Synthesis of Novel Organic Chromophores and Their .../67531/metadc... · Pokharel, Sundari D....

APPROVED: W. Justin Youngblood, Major Professor Thomas R. Cundari, Committee Member Mohammad A. Omary, Committee Member Rob Petros, Committee Member I. C. Khoo, Committee Member William E. Acree, Jr., Chair of the Department

of Chemistry Mark Wardell, Dean of the Toulouse Graduate

School

SYNTHESIS OF NOVEL ORGANIC CHROMOPHORES

AND THEIR CHARACTERIZATION

Sundari D. Pokharel, B.Sc., M.Sc.

Dissertation Prepared for the Degree of

DOCTOR OF PHILOSOPHY

UNIVERSITY OF NORTH TEXAS

December 2014

Pokharel, Sundari D. Synthesis of Novel Organic Chromophores and Their

Characterization. Doctor of Philosophy (Chemistry - Organic Chemistry), December 2014, 100

pp., 4 tables, 39 figures, 15 schemes, chapter references.

Nonlinear organic liquids that exhibit two-photon absorption (TPA) function as good

optical limiters for sensor protection from laser pulses. L34 (4-butyl-4'-propyl-diphenylethyne) is

a liquid organic compound exhibiting nonlinear optical absorption. A thiol- derivatized analog of

L34 (“thiol-L34”) was prepared to bind the molecules to the surface of gold nanoparticles.

Surface binding is necessary to investigate synergy between nonlinear optical absorption of gold

nanoparticles and thiol-L34. Thiol-L34 was prepared in a six-step organic synthesis starting

from 3-(4-bromophenyl) propionic acid. Au nanoparticles with <15 nm diameter have been

prepared and sensitized with the thiol-L34 compound for assessment of their nonlinear optical

behavior. Diazolylmethenes a class of metal-coordinating dyes that are similar to dipyrrins with

some substitutions of nitrogen atoms in place of carbon atoms. Modification in the framework of

dipyrrinoid dyes via this replacement of nitrogen for carbon atoms may lead to compounds that

serve as effective agents for bioimaging and/or photodynamic therapy. Several routes to the

synthesis of di-(1,2,3)-triazolylmethenes, di-(1,2,4)-triazolylmethenes, and ditetrazolylmethenes

are presented.

Copyright 2014

By

Sundari D. Pokharel

ii

ACKNOWLEDGEMENTS

Thanks are first and foremost due to Goddess Paudeshwori, the compassionate, and the

merciful, for all the blessings that she has bestowed upon me. A special thanks go to Prof. W.

Justin Youngblood, my Ph.D. thesis advisor, for his supervision, guidance, and undying support

throughout this endeavor. His encouragement, fortitude and inspiration only add to the great

scientific experience that Dr. Youngblood has. I will always be thankful for and appreciative of

his scientific advice and personal friendship. I will be indebted for his optimism, support and

leadership that laid the foundation in the beginning of my higher academic career.

I would like to thank all of the Youngblood group members, past and present, for all of

their support and friendship. I am grateful to my advisory committee for their feedback,

suggestions and improvements for this dissertation.

I wish to thank my collaborator, Professor I. C. Khoo for his help and guidance in my

projects. Special thanks go to Dr. Vladimir Nesterov for the wonderful X-ray crystallography of

the various samples presented throughout this dissertation. My sincere gratitude go to Dr. Jose

Calderon and Dr. Hongjun Pan, for all their help with the departmental analytical

instrumentation.

Great appreciation goes to the University of North Texas for the funding and support for

this research.

Last, but certainly not least, my deepest heartfelt gratitude goes to my family for their

earnest support and encouragement that has truly given me the strength to complete this

dissertation and my graduate studies.

iii

TABLE OF CONTENTS

Page

ACKNOWLEDGEMENTS ........................................................................................................... iii LIST OF TABLES ......................................................................................................................... vi LIST OF FIGURES ...................................................................................................................... vii LIST OF SCHEMES...................................................................................................................... ix LIST OF ABBREVIATIONS ......................................................................................................... x CHAPTER 1 INTRODUCTION .................................................................................................... 1

1.1 Overview and Objectives of Dissertation ............................................................... 1

1.2 Nonlinear Organic Liquid Materials ....................................................................... 1

1.3 Synthesis of Nitrogen-Enriched BODIPY Dyes ..................................................... 5

1.4 References ............................................................................................................... 9 CHAPTER 2 PREPARATION OF A COLLOIDAL OPTICAL-LIMITING MATERIAL BASED ON DIARYLALKYNE-SENSITIZED GOLD NANOPARTICLES ............................ 13

2.1 Introduction ........................................................................................................... 13

2.2 Synthesis ............................................................................................................... 17

2.2.1 General Procedures ................................................................................... 17

2.2.2 Experimental Section ................................................................................ 17

2.2.3 Characterization and Physical Measurements .......................................... 23

2.3 Results and Discussion ......................................................................................... 25

2.4 Conclusion and Future Works .............................................................................. 26

2.5 References ............................................................................................................. 27 CHAPTER 3 SYNTHESIS AND CHARACTERIZATION OF A NEW CLASS OF BODIPY DYES- DITRIAZOLYLMETHENE DYES AND THEIR DERIVATIVES ............................... 30

3.1 Introduction ........................................................................................................... 30

3.2 Synthesis ............................................................................................................... 39

3.2.1 General Procedure ..................................................................................... 39


3.2.3 Characterization and Physical Properties.................................................. 46

3.3 Results and Discussions ........................................................................................ 50

iv


3.5 References ............................................................................................................. 66 CHAPTER 4 SOME OTHER ROUTES OF SYNTHESIS OF A NEW CLASS OF BODIPY DYES- DITETRAAZOLYLMETHENE DYES AND THEIR DERIVATIVES ........................ 71

4.1 Introduction ........................................................................................................... 71

4.2 Synthesis ............................................................................................................... 71


4.2.3 Characterization and Physical Properties.................................................. 75



4.5 References ............................................................................................................. 77 CHAPTER 5 A GREENER SYNTHESIS OF 6-METHYLNAPHTHOQUINONE .................. 79

5.1 Introduction ........................................................................................................... 79

5.2 Synthesis ............................................................................................................... 81





5.5 References ............................................................................................................. 85 APPENDIX SUPPLEMENTAL DATA...................................................................................... 86

v

LIST OF TABLES

Pagr

Table 3.1 Crystallography data for phenylpropanedinitrile ...........................................................47

Table 3.2 Crystalography data 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol , (21C) .....49

Table 3.3 Crystallography data for I – Stilbene .............................................................................58

Table 3.4 Crystallography data p-tolyl(2H-triazol-4-yl)methanone ..............................................63

vi

LIST OF FIGURES

Page

Figure 1.1 Schematic diagram of the nonlinear optical limiting mechanisms in a fiber array (not drawn to scale) .................................................................................................................................2

Figure 1.2 Molecular structure of L34 and its linear absorption spectrum ......................................3

Figure 1.3 Energy-level diagram for the nonlinear organic fiber core liquid L34 ..........................4

Figure 1.4 Structures of L34 and thiol-L34 .....................................................................................5

Figure 1.5 Structure of s-indacene and aza-indacene analogs .........................................................6

Figure 1.6 Synthesis of first boron dipyrrin dye by Treibs and Kreuzer .........................................6

Figure 1.7 Synthesis of unsubstituted BODIPY 59C ......................................................................7

Figure 1.8 The structure of dimethylBODIPY- phenyl 01C ............................................................7

Figure 1.9 UV-vis spectrum of dimethylBODIPY-phenyl ..............................................................7

Figure 1.10 Fluorescence spectrum of dimethylBODIPY-phenyl ...................................................8

Figure 1.11 Synthesis of new diazolylmethene dyes having more than three nitrogen atoms ........9

Figure 2.1 Predicted reaction mechanism of Sonogashira reaction ...............................................14

Figure 2.2 Synthesis of 4-(4-butylphenyl)-2-methylbut-3-yn-2-ol (01B) .....................................14

Figure 2.3 Synthesis of 1-butyl-4-ethynylbenzene (02B) ..............................................................14

Figure 2.4 IR spectrum of Thiol-L34 .............................................................................................23

Figure 2.5 UV-visspectrum of thiol-L34 .......................................................................................24

Figure 2.6 UV-vis spectrum of L34 ...............................................................................................24

Figure 2.7 1H NMR of By product (09B) of the reduction of 05B ...............................................26

Figure 2.8 1H NMR of By product (09B) of the reduction of 05B ...............................................26

Figure 2.9 Concentration dependent nonlinear property of L34....................................................27

Figure 3.1 Mechanism of synthesis of 1,4-dialkyne from alcohol ................................................35

Figure 3.2 Oxidation of 29C using DDQ .......................................................................................46

vii

Figure 3.3 Crystal structure of phenylpropanedinitrile ..................................................................47

Figure 3.4 The crystal structure of 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol (21C) ........................................................................................................................................................49

Figure 3.5 1H NMR of 49C ............................................................................................................54

Figure 3.6 1H NMR of toluoyl malondialdehyde...........................................................................55

Figure 3.7 Formation of I Stilbene instead of 44C ........................................................................57

Figure 3.8 The crystal structure of I - Stilbene ..............................................................................58

Figure 3.9 The structure of (5Z)-3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-triazole (46C) .................................................................................................................................61

Figure 3.10 UV-vis of pink compound 1H- 1,2,4 Ditriazolylmethene (expected compound (5Z)-3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-triazole (46C)) ................................61

Figure 3.11 Synthesis of 47C .........................................................................................................62

Figure 3.12 Crystal structure of p-tolyl(2H-triazol-4-yl)methanone (47C) ...................................62

Figure 4.1 Mechanism of 5-substituted 1H tetrazole from nitrile .................................................72

Figure 4.2 The crystal structure of (44C).......................................................................................75

Figure 4.3 UV-vis spectrum of ditetraazole (01D) ........................................................................76

Figure 5.1 Naphthacenequinone-2-carboxylic acid .......................................................................79

Figure 5.2 Schematic diagrams of solar cell types: photogalvanic (“PSC”, left), dye-sensitized (“DSC”, center), and photogalvanic dye-sensitized (“P-DSC”, right). Within diagrams: SC = semiconductor; D = donor; A = acceptor; hν = photoexcitation; e− = electron; I−/I3

− = iodide/triiodide ...............................................................................................................................82

Figure 5.3 Laser flash photolysis of a thin film blend of 2-methylnaphthacenequinone (NcQ-2Me) and spiroMeOTAD. A: Time resolved spectra. B: Monochromatic decay rates for the radical cation spiro-MeOTAD(•+) at 500 nm, and for the radical anion NcQ-2Me(•−) at 603 nm. Traces are normalized with respect to ΔOD at 740 fs. Inset: overlaid decay traces for initial 9 ps ....................................................................................................................................................83

Figure 5.4 Laser flash photolysis of a ternary TiO2/naphthacenequinone-carboxylic acid /spiro-MeOTAD film consisting of rutile TiO2 nanorods with surface chemisorbed naphthacenequinone-carboxylic acid and spin-coated spiroMeOTAD. A: Time resolved spectra. B: Monochromatic decay rates for the radical cation spiroMeOTAD(•+) at 490 nm, and for the radical anion of naphthacenequinone-carboxylic aicd(•−) at 600 nm, normalized with respect to ΔOD at 605 fs. Inset: overlaid decay traces for initial 30 ps .........................................................84

viii

LIST OF SCHEMES

Page

Scheme 2.1 Synthesis thiol-L34 ....................................................................................................16

Scheme 3.1 Synthesis of ditriazolylmethene and its metal chelate ..............................................31

Scheme 3.2 Synthesis of penta-1,4-diyn-3-ylbenzene (06C) from α,α- dibromobenzene .............32

Scheme 3.3 Synthesis of penta-1,4-diyn-3-ylbenzene (06C) The starting from 1-phenyl-2-propyn-1-ol ....................................................................................................................................33

Scheme 3.4 Synthesis of ditriazolylmethane 26C ..........................................................................34

Scheme 3.5 Synthesis of 1-methyl-4-(penta-1,4-diyn-3-yl)benzene (34C) The starting from tolualdehyde and copper triflate.....................................................................................................36

Scheme 3.6 Synthesis of (34C) The starting with toluoyl malondialdehyde .................................37

Scheme 3.7 Protection of enolic proton of toluoyl malondialdehyde ............................................38

Scheme 3.8 Synthesis of (5Z)-3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-triazole (46C) starting from phenylpropanedinitrile ......................................................................39

Scheme 3.9 Protection of enol of toluoyl malonaldehyde .............................................................56

Scheme 3.10 Synthesis of 34C The starting from protected toluoyl malondialdehyde .................65

Scheme 4.1 Synthesis of ditetraazolylmethene (02D) starting from phenylpropanedinitrile ........73

Scheme 4.2 Synthesis of 02D from 01D using NBS .....................................................................77

Scheme 5.1 Synthesis of 6-methylnaphthoquinone .......................................................................80

Scheme 5.2 Overall synthesis of naphthacenequinone-2-carboxylic acid using chromic acid to prepare the 6-methylnaphthoquinone ............................................................................................80

ix

LIST OF ABBREVIATIONS

BODIPY: Boron dipyrrin, 4,4-difluoro-4-bora-3ª,4ª-diaza-s-indacene

CuAAC: Copper - catalyzed azide - alkyne cycloaddition

DDQ: 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone

DMF: N,N-dimethylformamide

DMSO: Dimethyl sulfoxide

ESA: Excited State Absorption

IR: Infrared (light)

MS: Molecular seives

NMR: Nuclear magnetic resonance

RSA: Reverse saturable absorption

RuAAC: Ruthenium - catalyzed azide - alkyne cycloaddition

SEM: Scanning electron microscope

TBAF: Tetrabutylammonium fluoride

TFA: Trifluoroacetic acid

THF: Tetrahydrofuran

TLC: Thin layer chromatography

TMS: Trimethylsilyl

TPA: Two photon absorption

UV: Ultraviolet

UV-vis: Ultraviolet-visible light

x

CHAPTER 1

INTRODUCTION

1.1 Overview and Objectives of Dissertation

This dissertation represents part of the work performed by the author during her graduate

study at UNT. This dissertation is a study of two major topics that involve synthetic strategies of

nonlinear organic liquid material thiol-L34 and the synthesis of nitrogen-enriched derivatives of

BODIPY dyes.

1.2 Nonlinear Organic Liquid Materials

Nowadays lasers are being used in different applications such as sensing, switching,

medical, surveying and ranging, recreation and entertainment, communication and in military

applications. Direct exposure of intense laser on human eyes or on sensors can cause temporary

or permanent damage to them. When the wavelength of a laser is known, an appropriate

wavelength filter can be used to protect sensors or eyes from the high intensity light of the laser.

