case the laser pulse durations are much shorter
(690 fs) than in the IR case (1200 fs). However, upon including
the excited state S2 in the calculations the population trans-
ferred back to S0 is excited to S2 by the dump pulse such that at
the end of the propagation only 50% of the population is
transferred to the R states of S0 (not shown). Hence, we have a
loss of efficiency, when S2 is included. When including more
states up to S10 there is only additional population transfer to
S6 by 2%. There will be, however, no population transfer to
S3, S4, S7 and S8 as the transitions from S0 are symmetry
forbidden in x and z direction. For energetic reasons there is
also no population transfer to S9 or S10. Furthermore, due to
the different sign of the transition dipole moment of S5 in the z
direction the coupling to the x–z polarized dump pulse is
rather weak due to the improper polarization. Therefore, no
significant population transfer to S5 takes place. Here we also
note, that a more precise description of the electronic excited
state potentials might be necessary in order to correctly
account for avoided crossings in the regions of a = 1651 to
2151 which might lead to nonadiabatic transitions. In sum-
mary, while the laser induced switching via electronic excited
states is faster and allows for more realistic laser parameters—
at least within the framework of our model—the efficiency is
reduced due to undesired electronic excitations mainly to S2.
4. Summary and conclusions
Quantum simulations for a laser driven model system were
presented based on the approximate description of the nitro-
gen inversion in two azabicycles. Each of the two proposed
molecules, cis- and trans-5-X-2-R-2-azabicyclo[1.1.1]pentane,
possesses two stable conformers due to the sterically hindered
N-inversion. The molecules change the size and direction of
their dipole moment upon N-inversion where the electronega-
tive substituent X/Y mainly determines this property. The
substituent R can be used to immobilize the system, for
instance, by mounting it via a linker group R on a surface.
To investigate the possibilities of laser control we chose here
for a toy model X/Y = F and R= CH3. For trans-5-fluoro-2-
methyl-2-azabicyclo[1.1.1]pentane a two-dimensional poten-
tial along a and b was calculated, where a models the
N-inversion and b describes the free rotation of the methyl
group around its single bond to N. For the cis-isomer the
potential energy curve only along the nitrogen inversion
coordinate (a) was computed. In addition, the potential energy
curve was evaluated along a for several electronic excited
states. The designed laser pulse sequences allow to transfer
the molecules from their energetically more stable conformer
(Min1) to the less stable conformer (Min3) along the model
reaction coordinate (N-inversion). Linearly polarized laser
pulses were used to switch the molecule by either IR induced
ladder climbing or alternatively using the electronic excited
state (S1) as intermediate state in case of the cis-isomer.
In the case of vibrational ladder climbing two overlapping
laser pulses with chirped frequencies in the IR range were used
to switch the molecules. Thereby excitation and de-excitation
were mainly controlled by changing the chirp and the polari-
zation of the laser pulse. But the obtained laser intensities are
rather high.
Hence, we applied a control mechanism for the cis-isomer via
the first electronic excited S1. In this case the molecule is initially
excited by a UV pump laser pulse to a highly vibrational state
Fig. 9 Laser pulse sequence for the transformation of the cis-isomer
via the excited state S1 from cis-Min1 to cis-Min3; for the laser pulse
parameters see Table 3. Time evolution of (a) the x- and z-component
of the envelope function of the electric field, (b) the expectation value
of the inversion angle hai, and (c) the population in S0, S1 and R-states.
Table 3 Laser pulse parameters for the UV laser pulse sequencedepicted in Fig. 9(a)
Pulsetype j (1)
fwhm/fs tc/fs
E0/GVm�1
o0/cm�1
_o/cm�1
fs�1 Z/rad
Pump �83.20 180 180 2.5 58170.0 0.0 0.0Dump 10.50 155 535 4.5 51387.0 0.86 0.0
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 186–195 | 193
of S1. Afterwards a second UV laser pulse brings it down to the
electronic ground state in the right potential well.
In all cases the molecule was switched effectively as at least
90% of population was found in the target potential well.
However, if the second excited state S2 is considered as well
there is only population transfer of 50% to the R states in case
of UV pulses.
The efficiency of the population transfer could be dimin-
ished due to dissipative effects as intramolecular vibrational
redistribution (IVR). However, due to the overlapped pump-
dump control scheme the system will most probably return to
its thermal equilibrium geometry from where it can be
switched again, cf. ref. 14. The inversion mode may also
couple to other bending modes of the methyl group making
the proposed control strategy more complicated. Here, simu-
lations including more degrees of freedom could help to
quantify the effect. In this sense the mechanism via electronic
excited states could be more efficient as the switching process is
faster than in the case of vibrational ladder climbing. The
switching process via electronic excited states contains, how-
ever, the possible risk of undesired photochemical pathways
which could lead to a diminution of the desired control.
The degree of orientation of the molecule with respect to the
polarization vector of the laser field determines the efficiency
of the control mechanism. There are, however, theoretical and
experimental methods for orienting or aligning molecules, e.g.
in strong electric fields,39,40 using elliptically polarized lasers41
or applying optimal control theory.42
For the molecular system to be used in electronic devices, it
should be immobilized e.g. by adsorption to a surface. For this
one has to find a suitable linking group. By immobilizing the
molecule on a surface the switching mechanism will be different
from those presented here since the azabicycle will flip instead
of the R-group. Investigations along this thread are on the way.
Still, different fixed molecular orientations (with potentially
restricted rotations with respect to the surface normal) are
possible upon chemisorption depending on the symmetry of
the surface and the linker group. For surface mounted mole-
cules with different orientation along the surface normal sto-
chastically optimized elliptically polarized laser pulses were
found efficient for control of molecular isomerization.43 Note
that the coupling of the vibrational and electronic degrees of
freedom of the molecule to the surface degrees of freedom
(phonons, electron-hole pairs) may intensify energy dissipation
depending on the nature of the solid and the linking groups.
Nevertheless, the model molecules presented here could be a
good supplement to the model molecular switches which are
based on cis–trans isomerization or photocyclization reaction.
Acknowledgements
We thank P. Saalfrank for stimulating discussions. Financial
support by the Deutsche Forschungsgemeinschaft, project KR
2942/1 is gratefully acknowledged.
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This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 186–195 | 195
How does non-covalent Se� � �SeQO interaction stabilize selenoxides at
naphthalene 1,8-positions: structural and theoretical investigationsw
Satoko Hayashi,a Waro Nakanishi,*a Atsushi Furuta,a Jozef Drabowicz,b
Takahiro Sasamoricand Norihiro Tokitoh
c
Received (in Montpellier, France) 9th June 2008, Accepted 25th September 2008
First published as an Advance Article on the web 17th November 2008
DOI: 10.1039/b809763a
Bis-selenides (LL), such as 8-[MeSe(X)]-1-[MeSe(Z)]C10H6 (1 (LL)), 8-[EtSe(X)]-1-[EtSe(Z)]C10H6
(2 (LL)), 8-[p-YC6H4Se(X)]-1-[MeSe(Z)]C10H6 (3 (LL)) and 8-[p-YC6H4Se(X)]-1-[p-YC6H4Se(Z)]C10H6
(4 (LL)) were oxidized with ozone at 0 1C, where (X, Z) = (lone pair, lone pair) for LL.
Bis-selenoxides, 1 (OO), 3 (OO) and 4 (OO) where (X, Z) = (oxygen, oxygen), were obtained in
the oxidation of 1 (LL), 3 (LL) and 4 (LL), respectively, via corresponding selenide-selenoxides,
1 (LO), 3 (LO) and 4 (LO), respectively. A facile Se–C bond cleavage was observed in 2 (LL).
The structures of 1 (LO) and 1 (OO) were determined by the X-ray analysis. Three Se� � �SeQO
atoms in 1 (LO) and four OQSe� � �SeQO atoms in 1 (OO) align linearly. While the non-covalent
Se� � �SeQO 3c–4e interaction operates to stabilize 1 (LO), the non-covalent OQSe� � �SeQO 4c–4e
interaction would not stabilize 1 (OO). The 3c–4e interaction must play an important role to
control the stereochemistry of selenoxides. The 8-G-1-[MeSe(OH)2]C10H6 (n (OH�OH)) are the key
intermediates in the racemization of 8-G-1-[MeSe(O)]C10H6 (n (O)) in solutions, where G = SeMe
(1), H (5), F (6), Cl (7) and Br (8). Energies of n (OH�OH), relative to n (O), are evaluated based
on the theoretical calculations. G of SeMe is demonstrated to operate most effectively to protect
from racemization of selenoxides among n = 1 and 5–8, since the relative energies
for G of cis- and trans-SeMe are largest.
Introduction
Selonoxides1–4 [RSe(O)R0] afford optically active enantiomers,
as well as sulfoxides,5,6 if R and R0 are not the same, since Se
in each selenoxide is three-coordinated containing a lone pair.
