Hindawi Publishing CorporationAdvances in Physical ChemistryVolume 2013 Article ID 835610 11 pageshttpdxdoiorg1011552013835610
Research ArticlePolyethylene Glycols as Efficient Catalysts for the Oxidation ofXanthine Alkaloids by Ceric Ammonium Nitrate in AcetonitrileA Kinetic and Mechanistic Approach
S Shylaja K C Rajanna K Ramesh K Rajendar Reddy and P Giridhar Reddy
Department of Chemistry Osmania University Hyderabad 500 007 India
Correspondence should be addressed to K C Rajanna kcrajannaouyahoocom
Received 1 January 2013 Revised 23 April 2013 Accepted 7 May 2013
Academic Editor Jeffrey M Zaleski
Copyright copy 2013 S Shylaja et alThis is an open access article distributed under the Creative CommonsAttribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Kinetics of oxidation of xanthine alkaloids such as Xanthine (XAN) hypoxanthine (HXAN) caffeine (CAF) theophylline (TPL)and theobromine (TBR) have been studied with ceric ammonium nitrate (CAN) using poly ethylene glycols (PEG) as catalystsReaction obeyed first order kinetics in both [CAN] and [Xanthine alkaloid] Highly sluggish CAN-xanthine alkaloid reactions(in acetonitrile media even at elevated temperatures) are enhanced in presence PEGs (PEG-200 -300 -400 -600) An increase in[PEG] increased the rate of oxidation linearly This observation coupled with a change in absorption of CAN in presence of PEG[Hndash(OCH
2ndashCH2)nndashOndashNH4Ce(NO3)4(CH3CN)] (PEG bound CAN species) is considered to be more reactive than CAN The
mechanism of oxidation in PEG media has been explained by Menger-Portnoyrsquos enzymatic model
1 Introduction
There has been an increasing interest in the kinetics ofelectron transfer reactions since more than half a centurybecause of their ever green importance in understanding themechanisms of industrially pharmaceutically and biologi-cally important redox reactions [1ndash11] A special focus hasbeen paid to single electron transfer (SET) oxidations [1ndash18]In this context ceric ammonium nitrate (CAN) has emergedas one of the most valuable and notable SET oxidants for avariety of reactions [19ndash30] due to its relative abundanceease of preparation low cost and low toxicity During theoxidation of organic substrates the initial formation of aradical or radical cation is usually followed by rearrangementor follow-up reactions that led to other free radical interme-diates Typically the free radical reacts with another substrate(olefin etc) to form a new CndashC bond and a product radicalOxidation of the free radical intermediate to a cation leadsto capture of solvent or nitrate expelled from CAN uponits reduction to Ce(III) and these alternative mechanisticpathways result in many of the side products prevalent inoxidationsTherefore preparativeCe(IV) initiated oxidations
cannot be achieved in many instances Chemical intuitionsuggests that these pathways can be depressed by under-standing the interrelationship between the mechanism ofoxidation by Ce(IV) the effect of solvent on the stability ofthe initially formed radical cation intermediate and the rates(mechanisms) of various available pathways
Polyethylene glycol (PEG) is a polyether compoundwith many applications from industrial manufacturing tomedicine It has also been known as polyethylene oxide(PEO) or polyoxyethylene (POE) depending on itsmolecularweight PEG is a neutral hydrophilic polyether and lessexpensive It avoids the use of acid or base catalysts andreagent can be recovered and reused Thus it offers aconvenient inexpensive nonionic nontoxic and recyclablereaction medium for the replacement of volatile organicsolvents (see Scheme 1)
Polyethylene glycol (PEG) is a condensation polymerof ethylene oxide and water with the general formula[H(OCH
2CH2)119899OH] where 119899 is the average number of
repeating oxyethylene groups typically from 4 to about 180The low molecular weight members from 119899 = 2 to 4 arediethylene glycol triethylene glycol and tetra ethylene glycol
2 Advances in Physical Chemistry
HHO
O119899