Fixed- wavelength filters cannot be used for tunable lasers since they range from the UV light to

the far infrared region. Tunable filters are also not useful for short laser pulses because they

respond very slowly. Usually a laser pulse ranges from picoseconds to nanoseconds in duration

and the pulse energy ranges from micro joules to joules. Exposure to high-intensity pulsed laser

for a very short duration can damage an optical sensor.1

Research is being focused on non-linear absorbing materials to protect optical sensors

against intense laser pulses. 2–15,32–48 These materials have multi-photon absorption properties

such as reverse saturable absorption (RSA),36–39 two photon absorption (TPA) and excited state

absorption (ESA),40–50 and non-linear scattering properties.51 When the light intensity is low the

absorption of light is also weak but these materials become increasingly opaque with increasing

1

intensity of light. The reason they become opaque with increasing intensity of light is due to

multiple photon absorption. Materials which have the properties of two-photon absorption and

strong excited-state absorption are in demand.

Figure 1.1. Schematic diagram of the nonlinear optical limiting mechanisms in a fiber array (not drawn to scale). There is usually a thin (0.2–0.5mm) layer of liquid between the fiber array and the front window in some of the actual constructed devices.1

Most known 2PA materials are solid materials in their pure state at room temperature,

and typically do not have good enough solubility to actually effect significant transmittance

changes despite their non-linear absorption properties due to the dilute concentrations available.

Maximum concentrations of TPA chromophores are about 10-3 to 10-2 M. TPA chromophores

that are liquid in their pure form at room temperature are desired for optical limiting applications

(Figure 1.1), because these chromophores can maintain their linear and nonlinear optical

absorption properties at 100%. Examples of liquid TPA chromophores are L3446–49, a

diarylethyne compound (Figures 1.2 and 1.3), and certain liquid crystalline chromophores in

their isotropic phase.50 Designing new TPA compounds with high solubility and/or a liquid state

in pure form at ambient temperature is an important area of research.

2

Figure 1.2. Molecular structure of L34 and its linear absorption spectrum.30

4-propyl-4′-butyl diphenyl acetylene called as L34 is an organic compound which

behaves as nonlinear liquid material. This compound was prepared by the group Khoo et.al.

Figure 1.2 is the UV-vis spectrum of L34 which demonstrates the absorption between 200-

300nm.

Two-photon absorbers are transparent at low intensity of light and become increasingly

absorptive with increase in the intensity of light.11,14, 24-27 L34 has TPA property. In figure 1.3 N1

is the ground state of L34. When a low intensity laser is passed through L34 fiber core it absorbs

one photon and goes to the lower singlet state N4. When the intensity of the laser is high there is

higher probability of two photons simultaneously striking a molecule of the nonlinear material

and being absorbed at a time and it goes to the higher singlet state N2. From higher singlet state

N2 the chromophore loses energy and goes to inter- system crossing. N5 and N3 are the lower and

higher triplet states of the molecule. After inter system crossing it goes to N5 where it can absorb

the photon and can go to the higher triplet state N3.

3

Figure 1.3. Energy-level diagram for the nonlinear organic fiber core liquid L34.1

The author in her first project has targeted the synthesis of a thiol derivative of nonlinear

compound L34 which will be called thiol-L34 now on. The structure of L34 and thiol-L34 is

given below. Thiol group will be bonded at the one end of the L34 molecule. It is assumed that

there will be no significant difference in nonlinear properties of these two compounds because

the thiol group is very far from the conjugation system of the molecule hence there is no

electronic interaction between them. The main purpose of synthesizing thiol-L34 is to anchor

gold nanoparticles at thiol group. The reason to bond gold nanoparticles on thiol-L34 is to see a

synergetic effect in optical limiting. Because thiol-L34 is a thiol derivative of L34, it is expected

to show nonlinear property towards lasers and gold nanoparticles show nonlinear property

towards lasers. It is expected to see enhanced TPA of thiol-L34 in the presence of Au

nanoparticle due to energy transfer from thiol-L34 to Au.

4

Figure 1.4. Structures of L34 and thiol-L34

1.3 Synthesis of Nitrogen-Enriched BODIPY Dyes

Aza-indacenes are rigidified cyclic cyanine dyes that resemble s-indacene in shape

(Figure 1.5).62 Dipyrrolylmethenes (dipyrrins) and azadipyrrolylmethenes (aza dipyrrins) dyes

are two of the most commonly known aza-indacene dyes. Dipyrrins have a carbon atom at the

meso position and azadipyrrins have a nitrogen atom at the meso position.63 These two classes of

dyes differ in their optoelectronic properties as a result of the different atom at the meso position.

Both dipyrrin and azadipyrrin dyes have strong absorbance in the visible region. Metal

complexes of dipyrrins such as Zn(II), Sn(II), and Cd(II)64,65 are fluorescent. Both types of dyes

are used as fluorescent probes of pH, various metal and halide ions, and for some small

molecules. They are stable in physiological pH-range and their optical behavior is not strongly

dependent on solvent polarity. They decompose only in strongly acidic and basic conditions.64

They are also used in biomolecule tagging and tissue-scale bioimaging.66,67,68 They have

application in solar cells for harvesting solar energy.68

5

NNH

N

NNHArAr

Ar Ar

NNB

RR

ArN

NNB

RR

Ar

Ar Ar

s Indacene Dipyrrolylmethene BODIPY

(Dipyrrin) (bora diaza indacene) azadipyrrolylmethene(azadipyrrin)

azaBODIPY(bora triaza indacene)

Figure 1.5. Structure of s-indacene and aza-indacene analogs.

Highly fluorescent compound 55C was synthesized accidentally in 1968 by Treibs and

Kreuzer which was the first appearance of BODIPY dyes (Figure 1.6). Acylation of 2,4-

dimethylpyrrole 52C was carried out with acetic anhydride and boron trifluoride to synthesize

the compound 53C.68 In the presence of acid the condensation of pyrroles 52C and 53C took

place to form dipyrrin 54C and which followed the complexation with boron difluoride to give

55C.

54C 55C

NH

NH

OAc2O

BF3.Et2O

52C 53C

H+

NNH NNB

F F

Ac2O

BF3Et2O

Figure 1.6. Synthesis of first boron dipyrrin dye by Treibs and Kreuzer

In 2009 three groups simultaneously reported the synthesis of unsubstituted BODIPY

59C69 given in figure 1.7. The synthesis of 59C gave problems while following the commonly

known route because the intermediate compound 58C is not stable over -40°C.70 Tram et al.

synthesized 58C at -78°C with the yield of 5-10%. Schmitt et al. carried out McDonald

condensation from pyrrole-2-carbaldehyde 57C and pyrrole in the presence of trifluoroacetic

acid and prepared unsubstituted dipyrrin 58C. Pena-Cabrera et al. reduced a thiomethyl

substituted BODIPY dye 60C to form 59C.The unsubstituted dye 59C is a highly fluorescent

compound and has a fluorescence quantum yield of 90% in water.

6

NH

NH

NNH NNB

FF

NN

S

BFF

NH H

ONH

+

DDQ

TFA

Et3SiH

Pd2(dba)3,CuTC, TFP

56C

57C

58C

59C 60C

BF3.Et2O

Figure 1.7. Synthesis of unsubstituted BODIPY 59C

Dipyrrins (dipyrrolylmethenes) and azadipyrrins (azadipyrrolylmethenes) have strong

absorbance in the visible spectrum around 500 nm. Chelation of these two dyes with boron give

a strong red shift (50-60 nm) and boron chelation makes them highly emissive.71 UV-vis and

fluorescence spectra of dimethylBODIPY- phenyl (01C) are given in figures 1.9 and 1.10

respectively.

01C

N N

B

F F Figure 1.8. The structure of dimethylBODIPY- phenyl 01C

Figure 1.9. UV-vis spectrum of dimethylBODIPY-phenyl71

7

Figure 1.10. Fluorescence spectrum of dimethylBODIPY-phenyl71

The second project targeted the synthesis of compounds 02C, 03C, 04C and 05C to study

their optoelectronic properties. BODIPY (bora-diaza-indacene) dyes are highly fluorescent

molecules. When the C atom at meso position of BODIPY is replaced by N- atom its fluorescent

is red-shifted. In this project the author targeted to substitute C- atom to N –atom in non-ital

positions and expand the aza-indacene members including pyrazole, triazoles (1,2,3 and 1,2,4)

and tetrazole rings in the structure. It is expected that this research will bring new insight in the

optoelectronics, coordination and the reactivity of aza-indacene compounds with N-atom

substitution in different positions. These new compounds/complexes will have different

applications as ligands and as chromophores. The author has attempted to synthesize aza-

indacenes in which 4-8 nitrogen atoms are substituted for carbon atoms within the indacene

system. In chapter three the synthesis of the molecules 03C and 04C is discussed and in chapter

4 the synthesis of the molecule 02C is described.

8

N

N

NN

N

NN

N BF F

N

N

N

N

NN BF F

N NN

NN

N BF F

N NNN BF F

02C 04C 03C 05C Figure 1.11. Synthesis of new diazolylmethene dyes having more than three nitrogen atoms

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9

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12

CHAPTER 2

PREPARATION OF A COLLOIDAL OPTICAL-LIMITING MATERIAL BASED ON

DIARYLALKYNE-SENSITIZED GOLD NANOPARTICLES

2.1 Introduction

Chapter two describes the synthesis and characterization of a thiol derivative of L34 (4-

propyl-4′-butyldiphenyl acetylene) compound. It is a six steps synthetic route given in Scheme

1.1. After the synthesis of thiol-L34 gold nanoparticles are grown on it. L34 is a compound that

exhibits nonlinear optical absorbance which is used to prevent sensors against high intensity

lasers. The purpose of synthesizing thiol-L34 is to grow gold nanoparticles at the end of thiol

group. Gold also exhibits nonlinear optical absorbance. By growing gold nanoparticles on thiol-

L34 a synergetic effect will be studied. It is expected to see enhanced TPA of the organic

absorber in the presence of Au nanoparticle due to energy transfer from thiol-L34 to Au.

The compounds 01B and 04B are synthesized by Sonogashira cross coupling reaction. In

Sonogashira cross-coupling reaction, coupling between vinyl or aryl halides and terminal alkynes

takes place using Pd(0) catalyst, a copper(I) co-catalyst, and an amine base.5 Because it is

difficult to isolate and analyze the organometallic compounds that are present as intermediates in

the reaction, the reaction mechanism of the Sonogashira reaction is not completely understood.

The predicted mechanism of the reaction is given below.3

The compound 03B was prepared by the acid catalyzed esterification of p-bromophenyl

propanoic acid and methanol.

13

Figure 2.1. Predicted reaction mechanism of Sonogashira reaction.3

BrHCCCOH(CH3)2, CuI

PdCl2(PPh3)2, PPh3, 80 oCOH

01B 80%

Figure 2.2. Synthesis of 4-(4′-butylphenyl)-2-methylbut-3-yn-2-ol (01B)

OH69%

01B 02B

NaOH, Toluene

Reflux 6 hours

Figure 2.3. Synthesis of 1-butyl-4-ethynylbenzene (02B)

Lithium aluminium hydride is widely used as a reducing agent. It can convert esters,

carboxylic acids, acyl chlorides, aldehydes and ketones into corresponding alcohols. Compared

14

to sodium borohydride, LiAlH4 is a stronger reducing agent because the Al-H bond is weaker

than the B-H bond.4 Esters can easily be reduced by LiAlH4 into alcohols. The reaction requires

2 equivalents of hydride (H-), first to reduce ester to aldehyde and second to reduce aldehyde to

alcohol. The reaction is followed by an acid work up. The compound 05B will be prepared by

the reduction of 04B with LiAlH4.

The Appel reaction is used to convert an alcohol to an alkyl halide using a

tetrahalomethane (CCl4 or CBr4) and triphenylphosphine (PPh3). In the first step lone pair of

electrons of phosphorus attack halogen atom and phosphonium halide is formed along with

trihalomethyl cation. Then trihalomethyl cation attack hydrogen of alcohol group and alkoxide

ion is formed. The alkoxide ion subsequently attacks the phosphorous and a halide ion is released

as a leaving group. In a nucleophilic substitution reaction (SN2), the halide (nucleophile) attacks

the carbon stereocenter and SN2 reaction takes place resulting in the formation of alkyl halide.

Because of the SN2 mechanism, inversion of the configuration takes place and the reaction gives

the product with inverted stereochemistry. Triphenylphosphine oxide is the byproduct of this

reaction which is favored by the strong P=O bond formation.5 The conversion of 05B to 06B is

carried out through Appel reaction using PPh3 and CBr4. In the compound 05B the carbon

bonded with alcohol group has no steric center hence it will not undergo any inversion of

configuration after the SN2 step.

The compound 07B can be prepared by treating 06B with potassium thioacetate.

Thioacetate attacks the carbon atom containing bromine and an SN2 reaction takes place.

Bromine departs as a leaving group. Since polar aprotic solvent accelerates the rate of SN2

reaction, acetone is used as the solvent.

15

Br O

O CH3

O

O CH3CH3

CH3 OH

PdCl2(PPh3)2, PPh3CuI, TEA, 80 °C CH3

CH

LiAlH4 THF

Br

OH

O

CH3OH H2SO4, ∆

CH3 S

CH3

O

CH3 Br

AcetoneCH3

O

S

K

CBr4, PPh3 THF

HCl, MeOH ∆, Ar

03B

04B

05B

06B

07B

08B

90%

78%

77%

65%

84%

72%

CH3 SH

Scheme 2.1. Synthesis thiol-L34

16

The compound 08B is synthesized from 07B by treating it with HCl and methanol. HCl

reacts with methanol to form (CH3OH2+)Cl-. The carbonyl oxygen is protonated by CH3OH2 and

an oxonium ion is formed. Then lone pair of electrons on oxygen atom of methanol attacks on

carbonyl carbon atom and one of the double bond of C-O bond breaks. The proton from

protonated methanol leaves. Then, the double bond is formed between C-O atoms and alkyl

sulfide leaves as a leaving group. After protonation, the alkyl sulfide forms thiol (08B).