However, it is usually difficult to utilize optical active selen-
oxides to introduce the optical activity in a target mole-
cule,1,2,4,7 since the racemization of optical active selenoxides
is usually very fast. Nevertheless, some efforts have been made
to stabilize the stereochemistry of selenoxides, by taking
advantage of non-covalent coordination by the neighboring
groups (G) of the G� � �SeQO type.2,4,7
Naphthalene 1,8-positions supply a good system to investi-
gate such interactions, since the non-bonded distances between
heteroatoms at the positions are close to the sum of the van
der Waals radii minus 1 A.8,9 Various types of non-covalent
interactions are detected in naphthalene 1,8-positions.8–11 The
s-type three center-four electron interactions (s(3c–4e)),12–14
s(2c–4e),12 p(2c–4e),12 distorted p(2c–4e),12 and Z4 4c–6e13
are typical examples. Such non-covalent interactions are
demonstrated to control the fine structures of molecules.15
Recently, we investigated fine structures of 8-G-1-(arylseleninyl)-
naphthalene with G = H, F, Cl and Br, together with
the factors to control the structures, as the first step to
control the stereochemistry of selenoxides.16 The factors are
called G, O and Y dependences, which originate from the
np(G)� � �s*(Se–O), np(O)� � �p(Nap) and np(O)� � �p(Ar) interac-
tions, respectively.16
We paid much attention to G = MeSe and ArSe in 8-G-1-
(arylseleninyl)naphthalenes, since many conformers are plau-
sible around the two Se–CNap bonds, relative to the case of
G = H and halogens. Scheme 1 shows the orbitals taking part
in the non-covalent Se� � �SeQO interaction. A bis-selenide
Scheme 1 Orbitals taking part in the non-bonded Se� � �SeQO inter-
actions in naphthalene 1,8-positions.
aDepartment of Material Science and Chemistry, Faculty of SystemsEngineering, Wakayama University, 930 Sakaedani, Wakayama640-8510, Japan. E-mail: [email protected];Fax: +81 73 457 8253; Tel: +81 73 457 8253
bCenter of Molecular and Macromolecular Studies, Polish Academyof Science, Sienkiewicza, 112, 90-363 Lodz, Poland
c Institute for Chemical Research, Kyoto University, Gokasho, Uji,Kyoto 611-0011, Japanw Electronic supplementary information (ESI) available: Energies andrelative energies for 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5), F(6), Cl (7) and Br (8) with X = lone pair (L), O (O), OH+ (OH+) andO2H2 (OH�OH)], the packing structures of 1 (OO), counter map for1 (OO), Cartesian coordinates for optimized structures of 1 and 5–8
with X = lone pair (L), O (O), OH+ (OH+) and O2H2 (OH�OH)].CCDC reference numbers 688690 (1 (LO)) and 688691 (1 (OO)). ForESI and crystallographic data in CIF or other electronic format seeDOI: 10.1039/b809763a
196 | New J. Chem., 2009, 33, 196–206 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPER www.rsc.org/njc | New Journal of Chemistry
contains double ns(Se), np(Se), s(Se–C) and s*(Se–C) orbitals.However, ns(O), np(O), np0(O), s(Se–O) and s*(Se–O) appear
newly with the quit of an np(Se), when a selenide-selenoxide is
formed from the bis-selenide.
The oxidation and formation of 8-[2RSe(X)]-1-
[1RSe(Z)]C10H6 (1 (1R = 2R = Me), 2 (1R = 2R = Et), 3
(1R =Me, 2R = p-YC6H4: Y = H (a), MeO (b) and NO2 (d))
and 4 (1R = 2R = p-YC6H4: Y = H (a) and tBu (c)) are
investigated for LL where (X, Z) = (lone pair, lone pair), LO
(lone pair, oxygen) and OO (oxygen, oxygen) (Chart 1). The
reactions are easily controlled and each process is followed by
the spectroscopic method. Non-bonded OQSe� � �SeQO
interactions are also the subject of interest.
The structures around the naphthyl group (Nap) in 8-G-1-
RSeC10H6 are well explained by three types, type A (A), B and
C.8c,d,f–h,17,18 The combined notation are used to specify the
structures of 1–4 with G = RSe, where the notation, such as
AA, BA or CA, shows the conformers around the two CNap–Se
bonds. Scheme 2 draws the notations employed in this work,
exemplified by 1 (LO).
The structures of 1 (LO) and 1 (OO) are determined by
X-ray crystallographic analysis. Quantum chemical (QC) cal-
culations are performed on 1 (LO) and 1 (OO), to elucidate the
role of the Se� � �SeQO interaction in 1 (LO) and the
OQSe� � �SeQO interaction in 1 (OO) as the factor to control
the fine structures. Orbitals of two Se atoms in 1 (LO) and
1 (OO) must overlap directly with each other, which would
stabilize the fine structures. QC calculations are also
performed on 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5),
F (6), Cl (7) and Br (8) with X = lone pair (L), O (O), OH+
(OH+) and O2H2 (OH�OH)], where OH�OH must be the key
intermediate in the racemization of 1 and 5–8, in the presence
of a trace of water. The relative energy [DE = E(n (OH�OH))
� (E(n (O)) + E(H2O)) (n = 1 and 5–8)] is evaluated: that for
G = MeSe is largest among them. The larger value must
correspond to a selenoxide with the stronger resistance for
racemization, although n (OH�OH) is not the transition state.
The G� � �SeQO interactions containing the Se� � �SeQO
and OQSe� � �SeQO interactions are also analyzed with the
natural orbital (NBO)19,20 and atoms-in-molecules (AIM)21,22
analyses.
Oxidation of 1,8-bis(selanyl)naphthalenes (LL) with ozone
is well controlled and monitored, which gives 1,8-bis(seleninyl)-
naphthalenes (OO) via 8-selanyl-1-seleninylnaphthalenes (LO).
Factors to control the fine structures of 1 (LO) and 1 (OO) are
clarified based on QC calculations, after determination of the
structures. The Se� � �SeQO interaction is demonstrated to
control the fine structure of 1 (LO), whereas the role of the
OQSe� � �SeQO interaction in 1 (OO) is critically discussed.
The role of G in 1 and 5–8 in the racemization process is also
evaluated.
Results and discussion
Survey of oxidation
Bis-selenides (n (LL): n= 1–4) were oxidized with ozone in the
methylene dichloride solution of each bis-selenide at 0 1C. The
bis-selenides (n (LL)) gave corresponding bis-selenoxides
(n (O)) via corresponding selenide-selenoxides (n (LO)), except
for 2 (LL). While 1 (LL) gave 1 (LO), followed by the quanti-
tative formation of 1 (OO), a facile Se–C bond cleavage
occurred on the oxidation of 2 (LL), resulting in the formation
of naphtho-1,8-[c,d]-1,2-diselenole (9).23 b-Elimination of the
selenoxide may be responsible for the facile Se–C bond
cleavage. In the case of 3 (LL), the methylselanyl Se atoms
were attacked exclusively. 3 (LO) were consumed to produce
the corresponding 3 (OO) with more ozone. 4 (LO) were also
produced from the corresponding 4 (LL) with ozone, followed
by the formation of the corresponding 4 (OO), respectively.
The results are summarized in Chart 1. The reactions are well
followed by NMR.
Structures of 1 (LO) and 1 (OO)
Single crystals of 1 (LO) and 1 (OO) were obtained via slow
evaporation of methylene dichloride-hexane solutions and one
of suitable crystals was subjected to X-ray crystallographic
analysis for each compound.24 Only one type of structure
corresponds to each of 1 (LO) and 1 (OO) in the crystals.
Table 1 shows the crystallographic data of 1 (LO) and
1 (OO). Fig. 1 shows the structures of 1 (LO) and 1 (OO).25
The packing structure of 1 (OO) is shown in Fig. S1 of the
Electronic Supplementary Information (ESIw). Selected inter-
atomic distances, angles and torsional angles of the com-
pounds 1 (LO) and 1 (OO) are collected in Table 2, together
with those of 1 (LL), which contains two types, 1 (LL)Aand 1 (LL)B.
26
Chart 1 Bis(selanyl)naphthalenes, 1–4, together with 5–8.
Scheme 2 Structures around naphthyl group in 8-G-1-[RSe(X)]C10H6,
exemplified by 1 (LO).
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 196–206 | 197
The structures of 1 (LO) and 1 (OO) are all AA for two
methyl groups (Fig. 1 and Table 2).15 The planarity of the
naphthyl (Nap) planes is very good. All Se–O bonds are placed
in the naphthyl plane. The superior tendency of the Se–O
bonds to stay on the naphthyl plane (O dependence)16 must be
the driving force for the structures of 1 (LO) and 1 (OO). Three
Se� � �Se–O atoms align linearly (+SeSeO = 173.31(15)1) and
the Se–O bond is almost perpendicular to another CNapSeCMe
plane in 1 (LO). The non-covalent np(Se)� � �s*(Se–O) 3c–4e
interaction operates effectively to keep the Se–O bond on the
naphthyl plane in 1 (LO) (G dependence).16 These results show
that the structure of 1 (LO) is well stabilized by the O and G
dependences observed in 1-naphthyl selenoxides.16
On the other hand, there is no np(Se) in 1 (OO). Therefore,
the G dependence of the np(Se)� � �s*(Se–O) type cannot
operate in 1 (OO). Consequently, the driving force for the
structure must come from the O dependence for both Se–O
bonds. Namely, the non-covalent O–Se� � �Se–O s(4c–4e) in-
teraction must be carefully examined as a factor to stabilize the
fine structure of 1 (OO), although the non-bonded Se� � �Sedistances are less than the sum of van der Waals radii by
ca. 0.65 A.27 The s(4c–4e) interaction seems not so important.
How does G of MeSe control the fine structure and the
behavior? QC calculations are performed on 1 and 5–8.
QC calculations
QC calculations were performed on 1 (LO) with the B3LYP/
6-311+G(d) method of the Gaussian 98 program.28–30 QC
calculations revealed energy profiles of the compounds.31
Table 3 collects the results of the QC calculations. The NBO
analysis19,20 were performed on 1 (LO) and 1 (OO) with the
B3LYP/6-311+G(d) method. The results are shown in
Table 4. The AIM parameters21,22 are calculated for 1 (LO)
and 1 (OO) with the Gaussian 03 program32 employing the
6-311+G(3df) basis sets for Se with the 6-311+G(3d,2p) basis
sets for C and H at the B3LYP level. They are analyzed
employing the AIM 2000 program.33 Table 5 collects the
results of AIM calculations.
Indeed, the results of QC calculations essentially correspond
to those in the gas phase, but the factors to control and/or
stabilize the structures in gas phase must also operate in solid
states and in solutions. Therefore, it must be instructive to
consider those predicted by QC calculations, although we
must be careful for the crystal packing effect in crystals and
the solvent effect in solutions, since such effects often larger
than the predicted factors.
The effect of G to stabilize 8-G-1-[MeSe(X)]C10H6 [G =
MeSe (1), H (5), F (6), Cl (7) and Br (8) with X = lone pair
(L), O (O), OH+ (OH+) and O2H2 (OH�OH)] will be dis-
cussed in detail, here. The results clarified the factors for the
racemization of selenoxides. n (OH�OH) (n = 1 and 5–8) must
be the key intermediates in the racemization of n (O), in the
presence of (a trace of) water in solutions.