Scheme 1 Structure of polyethylene glycol (PEG)
respectively which are produced as pure compounds Thewide range of chain lengths provides identical physical andchemical properties for the proper application selectionsdirectly or indirectly in the field of chemical and biologicalsciences In recent past polyethylene glycols (PEGs) havebeen used as catalysts and catalyst supports and also havebeen found to be an inexpensive non-toxic environmentallyfriendly reactionmedium which avoid the use of acid or basecatalysts Moreover PEG can be recovered after completionof the reactions and recycledreused [31ndash37] in anotherbatch Inspired by the striking features of PEG the authorwants to use it as a catalyst by avoiding the use of acid inthe present study namely ceric ammonium nitrate (CAN)triggered oxidation of certain xanthine alkaloid compoundsAcetonitrile is used as solvent in order to facilitate kineticstudies
2 Experimental Details
Poly ethylene glycols were procured from E-Merck andother materials used were similar to those given in previouschapters Thermostat was adjusted to desired reaction tem-perature Flask containing known amount of ceric ammo-nium nitrate (CAN) in acetonitrile solvent and another flaskcontaining the substrate (Xanthine alkaloid) and suitableamount of PEG solutions were clamped in a thermostaticbath Reaction was initiated by mixing requisite amountof CAN to the other contents of the reaction vessel Theentire reaction mixture was mixed thoroughly Aliquots ofthe reaction mixture were withdrawn into a cuvette andplaced in the cell compartment of the laboratory visible spec-trophotometer Cell compartment was provided with an inletand outlet for circulation of thermostatic liquid at a desiredtemperature The CAN content could be estimated from thepreviously constructed calibration curve showing absorbanceversus [CAN] Absorbance values were in agreement to eachother with an accuracy of plusmn3 error
21 Determination of the Order of Reactionand Salient Kinetic Features
(1) Reactions were conducted under two different condi-tions Under pseudo first order conditions [CAF] ≫
[CAN] plots of ln(1198600119860119905) that is ln[119886(119886minus119909)] versus
time were straight lines with positive slopes passingthrough origin indicating first order (119909) with respectto [oxidizing agent] (Figure 1)
(2) This reaction is also conducted under second orderconditions with equal concentrations of [CAF]
0=
[CAN]0 Under these conditions kinetic plots of
[1(119860119905)] versus time have been found to be linear
0
01005
02
03
04035
025
015
05045
0 10 20 30 40 50 60 70Time (min)
119910 = 00076119909
1198772 = 0988
ln(119860
0119860
119905)
Plot of ln(1198600119860119905) versus time
Figure 1 Pseudo first order kinetic plots of caffeine with MeCN at310 K [CAF] = 0016mol dmminus3 [CAN] = 00041mol dmminus3 [PEG-300] = 0062mol dmminus3
0
05
1
15
2
25
0 50 100 150 200 250 300Time (min)
119910 = 00043119909 + 10334
1198772 = 09918
Plot of ln(1119860119905) versus time
1119860
119905
Figure 2 Second order kinetic plots of caffeine withMeCN at 310K[CAF] = 0002mol dmminus3 [CAN] = 0002mol dmminus3 [PEG-300] =0375mol dmminus3
with a positive gradient and definite intercept onordinate (vertical axis) indicating overall secondorder kinetics (Figure 2) Since the order with respectto [CAN] is already verified as one under pseudoconditions this observation suggests that order in[CAF] is also one
(3) In PEG mediated reactions an increase in the [PEG]increased the reaction rates depending on the natureof PEG By and large reaction rates were found highin PEG-200 media over other PEGs (Tables 2 3 4 5and 6)
(4) In the present study kinetic data have been collectedat three to four different temperatures within therange of 300 to 320K Activation parameters suchas Δ119867
and Δ119878 have been evaluated by Eyringrsquos
equation Free energy of activation (Δ119866) is obtained
from Gibbs-Helmholtz equation The data related toactivation parameters are compiled in Tables 2 to 6