2.2 Synthesis

2.2.1 General Procedures

Manipulations were carried out under an atmosphere of purified argon using standard

Schlenk techniques wherever needed. Solvents were purchased from commercial sources, dried

over molecular sieves whenever needed for anhydrous conditions, and degassed by purging with

argon gas. All other chemicals were reagent grade and were used as received. Glassware were

oven-dried at 150ºC overnight. NMR solvent CDCl3 was reagent grade and stored over 4 Å

molecular sieves prior to use. Analytical TLC was performed on glass backed, pre-coated silica

gel plates and visualization was accomplished with UV light. Silica gel 60 μm (average particle

size) was used for column chromatography. UV-vis data were collected with a Varian Cary

spectrophotometer. 400Hz was used for 1H and 75 MHz was used 13C NMR spectra in CDCl3

unless noted otherwise.

2.2.2 Experimental Section

• Synthesis of 4-(4-butylphenyl)-2-methylbut-3-yn-2-ol (01B)

An oven-dried Schlenk flask with magnetic stir bar was charged with CuI (0.16 g, 0.86

mmol), PdCl2(PPh3)2 (0.60 g, 0.86 mmol) and PPh3 (0.45 g, 1.7 mmol) and evacuated and purged

with argon three times successively. In another oven-dried round bottom flask with magnetic stir

17

bar 1-bromo-4-butylbenzene (3.76 g, 17.6 mmol), 2-methyl-3-butyl-2-ol (1.48 g, 17.6 mmol) and

freshly dried TEA (100 mL) was taken and purged with argon for 40 minutes. It was transferred

in Schlenk flask. The reaction was left overnight at 80̊C. Then mixture was extracted with

hexanes and deionized water. The organic layer was separated and washed with a saturated

solution of NaHCO3 and then with brine. The organic layer was isolated and dried over

anhydrous Na2SO4. The product was purified by column chromatography using hexanes: ethyl

acetate in 6:1 ratio. The product was isolated as a transparent liquid (3.03 g, 0.02 mol, yield=

80%) , 1H NMR (CDCl3) δ 0.89-0.93 (t, 3H, J = 16 Hz), 1.28-1.37 (m, 2H), 1.53-1.60 (m, 8H),

1.92 (s, OH), 2.56-2.60 (t, 2H, J = 16 Hz), 7.09-7.12 (d, 2H, J = 12 Hz), 7.31-7.33 (d, 2H, J =

8Hz).

• Synthesis of 1-butyl-4-ethynylbenzene (02B)

An oven-dried round bottom flask with a magnetic stir bar was charged with 01B (0.50 g,

0.02 mol), 1-butanol (1 mL) and toluene (25 mL). Finely grounded NaOH (0.02 g, 0.46 mmol)

was added and a condenser was connected. The reaction was refluxed for 6 hours. The reaction

mixture was cooled at room temperature then extracted with deionized water and hexanes. The

organic layer was first washed with saturated solution of NaHCO3 then with brine. The organic

layer was isolated and dried over anhydrous Na2SO4. It was filtered and solvent was removed by

rotary evaporation. The product was purified using rotary chromatography. Hexanes was used as

eluent. The product (0.25 g, 1.58 mmol, yield= 69%) , 1H NMR (CDCl3) δ 0.89-0.93 (t, 3H, J =

16 Hz), 1.29-1.38 (m, 2H), 1.53-1.61 (m, 2H), 2.58-2.63 (t, 2H, J = 20 Hz), 3.02 (s, 1H), 7.11-

7.14 (d, 2H, J = 12 Hz), 7.39-7.41 (d, 2H, J = 8 Hz).

18

• Synthesis of methyl 3-(4-bromophenyl)propanoate (03B)

An oven-dried 500 mL round bottom flask was charged with a magnetic stir bar, 3-(4-

bromophenyl)propanoic acid (5.33g, 23.3 mmol), methanol (250 mL) and concentrated H2SO4 (5

mL) and the mixture was refluxed overnight. Then, it was cooled to room temperature and dried.

The mixture was extracted with deionized water and diethyl ether. The organic layer was isolated

and dried over anhydrous MgSO4. Purified product was obtained using rotary chromatography

(SiO2, hexanes;ether, 1:1). The product (5.09 g, 0.02 mol, yield = 90%), 1H NMR (CDCl3) δ

2.59-2.63 (t, 2H, J = 16 Hz), 2.88-2.92 (t, 2H, J = 16 Hz), 3.66 (s, 3H), 7.06-7.09 (d, 2H, J = 12

Hz), 7.39-7.41 (d, 2H, J = 8 Hz).

• Synthesis of methyl 3-{4-[(4-butylphenyl)ethynyl]phenyl}propanoate (04B)

An oven-dried Schlenk flask was charged with 2 stir bar, methyl 3-(4-

bromophenyl)propanoate (0.75 g, 3.1 mmol), PdCl2(PPh3)2 (0.11 g, 0.15 mmol), PPh3 (.079 g,

0.30 mmol) and CuI (0.030 g, 0.15 mmol) and purged three times with vacuum and dry argon

gas. Another oven-dried round bottom flask was charged with a stir bar, dry TEA and 1-butyl-4-

ethynylbenzene and purged with dry N2 for 30 minutes. This mixture was transferred to a

Schlenk flask and heated at 80˚C overnight. Then the reaction was cooled to room temperature

and TEA was removed by rotary evaporation. The mixture was extracted with deionized water

and hexanes. The organic layer was isolated and washed with a saturated aqueous solution of

NH4Cl. The organic layer was then isolated and dried over anhydrous Na2SO4. The mixture was

purified in rotary chromatography (SiO2, hexanes:ethyl acetate, 6:1). The product was obtained

as pale yellow solid ( 0.76 g, 2.38 mmol, yield= 78%), 1H NMR (CDCl3) δ 0.88-0.92 (t, 3H, J =

16 Hz), 1.28-1.38 (m, 2H), 1.54-1.61 (m, 2H), 2.57-2.64 (m, 4H), 2.91-2.96 (t, 2H, J = 20 Hz),

3.65 (s, 3H), 7.12-7.16 (t,4H, J = 16 Hz), 7.39-7.43 (t, 4H, J = 16 Hz).

19

• Synthesis of 3-{4-[(4-butylphenyl)ethynyl]phenyl}propan-1-ol (05B)

In an oven-dried round bottom flask with a magnetic stir bar, methyl 3-{4-[(4-

butylphenyl)ethynyl]phenyl}propanoate (0.51 g, 1.6 mmol), LiAlH4 (0.11 g, 3.2 mol) and dry

THF (25 mL) were combined. The mixture was stirred for 11 hours.The mixture was quenched

with methanol, and extracted with deionized water and ethyl acetate. The organic layer was

isolated and dried over anhydrous MgSO4. The product was purified using rotary

chromatography using the eluent hexanes: ethyl acetate in 3:1 ratio. The product was obtained

dull white liquid (0.35 g, 1.2 mmol, yield= 77% ), 1H NMR (CDCl3) δ 0.90-0.94 (t, 3H, J = 16

Hz), 1.30-1.39 (m, 2H), 1.45 (s, OH), 1.55-1.63 (m, 2H), 1.86-1.92 (m, 2H), 2.59-2.63 (t, 2H, J =

16 Hz), 2.70-2.74 (t, 2H, J = 16 Hz), 3.66-3.69 (t, 2H, J = 12 Hz), 7.14-7.18 (t, 4H, J = 16 Hz),

7.41-7.45 (t, 4H, J = 16 Hz). 13C NMR (75 MHz, CDCl3) δ 13.96, 22.31, 31.46, 31.98, 33.42,

34.00, 35.59, 61.99, 62.17, 89.13, 119.56, 120.48, 120.96, 128.45, 130.20, 131.43, 131.60.

Synthesis of 1-(3-bromopropyl)-4-[(4-butylphenyl)ethynyl]benzene (06B)

An oven-dried round bottom flask with a magnetic stir bar was charged with PPh3 (0.38

g, 1.44 mmol). Another oven-dried round bottom flask with magnetic stir bar was charged with

CBr4 (0.48 g, 1.4 mmol) and 05B (0.21 g, 0.72 mmol). Both the flasks were evacuated and

purged with argon for three times successively. Dry THF was added in both flasks then they

were submerged in ice bath. The solution from the first flask was transferred to the second flask

by cannulation. The ice bath was removed and the reaction was run for 45 minutes. The reaction

mixture was extracted with hexanes and deionized water, then washed with brine and dried over

anhydrous Na2SO4. The product was purified by rotary chromatography using the eluent

hexanes: ethyl acetate in 9:1 ratio. The product (0.17 g, 0.47 mmol, yield = 65%), 1H NMR ( 75

MHz, CDCl3) δ 0.91-0.94 (t, 3H, J = 12 Hz), 1.3-1.4 (m, 2H), 1.56-1.63 (m, 2H), 2.13-2.20 (m,

20

2H), 2.60-2.63 (t, 2H, J = 12 HZ), 2.77-2.81(t, 2H, J = 16 Hz), 3.37-3.41 (t, 2H, J = 16 Hz), 7.14-

7.19 (t, 4H, J = 20 Hz), 7.42-7.46 (t, 4H, J = 16 Hz). 13C NMR (75 MHz, CDCl3) δ 13.91, 22.30,

30.92, 33.40, 33.85, 35.59, 88.60, 89.30, 120.46, 121.36, 128.47, 128.59, 131.46, 140.69,

143.31,207.09.

• Synthesis of S-methyl 3-{4-[(4-butylphenyl)ethynyl]phenyl}propanethioate (07B)

An oven-dried round bottom flask with a magnetic stir bar was charged with 06B (0.16 g,

0.47 mmol), potassium thioacetate (0.070 g, 0.57 mmol) and acetone (4 mL). A septum was put

on. The reaction was left stirring overnight at room temperature. The solution was then removed

using rotary evaporation. The reaction mixture was extracted using deionized water and ethyl

acetate. The organic layer was washed with brine and dried over anhydrous Na2SO4. The product

was purified by rotary chromatography using hexanes: ethyl acetate in 12:1 ratio. The product

was isolated as a pale yellow liquid (0.14 g, 0.39 mmol, yield = 84%), 1H NMR (CDCl3) δ 0.90-

0.94 (t, 3H, J = 16 Hz), 1.30-1.39 (m, 2H), 1.55-1.63 (m, 2H), 1.86-1.93 (m, 2H), 2.34 (s, 3H),

2.59-2.63 (t, 2H, J = 16 Hz), 2.67-2.71 (t, 2H, J = 16 Hz), 2.86-2.90 (t, 2H, J = 16 Hz), 7.13-7.16

(m, 4H), 7.41-7.45 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 13.94, 22.31, 28.49, 30.66, 30.91,

33.41, 34.74, 35.59, 88.69, 89.18, 120.47, 121.12, 128.44, 128.46, 131.44, 131.61, 141.33,

143.26, 195.83.

• Synthesis of 3-{4-[(4-butylphenyl)ethynyl]phenyl}propane-1-thiol (08B)

An oven-dried two-necked round bottom flask with a stir bar was charged with 07B (0.11

g, 0.30 mmol) and a condenser was connected. It was purged with argon for 10 minutes.

Methanol (15 mL) and HCl (5 drops) were added and the mixture was refluxed for 5 hours. The

reaction was allowed to cool. The reaction mixture was concentrated using rotary evaporation. It

was extracted using deionized water and ethyl acetate. The organic layer was washed with brine

21

and dried over anhydrous Na2SO4. The product was purified by rotary chromatography using

hexanes: ethyl acetate in 12: 1 ratio. The product was isolated as a pale yellow liquid (0.06 g,

0.22 mmol, yield = 72%), 1H NMR (CDCl3) δ 0.90-0.94 (t, 3H, J = 16 Hz), 1.25 (s, SH), 1.32-

1.39 (m, 2H, J = 28 Hz), 1.89-1.97 (m, 2H, J = 32 Hz), 2.50-2.56 (m, 2H, J = 24 Hz), 2.59-2.63

(t, 2H, J = 16 Hz), 2.72-2.76 (t, 2H, J = 16 Hz), 7.14-7.16 (m, 4H,), 7.41-7.45 (m, 4H). 13C NMR

(75 MHz, CDCl3) δ 13.94, 22.30, 23.92, 33.40, 34.25, 35.21, 35.59, 88.68, 89.20, 120.47,

121.08, 128.45, 128.49, 131.44, 131.61, 141.46, 143.28.

• Growth of gold nanoparticles

In a conical flask HAuCl4.3H2O (0.070 g, 0.17 mmol) was dissolved in deionized water

(5.73 mL). In another flask tetraoctyl ammonium bromide (0.43 g, 0.17 mmol) was dissolved in

toluene (18.6 mL) to make a 0.04M solution. The second solution was added to the first solution

and the mixture was stirred vigorously. An intense red/orange color was formed. When all the

red/orange color had moved to the upper (organic) layer, 08B (0.050 g, 0.17 mmol) in toluene (4

mL) was added and stirred for 30 minutes. Then in another flask NaBH4 (0.070 g, 0.17 mmol)

was dissolved in deionized water (5.66 mL) to make 0.34 M solution and was added to the above

solution. Simultaneously, the color changed to black/brown. The reaction was left stirring for 16

hours. The organic layer was separated and reduced to 5 mL using rotary evaporation. Ethanol

(50 mL) was added and the mixture was centrifuged for 1 hour. The supernatant was separated

with a pipette. Again, ethanol (50 mL) was added and the mixture was centrifuged for 1 hour and

the supernatant was removed. The residue was dissolved in toluene, filtered and concentrated by

rotary evaporation. The product (0.040 g) was collected as a black powder.

22

2.2.3 Characterization and Physical Measurements

C-S and C-S-H stretching vibrations give very weak absorption in the infrared spectrum.

Infrared spectrum of thiol-L34 is given in figure 2.4. The weak peak around 2567cm-1 is the

peak for S-H stretching. Another weak peak around 644cm-1 could be the peak for C-S-H

stretching where the carbon atom is aliphatic. The very weak peak around 2100cm-1 may be the

peak for internal alkyne C-C triple bond stretching, although that region is noisy due to difficulty

in accurately baselining the absorption by ambient CO2.

Figure 2.4. IR spectrum of Thiol-L34

Figure 2.5 is the UV-vis absorbance spectrum of thiol-L34. Here absorbance can be seen

around 300 nm. Figure 2.6 is the UV-vis absorbance spectrum of the L34 which is copied from

the article.6 While comparing between these two figures it is observed that there is a similar

23

pattern of absorbance around 300 nm in both the compound L34 and thiol-L34. This is what was

expected because in thiol-L34 thiol group is very far from the unsaturated system within the

molecule hence there is no interaction between unsaturated system and thiol group within the

molecule.