Effect of G in 1 and 5–8
Racemization of an optically active selenoxide is believed to
proceed via a selenide dihydroxide (n (OH�OH)).4a–d Scheme 3
shows a hypothetical racemization process of optically active
n (O*) via n (OH�OH).
Protonation of n (O*) occurs at O of an optically active
isomer of n (O*: R) to give n (O*H+: R) at the initial stage of
the reaction. n (OH�OH) will form in the reaction of n (O*H+:
R) with water followed by the deprotonation to yield n (OH�OH). Elimination of water from n (OH�OH) results in the
racemization, since of n (OH�OH) is not optically active as a
whole. Similar reactions occur starting from n (O*: S) to yield
n (OH�OH) via n (O*H+: S), which also leads to racemization.
Table 1 Crystallographic data for 1 (LO) and 1 (OO)
1 (LO) 1 (OO)
Empirical formula C12H12OSe2 C12H12O2Se2�2.5H2OFormula weight 330.14 391.18Temperature/K 298(2) 103(2)Crystal system Monoclinic MonoclinicSpace group P21/n (#14) C2/c (#15)a/A 5.8460(19) 25.549(9)b/A 14.473(3) 5.8653(18)c/A 14.1490(16) 20.850(8)b/1 97.660(17) 117.329(4)V/A3 1186.5(5) 2775.6(16)Z 4 8Dc/g cm�3 1.848 1.872F(000) 640 1544Reflections observed [I 4 2s(I)] 2200 2435Parameters 136 190R1 [I 4 2s(I)] 0.032 0.021R1 [all data] 0.082 0.022oR2 [I 4 2s(I)] 0.065 0.053oR2 [all data] 0.077 0.054Goodness-of-fit on F2 1.029 1.109
Fig. 1 Structures of 1 (LO) (a) and 1 (OO) (b) with atomic numbering
scheme for selected atoms (thermal ellipsoids are shown at the 50%
probability level).
198 | New J. Chem., 2009, 33, 196–206 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Table 2 Selected interatomic distances (A), angles (1) and torsional angles (1) around Se atom in 1 (LO) and 1 (OO), together with those of 1 (LL)
1 (LL)Aa
1 (LL)Ba
1 (LO) 1 (OO)
Interatomic distancesSe1–Se2 3.051(4) 3.064(4) 3.1587(10) 3.1512(8)Se1–C1 1.929(4) 1.932(3) 1.983(5) 1.959(2)Se1–C11 1.944(4) 1.953(4) 1.954(5) 1.940(2)Se1–O1 1.653(4) 1.6771(15)Se2–C9 1.926(4) 1.932(4) 1.928(5) 1.970(2)Se2–C12 1.944(4) 1.949(4) 1.938(6) 1.934(2)Se2–O2 1.680(15)
AnglesSe2–Se1–C11 164.47(3) 146.46(3) 85.93(16) 88.26(7)Se2–Se1–O1 173.31(15) 167.54(5)Se1–Se2–C12 150.34(3) 159.73(3) 85.65(18) 89.41(7)Se1–Se2–O2 167.51(5)Se1–C1–C10 122.9(3) 123.9(3) 126.9(4) 124.33(16)C1–Se1–C11 99.29(16) 98.41(16) 96.0(2) 94.73(9)C1–Se1–O1 101.1(2) 102.69(8)C11–Se1–O1 100.7(2) 102.85(9)Se2–C9–C10 123.9(3) 122.9(3) 124.1(4) 124.67(16)C9–Se2–C12 99.27(16) 98.50(16) 98.1(2) 93.38(9)C9–Se2–O2 102.21(8)C12–Se2–O2 102.29(9)C1–C10–C9 126.4(3) 127.2(3) 127.0(4) 128.1(2)
Torsional anglesSe1–C1–C10–C5 173.5(2) �176.0(2) �177.6(4) 179.19(15)C10–C1–Se1C11 �154.1(3) 136.8(3) 82.8(4) �86.49(19)C10–C1–Se1–O1 �175.0(4) 169.19(17)Se2–C9–C10–C5 172.2(2) �170.2(2) 178.8(4) 178.90(15)C10–C9–Se2–C12 �138.8(3) 148.0(3) 84.6(4) �87.10(19)C10–C9–Se2–O2 169.54(18)O1–Se1–Se2–O2 140.3(3)
a Ref. 26.
Table 3 Energies and relative energies for 8-G-1-[MeSe(OiHj)]C10H6
(i, j = 0, 1 and 2)a
Form O: A/AAb OH+: A/AAb OH�OH: AC
5 (G = H) �2902.0303 �2902.4017 �2978.4686Qn(Se) 1.309 1.307 1.324Qn(O) �0.968 �0.837 �0.996, �0.993Qn(H) 0.497 0.433, 0.433+Wc �2978.4741 �2978.2198 �2978.4686Dd,e as 0.0 667.7 (as 0.0) 14.4 (as 0.0)6 (G = F) �3001.3000 �3001.6744 �3077.7371+Wc �3077.7438 �3077.4925 �3077.7371Dd,e as 0.0 659.8 (�7.9) 17.6 (3.2)7 (G = Cl) �3361.6478 �3362.0250 �3438.0833+Wc �3438.0916 �3437.8431 �3438.0833Dd,e as 0.0 652.4 (�15.2) 21.8 (7.4)8 (G = Br) �5475.5651 �5475.9442 �5552.0007+Wc �5552.0089 �5551.7623 �5552.0007Dd,e as 0.0 647.4 (�20.2) 21.5 (7.1)1 (G = trans-MeSe) �5342.8896 �5343.2854 �5419.3241+Wc �5419.3334 �5419.1035 �5419.3241Dd,e as 0.0 603.6 (�64.1) 24.4 (10.0)1 (G = cis-MeSe) �5342.8869 �5343.2821 �5419.3214+Wc �5419.3307 �5419.1002 �5419.3214Dd,e as 0.0f 612.3 (�55.4) 31.5 (17.1)
a Calculated with the B3LYP/6-311+G(d) method. bA for 5–8 and
AA for 1. c Evaluated based on the values of E(H2O2) = �151.5891 au,
E(H2O) = �76.4438 au and E(OH�) = �75.8181 au calculated with
the same method. d Relative to that of the corresponding n (O): A.e Relative to the same structure derived from 5 (G = H) being
given in parenthesis. f 7.1 kJ mol�1 from the corresponding species of
1 (G = trans-MeSe; O): AA.
Table 4 Second order perturbation energies in the donor (D)–accep-tor (A) interactions of the n(G)� � �s*(Se–O) type in 8-G-1-[MeSe(O)]-C10H6 and 8-G-1-[MeSe+(OH)]C10H6, calculated with the NBOmethodab
D; A np(G); s*(Se–O) np(G): s*(Se+–OH)
G = F 1.44 9.15 (0.87)c
G = Cl 3.29 13.65 (1.09)c
G = Br 3.73 27.95 (1.19)c
G = cis-SeMe 4.77d 34.99 (1.76)c
G = trans-SeMe 5.52 41.86 (2.69)c
G = trans-SeMee 5.86G = trans-Se(O)Mee 1.53 (�2)fa The 6-311+G(d) basis sets being employed. b In kcal mol�1. c Corres-
ponding to the ns(G)� � �s*(Se+–OH) interaction. d 0.76 kcal mol�1 for
the ns(Se)� � �s*(Se–O) type interaction. e The 6-311+G(3df) basis sets
being employed for Se with the 6-311+G(3d,2p) basis sets for C and
H. f Corresponding to the ns(Se)� � �s*(Se–O) interactions.
Table 5 Second order perturbation energies in the donor–acceptorinteractions of the n(G)� � �s*(Se–O) type at the naphthalene 1,8-positions in 1 (LO) and 1 (OO), calculated with the NBO methoda
Compound ro(Se, Se)/A rb(rc)/eao�3 Drb(rc)/eao
�5 Hb(rc)/au
1 (LO) 3.2521 0.0195 0.0420 �0.00051 (OO) 3.2851 0.0160 0.0393 0.0002
a The 6-311+G(3df) basis sets being employed for Se and the
6-311+G(3d,2p) basis sets for C and H.
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Water may originate from the solvent and the racemization
would proceed under the neutral conditions. The stability of
n (OH�OH) must affect on the rates of racemization for the
optical active selenoxides.
The effect of G on the stability of 8-G-1-[MeSe(OiHj)]C10H6
[1 and 5–8: L (i = j = 0), O (i = 1, j = 0), OH+ (i = j = 1)
and OH�OH (i = j = 2)] are examined based on the QC
calculations. The results of QC calculations performed with
the B3LYP/6-311+G(d) method are collected in Table 3.
Table 3 also contains natural charges (Qn) of Se and O
calculated employing the natural population analysis.20
Scheme 4 shows optimized structures of the global minimum
for each of 1 (LL), 1 (LO) and 1 (LOH+), together with the
three types, AA0, BB and AC, for 1 (LOH�OH). The values for
AC of n (LOH�OH) are given in Table 3, since AC is most
stable among the three for each.34
Energy differences of the reactions in Scheme 3 are exam-
ined based on the values shown in Table 3. The energy of n (O) +
H2O (E(n (O) + H2O)) is taken as the standard for each, for
convenience of comparison. How are the selenoxides stabilized
by G at the 8-position? The effect of G on the stabilization of
selenoxides is examined before discussion the energy profile
shown in Scheme 3.