(5) Addition of olefin monomer (acryl amide and acry-lonitrile) to the reaction mixture decreased the reac-tion rate When heated the contents of the reactionmixture turned viscous and indicated dense polymerformation This observation can be explained due tothe induced vinyl polymerization of addedmonomershowing the presence of free radicals in the system
Advances in Physical Chemistry 3
Table 1 Binding constants of [CAN-PEG] at 303∘K using Benesi-Hildebrand method
S N PEG Benesi-Hildebrand Equation 119870 120576 minusΔ119866 (kJmol)1 PEG-200 119910 = 7119864 minus 05119909 + 0052 743 1923 1672 PEG-300 119910 = 9119864 minus 05119909 + 0055 611 1818 1623 PEG-400 119910 = 5119864 minus 05119909 + 0071 1420 1408 183
Table 2 Activation parameters of caffeine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K
Equation obtained for plot ofln(11989610158401015840119879) versus (103119879) 119877
22 CAN-PEG Binding Studies UV-Visible Spectrophoto-metric studies were performed in order to throw light onCAN binding with PEG (Poly ethylene glycol) Absorptionspectra of CAN in acetonitrile indicated a band at 459 nmthis band underwent a hypsochromic shift from 459 nm to441 nm in presence of 01mol PEG suggesting the interactionof PEG with CAN (Figure 3)
Hndash(OCH2ndashCH2)119899ndashOH
(PEG)+ (NH
4) [Ce(NO
3)5(ACN)]
(CAN)
119870
999445999468 [PEGndashNH4Ce(NO
3)5] (ACN)
Complex (C) or [PEG-CAN]
(1)
The [CAN-PEG] binding constants were evaluated by Benesi-Hildebrand equation according to themethod reported in theliterature [38] as elaborated in our earlier paper
0
05
1
15
2
25
383 403 423 443 463 483 503 523 543
Abso
rban
ce (O
D)
Wavelength (nm)
Absorption spectrum of CAN in presence of PEG
Series 1Series 2
Series 3Series 4
series 1 (CAN) series 2 (CAN + PEG-200)series 3 (CAN + PEG-300) series 4 (CAN + PEG-400)
Figure 3 Absorption of spectra of CAN in presence of PEG
4 Advances in Physical Chemistry
Table 3 Activation parameters of Xanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
The equilibrium constant 119870 = [C][CAN][PEG] where[CAN] [PEG] and [C] are equilibrium concentrations ofacceptor (CAN) donor (PEG) and complex respectivelyFor the above equilibrium concentration of [PEG-CAN]complex ([C]) can be correlated to the formation constant (119870)
by the following relationship If [CAN]0and [PEG]
0represent
initial concentrations of CAN and PEG respectively then
[C] =119870[CAN]0[PEG]0
1 + 119870[PEG]0 (2)
But according to Lambert-Beerrsquos law absorbance (119860) = 120598119888119897In the above equations 119897 is path length 119889 is absorbance
120598 is the molar extinction coefficient and 119870 is formationconstant of the complex respectively For one cmpath lengthabove equation can be written as (119860) = 120598119888
[C] =119860
120598119897=
119870[CAN]0[PEG]0
1 + 119870[PEG]0 (3)
Further taking the reciprocals to the above equation it rear-ranges to
[CAN]0
119860=
1
119870[PEG]0120598+
1
120598 (4)
However the absorbance of CAN and [CAN-PEG] absorbin the same region significantly therefore the observedabsorbance (119860) could be written as
119860 = 119860(CAN) + 119860
(Complex)
119860(Complex) = Δ119860 = 119860 sim 119860
(CAN)(5)
Therefore a plot of ([CAN]0Δ119860) versus 1[PEG]
0should
give a straight line according to the above equation Theseplots have been realized in the present study (Figure 4)Formation constant (119870) has been calculated from the ratioof intercept to slope while inverse of the intercept gave molarextinction coefficient (120598) and is represented in Table 1
3 Results and Discussion
31 Mechanism of CAN Oxidation of Xanthine Alkaloids inMeCN Medium Earlier reports on CAN oxidation stud-ies from our laboratory and elsewhere show that a vari-ety of CAN species such as Ce(NO
3)6
2minus Ce(NO3)5
minusCe(OH)(NO
3)4
minus Ce(NO3)4 and Ce(OH)
3+ may exist innitric acidmedium [39ndash43] However CAN species inMeCNmedium could be entirely different Since MeCN is large
Advances in Physical Chemistry 5