Figure 2.5. UV-vis spectrum of thiol-L34

Figure 2.6. UV-vis spectrum of L346

24

2.3 Results and Discussion

Compounds 01B and 04B were synthesized using a Pd(0) catalyst according to the

typical conditions for the Sonogashira reaction. While synthesizing 01B for the first time, the

reaction was made at room temperature. There was no reaction and the starting compound was

recovered. The second time, the reaction was run at 80ºC and 01B was formed and the yield was

80%. In synthesizing 04B first the reaction was ran at 80ºC and the yield was lower and when the

reaction was ran at 40ºC the yield was 79%. It was seen that in Sonogashira reaction yield

depends on using an optimal temperature which depends on the starting compounds.

During the synthesis of compound 02B, the yield was very low in the initial attempts.

Later it was found that compound is volatile. When the reaction was refluxed overnight some of

the compound escaped. After purification, the compound was kept under high vacuum and it

escaped. Later it was recovered from the trap of the high vacuum. This is very important to use

trap if the molecules are small in size.

05B was synthesized by reducing 04B using the reducing agent LiAlH4. LiAlH4 was

taken in an oven-dried round bottom flask with a magnetic stir bar and purged with argon for 5

minutes. Dry THF was added. Then 05B was dissolved in dry THF and added. After two hours a

TLC was done using SiO2 plate as stationary phase and the eluent hexanes: ethyl acetate in 2:1

ratio. By assuming that LiAlH4 is not in good condition an excess of LiAlH4 was added and the

reaction was left running for 3 days. After purification it was found that trans-alkene (09B) (the

structure is given below) was formed as major product along with desired product. 1H NMR

spectrum of this product is given below.

25

OH3-{4-[(E)-2-(4-butylphenyl)ethenyl]phenyl}propan-1-ol

09B

Figure 2.7. 1H NMR of by product (09B) of the reduction of 05B.

10B

Figure: 2.8. Dimer of 02B

During the synthesis of the compound 02B, dimer 10B was formed as by product. The 1H

NMR of 10B is given in the appendix.

The compound synthesized here is thiol derivative of L34 and to enhance the optical

limiter property gold nanoparticles are also grown. We expect the behavior of our compound will

be similar to this compound. We are growing gold naoparticles to improve the range of the

radiation compound can absorb. We expect that our compound will only show TPA properties

not the ESA property.

2.4 Conclusion and Future Works

Thiol-L34 was synthesized in a six-steps synthesis starting from 3-(4-

bromophenyl)propanoic acid. Gold nanoparticles were grown on thiol-L34. Both the material

26

neat thiol-L34 and gold nanoparticles capped with thiol-L34 were synthesized. Gold

nanoparticles capped with thiol-L34 will be characterized by SEM and/or TEM imaging.

Figure 2.9. Concentration dependent nonlinear property of L341,2

Both the materials have already been sent to collaborator professor I. C. Khoo from Penn

State University for further investigation of the properties and effectiveness of the material in

controlling the intensities of the laser. Figure 2.9 shows the nonlinear property of L34 dependent

on the concentration of the compound. From the figure it is seen that the nonlinear property

improves as the concentration of the compound is increased. Gold nanoparticles capped with

thiol-L34 will be mixed with L34 and the nonlinear optical absorption will be studied.

2.5 References

1. Khoo, I. C. et al J. Opt. Soc. Am. 2004, B21, 1234-1240.

2. Khoo, I. C. IEEE J. Selected Topics in Quantum Electronics JSTQE, 2008, 14, 3, 946 – 951.

3. Chinchilla, R.; Nájera, C., Chemical Reviews. 2007, 107, 874 – 922.

4. Brown, H. C. Organic The reactions. 1951, 6, 469.

5. Appel, R. Angew. Chem. Int. Ed. Engl. 1975, 14, 801-811.

27

6. Khoo, I. C.; Webster, S.; Kubo, S.; Youngblood, W. J.; Liou, J. D.; Mallouk, T. E.; Lin, P., Hagan, D. J.; Van Stryland, E. W. J. Mater. Chem. 2009, 19, 7525–7531

7. Okuyama, K.; Cockett, M. C. R.; Kimura, K. J. Chem. Phys., 1992, 97, 1649–1654.

8. Okuyama, K.; Hasegawa, T.; M. Ito, M.; Mikami, N. J. Phys. Chem., 1984, 88, 1711–1716.

9. Sutherland, R. L.; Brant, M. C.; Brandelik, D. M.; Fleitz, P. A.; D. G. McLean, D. G.; Pottenger, T. Optics Letters, 1993, 18, 858–860.

10. Barroso, J.; Costela, A.; Garcia-Moreno, I.; Saiz, J. L. Journal of Physical Chemistry A, 1998, 102, 2527–2532.

11. Ehrlich, J. E.; Wu, X. L.; Lee, I. Y. S.; Hu, Z. Y.; Rockel, H.; Marder, S. R.; Perry, J. W. Optics Letters, 1997, 22, 1843–1845.

12. Khoo, I. C.; Wood, M. V.; Guenther, B. D.; Shih, M. Y.; Chen, P. H.; Z. Chen, Z.; Zhang, X. Optics Express, 1998, 2(12), 471–482.



15. Nakatsuji, N. Chem. Phys. Lett., 1978, 59, 362–364.

16. Khoo, I. C.; Chen, P. H.; Wood, M. V.; Shih, M. Y. Chemical Physics, 1999, 245, 517-531.

17. Khoo, I. C.; Wood, M. V.; Guenther, B. D.; Shih, M. Y.; Chen, P. H. J. Opt. Soc. Am. B, 1998, 15, 1533–1540.

18. Khoo, I. C. IEEE J. Selected Topics in Quantum Electronics JSTQE, 2008, 14(3), 946–951.

19. Miyaura, N.; Suzuki, A.; Chem. Rev., 1995, 95, 2457–2483.

20. Sekine, C.; Iwakura, K.; Konya, N.; Minai, M.; Fujisawa, K.; Liq. Cryst., 2001, 28, 1375-1387.

21. Fujita, Y.; Misumi, Y.; Tabata, M.; Masuda, T. J. Polym. Sci. Pol Chem., 1998, 36, 3157-3163.

22. Grant, B. Mol. Cryst. Liq. Cryst., 1978, 48, 175–182.

23. Hirata, Y.; Okada, T.; Nomoto, T.; Chem. Phys. Lett., 1998, 293, 371–377.

24. Sheik-Bahae, M.; Said, A. A.; Van Stryland, E. W. Opt. Lett., 1989, 14, 955–957.

28

25. M. J. Frisch et al., Gaussian 03; Gaussian, Inc.: Wallingford CT, (2004).

26. He, G. S.; Tan, L. S.; Zheng, Q.; Prasad, P. N. Chem. Rev., 2008, 108, 1245–1330.

27. Sheik-Bahae, M.; Said, A. A.; Wei, T. H.; Hagan, D. J.; Van Stryland, E. W. IEEE J. Quant. Electron, 1990, 26, 760–769.

28. He, G. S.; Lin, T. C.; Prasad, P. N.; Cho, C. C.; Yu, L. J. Appl. Phys. Letts., 2003, 82, 4717–4719.

29. Mansour, K.; Soileau, M. J.; Van Stryland, E. W. J. Opt. Soc. Am., 1992, B9, 1100–1109.

30. Meng, J. H. B.; Dalton, L. D.; Wu, S. T. Mol. Cryst. Liq. Cryst. 1994, 250, 303–314.

31. Amatatsu, Y.; Hosokawa, M. J. Phys. Chem. A, 2004, 108, 10238–10244.

32. Nagano, Y.; Ikoma, T.; Akiyama, K.; Tero-Kubota, S. JACS, 2003, 125, 14103–14112.

29

CHAPTER 3

SYNTHESIS AND CHARACTERIZATION OF A NEW CLASS OF BODIPY DYES-

DITRIAZOLYLMETHENE DYES AND THEIR DERIVATIVES

3.1 Introduction

When C-atom from dipyrrin is replaced by an N-atom at the meso position, the intensity

of the fluorescence was significantly red-shifted. In this chapter the attempt of replacement of C-

atom by N-atom at non-meso positions of the dipyrrin scaffold is described. This chapter mainly

describes the different routes of synthesis of ditriazolylmethene that were attempted.

In Scheme 3.1, 1,2,3-triazole synthesis is planned using 06C and 07C with ruthenium

catalyst10,11 and it will give 1,5-substitution. Among [Cp*RuCl] complexes

[Cp*RuCl]4, Cp*RuCl(COD), Cp*RuCl(PPh3)2, and Cp*RuCl(NBD), are the common catalysts

used in the cycloaddition of azides with terminal alkynes which leads to regioselectivity, 1,5-

disubstituted 1,2,3-triazoles. In contrast to the CuAAC, ruthenium catalyzed reaction RuAAC,

gives cycloaddition reaction of azides with internal alkynes easily to produce 1,2,3-triazoles,

providing access to fully substituted 1,2,3-triazoles.19-25The compound 08C must be treated with

TBAF to give free triazole 10C. 10C can exist in two tautomeric form 1H or 3H. Further, 10C

must be oxidized using p-chloranil to form 12C.

30

BF3

-HFNNN

R

NN NB

F F

N

N

N

N

R

N

NN

N

N

N

R

N

N

M

NHNN

R

NN N

R

SiNN N

+N+

N-N

-

SiNN N

NN

N

R

NHN NN

NNH

R

NHNH NN

NN

R

O

O

ClCl

Cl Cl

R = H, Aryl, AlkylTBAF

PT

Cp*RuCl(COD)

M = Cu,Zn

06C

07C

08C

10C

09C

12C

11C13C

Scheme 3.1. Synthesis of ditriazolylmethene and its metal chelate

In Scheme 3.2, trimethylsilylacetylene is treated with n-butyllithium to form trimethylsilyl

lithium acetylide. When trimethylsilyl lithium acetylide is treated with α,α- dibromobenzene it

will form the compound 14C through SN2 reaction. Treating 14C with TBAF will result in the

formation of 06C.

31

Br

Br

Si(CH3)3

Si(CH3)3

Si(CH3)3

n butyllithiumSi(CH3)3Li

Si(CH3)3Li

THF, TBAF

14C

06C

Scheme 3.2. Synthesis of penta-1,4-diyn-3-ylbenzene (06C) from α,α- dibromobenzene

In Scheme 3.3, the compound 07C is oxidized to form 08C with DDQ. When 08C is

treated with trimethylsilyl lithium acetylide it will attack carbonyl carbon and an intermediate of

lithium alkoxide salt is formed. After quenching with NaHCO3 it is protonated and gives 09C.

The trimethylsilyl groups can be cleaved with TBAF and 10C will be formed. When 10C is

treated with TFA and triethylsilane the mixture of 06C, 12C, 61C and 13C is expected to be

formed.

32

OH O

OH

Si(CH3)3

DDQ

OH

TFAEt3SiH

Si(C2H5)3

Si(C2H5)3

+

Si(C2H5)3

H

+

H

H

66%

26%

66%

07C 08C

09C

10C

06C 12C 13C

1. LiCCSi(CH3)3, THF, -78 oC 2. NaHCO3

TBAF CH2Cl2

Si(C2H5)3

Si(CH3)3

+

61C

Scheme 3.3. Synthesis of penta-1,4-diyn-3-ylbenzene (06C) The starting from 1-phenyl-2-propyn-1-ol

In Scheme 3.4, toluoyl chloride will be treated with trimethylsilyl lithium acetylide. First,

trimethylsilyllithium acetylide will attack to the carbon atom of the carbonyl group and negative

charge will be created on the oxygen atom. A double bond will be formed between the carbon

33

atom and oxygen atoms and chloride will leave. Again, another trimethylsilylithium acetylide

will attack the carbon atom of carbonyl carbon atom. After quenching with NaHCO3 21C will be

formed. Trimethylsilyl groups of 21C can be cleaved with TBAF to form 24C. Azide-Alkyne

Huisgen cycloaddition is carried out between 24C and 25C in the presence of Cp٭RuCl(COD)

catalyst to synthesize 26C.

OHSi(CH3)3

Si(CH3)3

Si(CH3)3

Si(CH3)3

OHSi(CH3)3

Si(CH3)3

OH

OH

+ SiNN

+N

-

NN+

N-

Cp*Ru Cl (COD)Toluene

OH

N NN

NN NSi

TFA, Et3SiH

rt

89%

25C26C

23C

24C

TBAF

THF

CH Si(CH3)3 Li Si(CH3)3

Cl

O 1. Li Si(CH3)3,

BuLi

THF, -78 °C

, THF, -78 °C

2. NaHCO3 29%

18C 19C

20C 21C

OH

Si(CH3)3

Si(CH3)3

Scheme 3.4. Synthesis of ditriazolylmethane 26C

In Scheme 3.5, tolualdehyde is treated with triisopropylsilyllithium acetylide then

quenching with NaHCO3 to form 29C. Then 29C is treated with triisopropylsilyl acetylene in the

34

presence of copper triflate to form 30C.63 Then 34C can be prepared by cleaving triisopropylsilyl

group with TBAF. In the mechanism shown below (figure 3.1) propargyl alcohol 1 is activated

by Lewis or Brønsted acid to form carbocation A. Now the nucleophilic attack of alkyne 2 will

form alkenyl cation B. After this step two pathways are possible path I, proton elimination and

path II, hydrolysis. Path I will give 1,4-diynes and path II will give γ-alkynyl ketones.63 Since in

Scheme 3.5 30C is expected to form so molecular sieves will be used in the reaction to minimize

the path II.

Figure 3.1. Mechanism of synthesis of 1,4-dialkyne from alcohol63

35

HO

2. NaHCO3

(iPr)3Si+BuLi (iPr)3Si C:-+

Li

OHSi(iPr)3

Si(iPr)3

(iPr)3Si

99%

THF

-78 oC 27C

28C

29C

30C

1. (iPr)3SiCCLi

(iPr)3SiCCH, Cu(OTf)2

TBAF, CH2Cl2

34C

DCE, MS, 84oC

Scheme 3.5. Synthesis of 1-methyl-4-(penta-1,4-diyn-3-yl)benzene (34C) The starting from tolualdehyde and copper triflate

36

In Scheme 3.6, a Corey-Fuchs procedure is used to convert aldehyde 31C to a terminal

alkyne 34C. In 1972, Corey and Fuchs published a method in which an aldehyde could be

converted to a terminal alkyne with one carbon derivativeation.77-79 This is a one pot synthesis of

alkyne which proceeds through two steps. In the first step CBr4 and PPh3 reagents are used to

convert aldehyde into dibromoolefin with derivativeation of one carbon atom, is called Ramirez

olefination.80 In the second step n-butyllithium is used followed by protonation with water to

form the alkyne.