Eqn (1) shows the energies of n (L) + H2O2 (E(n (L) +
H2O2)) relative to E(n (O) + H2O) [DE(n (LO) = E(n (L) +
H2O2) � E(n (O) + H2O)) (see Table S1 in the ESIw). Simi-
larly, eqn (2) and (3) exhibit DE(n (OH+)) and DE(n (OH�OH)),35
respectively, which are defined as [E(n (OH+) + HO�) �E(n (O) + H2O)] and [E(n (OH�OH)) � E(n (O) + H2O)],
respectively.36
DE(n (LO)) = E(n (L) + H2O2) � E(n (O) + H2O)
G = H (121.8 kJ mol�1) o F (131.3) o cis-MeSe (133.9)
o Cl (136.8) r Br (137.6) o trans-MeSe (141.0) (1)
DE(n (OH+)) = E(n (OH+) + HO�) � E(n (O) + H2O)
G = H (667.7 kJ mol�1) 4 F (659.8) 4 Cl (652.4) 4 Br
(647.4) c cis-MeSe (605.2) 4 trans-MeSe (603.6) (2)
DE(n (OH�OH)) = E(n (OH�OH)) � E(n (O) + H2O)
G = H (14.4 kJ mol�1) o F (17.6) o Cl (21.8) E Br (21.5)
o trans-MeSe (24.4) o cis-MeSe (31.5) (3)
The order in eqn (1) corresponds the energy lowering effect
by the G� � �Se–O interactions in the formation selenoxides
relative to the G� � �Se–C interactions in selenides. However, we
must be careful to examine the values for G = cis-MeSe and
trans-MeSe, since the structure of the corresponding selenide is
commonly CC (see Table S1 in the ESIw).Eqn (2) exhibits that the protonation on the seleninyl O
atom occurs more easily in the order of G = H o F o Cl oBr { cis-MeSe o trans-MeSe. The results show that the
protonation occurs more easily when G become better donors,
especially for G = MeSe. The evaluated DE(n (OH+)) values
are very large in magnitudes, however, they do not mean that
the process is very difficult to occur. The large magnitudes are
the results of the calculations for the charge separated species
of the n (OH+) + HO� type. Only the relative values are
important, since protonation will occur easily in solutions.
Resulting hypervalent np(G)� � �s*(Se–OH+) interactions sta-
bilize further the species in the order shown in eqn (2), relative
to the case of the selenoxides.
The activation energies for the racemization of optically
active selenoxides are closely related to the values shown in
eqn (3), although they are the energies for the intermediates,
n (OH�OH). The activation energies are expected to increase in
this order. The activation energy for G = cis-MeSe is pre-
dicted to be larger than that with trans-MeSe. However, cis-
MeSe and trans-MeSe isomers interconvert with each other.
Therefore, it may be better to evaluate the value by G= trans-
MeSe under the experimental conditions: The activation
energy of 1 (LO) with G = MeSe is estimated to be about
10 kJ mol�1 larger than that of 5 (L) with G = H and the
former is also larger than the case of G = Br by ca. 3 kJ mol�1.
Fig. 2 summarizes the effect of G given in eqn (2).
G at the 8-position will protect sterically from the racemiza-
tion of an optical active n (O*). G must stabilize the optical
active n (O*) and the protonated n (O*H+) whereas G would
destabilize n (OH�OH). The steric congestion at the backside
of the Se+–OH bond in n (O*H+) by G will block the space
for H2O to attack to produce n (OH�OH) (Scheme 4). We must
be careful, since G could also stabilize n (OH�OH) in some
Scheme 3 Mechanism for racemization of n (O*) via n (OH�OH) (n= 1
and 5–8).
Scheme 4 Optimized structures for 1 (G = SeMe) and the deriva-
tives.
200 | New J. Chem., 2009, 33, 196–206 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
cases. The calculated values might correspond to the total
effects of the electronic and steric effects. Energy profiles for
the racemization evaluated by above calculations must contain
main factors. The energies for the transition states must be
close to those of the intermediates, n (OH�OH).
NBO analysis for n(G)� � �r*(Se–O) interactions
Table 4 summarizes the second order perturbation energies
(E(2)) for the charge transfer (CT) interactions of the
n(G)� � �s*(Se–O) type in 8-G-1-[MeSe(O)]C10H6 and 8-G-1-
[MeSe+(OH)]C10H6 evaluated with the NBO method.37 The
B3LYP/6-311+G(d) method is employed for the calculations.
The E(2) values becomes larger in an order shown in eqn (4).
E(2): G = F (1.44) o Cl (3.29) o Br (3.73) o cis-MeSe
(4.77) o trans-MeSe (5.52) (4)
The E(2) values are also evaluated for 1 (LO) and 1 (OO),
employing the 6-311+G(3df) basis sets for Se and the
6-311+G(3d,2p) basis sets for C and H at the B3LYP level.38
Table 4 also contains the values. The np(G)� � �s*(Se–O) inter-
action are evaluated to be 5.9 kcal mol�1 for 1 (LO)39 and as
1.5 (� 2) kcal mol�1 for the ns(G)� � �s*(Se–O) interactions in
1 (OO). The larger value for 1 (LO) relative to 1 (OO) implies
the more effective interaction of the np(G)� � �s*(Se–O) type in
1 (LO). The contribution of the 4c–4e interaction of the
O–Se� � �Se–O type was not detected by the NBO analysis.
Fig. 3 summarizes the interactions.
The nature of the np(G)� � �s*(Se–O) interaction in 1 (LO)
and the ns(G)� � �s*(Se–O) interactions in 1 (OO) are evaluated
based on the AIM analysis, next.
AIM analysis of 1 (LO) and 1 (OO)
The AIM analysis are carried out on 1 (LO) and 1 (OO). The
6-311+G(3df) basis sets are employed for Se and the
6-311+G(3d,2p) basis sets for C and H at the B3LYP level.
Table 5 collects the AIM parameters of 1 (LO) and 1 (OO) for
the bond critical points (BCPs: rc) on the interaction lines
between non-bonded Se atoms.
The low values of electron densities at BCPs (rb(rc)) in
1 (LO) and 1 (OO) (0.016–0.020 eao�3) show that the interac-
tions are ionic in nature. Laplacian values of rb(rc) (Drb(rc))are both positive, whereas the total electron energy densities at
BCPs (Hb(rc)) for 1 (LO) is negative but it is positive for
1 (OO). The results strongly suggest that the np(G)� � �s*(Se–O)
interaction in 1 (LO) is the CT interaction in nature similarly
to the case of R2Se� � �Br2 (MC) but the ns(G)� � �s*(Se–O)
interactions in 1 (OO) seems weaker than such CT interac-
tions.40
Fig. 4 shows the counter map of rb(rc) in the SeSeC9 plane
for 1 (LO), together with BCPs ( ), ring critical points ( ),
bond paths and the interaction lines. BCP are detected on the
Se� � �Se and O� � �2H interaction lines. The BCP on the Se� � �Seinteraction line well visualize the np(Se)� � �s*(Se–O) interac-
tion in 1 (LO). While BCP is also detected on the O� � �2Hinteraction line, the interaction is very small. A similar counter
map is also drawn for 1 (OO), which is shown in Fig. S2 of the
ESI.w
Conclusion
X-Ray crystallographic analysis of 8-methylselanyl-1-(methyl-
seleninyl)naphthalene (1 (LO)) and 1,8-bis(methylseleninyl)-
naphthalene 1 (OO) revealed that the three Se� � �SeQO
atoms in 1 (LO) and the four OQSe� � �SeQO atoms in
1 (OO) align linearly. All Se–O bonds are placed in the
naphthyl plane. The superior tendency for the Se–O bonds
to stay on the naphthyl plane (O dependence) must be the
Fig. 2 Energies of n (OH�OH), relative to n (O) for n = 1 and 5–8.
Fig. 3 The np(G)� � �s*(Se–O) interaction in 1 (LO) and the
ns(G)� � �s*(Se–O) interactions in 1 (OO) evaluated by the NBOmethod.
Fig. 4 Contour map of rb(rc) for 1 (LO) in the SeSeC9 plane, together
with BCPs ( ), ring critical points ( ) and bond paths. The contours
[eao�3] are at 2l (l = �8, �7,. . .0) and 0.0047 (heavy line). Two Me
groups are located upside and downside of the SeSeC9 plane. The C2,
C3, C6 and C7 atoms with the C–H bonds deviate substantially from
the plane.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 196–206 | 201
driving force for the fine structures of 1 (LO) and 1 (OO). The
noncovalent np(Se)� � �s(Se–O) 3c–4e interactions (G depen-
dence) operate effectively to stabilize the structure of 1 (LO).
On the other hand, the driving force for the structure of 1 (OO)
must mainly come from the O dependence for each Se–O bond
in 1 (OO), since the G dependence cannot operate without
np(Se).
QC calculations clarify the factors that protect from race-
mization of selenoxides. The energies of 8-G-1-[MeSe(OH)2]-
C10H6 from (8-G-1-[MeSe(O)]C10H6 + H2O) are shown to be
in an order of G = H (14.4 kJ mol�1) o F (17.6) o Cl (21.8)
E Br (21.5) o trans-SeMe (24.4) o cis-SeMe (31.5). The
activation energies for the racemization should increase in this
order, since 8-G-1-[MeSe(OH)2]C10H6 must be the key inter-
mediates. The activation energy of 1 (LO: G = MeSe) is
evaluated to be larger than that of 5 (L: G = H) and 8
(L: G = Br) by 10 and 3 kJ mol�1, respectively. The results
will help to design the optically stable selenoxides. The NBO
and AIM analyses support the discussion and visualize the
interactions.
Investigations on the chiral 3a (LO), prepared in the oxida-
tion of 3a (LL) with chiral reagents, are in progress. Details
will be reported elsewhere.
Experimental
General considerations
Manipulations were performed under an argon atmosphere
with standard vacuum-line techniques. Glassware was dried at
130 1C overnight. Solvents and reagents were purified by
standard procedures if necessary. Melting points were deter-
mined on a Yanaco MP-S3 melting point apparatus and
uncorrected. NMR spectra were recorded at room tempera-
ture on a JEOL AL-300 spectrometer (1H, 300 MHz; 13C,
75 MHz) and on a JEOL Lambda-400 spectrometer (1H, 400
MHz; 77Se, 76 MHz). The 1H, 13C and 77Se NMR spectra were
recorded in CDCl3. Chemical shifts are given in ppm relative
to Me4Si for the 1H and 13C NMR spectra and relative to
reference compound MeSeMe for the 77Se NMR spectra.
Column chromatography was performed by using silica gel
(Fujishilysia PSQ-100B) and basic alumina (E. Merck) and
analytical thin layer chromatography was performed on pre-
coated silica gel plates (60F-254) with the systems (v/v)
indicated.