Table 4 Activation parameters of hypoxanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
Benesi-Hildebrand plot of ([CAN]Δ119860) versus (1[PEG-200])
Figure 4 Benesi-Hildebrand plot of CAN-PEG-200
excess over [CAN] MeCN may penetrate into the coordi-nation spheres of Ce(IV) and form solvated CAN speciesaccording to the following equilibrium
(NH4)2Ce(NO
3)6+ CH
3CN
(CAN)
999445999468 [(NH4)Ce(NO
3)5(CH3CN)] + NH
4NO3
(SolvatedCAN)
(6)
31 315 32 325 33 335
119910 = minus44045119909 + 77753
1198772 = 09999
103119879
minus58
minus6
minus62
minus64
minus66
minus68
minus7
ln(119896
998400998400119879
)
Eyringrsquos plot ln(119896998400998400119879) versus (103119879)
Figure 5 Eyringrsquos plot PEG-300 catalysed oxidation of caffeine byCAN
Solvated CAN may be able to oxidize the substrate to afforduric acid as product when Xanthine alkaloid is added to thereaction mixture (see Scheme 2)
32 Mechanism of Oxidation in PEG Media Progress ofthe reaction has been studied in the presence of a set ofpoly oxy ethylene compounds (PEGs) with varied molec-ular weights ranging from 200 to 6000 units and it was
6 Advances in Physical Chemistry
O
O
NN
N
H
O
O
N
NN
N
O
O
N
NN
N
OH
N
O
O
NH
NN
N
H
H
Slow
O
O
NH
NN
N
O
O NO
O
+
(CAN)
R3
R3
R3
R3 R3
R2
R2R2R2
R2
R1
R1 R1 R1
R1
∙ONO2
[Ce(III)ACN]
minusNO2
(Uric acid derivatives)
(Ce(III) nitrate) HNO3NO2minus + +CAN
NH4Ce(NO3)4(ACN)
minus
+
(NH4)[Ce(NO3)5(ACN)]
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
respectively which are produced as pure compounds Thewide range of chain lengths provides identical physical andchemical properties for the proper application selectionsdirectly or indirectly in the field of chemical and biologicalsciences In recent past polyethylene glycols (PEGs) havebeen used as catalysts and catalyst supports and also havebeen found to be an inexpensive non-toxic environmentallyfriendly reactionmedium which avoid the use of acid or basecatalysts Moreover PEG can be recovered after completionof the reactions and recycledreused [31ndash37] in anotherbatch Inspired by the striking features of PEG the authorwants to use it as a catalyst by avoiding the use of acid inthe present study namely ceric ammonium nitrate (CAN)triggered oxidation of certain xanthine alkaloid compoundsAcetonitrile is used as solvent in order to facilitate kineticstudies
2 Experimental Details
Poly ethylene glycols were procured from E-Merck andother materials used were similar to those given in previouschapters Thermostat was adjusted to desired reaction tem-perature Flask containing known amount of ceric ammo-nium nitrate (CAN) in acetonitrile solvent and another flaskcontaining the substrate (Xanthine alkaloid) and suitableamount of PEG solutions were clamped in a thermostaticbath Reaction was initiated by mixing requisite amountof CAN to the other contents of the reaction vessel Theentire reaction mixture was mixed thoroughly Aliquots ofthe reaction mixture were withdrawn into a cuvette andplaced in the cell compartment of the laboratory visible spec-trophotometer Cell compartment was provided with an inletand outlet for circulation of thermostatic liquid at a desiredtemperature The CAN content could be estimated from thepreviously constructed calibration curve showing absorbanceversus [CAN] Absorbance values were in agreement to eachother with an accuracy of plusmn3 error
21 Determination of the Order of Reactionand Salient Kinetic Features
(1) Reactions were conducted under two different condi-tions Under pseudo first order conditions [CAF] ≫
[CAN] plots of ln(1198600119860119905) that is ln[119886(119886minus119909)] versus
time were straight lines with positive slopes passingthrough origin indicating first order (119909) with respectto [oxidizing agent] (Figure 1)
(2) This reaction is also conducted under second orderconditions with equal concentrations of [CAF]
0=
[CAN]0 Under these conditions kinetic plots of
[1(119860119905)] versus time have been found to be linear
0
01005
02
03
04035
025
015
05045
0 10 20 30 40 50 60 70Time (min)