OH

H

O CBr4, PPh3

DCM

HBr

Br

H Br

Br

HBr

Br

H

O

1. BuLi 2. H2O

31C 32C

34C33C

H

H

O

OH

35C

Scheme 3.6. Synthesis of 1-methyl-4-(penta-1,4-diyn-3-yl)benzene (34C) The starting with toluoyl malondialdehyde

37

O

H

HO

SiOH

H

HO tBDPSi

CH2Cl2, Ar, rt

tBDPSi = (CH3)3CSi(Cl)(C6H5)2

42C

36%

H

H

O

OH

H

O

H

O

O

+O

H

O

O

O

O

O

O

H

TFA

DCM

40C

41C

Scheme 3.7. Proctection of enolic proton of toluoyl malondialdehyde

Oxidative cyclization of nitriles can be done with amidines in the presence of CuI. Atmospheric

oxygen will be used as an oxidant.73 This type of oxidative cyclization gives 1,2,4-triazole

(Scheme 3.8).

38

I CN

CN

CN

CN

CuI, K2CO3 DMSO, Reflux

H3CC(NH)(NH2), CuI, Cs2CO3 DMSO, 120 oC

NHNN

N

NH

N

DDQ, KH2PO4 DCM

NNN

NNH

N

+ 43C

44C

45C

46C

Scheme 3.8. Synthesis of (5Z)-3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-triazole (46C) The starting from phenylpropanedinitrile

3.2 Synthesis

3.2.1 General Procedure

All manipulations were carried out under an atmosphere of purified argon using standard


over molecular sieves and degassed by purging with argon gas. All other chemicals were reagent

39

grade and were used as received. Glassware were oven-dried at 150ºC overnight. NMR solvent

CDCl3 was reagent grade and stored over 4 Å molecular sieves prior to use. Analytical TLC was

performed on glass backed, pre-coated silica gel plates and visualization was accomplished with

UV light. Silica gel 60 μm (average particle size) was used for column chromatography. UV-vis

data were collected with a Varian Cary spectrophotometer. 400 MHz was used for 1H and 13C

NMR spectra in CDCl3 unless noted otherwise.


• Synthesis of 1-phenylprop-2-yn-1-one (08C)

A round bottom flask with a stir bar was charged with 07C (1.88g, 14.0 mmol), DDQ

(3.18 g, 14.0 mmol) and dichloromethane (140 mL). The reaction was run overnight and TLC

was performed using eluent hexanes: dichloromethane in 1.5:1 ratio. The starting compound was

seen in TLC. The reaction was left stirring 3 days. The reaction mixture was filtered through

silica gel using dichloromethane. The filtrate was concentrated. The product was collected as a

light orange liquid (1.21 g, 9.30 mmol, yield = 66%), 1H NMR (CDCl3) δ 3.38 (s, 1H), 7.26-

7.29 (t, 2H), 7.39-7.43 (t, 1H), 7.94-7.95 (d, 2H).

• Synthesis of (09C)

An oven-dried round bottom flask with a stir bar was charged with 08C (0.10 g, 0.77

mmol) and kept under argon gas. Dry tetrahydrofuran (15 mL) was added in it. Another oven-

dried round bottom flask with a stir bar was charged with trimethylsilyl lithium acetylide (0.50

M, 6.10 mL, 3.07 mmol) and dry tetrahydrofuran (10 mL) and kept under argon gas for 20

minutes. The solution of the first round bottom flask was transferred to the second round bottom

flask drop by drop with an oven-dried glass syringe. A red color appeared in the mixture. After 4

hours the reaction was evaluated by thin layer chromatography using the eluent hexanes:

40

dichloromethane in 1:1.5 ratio and it was found that all the starting compound 08C was

consumed. The reaction mixture was quenched with saturated solution of NaHCO3. It was

extracted with diethyl ether and deionized water. The organic layer was separated and dried over

anhydrous MgSO4. Then it was filtered, concentrated and purified by rotary chromatography.

The product (0.05 g 0.20 mmol, yield = 26%) 1H NMR (CDCl3) δ 0.23 (s, 9H), 1.64 (s, 1H),

2.79 (s, 1H), 7.38-7.40 (d, 3H), 7.78-7.80 (d, 2H).

• Synthesis of 3-phenylpenta-1,4-diyn-3-ol (10C)

A round bottom flask with a stir bar was charged with 09C (0.84 g, 3.70 mmol),

tetrabutylammonium fluoride (0.97g, 3.70 mmol) and tetrahydrofuran (25 mL). The reaction was

stirred for 1 hour at ambient temperature. The reaction mixture was concentrated and filtered

through silica gel and purified by rotary chromatography. The product (0.05 g, yield = 6%), 1H

NMR (CDCl3) δ 2.80 (s, 2H), 2.94 (s, broad, OH), 7.37-7.43 (t, 3H), 7.80-7.82 (d, 2H).

Synthesis of 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol , (21C)

An oven-dried round bottom flask with a stir bar was purged with argon for 10 minutes.

Dry THF (20 mL) was transferred with an oven-dried glass syringe and trimethylsilyl acetylene

(1.01 mL, 7.10 mmol) was added to it. Then the round bottom flask was merged in isopropyl

alcohol and a dry ice bath was applied to make the temperature -78ºC and n-butyllithium (4.93

mL, 7.10 mmol) was added. The reaction was run for one hour. Isopropyl alcohol and dry ice

were removed. At room temperature, toluoyl chloride (0.50 g, 3.23 mmol) was added and the

reaction was left running overnight. Then, it was quenched with saturated ammonium chloride

solution. Then it was extracted with deionized water and ether. The organic layer was separated

and dried over anhydrous magnesium sulfate. The mixture was purified by rotary

chromatography using the eluent hexanes: ethyl acetate in 10:1 ratio. The product was dried

41

under high vacuum. The product (0.40 g, 1.26 mmol, yield = 39%), 1H NMR (CDCl3) δ 0.22 (s,

1H), 2.37 (s, 3H), 2.78 (s, 1H), 7.18-7.20 (d, 2H), 7.66-7.69 (d, 2H). 13C NMR (75 MHz, CDCl3)

δ 0.031, 21.50, 65.83, 90.18, 104.96, 126.31, 129.31, 138.84, 139.01.

Synthesis of 3-(4-methylphenyl)penta-1,4-diyn-3-ol (24C)

In a round bottom flask with a stir bar 21C (0.14g, 0.44 mmol) was dissolved in 20 mL

THF and tetrabutylammonium fluoride (0.88 mL, 0.88 mmol) was added in it. The reaction was

run for one hour. After one hour the mixture was concentrated and filtered through silica gel

using the eluent ethyl acetate. Then the filtrate was concentrated and purified using rotary

chromatography and hexanes: dichloromethane in 1.5:1 ratio. The product was dried under high

vacuum. The product (0.07 g, 0.39 mmol, yield = 89%), 1H NMR (CDCl3) δ 2.37 (s, 3H), 2.78

(s, 1H), 7.21-7.22 (d, 2H), 7.68-7.70 (d, 2H).

• Synthesis of 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol, (29C)

An oven-dried round bottom flask with a stir bar was purged with argon gas for 10

minutes. Dry THF (75 mL) was added and the vessel was purged with argon for 10 minutes.

Triisopropylsilylacetylene (1.01 mL, 4.58 mmol) was added. Then, n-butyllithium (4.32 mL,

4.576 mmol) was added. The mixture changed to milky white appearance which disappeared

after 2-5 minutes. The reaction was run for 1 hour then p-tolualdehyde (0.50 g, 4.2 mmol) was

added in it. After 4 hours TLC was done using the eluent hexanes: dichloromethane in 1:1.5

ratio. The starting material was not consumed completely. The reaction was run overnight.

Afterwards, the color was changed to pale yellow. Then the mixture was quenched with saturated

solution of sodium bicarbonate. It was first extracted with hexanes and deionized water then with

brine. The organic layer was separated and dried over anhydrous sodium sulfate. The organic

layer was concentrated and purified using rotary chromatography and the eluent hexanes:

42

dichloromethane in 1: 1.5 ratio. The product was concentrated and kept under high vacuum. The

product (1.25 g, 4.10 mol, yield = 99%), 1H NMR (CDCl3) δ 1.09 (s, 21H), 2.36 (s, 3H), 5.44-

5.45 (d, 1H), 7.18-7.20 (d, 2H), 7.46-7.48 (d, 2H).

• Synthesis of 1-methyl-4-(1,1,5,5- tetrabromopenta-1,4-dien-3-yl)benzene (32C)

An oven-dried round bottom flask with a stir bar was charged with carbon tetrabromide

(0.82 g, 2.48 mmol) and dry dichloromethane (40 mL) and kept under argon gas. The round

bottom flask was submerged in ice bath to make the temperature 0ºC. After 10 minutes PPh3

(1.26 g, 4.80 mmol) was added in it. The color of the mixture changed to orange. Then toluoyl

malondialdehyde (0.40 g, 2.48 mmol) was adeed in it and ice bath was removed. The orange

color of the mixture was disappeared. The reaction mixture was evaluated by thin layer

chromatography and it was noticed that all the starting compound was consumed. The reaction

mixture was extracted with dichloromethane and deionized water. The organic layer was

separated and dried over anhydrous Na2SO4. The product was purified by rotary chromatography

using hexanes: dichloromethane in 1.5:1 ratio, concentrated in rotary evaporation and kept under

high vacuum. The product (0.08 g, Yield = 6%), 1H NMR (CDCl3) δ 1.59 (s, 1H), 2.43 (s, 3H),

7.19-7.21 (d, 2H), 7.65 (s, 1H), 9.66 (s, 1H).

• Synthesis of 4,4-dibromo-2-(4-methylphenyl)but-3-enal (33C)

An oven-dried round bottom flask with a stir bar was charged with carbon tetrabromide

(CBr4) (0.41 g, 1.23 mmol) and dry dichloromethane (15 mL), submerged in ice bath and kept

under argon gas. PPh3 (0.65 g, 2.50 mmol) was added in it. After 40 minutes triethylamine (0.39

mL) was added and the color of the mixture was changed to dark orange. After 2 hours the color

was changed from dark orange to purple. Then toluoyl malondialdehyde (0.20 g, 1.23 mmol) was

added and the reaction was left running overnight at ambient temperature. The reaction mixture

43

was extracted with deionized water and dichloromethane. The organic layer was separated and

dried over anhydrous Na2SO4. It was filtered, concentrated and purified by rotary

chromatography using hexanes: dichloromethane in 1.5:1 ratio. The product was collected,

concentrated and kept under high vacuum. The product (0.03 g, yield = 7%), 1H NMR (CDCl3) δ

2.44 (s, 3H), 6.26- 6.29 (d, 1H), 7.01- 7.04 (d, 1H), 7.10-7.13 (d, 2H), 7.28- 7.30 (d, 2H), 9.69 (s,

1H).

• Synthesis of (2Z)-3-hydroxy-2-(4-methylphenyl)prop-2-enal (35C)

An oven-dried round bottom flask with a stir bar was charged with CBr4 (0.20 g, 0.62

mmol) and dichloromethane (5 mL). It was kept under argon gas and was ubsmerged in an ice

bath to make the temperature 0ºC. Then PPh3 (0.33 g, 1.25 mmol) was added in it. The color

changed to orange. After 10 minutes TEA (0.20 mL, 1.40 mmol) was added. The change in color

from orange to purple was noticed after 35 minutes. In another oven-dried round bottom flask

toluoyl malonodialdehyde (0.10g, 0.61 mmol) was dissolved in dry dichloromethane (2.5 mL)

and transferred to the first round bottom flask. The reaction was evaluated by TLC using the

eluent hexanes: ethyl acetate in 3:1 ratio. The starting compound was not consumed completely.

The reaction was left running overnight. Then the reaction mixture was distillated by rotary

evaporation to remove the solvent. Then it was filtered through silica gel using the eluent

hexanes: dichloromethane in 1.5:1 ratio, and purified by rotary chromatography using the eluent

hexanes: dichloromethane in 1.5:1 ratio. The product was concentrated and kept under high

vacuum. The product (0.04 g, 0.13 mmol, yield = 41%).

• Synthesis of (Z)-5-[tert-butyl(diphenyl)silyl]oxy-3-(p-tolyl)pent-4-en-2-one (42C)

An oven-dried round bottom flask with a stir bar was charged with toluoyl

malonodialdehyde (0.40g, 2.50 mmol) and kept under argon gas. Dry dichloromethane (20 mL)

44

was added in it. When all the toluoyl malonodialdehyde was dissolved in dichloromethane, t-

butyl chlorodiphenyl silane (1.02 g, 3.70 mmol) and triethylamine (0.34 mL, 2.50 mmol) was

added. The reaction was evaluated by TLC using the eluent hexanes: diethyl ether in 3: 1 ratio.

Hence the the starting compound was not consumed completely reaction was run overnight.

Then the mixture was concentrated and purified in rotary chromatography using the eluent

hexanes: diethylether in 3:1 ratio. The compound was collected, concentrated and kept under

high vacuum. The product (0.36 g, 0.90 mmol yield = 36%) 1H NMR (CDCl3) δ 1.07 (s, 9H),

2.38 (s, 3H), 5.30 (s, 1H), 7.15 (s,1H), 7.22-7.24 (d, 2H), 7.36-7.45 (m, 5H), 7.48-7.52 (t, 3H),

7.62-7.64 (d, 3H), 7.70-7.72 (d, 1H), 9.26 (s, 1H).

• Synthesis of phenylpropanedinitrile (44C)

A two-necked oven-dried round bottom flask with a stir bar was charged with

malononitrile (0.26 g, 1.96 mmol), CuI (0.04 g, 1.96 mmol) and K2CO3 (1.09 g, 1.96 mmol). An

oven-dried condenser was set on it. Dry dimethyl sulfoxide (5 mL) was added. Then

iodobenzene (0.40 g, 1.96 mmol) was added in it. The mixture was refluxed overnight. Then, it

was cooled to room temperature and quenched with dilute hydrochloric acid. The mixture was

extracted with deionized water and diethyl ether. The organic layer was separated and dried over

anhydrous Na2SO4. The product was purified by rotatory chromatography using the eluent

hexanes: ethyl acetate in 6:1 ratio. The second band was collected, concentrated and kept under

high vacuum for 1 hour and the sample was taken for NMR. The product (0.10 g, 0.70 mmol,

Yield = 36%) 1H NMR (CDCl3) δ 5.07 (s, 1H), and 7.50 (s, 5H).