Syntheses
Bis(methylselanyl 1,8-bis(methylselanyl)naphthalene (1 (LL)).
To a solution of the dianion of naphtho[1,8-c,d]-1,2-diselenole,
which was prepared by reduction of the diselenole 923 (1.03 g,
3.64 mmol) with NaBH4 in an aqueous THF solution, was
added methyl iodide (1.29 g, 9.06 mmol) at room temperature.
After a usual workup, the crude was purified by column
chromatography (flash column, SiO2, hexane). Recrystalli-
zation of the chromatographed product from hexane gave
1 (LL) as colorless prisms in 98% yield, mp 85.0–85.5 1C, 1H
NMR (300MHz, CDCl3, d, ppm, TMS): 2.33 (s, 6H), 7.32 (t, 2H,
J = 7.7 Hz), 7.70 (dd, 2H, J = 1.2 and 8.2 Hz), 7.73 (dd, 2H,
J = 1.2 and 7.5 Hz); 13C NMR (75 MHz, CDCl3, d, ppm,
TMS): 13.3, 125.7, 128.3, 131.9, 132.3, 135.3, 135.6; 77Se NMR
(76 MHz, CDCl3, d, ppm, Me2Se): 231.4. Anal. Calc. for
1 (LL) (C12H12Se2): C, 45.88; H, 3.85%. Found: C, 45.73;
H, 3.77%.
8-Methylselanyl-1-(methylseleninyl)naphthalene (1 (LO)).
1 (LL) (0.98 mg, 3.12 mmol) was dissolved in 20 mL of CH2Cl2and the solution was bubbling with the ozone for 5 min. TLC
was checked for the completion of the reaction (rf = 0.07
(chloroform)). Then the solution was evaporated and dried
in vacuo. The crude product was purified by column chromato-
graphy (flash column, Al2O3, CH2Cl2). 1 (LO) gave 85% yield
as colorless powder, mp 129.8–130.1 1C; 1H NMR
(400 MHz, CDCl3, d, ppm, TMS): 2.29 (s, 3H), 2.78 (s, 3H),
7.48 (t, J 7.6 Hz, 2H), 7.76 (t, J 7.7 Hz, 2H), 7.98–8.05 (m, 2H),
8.10 (dd, J 1.1 and 7.2 Hz, 1H), 8.88 (dd, J 1.2 and 7.4 Hz,
1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS): 13.87, 41.12,
125.73, 126.28, 126.35, 126.57, 131.01, 132.44, 133.06, 136.13,
138.93, 141.34; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se):
210.8, 833.0. Anal. Calc. for 1 (LO) (C12H12OSe2): C, 43.66; H,
3.66%. Found: C, 43.61; H, 3.60%.
1,8-Bis(methylseleninyl)naphthalene (1 (OO)). 1 (LL) (0.58 g,
0.30 mmol) was dissolved in 20 mL of CH2Cl2 and the solution
was bubbling with the ozone for 15 min. TLC was checked for
the completion of the reaction (rf = 0.00 (chloroform)). Then
the solution was evaporated and dried in vacuo. The crude
product was purified by column chromatography (flash
column, Al2O3, CH2Cl2). 1 (OO) gave 59% yield as colorless
powder, mp 154.8–155.2 1C; 1H NMR (400 MHz, CDCl3, d,ppm, TMS): 2.71 (s, 6H), 7.84 (t, J 7.7 Hz, 2H), 8.18 (dd, J 1.2
and 6.9 Hz, 2H), 8.71 (dd, J 1.4 and 6.9 Hz, 2H); 77Se NMR
(76 MHz, CDCl3, d, ppm, Me2Se): 821.3. Anal. Calc. for
1 (OO) (C12H12O2Se2): C, 41.64; H, 3.49%. Found: C, 41.55;
H, 3.45%. Anal. Calc. for 1 (OO)�2.5H2O (C24H24O4Se4�5H2O): C, 36.84; H, 4.38%. Found: C, 36.87; H, 4.41%.
1,8-Bis(ethylselanyl)naphthalene (2 (LL)). Following the
similar method to that used for 1 (LL), 2 (LL) gave 80% yield
as colorless powder, mp 52.3–52.8 1C; 1H NMR (400 MHz,
CDCl3, d, ppm, TMS): 1.35 (t, J 7.4 Hz, 6H), 2.89 (q, J 7.5 Hz,
4H), 7.32 (t, J 7.6 Hz, 2H), 7.70 (dd, J 1.2 and 8.1 Hz, 2H),
7.76 (dd, J 1.1 and 7.2 Hz, 2H); 77Se NMR (76 MHz, CDCl3,
d, ppm, Me2Se): 341.7. Anal. Calc. for 2 (LL) (C14H16Se2): C,
49.14; H, 4.71%. Found: C, 49.23; H, 4.72%.
8-Phenylselanyl-1-(methylseleninyl)naphthalene (3a (LO)).
Following the similar method to that used for 1 (LO),
3a (LO) gave 80% yield as colorless needles, mp 129.8–130.2
1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.72 (s, 3H),
6.98–7.02 (m, 2H), 7.11–7.16 (m, 3H), 7.56 (t, J 7.6 Hz, 1H),
7.76 (t, J 7.7 Hz, 1H), 8.05 (dd, J 1.2 and 8.0 Hz, 1H), 8.10
(dd, J 1.3 and 8.1 Hz, 1H), 8.15 (dd, J 1.3 and 7.2 Hz, 1H),
8.82 (dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d,ppm, TMS) 40.56, 123.19, 126.51, 126.57, 126.75, 126.88,
128.42 (2J(Se,C) 5.9 Hz), 129.63, 131.95, 132.42, 133.03,
133.50, 136.29, 140.89, 141.37; 77Se NMR (76 MHz, CDCl3,
d, ppm, Me2Se): 398.2, 831.4. Anal. Calc. for 3a (LO)
(C17H14OSe2): C, 52.06; H, 3.60%. Found: C, 52.11;
H, 3.66%.
202 | New J. Chem., 2009, 33, 196–206 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
8-Phenylseleninyl-1-(methylseleninyl)naphthalene (3a (OO)).
Following the similar method to that used for 1 (OO),
3a (OO) gave 63% yield as colorless needles, mp 148.0–148.8 1C;1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.74 (s, 3H),
7.33–7.50 (m, 3H), 7.51–7.58 (m, 2H), 7.78 (t, J 7.7 Hz, 1H),
7.81 (t, J 7.7 Hz, 1H), 8.13 (dd, J 1.1 and 8.1 Hz, 1H), 8.14 (dd,
J 1.1 and 8.1 Hz, 1H), 8.63 (dd, J 1.4 and 7.4 Hz, 1H), 8.72
(dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d,ppm, TMS): 38.25, 126.72, 126.80, 126.85, 127.01, 127.64,
127.92, 130.02, 131.70, 133.33, 133.71, 135.55, 138.88,
139.22, 141.66; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se):
820.0, 832.5. Anal. Calc. for 3a (OO) (C17H14O2Se2): C, 50.02;
H, 3.46%. Found: C, 50.07; H, 3.57%.
8-p-Anisylselanyl-1-(methylseleninyl)naphthalene (3b (LO)).
Following the similar method to that used for 1 (LO),
3b (LO) gave 88% yield as colorless needles, mp 129.6–130.4 1C;1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.70 (s, 3H),
3.82 (s, 3H), 6.70 (d, J 8.8 Hz, 2H), 7.01 (d, J 8.8 Hz, 2H), 7.51
(t, J 7.2 Hz, 1H), 7.74 (t, J 7.2 Hz, 1H), 7.88 (dd, J 1.1 and
6.8 Hz, 1H), 8.01 (dd, J 1.1 and 6.8 Hz, 1H), 8.03 (dd, J 1.1
and 6.8 Hz, 1H), 8.10 (dd, J 1.1 and 6.8 Hz, 1H); 77Se NMR
(76 MHz, CDCl3, d, ppm, Me2Se): 385.9, 833.9. Anal. Calc.
for 3b (LO) (C18H16O2Se2): C, 51.20; H, 3.82%. Found: C,
50.98; H, 3.83%.
8-p-Anisylseleninyl-1-(methylseleninyl)naphthalene
(3b (OO)). Following the similar method to that used for
1 (OO), 3b (OO) gave 43% yield as colorless powder, mp
144.5–145.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS):
2.75 (s, 3H), 3.76 (s, 3H), 6.87 (d, J 8.9 Hz, 2H), 7.45 (d, J 8.9
Hz, 2H), 7.83 (t, J 7.7 Hz, 2H), 8.15 (dd, J 1.0, 8.2 Hz, 1H),
8.17 (dd, J 1.0, 8.2 Hz, 1H), 8.69 (dd, J 1.3, 9.1 Hz, 1H), 8.71
(dd, J 1.2, 9.1 Hz, 1H); 77Se NMR (76 MHz, CDCl3, d, ppm,
Me2Se): 821.6, 846.4. Anal. Calc. for 3b (OO) (C18H16O3Se2):
C, 49.33; H, 3.68%. Found: C, 49.30; H, 3.73%.
8-p-Nitrophenylselanyl-1-(methylseleninyl)naphthalene
(3d (LO)). Following the similar method to that used for
1 (LO), 3d (LO) gave 61% yield as colorless powder, mp
141.5–142.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS):
2.67 (s, 3H), 7.07 (dt, J 2.1 and 9.0 Hz, 2H), 7.64 (t, J 7.5 Hz,
1H), 7.83 (t, J 7.5 Hz, 1H), 7.99 (dt, J 2.4 and 9.0 Hz, 2H), 8.11
(dd, J 1.2 and 6.9 Hz, 2H), 8.18 (dd, J 1.2 and 4.2 Hz, 1H),
8.21 (dd, J 1.5 and 4.8 Hz, 1H), 8.84 (dd, J 1.2 and 6.0 Hz,
1H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 426.4,
835.6. Anal. Calc. for 3d (LO) (C17H13NO3Se2): C, 46.70; H,
3.00; N, 3.20%. Found: C, 46.75; H, 3.03; N, 3.22%.