119910 = 00076119909
1198772 = 0988
ln(119860
0119860
119905)
Plot of ln(1198600119860119905) versus time
Figure 1 Pseudo first order kinetic plots of caffeine with MeCN at310 K [CAF] = 0016mol dmminus3 [CAN] = 00041mol dmminus3 [PEG-300] = 0062mol dmminus3
0
05
1
15
2
25
0 50 100 150 200 250 300Time (min)
119910 = 00043119909 + 10334
1198772 = 09918
Plot of ln(1119860119905) versus time
1119860
119905
Figure 2 Second order kinetic plots of caffeine withMeCN at 310K[CAF] = 0002mol dmminus3 [CAN] = 0002mol dmminus3 [PEG-300] =0375mol dmminus3
with a positive gradient and definite intercept onordinate (vertical axis) indicating overall secondorder kinetics (Figure 2) Since the order with respectto [CAN] is already verified as one under pseudoconditions this observation suggests that order in[CAF] is also one
(3) In PEG mediated reactions an increase in the [PEG]increased the reaction rates depending on the natureof PEG By and large reaction rates were found highin PEG-200 media over other PEGs (Tables 2 3 4 5and 6)
(4) In the present study kinetic data have been collectedat three to four different temperatures within therange of 300 to 320K Activation parameters suchas Δ119867
and Δ119878 have been evaluated by Eyringrsquos
equation Free energy of activation (Δ119866) is obtained
from Gibbs-Helmholtz equation The data related toactivation parameters are compiled in Tables 2 to 6
(5) Addition of olefin monomer (acryl amide and acry-lonitrile) to the reaction mixture decreased the reac-tion rate When heated the contents of the reactionmixture turned viscous and indicated dense polymerformation This observation can be explained due tothe induced vinyl polymerization of addedmonomershowing the presence of free radicals in the system
Advances in Physical Chemistry 3
Table 1 Binding constants of [CAN-PEG] at 303∘K using Benesi-Hildebrand method
S N PEG Benesi-Hildebrand Equation 119870 120576 minusΔ119866 (kJmol)1 PEG-200 119910 = 7119864 minus 05119909 + 0052 743 1923 1672 PEG-300 119910 = 9119864 minus 05119909 + 0055 611 1818 1623 PEG-400 119910 = 5119864 minus 05119909 + 0071 1420 1408 183
Table 2 Activation parameters of caffeine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K
Equation obtained for plot ofln(11989610158401015840119879) versus (103119879) 119877
22 CAN-PEG Binding Studies UV-Visible Spectrophoto-metric studies were performed in order to throw light onCAN binding with PEG (Poly ethylene glycol) Absorptionspectra of CAN in acetonitrile indicated a band at 459 nmthis band underwent a hypsochromic shift from 459 nm to441 nm in presence of 01mol PEG suggesting the interactionof PEG with CAN (Figure 3)
Hndash(OCH2ndashCH2)119899ndashOH
(PEG)+ (NH
4) [Ce(NO
3)5(ACN)]
(CAN)
119870
999445999468 [PEGndashNH4Ce(NO
3)5] (ACN)
Complex (C) or [PEG-CAN]
(1)
The [CAN-PEG] binding constants were evaluated by Benesi-Hildebrand equation according to themethod reported in theliterature [38] as elaborated in our earlier paper
0
05
1
15
2
25
383 403 423 443 463 483 503 523 543
Abso
rban
ce (O
D)
Wavelength (nm)
Absorption spectrum of CAN in presence of PEG
Series 1Series 2
Series 3Series 4
series 1 (CAN) series 2 (CAN + PEG-200)series 3 (CAN + PEG-300) series 4 (CAN + PEG-400)
Figure 3 Absorption of spectra of CAN in presence of PEG
4 Advances in Physical Chemistry
Table 3 Activation parameters of Xanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
The equilibrium constant 119870 = [C][CAN][PEG] where[CAN] [PEG] and [C] are equilibrium concentrations ofacceptor (CAN) donor (PEG) and complex respectivelyFor the above equilibrium concentration of [PEG-CAN]complex ([C]) can be correlated to the formation constant (119870)
by the following relationship If [CAN]0and [PEG]
0represent
initial concentrations of CAN and PEG respectively then
[C] =119870[CAN]0[PEG]0
1 + 119870[PEG]0 (2)
But according to Lambert-Beerrsquos law absorbance (119860) = 120598119888119897In the above equations 119897 is path length 119889 is absorbance