• Synthesis of 1-(p-tolyl)-3-trimethylsilyl-prop-2-yn-1-one (51C)

A round-bottom flask with a stir bar was charged with 29C (1.25 g, 4.10 mmol) and 2,3-

Dichloro-5,6-dicyano-1,4-benzoquinone (0.93g, 4.10 mmol). Dichloromethane (140 mL) was

45

added in it. The color of the mixture changed to green. The reaction was left running for 3 days

and the color changed to orange. The mixture was concentrated and filtered through silica gel to

remove unreacted DDQ and purified by rotary chromatography using the eluent hexanes:

dichloromethane in 1:1.5 ratio. The product (1.08 g, yield = 87%) had following data 1H NMR

(CDCl3) δ 1.16 (s, 21H), 2.43 (s, 3H), 7.28-7.30 (d, 2H), 8.06-8.08 (d, 2H)

Si

OH

DDQSi

O

51C29C

Figure 3.2. Oxidation of 29C using DDQ

3.2.3 Characterization and Physical Properties

X-ray crystallographic data were collected by Dr. Vladimir Nesterov from the University

of North Texas, who also provided the following description of the crystallographic data and

details. Crystal structure determination for all complexes were carried out using a Bruker

SMATR APEX2 CCD-based X-ray diffractometer equipped with a low temperature device and

Mo-target X-ray tube (wavelength = 0.71073 Å). Measurements were taken at 100(2) K.

A few milligrams of phenylpropanedinitrile (44C) was dissolved in a minimum of

dichloromethane to make a saturated solution. The solution was left 3 days in the dark under the

fume hood. After 3 days pale yellow colored crystals were formed and the crystals were taken

for crystallography. The crystal structure of phenylpropanedinitrile is given in figure 3.3 and

other information is given in table 3.1in detail.

46

Figure 3.3. Crystal structure of phenylpropanedinitrile

Table 3.1 Crystallography data for phenylpropanedinitrile

Identification code p21c

Empirical formula C9 H6 N2

Formula weight 142.16

Temperature 100(2) K

Wavelength 0.71073 Å

Crystal system Monoclinic

Space group P 21/c

Unit cell dimensions a = 7.7578(9) Å = 90° .

b = 5.8315(7) Å = 101.061(2)° .

c = 15.9544(18) Å = 90° .

Volume 708.36(14) Å3

47

Z 4

Density (calculated) 1.333 Mg/m3

Absorption coefficient 0.083 mm-1

F(000) 296

Crystal size 0.27 x 0.20 x 0.04 mm3

Theta range for data collection 2.60 to 27.10°.

Index ranges -9<=h<=9, -7<=k<=7, -20<=l<=20

Reflections collected 9171

Independent reflections 1563 [R(int) = 0.0250]

Completeness to theta = 27.10° 99.6 %

Absorption correction Semi-empirical from equivalents

Max. and min. transmission 0.9970 and 0.9777

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 1563 / 0 / 100

Goodness-of-fit on F2 1.040

Final R indices [I>2sigma(I)] R1 = 0.0322, wR2 = 0.0882

R indices (all data) R1 = 0.0364, wR2 = 0.0929

Largest diff. peak and hole 0.268 and -0.165 e.Å-3

A few milligrams of 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol (21C) was

dissolved in minimum dichloromethane to make a saturated solution and left in the dark under

the hood for 3 days. Light orange colored crystals were formed which were taken for

crystallography. The crystal structure of (21C) is given in figure 3.4 and other information are

given in Table 3.2 in detail.

48

Figure 3.4. The crystal structure of 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol (21C)

Table 3.2. Crystalography data 3-(p-tolyl)-1,5-bis(trimethylsilyl)penta-1,4-diyn-3-ol , (21C)

Identification code c2c

Empirical formula C18 H26 O Si2





Space group C 2/c

Unit cell dimensions a = 15.6380(10) Å a= 90°.

b = 12.6630(9) Å b= 102.3610(10)°.

49

c = 20.8729(14) Å g = 90°.

Volume 4037.5(5) Å3

Z 8



F(000) 1360



Index ranges -20<=h<=20, -16<=k<=16, -26<=l<=26












3.3 Results and Discussions

To synthesize 06C, an oven-dried round bottom flask with magnetic stir bar was charged

with NaNH2 (0.31 g, 7.82 mmol) under argon gas. Dry diethyl ether (12 mL) was added in it.

50

Then, trimethylsilylacetylene (0.70 g, 7.10 mmol) was added. The color was changed to milky

white. α,α–dibromotoluene (0.81 g, 3.23 mmol) was added and the reaction was left overnight.

Then, reaction mixture was quenched with saturated solution of NaHCO3 and extracted with

diethyl ether and deionized water. The organic layer was separated and dried over anhydrous

MgSO4. Unfortunately the product 06C was not formed and the starting compound α,α-

dibromotoluene was recovered. Now, an oven-dried round bottom flask with magnetic stir bar

was charged with trimethylsilyllithium acetylide (7.76 mL, 3.88 mmol) and kept under argon

gas. Dry tetrahydrofuran (15 mL) was added in it. Then α,α–dibromotoluene (0.50 g, 1.94 mmol)

was added and reaction was left overnight. Then it was quenched with saturated solution of

NaHCO3 and extracted with diethyl ether and deionized water. The organic layer was separated

and dried over anhydrous MgSO4. The product was purified. Again, unfortunately The starting

compound α,α–dibromotoluene was recovered. It was concluded that the presence of two

electronegative atoms (bromine atoms) facilitate deprotonation of benzylic proton rather than the

substitution of bromine by trimethylsilylsodium acetylide/ trimethylsilyl lithium acetylide.

The compound 08C was synthesized by the oxidation of 1-phenyl-2-propyn-1-ol with

2,3-dichloro-5,6-dicyano-1,4-benzoquinone as given in experimental section. Then the

compound 09C was synthesized which is also described in experimental section of this

dissertation. The compound 09C was treated with tetrabutylammonium fluoride to cleave

trimethylsilyl group to form the compound 10C. The compound 10C was treated with

trifluoroacetic acid and triethylsilane. It was expected that the mixture of three compounds 06C.

12C and 13C will be formed. When the resulting mixture was evaluated by thin layer

chromatography a very large number of compounds were seen and it was not worthwhile to

purify the mixture.

51

To synthesize the compound 21C, n-butyllithium was titrated with diphenyl acetic acid.

n-butyllithium was treated with trimethylsilylacetylene (TMS-acetylene) to prepare lithium

trimethylsilylacetylide. p-toluoyl chloride was added in lithium trimethylsilyl acetylide. Then the

mixture was quenched with saturated solution of ammonium chloride. The compound 21C was

prepared successfully.

To synthesize the compound 23C, 21C was dissolved in dichloromethane under argon

gas (under inert condition) and triethylsilane was added. Then trifluoroacetic acid (TFA) was

added in it expecting to synthesize the mixture of compounds 06C, 12C, 61Cand 13C. Later, the

reaction was planned to treat with tetrabutyl ammonium fluoride (TBAF) to get the final product

23C. Unfortunately, the reaction did not succeed. A large number of compounds was formed in

the mixture and it was not possible to purify the compounds formed in the mixture and identify

them. When the synthesis of 6C, 12C, 61C and 13C did not succeed according to Scheme 3.3

compound 22C was used as it is to proceed to further reaction as given in Scheme 3.4. The

compound 22C was treated with tetrabutylammonium fluoride to synthesize 3-(4-

methylphenyl)penta-1,4-diyn-3-ol (24C). The detail of this reaction is given in the experimental

section. The next step was to make the click reaction by the ruthenium catalyzed 1,3-dipolar

azide-alkyne cycloaddition. An oven-dried round bottom flask with magnetic stir bar was

charged with Cp*RuCl(COD) (0.01 g) and purged with argon gas three times. Another oven-

dried round bottom flask with magnetic stir bar was charged with 24C (0.18 g, 1.10 mmol) and

25C (0.28 g, 1.10 mmol) and it was also purged with argon gas three times. Then dry toluene (5

mL) was added in both of the flasks. The second flask’s solution was canulated to the first flask.

The color of the mixture was changed to dark brown immediately. Progress of the reaction was

evaluated by thin layer chromatography. A very polar spot was noticed in TLC which did not

52

move in very polar solvents like acetone and ethanol. It was assumed that the product might have

been polymerized which is a drawback of double azide-alkyne cycloaddition. The mixture was

treated with NaF and ethanol and again it was evaluated by TLC. There was no change in TLC.

Now the mixture was treated with acetic acid and triethylamine and again evaluated by TLC.

TLC showed the same result. It was assumed that the –OH group at benzylic position might have

been reacted with Cp*RuCl(COD) catalyst. Now, it was necessary to synthesize the compound

06C or 34C and another route was followed which is given in Scheme 3.5.

In Scheme 3.5 tolualdehyde was treated with triisopropylsilyllithium acetylide to

synthesize the compound 29C. An oven-dried round bottom flask with stir bar was charged with

the compound 29C (0.40 g, 1.32 mmol) and dichloroethane (12 mL) and purged with argon gas

for 5 minutes. Another oven-dried round bottom flask with a stir bar was charged with Cu(OTf)2

(0.05 g, 0.13 mmol) and a reflux condenser was connected. The solution from the first round

bottom flask was transferred in second round bottom flask. Then trimethylsilyl acetylene

(0.129g, 0.13 mmol) was added in it. Round bottom flask was submerged in preheated oil bath

(84ºC). The reaction was refluxed for 5 minutes. The color of the mixture was changed to green.

Then the oil bath was removed. The product was purified by rotary chromatography.

Unfortunately the compound 30C was not formed. Instead, it appears that the compound 1,1'-

deca-1,4,6,9-tetrayne-3,8-diyldibenzene 49C and / or 50C was formed through Eglington

coupling. The NMR spectrum of this compound is given in given below in figure 3.5.

53

49C

50C

Figure 3.5. 1H NMR of 49C

In Scheme 3.6, Corey- Fuchs reaction was carried out to synthesize the compound 34C.

When toluoyl malondialdehyde was treated with PPh3 and CBr4 in the presence of triethylamine

in the place of 32C the compound 33C was formed. When toluoyl malondialdehyde was treated

with PPh3 and CBr4 the compound 32C was formed but the yield was very low. It was assumed

that the reason of low yield and the formation of the compound 33C was the enolic form of the

the starting compound toluoyl malondialdehyde as given below. There is possibility of hydrogen

bonding between enolic hydrogen and the oxygen atom of aldehyde group. IH NMR of the

compound is given in figure 3.6.

54

H

O

OHH

Enolic tautomer of toluoyl malondialdehyde

Figure 3.6. 1H NMR of toluoyl malondialdehyde

Now, it was necessary to protect the enolic proton. To protect the enol toluoyl

malondialdehyde was treated with acetic anhydride as given in Scheme 3.9. After work up and

purification it was found that the compound 36C was formed in a very little quantity and

majority of the compound fomed was 37C. Multiple acylation took place. The 1H NMR of these

two compounds are given in the Appendix.

Now toluoyl malondialdehyde was treated with dihydropyran as given in Scheme 3.7 to

form 40C. Again the majority of the compound was 41C not 40C.

55

H

H

O

OH

H

O

H

O

O

(Ph3P+CH2Br)Br-, t - BuOKTHF, -780C

H O

O

OO

O

OO

O

Ac2O, DMAP

CH2Cl2

Ac2O, TEA CH2Cl2

H

H

O

O

H

Br

1. BuLi 2. H2O

36C

37C

38C

39C

Scheme 3.9. Protection of enol of toluoyl malonaldehyde

When the protection of enol of toluoyl malondialdehyde with acetic anhydride or

dihydropyran did not give satisfactory result t-butylchlorodiphenyl silane was used for

protection. To protect the enolic proton of toluoyl malondialdehyde, it was treated with t-butyl

chlorodiphenyl silane and the compound 42C was synthesized. More information about the

synthesis of 42C is given in experimental section and further reactions are planned and given in

conclusion and future works of this chapter. 1H NMR and 13C NMR of this compound is given in

appendix.

When the synthesis of 06C took long time and many routes were followed and

simultaneously some other reactions were carried out to synthesize 10C and/or 12C. One of

56

them is given in Scheme 3.8. Several routes and attempts were carried out to synthesize

phenylpropanedinitrile (44C). In the first attempt, an oven-dried round bottom flask with a stir

bar was charged with KI and KCN. Dry DMF was added in it then alpha, alpha-dibromotoluene

was added. The reaction was refluxed overnight. First the color changed to brownish yellow,

then after 30 minutes brownish yellow color was disappeared. The reaction mixture was

evaluated by thin layer chromatography using silica gel plate as stationary phase and hexanes as

solvent. The starting compound (alpha, alpha-dibromotoluene) was not consumed completely.

The reaction was left running overnight. Then the color of the reaction mixture was yellow. The

reaction mixture was quenched with 2 M H3PO4. Then it was extracted with deionized water and

hexanes. The organic layer was separated and dried over anhydrous Na2SO4. The product was

purified by rotary chromatography using hexanes as solvent. The product was collected,

concentrated and dried over high vacuum and taken for NMR. The crystals of the product were

grown from dichloromethane solution. From the crystallography it was confirmed that the

crystals have monoclinic structure and the product was not phenylpropanedinitrile but (E)-

stilbene. Crystal structure of (E)–stilbene is given below in figure 3.8 and its other information

are given in Table 3.3. This crystal structure is already known in the literature.

Br

Br1. KCN, KI, DMF, Reflux

2. 2M H3PO4

CN

CN

44C

Figure 3.7. Formation of (E) Stilbene instead of 44C

57

Figure 3.8. The crystal structure of (E) - Stilbene

Table 3.3. Crystallography data for (E) - Stilbene

Identification code p21c

Empirical formula C14 H12





Space group P 21/c


58

b = 5.6808(11) Å b= 111.890(3)°.

c = 12.298(2) Å g = 90°.