8-p-Nitrophenylseleninyl-1-(methylseleninyl)naphthalene
(3d (OO)). Following the similar method to that used for
1 (OO), 3d (OO) gave 82% yield as colorless powder, mp
151.2–152.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS):
2.83 (s, 3H), 7.72–7.92 (m, 4H), 8.12–8.27 (m, 4H), 8.57 (dd,
J 1.1 and 6.2 Hz, 1H), 8.74 (dd, J 1.3 and 6.1 Hz, 1H); 77Se
NMR (76 MHz, CDCl3, d, ppm, Me2Se): 821.4, 849.0. Anal.
Calc. for 3d (OO) (C17H13NO4Se2): C, 45.05; H, 2.89; N,
3.09%. Found: C, 45.12; H, 2.83; N, 3.12%.
1,8-Bis(phenylselanyl)naphthalene (4a (LL)).Under an argon
atmosphere, 1,8-diiodonaphthalene (4.33 g, 11.40 mmol) was
dissolved in 100 mL of dry THF and the solution was added to
nBuLi (15.0 mL, 23.94 mmol, 1.6 N) at �78 1C. After 20 min,
a THF solution of phenylselenobromide (22.80 mmol) was
added to the above solution at �78 1C. Then the reaction
mixture was stirring for 2 h and warmed up room temperature.
Then, 20 mL of 5% acetone hydrochloric acid and 100 mL of
benzene were added. The organic layer was separated, washed
with brine, 10% aqueous solution of sodium hydroxide,
saturated aqueous solution of sodium bicarbonate and brine.
Then the solution was dried over sodium sulfate, evaporated
and dried in vacuo. The crude product was purified by column
chromatography (flash column, SiO2, hexane). 4a (LL) gave
89% yield as yellow prisms, mp 64.0–64.8 1C; 1H NMR
(300 MHz, CDCl3, d, ppm, TMS): 7.22–7.28 (m, 8H),
7.39–7.45 (m, 4H), 7.64 (dd, J 1.1 and 7.3 Hz, 2H), 7.74
(dd, J 1.1 and 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3,
d, ppm, TMS): 126.0, 127.4, 129.2, 129.4, 131.4, 133.4, 135.18,
135.19, 135.5, 135.9; 77Se NMR (76 MHz, CDCl3, d, ppm,
Me2Se): 435.4. Anal. Calc. for 4a (LL) (C22H16Se2): C, 60.29;
H, 3.68%. Found: C, 60.21; H, 3.75%.
8-Phenylselanyl-1-(phenylseleninyl)naphthalene (4a (LO)).
Following the similar method to that used for 1 (LO),
4a (LO) gave 65% yield as colorless prisms, mp 155.5–156.3 1C;1H NMR (400 MHz, CDCl3, d, ppm, TMS): 6.90–6.95
(m, 4H), 7.10–7.13 (m, 6H), 7.22–7.26 (m, 6H), 7.48–7.53
(m, 4H), 7.52 (t, J 8.2 Hz, 1H), 7.83 (d, J 7.7 Hz, 1H), 8.07
(dd, J 1.3 and 7.2 Hz, 1H), 8.08 (dd, J 1.3 and 8.2 Hz, 1H), 9.02
(dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm,
TMS): 123.90, 126.45, 126.51, 126.79, 127.86, 127.91, 128.70,
129.17, 129.49, 130.11, 131.73, 132.76, 133.27, 133.78, 136.31,
140.17, 140.71, 146.21; 77Se NMR (76 MHz, CDCl3, d, ppm,
Me2Se): 400.1, 863.7. Anal. Calc. for 4a (LO) (C22H16OSe2):
C, 58.17; H, 3.55%. Found: C, 58.11; H, 3.65%.
1,8-Bis(phenylseleninyl)naphthalene (4a (OO)). Following
the similar method to that used for 1 (OO), 4a (OO) gave
78% yield as colorless prisms, mp. 187.5–188.3 1C; 1H NMR
(400 MHz, CDCl3, d, ppm, TMS): 7.21–7.30 (m, 8H), 7.37 (tt,
J 1.5 and 6.8 Hz, 2H), 7.76 (t, J 7.7 Hz, 2H), 8.15 (dd, J 0.9 and
7.5 Hz, 2H), 8.47 (dd, J 1.1 and 6.2 Hz, 2H); 77Se NMR
(76 MHz, CDCl3, d, ppm, Me2Se): 877.1. Anal. Calc. for
4a (OO) (C22H16O2Se2): C, 56.19; H, 3.43%. Found: C, 56.22;
H, 3.53%.
1,8-Bis[(p-tert-butylphenyl)selanyl]naphthalene (4c (LL)).
Following the similar method to that used for 4a (LL),
4c (LL) gave 87% yield as yellow prisms, mp 97.8–98.3 1C;1H NMR (400 MHz, CDCl3, d, ppm, TMS): 1.30 (s 18H), 7.24
(t, J 7.7 Hz, 2H), 7.27 (d, J 8.6 Hz, 4H), 7.38 (d, J 8.6 Hz, 4H),
7.65 (dd, J 1.3 and 6.1 Hz, 2H), 7.73 (dd, J 1.3 and 7.0 Hz,
2H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 424.6.
Anal. Calc. for 4c (LL) (C30H32Se2): C, 65.45; H, 5.86%.
Found: C, 65.41; H, 5.88%.
8-[(p-tert-Butylphenyl)selanyl]-1-[(p-tert-butylphenyl)seleninyl]-
naphthalene (4c (LO)). Following the similar method to that
used for 1 (LO), 4c (LO) gave 86% yield as colorless powder,
mp 179.5–180.2 1C; 1H NMR (400 MHz, CDCl3, d,ppm, TMS): 1.22 (s, 9H), 1.27 (s 9H), 6.91 (d, J 8.3 Hz, 2H),
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 196–206 | 203
7.15 (d, J 8.1 Hz, 2H), 7.28 (d, J 8.8 Hz, 2H), 7.43 (d, J 8.6 Hz,
2H), 7.51 (t, J 7.9 Hz, 1H), 7.82 (t, J 7.7 Hz, 1H), 8.07 (d, J 8.3
Hz, 3H), 9.01 (dd, J 1.3 and 7.5 Hz, 1H); 77Se NMR (76 MHz,
CDCl3, d, ppm, Me2Se): 393.2, 861.2. Anal. Calc. for 4c (LO)
(C30H32OSe2): C, 63.61; H, 5.69%. Found: C, 63.55;
H, 5.58%.
1,8-Bis[(p-tert-butylphenyl)seleninyl]naphthalene (4c (OO)).
Following the similar method to that used for 1 (OO),
4c (OO) gave 87% yield as colorless powder, mp 172.5–173.2 1C;1H NMR (400 MHz, CDCl3, d, ppm, TMS): 1.63 (s, 18H),
7.39 (d, J 8.6 Hz, 4H), 7.47 (d, J 8.3 Hz, 4H), 7.83 (d, J 7.6 Hz,
2H), 8.16 (dd, J 0.8 and 7.3 Hz, 2H), 8.73 (dd, J 1.0 and 6.2
Hz, 2H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 843.7.
Anal. Calc. for 4c (OO) (C30H32O2Se2): C, 61.86; H, 5.54%.
Found: C, 61.93; H, 5.58%.
1-(Methylselanyl)naphthalene (5 (L)). Following the similar
method to that used for 1 (LL), 5 (L) gave 99% yield as pale
yellow oil; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.37
(s, 2JSe,H 11.7 Hz, 3H), 7.35 (dd, J 7.3 and 8.1 Hz, 1H), 7.47
(ddd, J 1.6, 6.9 and 8.2 Hz, 1H), 7.53 (ddd, J 1.6, 6.9 and 8.3
Hz, 1H), 7.66 (dd, J 1.1 and 7.3 Hz, 1H), 7.71 (d, J 8.2 Hz,
1H), 7.80 (dd, J 1.7 and 7.9 Hz, 1H), 8.24 (ddd, J 0.7, 1.6 and
8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS):
36.54, 122.08 (J 14.9 Hz), 124.03 (J 6.2 Hz), 126.11, 126.79,
127.56, 129.35, 130.27, 131.40, 133.88, 138.68; 77Se NMR
(76 MHz, CDCl3, d, ppm, Me2Se): 158.6. Anal. Calc. for 5 (L)
(C11H10Se): C, 59.74; H, 4.56%. Found: C, 59.90; H, 4.49%.
1-(Methylseleninyl)naphthalene (5 (O)). Following the simi-
lar method to that used for 1 (LO), 5 (O) gave 67% yield as
colorless needles, mp 97.2–97.8 1C; 1H NMR (400 MHz,
CDCl3, d, ppm, TMS): 2.71 (s, 2JSe,H 12.3 Hz, 3H),
7.56–7.65 (m, 2H), 7.70 (dd, J 7.4 and 8.2 Hz, 1H),
7.81–7.87 (m, 1H), 7.95–8.02 (m, 2H), 8.29 (dd, J 1.1 and 7.3
Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS): 7.52,
125.83, 126.14, 126.39, 126.63, 127.16, 128.58, 128.67, 131.10,
133.29, 133.77; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se):
809.3. Anal. Calc. for 5 (O) (C11H10OSe): C, 55.71; H, 4.25%.
Found: C, 55.88; H, 4.18%.
X-Ray crystal structure determination. The colorless crystals
of 1 (LO) and 1 (OO) were grown by slow evaporation of
methylene dichloride-hexane solutions at room temperature.
A crystal of 1 (LO) was measured on a Rigaku AFC5R
diffractometer with graphite monochromated Mo-Ka radia-
tion source (l= 0.71069 A) and a rotating anode generator at
298(2) K. That of 1 (OO) was measured on a Rigaku/MSC
Mercury CCD diffractometer equipped with a graphite-mono-
chromatedMo-Ka radiation source (l=0.71070 A) at 103(2) K.