Volume 1008.2(3) Å3

Z 4



F(000) 384



Index ranges -19<=h<=19, -7<=k<=7, -15<=l<=15












59

When the synthesis of 44C did not succeed from alpha,alpha-dibromotoluene a new route

was followed which is given in Scheme 3.8. When iodobenzene was treated with CuI, K2CO3

and malononitrile 44C was formed. Then, a pressure vessel with a stir bar was charged with

phenylmalononitrile 44C (0.08 g, 0.53 mmol), acetamidine (0.15 g, 1.60 mmol) Cs2CO3 (1.03 g,

3.16 mmol), CuI (0.01 g, 0.05 mol) and dimethylsulfoxide (1 mL) and sealed tightly. It was

heated in an oil bath at 120ºC for 24 hours. After 24 hours reaction was cooled to room

temperature and diluted with ethyl acetate. Then it was washed with a saturated solution of

NaHCO3 followed by deionized water. The organic layer was separated and dried over

anhydrous MgSO4, then concentrated and purified by rotary chromatography. A pink colored

compound was obtained. The yield of the compound was very low (< 1mg) so it could not be

characterized by NMR spectroscopy. UV-vis spectroscopy of the compound was done. In UV-

vis dipyrromethene gives a specific absorbance peak around 500nm which was seen in the UV-

vis of the pink compound. It is expected to be the compound 46C but further characterization is

needed to confirm the compound. The UV- vis spectrum of the pink compound is given below in

Figure 3.10

60

NN

N

NH

N

N

Figure 3.9. The structure of (5Z)-3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-

triazole (46C)

Figure 3.10. UV-vis of pink compound 1H- 1,2,4 Ditriazolylmethene (expected compound (5Z)-

3-methyl-5-[phenyl(1H-1,2,4-triazol-3-yl)methylene]-1,2,4-triazole (46C))

In the synthesis of 1H- 1,2,4 ditriazolylmethene (48C), an oven-dried round bottom flask

with a magnetic stir bar was charged with 21C (0.05 g, 0.16 mmol) and sodium azide (0.02 g,

0.16 mmol) and kept under argon gas. Then, dry dimethyl sulfoxide (5 mL) was added and the

reaction was run overnight at ambient temperature. Then, the reaction mixture was quenched

with dilute hydrochloric acid. It was extracted with deionized water and ethyl acetate. The

organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. A

few miligrams of the product were dissolved in dichloromethane to make a saturated solution

and left in dark under the hood for 48 hours. Pale yellow crystals were formed and crystal

structure was analyzed which is given below in Figure 3.12.

61

OHTMS

TMS

1. NaN3, DMSO, room temperature

2. Dilute HCl

OH

N NNH

TMSN

NNH

TMS

O

NNH

N47C

48C

21C

Figure 3.11. Synthesis of 47C

Figure 3.12. Crystal structure of p-tolyl(2H-triazol-4-yl)methanone (47C)

62

Table 3.4. Crystallography data p-tolyl(2H-triazol-4-yl)methanone

Identification code basf

Empirical formula C10 H9 N3 O





Space group C c


b = 11.6891(9) Å b= 92.4470(10)°.

c = 10.4713(8) Å g = 90°.

Volume 1784.2(2) Å3

Z 8



F(000) 784



Index ranges -18<=h<=18, -14<=k<=14, -13<=l<=13





63









The compound 42C was synthesized successfully. Now it has to be treated with PPh3 and

CBr4 to synthesize the compound 52C. Then 52C will be reacted first with BuLi then with H2O

to synthesize 53C. Then, 53C is to be treated with tetrabutylammonium fluoride followed by

methanol to produce 54C. Next the compound 54C must be reacted with PPh3 and CBr4 to form

55C. After treating 55C with BuLi then with water the Compound 34C will be formed. After

synthesizing the compound 34C the Scheme 3.1 will be followed replacing 34C to 06C.

Scheme 3.8 was followed to synthesize the compound 46C. In the step where reaction

was set up for the synthesis of the compound 45C, a pink colored compound was obtained. The

compound was not enough to do NMR spectroscopy. UV-vis of the pink compound gave the

absorption around 500 nm which is the specific character of dipyrromethene. For further

characterization more amount of the compound is needed.

64

OBr

Br H

52C

O

H

HO

PPh3, CBr4 CH2Cl2

42C

1. BuLi 2. H2O

O

H53C

H

O PPh3, CBr4

CH2Cl2 H

Br

Br1. BuLi

2. H2O

54C 55C 34C

TBAF CH3OH

Scheme 3.10. Synthesis of 34C starting from protected toluoyl malondialdehyde

65

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41. Kee, H.; Kirmaier, C.; Yu, L.; Thamyongkit, P.; Youngblood, W.; Calder, M.; Ramos, L.; Noll, B.; Bocian, D.; Scheidt, W.; Birge, R.; Lindsey, J.; Holten, D. J. Phys. Chem. B, 2005, 109, 20433.

42. Bonnier, C.; Piers, W.; A. Al-Sheikh, A. Thompson, M. Parvez, Organometallics, 2009, 28, 4845.

43. Bonnier, C.; Piers, W.; Parvez, M.; Sorensen, T. Chem. Commun., 2008, 38, 4593.

44. (a) Kim, T.; Castro, J.; Loudet, A.; Jiao, J.; Hochstrasser, R.; Burgess, K.; Topp, M.; J. Phys. Chem. 2006, 110, 20; (b) Wan, C.; Burghart, A.; Chen, J.; Bergström, F.; Johansson, L.; Wolford, M.; Kim, T.; Topp, M.; Hochstrasser, R.; Burgess, K. Chem. Eur. J., 2003, 9, 4430.

45. Strachan, J.; O'Shea, D.; Balasubramanian, T.; Lindsey, J. J. Org. Chem., 2000, 65, 3160.

46. (a) Baruah, M.; Qin, W.; Vallee, R.; Beljonne, D.; Rohand, T.; Dehaen,W.; Boens, N.; Org. Lett., 2005, 7, 4377; (b) Rohand, T.; Baruah, M.; Qin, W.; Boens, N.; Dehaen, W. Chem. Commun., 2006, 266.

47. Rihn, S.; Retailleau, P.; Bugsaliewicsz, N.; De Nicola, A.; Ziessel, R. Tetrahedron Lett., 2009, 50, 7008.

48. Fron, E.; Coutino-Gonzalez, E.; Pandey, L.; Sliwa, M.; Van der Auweraer, M.; De Schryver, F.; Thomas, J.; Dong, Z.; Leen, V.; Smet, M.; Dehaen, W.; Vosch, T. New J. Chem., 2009, 33, 1490.

68

49. Dilek, O.; Bane, S. Tetrahedron Lett, 2008, 49, 1413.

50. Dilek, O.; Bane, S. Bioorg Med Chem Lett., 2009, 19, 6911.

51. Li, L.; Nguyen, B.; Burgess, K. Bioorg. Med. Chem. Let., 2008, 18, 3112.

52. Cieslik-Boczula, K.; Burgess, K.; Nguyen, B.; Pandey, L.; De Borggraeve, W.; Van der Auweraer, M.; Boens, N. Photochem. Photobiol. Sci., 2009, 8, 1006.

53. Rohand, T.; Qin, W.; Boens, N.; Dehaen, W. Eur. J. Org. Chem., 2006, 4658.

54. Jiao, L.; Li, J.; Zhang, S.; Wei, C.; Hao, E.; Vicente, M. Org. Biomol. Chem., 2009, 33, 1888.

55. Smith, K.; Minnetian, O. J. Org. Chem., 1985, 50, 2073.

56. Forgie, J.; Skabara, P.; Stibor, I.; Vilela, F.; Vobecka, Z. Chem. Mater., 2009, 21, 1784.

57. Wories, H.; Koek, J.; Lodder, G.; Lugtenburg, J.; Fokkens, R.; Driessen, O.; Mohn, G. Recl.Trav. Chim. Pays-Bas, 1985, 104, 288.

58. Li, L.; Han, J.; Nguyen, B.; Burgess, K. J. Org. Chem., 2008, 73, 1963.

59. Cakmak, Y.; Akkaya, E. Org. Let., 2009, 11, 85.

60. Yogo, T.; Urano, Y.; Ishitsuka,Y.; Maniwa, F.; Nagano, T.; J. Am. Chem. Soc., 2005, 127, 12162.

61. Takuma, K.; Misawa, T.; Sugimoto, K.; Nishimoto, T.; Tsukahara, H.; Tsuda, T.; Imai, G.; Kogure, H.; 1998, JP Patent 10273504.

62. Jiao, Li.; Yu, C.; Li, J.; Wang, Z.; Wu, M.; Hao, E. J. Org. Chem., 2009, 74, 7525.

63. Wang, T.; Chen, X. L..; Chen, L.; Zhan, Z. P. Organic Letters, 2011, 13, 3324- 3327.

64. Boens,N.; Leen, V.; Dehaen, W. Chem. Soc. Rev. 2012, 41,1130-1172.

65. Beziau, A.; Baudron, S. A.; Guenet, A.; Hosseini, M. W., Chem. Eur. J. 2013, 19, 3215-3223.

66. Nepomnyashchii, A. B.; Broring, M.; Ahrens, J.; Bard, A. J. J. Am. Chem. Soc. 2011, 133, 8633-8645.

67. Baudron, S. A. Dalton Trans. 2013, 42, 7498-7509.

68. Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem. Int. Ed. 2008, 47, 1184-1201.

69. Vuluga, D.; Legros, J.; Crousse, B.; Bonnet- Delpon, D. Green Chem. 2009, 11, 156-159.

69

70. Lutz, J.-F. Angew. Chem., Int. Ed. 2007, 46, 1018.

71. Wu, P.; Fokin, V. V. Aldrichimica Acta 2007, 40, 7.

72. Moses, J. E.; Moorhouse, A. D. Chem. Soc. ReV. 2007, 36, 1249.

73. Nandivada, H.; Jiang, X.; Lahann, J. AdV. Mater. (Weinheim, Germany) 2007, 19, 2197.

74. Matsumoto, T.; Urano, Y.; Shoda, T.; Kojima, H.; Nagano, T. Org. Lett., 2007, 9, 3375.

75. (a) Amat-Guerri, F.; Liras, M.; Carrascoso, M.; Sastre, R.; Photochem. Photobiol., 2003, 77, 577; (b) DiCesare, N.; Lakowicz, J. Tetrahedron Lett, 2001, 42, 9105.

76. Wu, Y.; Peng, X.; Guo, B.; Fan, J.; Zhang, Z.; Wang, J.; Cui, A.; Gao, Y. Org. Biomol. Chem., 2005, 3, 1387.

77. Habrant, D.; Rauhala, V.; Koskinen, Ari M. P., Chem. Soc. Rev., 2010, 39, 2007- 2017.

78. Quesada, E.; Raw, S. A.; Reid, M.; Roman, E.; Taylor, R. J. K., Tetrahedron, 2006, 62, 6673- 6680.

79. Corey, E. J.; Fuchs, P. L., Tetrahedron Lett, 1972, 13, 3769- 3772.

80. Desai, N. B.; McKelvie, N.; Ramirez, F. J. Am. Chem. Soc., 1962, 84, 1745- 1747.

70

CHAPTER 4

SOME OTHER ROUTES OF SYNTHESIS OF A NEW CLASS OF BODIPY DYES-

DITETRAAZOLYLMETHENE DYES AND THEIR DERIVATIVES

4.1 Introduction

Aryl halides such as iodobenzene can be reacted with malononitrile in the presence of

CuI and K2CO3 to form the compound 44C. Copper salt promotes the formation of carbon

nucleophile as the anion of active methylene.12 This carbon nucleophile attacks the carbon atom

of an aryl halide where a halide (iodine in case of iodobenzene) is bonded and the halide is

substituted.

Tetrazole can be prepared by Huisgen cyclization between azide and nitriles in the

presence of Zn catalyst.7 Two reaction mechanisms are supported for this reaction, a two-steps

mechanism and a concerted [2+3] cycloaddition. The studies showed that zinc has more than the

role of a Lewis acid. When Lewis acids other than Zinc were used there was no or a little

acceleration in the rate of the reaction. Almost 0.5 molar equivalent of the zinc salt (usually

ZnBr2) is required for fast formation of tetrazole. In this reaction hydrolysis of the nitrile to the

primary amide competes with tetrazole. The two mechanisms for this reaction are given in

Figure 4.1.13

4.2 Synthesis






71




data were collected with a Varian Cary spectrophotometer. 400 MHz was used for 1H and 13C

NMR spectra in CDCl3 unless noted otherwise.

Figure 4.1. Mechanism of 5-substituted 1H tetrazole from nitrile13

72

I

CN

CN+

CN

CN

N

N

N

NH

NNN NH

CuI, K2CO3DMSO

ZnBr2, NaN3 H2O, Reflux

DDQ, KH2PO4 DCM

NNN N

N

NNH

N

43C

44C

01D

02D

Scheme 4.1. Synthesis of ditetraazolylmethene (02D) starting from phenylpropanedinitrile

73


• Synthesis of 5-[phenyl(2H-tetrazol-5-yl)methyl]-2H-tetrazole (01D),

A pressure vessel with magnetic stir bar was charged with phenylmalononitrile (0.02 g,

0.14 mmol), zinc bromide (0.03 g, 0.28 mmol), sodium azide (0.03 g, 0.42 mmol) and H2O (2.5

mL). The vessel was tightly closed and submerged in a preheated sand bath 170ºC overnight.

Then, the vessel was cooled down to room temperature. Hydrochloric acid (3N, 0.42 mL) was

added to achieve the pH 1 of the aqueous layer. Then ethyl acetate (3 mL) was added and the

mixture was stirred vigorously until all solid was dissolved. The organic layer was separated and

aqueous layer was extracted with 3 mL of ethyl acetate twice. All the organic layers were

combined and concentrated by rotary evaporation. Then, NaOH (0.25 N, 8.40 mL) was added

and stirred for 30 minutes until the original precipitate was dissolved and the suspension of zinc

hydroxide was formed. The suspension was filtered and the solid was washed with NaOH (1 N,

0.840 mL). HCl (3 N, 1.68 mL) was added in the filtrate and stirred vigorously until the

precipitate of ditetraazolylmethane was formed. Ditetraazolylmethane was collected and washed

with HCl (3N, 0.84 mL) twice. The product was kept under high vacuum to dry and the sample

was taken for NMR. NMR spectra of this compound is given in Appendix. The product is

collected as pale yellow solid (0.01 g, yield = 38%) 1H NMR (DMSO-d6) δ 1.91 (s,NH), 6.51 (s,

1H), 7.36-7.43 (m, 5H).

• Synthesis of 5-[phenyl(2H-tetrazol-5-yl)methylene]tetrazole (02D)

A round bottom flask with a magnetic stir bar was charged with ditetraazolylmethane

(01D) (0.03 g, 0.132 mmol), 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (0.03 g, 0.13

mmol) and potassium phosphate monobasic (KH2PO4) (0.02 g, 0.13 mmol). Dichloromethane (2

mL) was added. After 30 minutes the reaction mixture turned black. The mixture was evaluated

74

by thin layer chromatography (TLC) using hexanes: ethyl acetate in different ratios, 15:1, 10:1,

8:1, 6:1, 3:1, 1:1 and at last in straight ethyl acetate. Unfortunately, from TLC it was noticed that

there is not a single major product in mixture and it is the mixture of many compounds which

could not be collected separately.

4.2.3 Characterization and Physical Properties

A saturated solution of 44C in dichloromethane was made and left in the dark under the

hood for weekend. The crystals were collected and taken for crystallography. The crystal

structure of 44C is given in Figure 4.2.

Figure 4.2. The crystal structure of (44C)

The UV-vis absorbance of 01D is given in figure 4.3. The absorbance peak is seen around 225

nm.

75

-0.5

0

0.5

1

1.5

2

2.5

3

3.5

0 200 400 600 800 1000

Abso

rban

ce (a

u)

Wavelength (nm)

Figure 4.3. UV-vis spectrum of ditetraazole (01D)


The compound 44C was prepared using iodobenzene and malonitrile in the presence of

CuI and K2CO3. 44C is characterized by crystallography and 1H NMR. The compound 01D was

synthesized successfully and characterized by 1H NMR spectrum which is given in Appendix.


The compound 01D was synthesized in aqueous medium. When 01D was oxidized with

DDQ to form 02D a black paste was formed. In evaluating with thin layer chromatography it was

a large number of compounds in very small quantity each. It seems 01D decomposed in the

presence of DDQ and some mild oxidizing agent is needed to oxidize 01D to 02D. To synthesize

02D to 01D 01D will be treated with NBS to form brominated compound 03D. 03D will be

treated with a mild base such TEA to form 04D. Scheme 4.2 shows the next step.

76

N

N

N

NH

NNN NH

01D

NNN N

N

NNH

N

02D

TEA

NBS

N

N

N

NH

NNN NH

Br03D

Scheme 4.2. Synthesis of 02D from 01D using NBS

4.5 References

1. Boren, B. C.; Narayan, S.; Rasmussen, L. K.; Zhang, L.; Zhao, H.; Lin, Z.; Jia, G.; Fokin, V. V., J. Am. Chem. Soc. 2008, 130, 8923-8930.

2. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett., 1972, 13, 3769- 3772.

3. Desai, N. B.; McKelvie, N.; Ramirez, F. J. Am. Chem. Soc., 1962, 84, 1745- 1747.

4. Zhang, Y.; Chen, X.; Xue, P.; Sun, H. H. Y.; Williams, I. D.; Sharpless, K. B. Fokin, V. V. Jia, G. J. Am. Chem. Soc. 2005, 127, 15998- 15999.

5. Habrant, D.; Rauhala, V.; Koskinen, Ari M. P. Chem. Soc. Rev., 2010, 39, 2007- 2017.

6. Journet, M.; Cai, D.; Kowal, J. J.; Larsen, R. D. Tetrahedron Lett. 2001, 42, 9117-9118.

77

7. Demko, Z. P.; Sharpless, K. B. J. Org. Chem. Soc. 2001, 66, 7945-7950.

8. Rostovtsev, V. V.; Green, L. G. Fokin, V. V. Sharpless, K. B. Angew. Chem. Int. Ed. 2002, 41, 2596-2599.

9. Quesada, E.; Raw, S. A.; Reid, M.; Roman, E.; Taylor, R. J. K. Tetrahedron, 2006, 62, 6673-6680.

10. Okuro, K.; Furunne, M.; Miura, M.; Nomura, M. J. Org. Chem. 1993, 58, 7606-7607.

11. Ueda, S.; Nagasawa, H. J. Am. Chem. Soc. 2009, 131, 15080-15081.

12. (1) (a) Lmdley, J. Tetrahedron 1984, 40, 1433. (b) Setaune, J.; Matsukawa, K.; Wakemoto, H.; Kitao, T. Chem. Lett. 1981, 367. (c) Suzuki, H.; Kobayashi, T.; Yoshida, Y.; Osuka, A. Chem. Lett. 1983,193. (d) Suzuki, H.; Kobayashi, T.; Osuka, A. Chem. Lett. 1983,589. (e) Suzuki, H.; Yi, Q.; Inoue, J.; Kusume, K.; Ogawa, T. Chem. Lett. 1987,887.

13. Demko, Z. P. and Sharpless, K. B. J. Org. Chem. 2001, 66, 7945-7950

78

CHAPTER 5

A GREENER SYNTHESIS OF 6-METHYLNAPHTHOQUINONE

5.1 Introduction

Naphthoquinones with substituents at the 6-position can be prepared in a two-step

process that begins with the Diels-Alder reaction between benzoquinone and a butadiene

compound and is completed by the oxidation of the initial product using an oxidant (Scheme

5.1).1,2 The oxidation removes the equivalent of 2 hydrogen atoms from the naphthoquinone (4e-,

4H+). Chromium-based oxidants such as CrO3 have been previously reported to oxidize the

intermediate adduct to the naphthoquinone, but chromium is a toxic element. It would be helpful

to replace the chromium-based oxidation method with a method that uses non-toxic elements.

This chapter describes my work to develop a greener synthesis of 6-methylnaphthoquinone that

uses a nontoxic oxidant, iron trichloride (FeCl3) as an oxidation catalyst together with ambient

oxygen (O2) as a stoichiometric oxidant. I did this work together with Eunsol Park, a graduate

student in the Youngblood group. Each of us tried the Diels-Alder reaction and FeCl3-based

oxidation method and reported our results to our professor, Dr. Youngblood. We obtained very

similar results. The quantity of 6-methylnaphthoquinone that we produced was contributed to

another graduate student, Seare Berhe, who used our compound in the overall synthesis of

another quinone compound, naphthacenequinone-2-carboxylic acid (01E) (Figure 5.1).

O

OH

O

O

01E

Figure 5.1. Naphthacenequinone-2-carboxylic acid

79

Scheme 5.1. Synthesis of 6-methylnaphthoquinone.

In the previous synthesis of 6-methylnaphthoquinone, chromic acid or Na2Cr2O7/H2SO4

was used to oxidize 6-methyl-4a,5,8,8a-tetrahydronaphthalene-1,4-dione (02E) into 6-

methylnaphthoquinone (03E) (Scheme 5.2).1,3 Chromium is a toxic element. In the new method,

FeCl3 was used as an environmentally safer oxidizing agent. The overall synthesis still uses one

step with Na2Cr2O7, so it is not entirely a ‘green’ synthesis. The naphthacenequinone-2-

carboxylic acid (NcQ in Scheme 5.2) was used to make a new kind of solar cell called a

“photogalvanic solid-state dye-sensitized solar cell” and our group published a paper on this

topic that includes myself and Eunsol Park as coauthors along with Seare Berhe and Haptom

Gobeze (a student in the D’Souza group).4 This paper included the synthesis of organic dyes, the

assembly and testing of solar cells, and the time-resolved studies of photoinduced electron

transfer between the dyes and an arylamine donor compound

(octakis(methoxyphenyl)spirobifluorenyl-tetramine, also known as spiroMeOTAD), as well as

the thermal (dark) electron transfer between the dyes and an oxide semiconductor (titanium

dioxide, TiO2). This paper was published in 2014.

Scheme 5.2. Overall synthesis of naphthacenequinone-2-carboxylic acid using chromic acid to prepare the 6-methylnaphthoquinone.3

80

5.2 Synthesis









data were collected with a Varian Cary spectrophotometer. 400 MHz was used for 1H and 75

MHz was used for 13C NMR spectra in CDCl3 unless noted otherwise.


• Synthesis of 6-methylnaphthoquinone

An oven-dried round-bottom flask with a magnetic stir bar was charged with

benzoquinone (0.53 g, 7.50 mmol) and LiClO4 (0.53 g, 5mmol). Diethyl ether (10 mL) was

added and stirred until all solid was dissolved. Then, isoprene (0.75 mL, 7.5 mmol) was added.

Immediately, white colored precipitate was formed. The reaction was run for 24 hours. The

mixture was extracted between deionized water and ethyl acetate. The organic layer was

separated and dried over anhydrous Na2SO4. It was filtered and concentrated. The mixture had

the intermediate compound 6-methyl-4a,5,8,8a-tetrahydronaphthalene-1,4-dione (02E) which

was used as it is to oxidize into 6-methylnaphthoquinone (03E). In the mixture, DMF (10 mL)

and FeCl3.6H2O (4.05 g, 15.0 mmol) were added. The mixture was heated at 110ºC for 24 hours

black colored mixture was formed. Then, it was cooled to room temperature and filtered through

81

silica gel using chloroform. After filtration yellow color solid compound was obtained (0.67 g,

yield = 52%) 1H NMR (CDCl3) δ 2.50 (s, 3H), 6.94 (m, 2H), 7.53-7.56 (d, 1H), 7.88 (s, 1H),

7.96-7.98 (d, 1H). The proton spectrum of 03E is given in Appendix.


6-methylnaphthoquinone was synthesized in one pot starting from benzoquinone and

isoprene. First, 6-methyl-4a,5,8,8a-tetrahydronaphthalene-1,4-dione (02E) was synthesized and

it was oxidized in the same vessel with FeCl3.6H2O to get 6-methylnaphthoquinone (03E). The

6-methylnaphthoquinone was used to make more of the naphthacenequinone-2-carboxylic acid,

which is an electron-accepting dye compound. We explored this dye compound in photogalvanic

solar cells, which was a project guided by my advisor Prof. Youngblood and most experiments

were led by our former group member, Seare Berhe.

Figure 5.2. Schematic diagrams of solar cell types: photogalvanic (“PSC”, left), dye-sensitized (“DSC”, center), and photogalvanic dye-sensitized (“P-DSC”, right). Within diagrams: SC = semiconductor; D = donor; A = acceptor; hν = photoexcitation; e− = electron; I−/I3

− = iodide/triiodide.4 Photogalvanic cells (PSCs) produce electrochemical potential by the photoinitiated

perturbation of a redox equilibrium between donor and acceptor compounds in an electrolyte

(Figure 5.2-left). This is distinct from the photogeneration of charge directly across the

molecule-semiconductor interface, which is the standard mechanism in dye-sensitized solar cells

(DSCs, Figure 5.2-center). Some researchers had previously attempted to make a modified form

82

of photogalvanic solar cell that had primary charge separation between a dye that is bound to a

semiconductor and an electron donating species that was dissolved in the electrolyte. This is

called a photogalvanic dye-sensitized solar cell (P-DSC, Figure 5.2-right). In our paper, we

explored this model of P-DSC but we replaced the liquid electrolyte with a solid state hole

conductor called spiroMeOTAD. With the use of transient absorption spectroscopy, we were

able to observe primary charge separation between electron accepting dyes and the

SpiroMeOTAD. Figure 5.3 shows the charge separation in a blend of 2-

methylnaphthacenequinone, which is the compound that is used to make naphthacenequinone-2-

carboxylic acid at the last step of the overall synthesis.

Figure 5.3. Laser flash photolysis of a thin film blend of 2-methylnaphthacenequinone (NcQ-2Me) and spiroMeOTAD. A: Time resolved spectra. B: Monochromatic decay rates for the radical cation spiro-MeOTAD(•+) at 500 nm, and for the radical anion NcQ-2Me(•−) at 603 nm. Traces are normalized with respect to ΔOD at 740 fs. Inset: overlaid decay traces for initial 9 ps.4

The transient absorbance spectra in Figure 5.3 shows that the charge separation between

the 2-methylnaphthacenequinone and spiroMeOTAD decays at the same rate, except for a brief

decay at the early decay of the reduced form of the quinone species, which we identified as

electron transfer to ambient oxygen, since this reaction was done in the open air. The fact that the

majority of the decay of the signals for the two charged species has the same rate is evidence that

there is only one process that is occurring: the electron is going back to the spiroMeOTAD from

83

the reduced quinone species. When we prepared a ternary interface that had a

naphthacenequinone bound to titanium dioxide (TiO2), and put the spiroMeOTAD as the

electron donor, we observed that the rates of the decay of the different signals for the charged

molecular species are no longer the same. We infer from this evidence that there is not only one

process that can happen after the primary charge separation, but more than one process. We

identify that the reduced quinone can send an electron back to the spiroMeOTAD, or it can send

an electron to the TiO2. Both processes are happening in the material.

Figure 5.4. Laser flash photolysis of a ternary TiO2/naphthacenequinone-carboxylic acid /spiro-MeOTAD film consisting of rutile TiO2 nanorods with surface chemisorbed naphthacenequinone-carboxylic acid and spin-coated spiroMeOTAD. A: Time resolved spectra. B: Monochromatic decay rates for the radical cation spiroMeOTAD(•+) at 490 nm, and for the radical anion of naphthacenequinone-carboxylic aicd(•−) at 600 nm, normalized with respect to ΔOD at 605 fs. Inset: overlaid decay traces for initial 30 ps.4


The FeCl3-mediated oxidation provided 6-methylnaphthacenequinone without the use of

chromic acid. This naphthoquinone compound was used to make naphthacenequinone-2-

carboxylic acid, which was used in a study of photogalvanic dye-sensitized solar cells. This

study was the first report of a photogalvanic dye-sensitized system that actually allowed the

observation of the formation and decay of the reduced form of an electron-accepting dye that

was bound to an oxide semiconductor.

84

5.5 References

1. Bruce, D. B.; Thomson, R. H. J. Chem. Soc., 1952, 2759-2766.

2. Jenner, G.; Ben Salem, R. Tetrahedron, 1997, 53, 4637-4648.

3. Berhe, S. A.; Zhou, J. Y.; Haynes, K. M.; Rodriguez, M. T.; Youngblood, W. J. ACS Appl. Mater. Interfaces, 2012, 6, 2955−2963.

4. Berhe, S. A.; Gobeze, H. B.; Pokharel, S. D.; Park, E.; Youngblood, W. J. ACS Appl. Mater. Interfaces, 2014, 6, 10696−10705.

85

APPENDIX

SUPPLEMENTAL DATA

86

1H NMR of methyl 3-(4-bromophenyl)propanoate (03B)

1H NMR of 04B

87

1H NMR of 05B

1H NMR of 09B

88

1H NMR of 1-(3-bromopropyl)-4-[(4-butylphenyl)ethynyl]benzene (06B)

1H NMR of 07B

89

1H NMR of 08B

13C NMR of 10B

90

1H NMR of 08C

1H NMR of 09C

91

1H NMR of 10C

1H NMR of 21C

92

1H NMR of 24C

1H NMR of 29C

93

1H NMR of 32C

1H NMR 33C

94

1H NMR of 36C

1H NMR of 42C

95

1H NMR of 44C

1H NMR of 51C

96

1H NMR of Multiple acylation of toluoyl malondialdehyde

1H NMR of protected enol (42C)

97

13C NMR of 42C

1H spectrum of 21C

98

13C NMR of 21C

1HNMR of 49C (through Eglington coupling)

99

1H NMR of 01D

1H NMR of 03E

100

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