The structures of 1 (LO) and 1 (OO) were solved by direct
method (SHELXS-97)41 and refined by full-matrix least-
square method on F2 for all reflections (SHELXL-97).42 All
the non-hydrogen atoms were refined anisotropically.
QC calculations
QC calculations are performed on 1 (LO) and 1 (OO), as the
models of n (LO) and n (OO) (n = 1, 3 and 4), respectively,
employing the 6-311+G(d) basis sets of the Gaussian 98
program.27 Calculations are performed at the density func-
tional theory (DFT) level of the Becke three parameter hybrid
functionals combined with the Lee-Yang-Parr correlation
functional (B3LYP).28,29 QC calculations are also performed
on 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5), F (6), Cl (7)
and Br (8) with X = lone pair (L), O (O), OH+ (OH+) and
O2H2 (OH�OH)], employing the B3LYP/6-311+G(d) method.
The NBO19,20 analysis were performed with the B3LYP/
6-311+G(d) method. The AIM21,22 analysis are performed on
1 (LO) and 1 (OO) with the Gaussian 03 program employing the
6-311+G(3df) basis sets for Se with the 6-311+G(3d,2p) basis
sets for C and H at the B3LYP level. They are analyzed
employing the AIM 2000 program.21,22 NBO analysis are also
performed on 1 (LO) and 1 (OO) with the same method for the
AIM analysis. Optimized structures and the molecular orbitals
are drawn using MolStudio R3.2 (Rev 1.0).43
Acknowledgements
This work was partially supported by a Grant-in-Aid for
Scientific Research (Nos. 16550038, 19550041 and 20550042)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
References
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18 The structure is A if the Se–CAr bond is placed almost perpendi-cular to the naphthyl plane, it is B when the bond is located on theplane and C is the intermediate between A and B.
19 A. E. Reed, R. B. Weinstock and F. Weinhold, J. Chem. Phys.,1985, 83, 735–746; J. E. Carpenter and F. Weinhold, J. Mol.Struct. (THEOCHEM), 1988, 169, 41–62.
20 E. D. Glendening, A. E. Reed, J. E. Carpenter and F. Weinhold,NBO Ver. 3.1.
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23 J. Meinwald, D. Dauplaise and J. Clardy, J. Am. Chem. Soc., 1977,99, 7743–7744.
24 The structures of 3b (LO) and 3a (OO) are also determined by theX-ray crystallographic analysis. The results are essentially the sameas those of 1 (LO) and 1 (OO), respectively, which will be reportedelsewhere.
25 Water molecules in 1 (OO) are omitted for clarity.26 S. Hayashi and W. Nakanishi, Bull. Chem. Soc. Jpn., 2008, 12, in
press (CCDC 640537 for 1 (LL)).27 A. Bondi, J. Phys. Chem., 1964, 68, 441–451.28 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.Montgomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich,J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain,O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi,B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma, P. Salvador,J. J. Dannenberg, D. K. Malick, A. D. Rabuck, K. Raghavachari,J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul,B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi,R. Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill,B. G. Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez,M. Head-Gordon, E. S. Replogle and J. A. Pople, GAUSSIAN 98(Revision A.11), Gaussian, Inc., Pittsburgh, PA, 2001.
29 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785–789;B. Miehlich, A. Savin, H. Stoll and H. Preuss, Chem. Phys. Lett.,1989, 157, 200–2006.
30 A. D. Becke, Phys. Rev. A, 1988, 38, 3098–3100; A. D. Becke,J. Chem. Phys., 1993, 98, 5648–5652.
31 S. Hayashi and W. Nakanishi, J. Mol. Struct. (THEOCHEM),2007, 811, 293–301.
32 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr, T. Vreven,K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi,V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox,H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma,G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski,S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick,A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz,Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov,G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin,D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen,M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 03(Revision B.05), Gaussian, Inc., Pittsburgh, PA, 2003.
33 The AIM2000 program (Version 2.0) is employed to analyze andvisualize atoms in molecules: F. J. Biegler-Konig, Comput. Chem.,2000, 21, 1040–1048; see also ref. 22g.
34 Data for A and B, together with LL, are given in the ESIw.35 The type C of 1 (OH�OH) is discussed which is predicted to be most
stable among the three44.36 Eqn (R1) shows the energies of n (L) + H2O2 (E(n (L) + H2O2))
relative to E(n (O) + H2O) [DE(n (LO)) = E(n (L) + H2O2) �E(n (O) + H2O)], although E(n (L)) are not given in Table 3.45
DE(n (LO)) = E(n (L) + H2O2) � E(n (O) + H2O)G = H (121.8 kJ mol�1) o F (131.3) o cis-MeSe (133.9)o Cl (136.8) r Br (137.6) o trans-MeSe (141.0) (R1)
37 NOB analysis were also performed on the AC conformer of 8-G-1-[MeSe(O2H2)]C10H6. However, the corresponding CT interactionswere not detected.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 196–206 | 205
38 The nonbonded Se� � �Se distance in 1 (LO) is predicted to beshorter than that of 1 (OO) by ca. 0.03 A, while the observedvalues are almost equal (see Table 5). The crystal packing effectmight contribute to the results.
39 The value is very close to that evaluated with the B3LYP/6-311+G(d) method.
40 W. Nakanishi, S. Hayashi and K. Narahara, unpublished results.41 G. M. Sheldrick, SHELXS-97, Program for Crystal Structure
Solution, Universitat Gottingen, Germany, 1997.42 G. M. Sheldrick, SHELXL-97, Program for Crystal Structure
Refinement, University of Gottingen, Germany, 1997.43 MolStudio R3.2 (Rev 1.0), NEC Corporation, 1997–2003.
44 Three structures (type A, type B and type C) were optimizedfor each of n (OH�OH). The type C is the global minimum,which is slightly stable than type B and much stable thantype A, although the steric repulsion between OH and G seemslargest.
45 Eqn (R1)36 shows that selenoxides are stabilized in this orderthrough the non-bonded n(G)� � �s*(Se–O) 3c–4e interactions,together with the O dependence.16 While G = trans-MeSe isdemonstrated to be most effective to stabilize in the selenoxiderelative to the corresponding bis-selenide, the effect of G = cis-MeSe places between F and Cl, where the CC form is postulatedfor the bis-selenide.
206 | New J. Chem., 2009, 33, 196–206 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
Mechanistic aspects of nitrate ion reduction on silver electrode:
estimation of O–NO2�bond dissociation energy using
cyclic voltammetry
Mohsin Ahmad Bhat,w Pravin Popinand Ingole, Vijay Raman Chaudhari
and Santosh Krishna Haram*
Received (in Montpellier, France) 27th August 2008, Accepted 9th October 2008
First published as an Advance Article on the web 18th November 2008
DOI: 10.1039/b814895c
Voltammetric investigations of mechanistic aspects and estimation of thermo-chemical parameters
of nitrate ion reduction at silver electrode, in alkaline medium are reported. The activation barrier
determined from cyclic voltammetry fits a quadratic relation rather than the expected Butler-
Volmer kinetics. Intrinsic barrier calculations show that the reduction of nitrate ion on silver
follows a concerted mechanism, involving electron transfer initiated bond cleavage, followed by
chemical reaction. The bond dissociation energy for the O–NO2� bond was estimated to be
48.40 kcal mol�1, which matches well with the reported value of 47.5 kcal mol�1, determined
from photodissociation experiments.
1. Introduction
The high water solubility of nitrate ions is responsible for its
virtual presence everywhere. Serious clinical symptoms have
been reported to be caused by their ingestion,1–3 which neces-
sitates effective monitoring and development of sensing tools
for this ion. For its detection and estimation, a series of
methods have been proposed in refs. 4–8. Among them, the
electrochemical methods have proved to be advantageous in
terms of reproducibility, accuracy, time response and durability.9
The voltammetric detection is based on the irreversible two-
electron transfer process shown in eqn (1):10
O–NO2� + 2e + H2O - NO2
� + 2OH� (1)
Using conventional voltammetry,11,12 in combination with
electrochemical scanning tunneling microscopy, surface
enhanced Raman spectroscopy,13 and differential electro-
chemical mass spectrometry,14 it is reported that the nitrate
ion reduction is very sensitive to the solution conditions, pH
and the nature of the electrode material. For example, on
polycrystalline platinum electrode, it proceeds through a dis-
sociative adsorption pathway,15 albeit with slow kinetics.
Similar results have been also reported for palladium electro-
des,16 while on Cu, the reduction is found to be very facile
and proceeds through the formation of NO2� in alkaline
medium.13 Dima et al.14 have reported varying activity of
transition and coinage metals and proposed a probable general
scheme for the nitrate ion reduction process. In general, nitrate
reduction is understood to be a multistep process with the first
electron transfer as the rate determining step.12–14 Among
all the metals studied, silver shows highest sensitivity for
nitrate ion reduction, and is thus strongly advocated for
their electrochemical sensing.10,17,18 For better understanding
and development of Ag as a nitrate ion sensor, it is of utmost
importance to have knowledge about the mechanism of this
reduction—especially with respect to the rate determining
step. To our knowledge, these aspects have not been con-
sidered so far. Thus, it was of our immense interest to study the
mechanism of this reaction on Ag-electrode, voltammetrically.
With this aim, the kinetic investigations of nitrate ion
reduction in alkaline media were undertaken through cyclic
voltammetry. Our analysis for the first time revealed that the
nitrate ion reduction on Ag follows a dissociative electron
transfer mechanism. Besides, the related calculations led
to the quantification of thermo-chemical parameters, such
as bond dissociation energy of the O–NO2� bond, which is
otherwise estimated through thermal- and photo-dissociation
measurements.19
2. Experimental
Potassium nitrate and sodium hydroxide were purchased from
Merck. Ag-bulk electrode was prepared by sealing a 2 mm
diameter Ag (99.9%) wire in a glass tube, with the help of
epoxy adhesive. The electrode surface was exposed by grinding
it on emery paper. It was polished with commercially available
silver cleaner, followed by 0.2 mm alumina powder. Ag/AgCl,
KCl (3.0 M), and a Pt rod from Metrohm devices were used as
reference and counter electrodes, respectively. Cyclic voltam-
metric (CV) investigations were performed using Metrohm
PGSTAT 100 POTENTIOSTAT/GALVANOSTAT in a
three-electrode setup. All the measurements were performed
under an argon atmosphere. Prior to measurements, the Ag
electrode was electrochemically activated by cycling the
potential twenty times (scan rate 1 V s�1) in the potential
range �1.3 to 1.0 V, followed by ten potential steps
(of 1 s duration) in increasing order of potential, ranging from
Department of Chemistry, University of Pune, Ganeshkhind, Pune,411007, India. E-mail: [email protected];Fax: +91 20 2569 3981; Tel: +91 20 2560 1394w Permanent address: Department of Chemistry, University of Kashmir,Srinagar-190006, India.
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 207–210 | 207
PAPER www.rsc.org/njc | New Journal of Chemistry
�0.25 to 0.9 V in 2.0 M NaOH. CVs used for analysis were
background corrected for the charging current. In view of the
reported complications observed during nitrate ion reduction
at Ag-electrode,17 every scan used for the analysis was re-
corded on a freshly polished and electrochemically cleaned
electrode surface. All the measurements were carried out in
thermostatted condition at 298 � 0.1 K.
3. Results and discussion
A typical CV recorded using the Ag electrode in 10 mMKNO3
and 2 M NaOH (pH = 12) at the scan rate of 10 mV s�1 is
shown in Fig. 1. High pH helps to shift hydrogen evolution
towards more negative potential in comparison to the nitrate
ion reduction. A cathodic peak at �0.94 V is assigned to the
reduction of nitrate ions. The linear relationship between ipand the square root of scan rate (n1/2) (Fig. 1, inset) indicatesthat the process is diffusion controlled.20 The scan rate depen-
dent shift in peak potential (Ep), as shown in Fig. 2, is
attributed to the irreversibility in the electron transfer process.
The magnitude of Ep � Ep/2 was in the range 47 to 96 mV,
which is an indication of electron transfer being the rate
determining step.21 Interestingly, ip/n1/2 (Fig. 3) and Ep �
Ep/2 (Table 1) were found to be scan rate dependent. Addi-
tionally, peak broadening with increase in scan rate is ob-
served (Fig. 2). Prima facie, both these observations could
be attributed to the uncompensated iR drop and charging
current contributions. However, the electrolyte used was
highly conducting and moreover, we had subtracted back-
ground charging current. Therefore, the contributions of iR
drop and the capacitance are ruled out. Thus, the shift in
the potential and Ep � Ep/2 with the scan rate are attributed
to the potential dependent electron transfer coefficient (a)for the reaction22 and nitrate ion reduction does not follow
a normal Butler–Volmer kinetics. Since the ip vs. n1/2 plot
shows that the process is diffusion controlled, it also suggests
that the potential dependent free energy of activation for the
reaction is a quadratic function of electrode potential, as per
eqn (2):23
DGz ¼ DG zo 1þ DGo
4DG zo
� �2
ð2Þ
Fig. 1 Typical cyclic voltammogram recorded on Ag electrode in
10 mM KNO3 and 2 M NaOH, at a scan rate of 10 mV s�1. Inset
shows a linear fit of the peak current (ip) vs. square root of scan rate
(n1/2), which indicates diffusion controlled reaction.
Fig. 2 Cyclic voltammograms recorded on Ag electrode in 10 mM
KNO3 and 2 M NaOH, at varying scan rates from 10 to 500 mV s�1.
Inset shows peak potential vs. scan rate, which indicates that the
reduction is irreversible.
Fig. 3 ip/n1/2 vs. scan rate for NO3 reduction on Ag electrode in
alkaline medium, indicating a deviation from Butler-Volmer kinetics.
Table 1 Analysis of cyclic voltammetric (CV) data obtained fornitrate ion reduction (10 mM) at an Ag electrode in 2 M NaOH at298 K
Scan rate/V s�1 104Ip/A Ep/V (Ep � Ep/2)/VDGo
z/kcal mol�1
0.01 0.891 �0.944 0.060 19.970.02 1.40 �0.920 0.065 19.560.04 2.01 �0.926 0.072 19.660.08 2.70 �0.932 0.078 19.770.1 2.80 �0.934 0.083 19.800.2 3.74 �0.944 0.085 19.970.3 4.27 �0.948 0.087 20.040.4 4.77 �0.958 0.089 20.220.5 5.03 �0.962 0.094 20.28
208 | New J. Chem., 2009, 33, 207–210 This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
where,
DGo = F(E � Eo0) (3)
in which Eo0 is the formal potential for overall reaction and
has a value of 0.01 V24 and DGoz, is the intrinsic energy barrier
for the reduction reaction.
The potential dependent rate constant (k(E)) is given by
eqn (4):
kðEÞ ¼ Z: exp�DGzRT
� �
ð4Þ
where, Z (= (RT/2pM)1/2,M is the molecular mass of NO3�) =
2521.79 cm s�1.
Such dissociative redox reactions initiated with electron
transfer can occur through two plausible mechanisms, namely
stepwise (eqn (5) and (6)) and concerted (eqn (7)):
A–B + e� - A–B�� (5)
A–B�� - A�–B� (6)
A–B + e� - A� + B� (7)
Products formed through both these mechanisms can un-
dergo further electron transfer or chemical reactions, which
affect the thermodynamic and kinetic aspects of the overall
process. Theory as well as experimental predictions associated
with these mechanisms for alkyl halides,25 peroxides22,26 and
other analytes27,28 have been well documented in the literature.
The two mechanisms can be differentiated on the basis of
difference in the value of intrinsic energy barrier, as given
below (eqn (8) and (9)):
DG zo ðstepwiseÞ ¼l0 þ li
4ð8Þ
DG zo ðconcertedÞ ¼l0 þ li þ BDFE
4ð9Þ
where, BDFE is the bond dissociation free energy, and l0, thesolvent reorganization energy, which is calculated through the
Marcus equation (10):
l0 ¼e
8peoao
1
eo� 1
es
� �
ð10Þ
Here, eo and es are the optical and static dielectric constants of
the solvent, respectively and ao, the effective radius of the
analyte, which is calculated using eqn (11):
ao ¼ aB2aAB � aB
aAB
� �
ð11Þ
where aAB = aNO3� = 2.64 A and aB = aO� = 1.76 A are as
reported previously.29 li is regarded as the internal reorgani-
zation energy and can be neglected due to its comparatively
small magnitude. l0 was calculated using reported values for
optical and static dielectric constants for water.30 Use of
convolutive analysis of CVs has been reported for the calcula-
tion of intrinsic barriers and other mechanistic details of such
electron transfer reactions. Though, the method has many
advantages, its use is limited due to the requirement of
information regarding the double layer structure. Except for
mercury, such information is not available for other metal
electrodes. We used another simple approach for calculation
of the barrier using cyclic voltammetry, without any convolu-
tion analysis, which is as follows.
The free energy of activation at peak potentials obtained in
cyclic voltammograms is given by eqn (12):31
DG zP ¼RT
Fln Z
ffiffiffiffiffiffiffiffiffiffiffiffiRT
FanD
r !
� 0:78
" #
ð12Þ
Knowing the value of a calculated from Ep � Ep/2, where Ep
is the peak potential and Ep/2 is the potential where the current
is at half the peak value (Table 1), through eqn (13):20
a ¼ 1:86RT
FjEp � Ep=2j
� �
ð13Þ
and D (1.9 � 10�5 cm2 s�1), DGPz values for the various scan
rates were calculated. These values were substituted in eqn (2)
and the resulting quadratic equation was solved for DGoz with
the help of the FORTRAN program, written specifically for
this purpose. Among the two roots obtained, the negative root
was not considered as the value emerged out to be less than
that obtained from eqn (8), which is the bare minimum value
expected for the overall reaction. The positive root, gives a
value of DGoz much greater than that expected for a stepwise
mechanism (eqn (5) and (6)) and hence negating the possibility
that the reduction follows a stepwise mechanism. Therefore,
the reaction occurring through the concerted mechanism as
shown in eqn (7) is inferred. Preference of a concerted
mechanism over a stepwise one is also realized by considering
the resonance structure of nitrate ion and the nitrite ion as
against the open shell structure of NO3�2�—an intermediate
which would be formed in a stepwise mechanism.
The bond dissociation energy was calculated by substituting
the value of DGoz (from the above procedure) and lo
(from eqn (10)) in eqn (9) and found to be ca. 48.4 kcal mol�1,
which matches well with the value of 47.5 kcal mol�1, reported
from photodissociation measurements.19 The small difference
is attributed to the neglecting the value of li in the calculations
as a first approximation.
Based on our experimental findings and earlier re-
ports,13,14,32,33 we conclude that, electron transfer to the
nitrate ion is the rate determining step, similar to the process
reported for Cu, and following the overall reaction scheme
given by eqn (14) and (15):
NO3� + e� - NO2
� + O�� (rate determining step) (14)
O�� + e� + H2O - 2OH� (15)
Results published recently by Broder et al.34 also suggest the
formation of O�� as an intermediate in reduction of nitrate ion
at Pt electrode in room-temperature ionic liquids.
4. Conclusion
For the first time, we have used a simple procedure for
analyzing the cyclic voltammetric data for nitrate ion reduc-
tion at a silver electrode. Data fits very well in the dissociative
electron transfer concerted mechanism. Besides, the value of
This journal is �c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 207–210 | 209
the bond dissociation energy, ca. 48.4 kcal mol�1, calculated
from these investigations, matches with 47.5 kcal mol�1 the
value obtained from photodissociation measurements. This
knowledge of mechanistic and thermo-chemical parameters is
believed to be useful in designing Ag electrodes as nitrate ion
sensors.
Acknowledgements
M. A. B. would like to thank the University authorities,
especially Vice Chancellor, University of Kashmir, and Head,
Department of Chemistry, University of Kashmir, for sanction
of study leave. P. P. I. thanks CSIR—India, for a fellowship.
V. R. C. thanks the BARC–Pune University collaborative PhD
program for financial support. The authors would like to thank
CNQS, University of Pune, for financial support.
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