120598 is the molar extinction coefficient and 119870 is formationconstant of the complex respectively For one cmpath lengthabove equation can be written as (119860) = 120598119888
[C] =119860
120598119897=
119870[CAN]0[PEG]0
1 + 119870[PEG]0 (3)
Further taking the reciprocals to the above equation it rear-ranges to
[CAN]0
119860=
1
119870[PEG]0120598+
1
120598 (4)
However the absorbance of CAN and [CAN-PEG] absorbin the same region significantly therefore the observedabsorbance (119860) could be written as
119860 = 119860(CAN) + 119860
(Complex)
119860(Complex) = Δ119860 = 119860 sim 119860
(CAN)(5)
Therefore a plot of ([CAN]0Δ119860) versus 1[PEG]
0should
give a straight line according to the above equation Theseplots have been realized in the present study (Figure 4)Formation constant (119870) has been calculated from the ratioof intercept to slope while inverse of the intercept gave molarextinction coefficient (120598) and is represented in Table 1
3 Results and Discussion
31 Mechanism of CAN Oxidation of Xanthine Alkaloids inMeCN Medium Earlier reports on CAN oxidation stud-ies from our laboratory and elsewhere show that a vari-ety of CAN species such as Ce(NO
3)6
2minus Ce(NO3)5
minusCe(OH)(NO
3)4
minus Ce(NO3)4 and Ce(OH)
3+ may exist innitric acidmedium [39ndash43] However CAN species inMeCNmedium could be entirely different Since MeCN is large
Advances in Physical Chemistry 5
Table 4 Activation parameters of hypoxanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
Benesi-Hildebrand plot of ([CAN]Δ119860) versus (1[PEG-200])
Figure 4 Benesi-Hildebrand plot of CAN-PEG-200
excess over [CAN] MeCN may penetrate into the coordi-nation spheres of Ce(IV) and form solvated CAN speciesaccording to the following equilibrium
(NH4)2Ce(NO
3)6+ CH
3CN
(CAN)
999445999468 [(NH4)Ce(NO
3)5(CH3CN)] + NH
4NO3
(SolvatedCAN)
(6)
31 315 32 325 33 335
119910 = minus44045119909 + 77753
1198772 = 09999
103119879
minus58
minus6
minus62
minus64
minus66
minus68
minus7
ln(119896
998400998400119879
)
Eyringrsquos plot ln(119896998400998400119879) versus (103119879)
Figure 5 Eyringrsquos plot PEG-300 catalysed oxidation of caffeine byCAN
Solvated CAN may be able to oxidize the substrate to afforduric acid as product when Xanthine alkaloid is added to thereaction mixture (see Scheme 2)
32 Mechanism of Oxidation in PEG Media Progress ofthe reaction has been studied in the presence of a set ofpoly oxy ethylene compounds (PEGs) with varied molec-ular weights ranging from 200 to 6000 units and it was
6 Advances in Physical Chemistry
O
O
NN
N
H
O
O
N
NN
N
O
O
N
NN
N
OH
N
O
O
NH
NN
N
H
H
Slow
O
O
NH
NN
N
O
O NO
O
+
(CAN)
R3
R3
R3
R3 R3
R2
R2R2R2
R2
R1
R1 R1 R1
R1
∙ONO2
[Ce(III)ACN]
minusNO2
(Uric acid derivatives)
(Ce(III) nitrate) HNO3NO2minus + +CAN
NH4Ce(NO3)4(ACN)
minus
+
(NH4)[Ce(NO3)5(ACN)]
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
22 CAN-PEG Binding Studies UV-Visible Spectrophoto-metric studies were performed in order to throw light onCAN binding with PEG (Poly ethylene glycol) Absorptionspectra of CAN in acetonitrile indicated a band at 459 nmthis band underwent a hypsochromic shift from 459 nm to441 nm in presence of 01mol PEG suggesting the interactionof PEG with CAN (Figure 3)
Hndash(OCH2ndashCH2)119899ndashOH
(PEG)+ (NH
4) [Ce(NO
3)5(ACN)]
(CAN)
119870
999445999468 [PEGndashNH4Ce(NO
3)5] (ACN)
Complex (C) or [PEG-CAN]
(1)
The [CAN-PEG] binding constants were evaluated by Benesi-Hildebrand equation according to themethod reported in theliterature [38] as elaborated in our earlier paper
0
05
1
15
2
25
383 403 423 443 463 483 503 523 543
Abso
rban
ce (O
D)
Wavelength (nm)
Absorption spectrum of CAN in presence of PEG
Series 1Series 2
Series 3Series 4
series 1 (CAN) series 2 (CAN + PEG-200)series 3 (CAN + PEG-300) series 4 (CAN + PEG-400)
Figure 3 Absorption of spectra of CAN in presence of PEG
4 Advances in Physical Chemistry
Table 3 Activation parameters of Xanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
The equilibrium constant 119870 = [C][CAN][PEG] where[CAN] [PEG] and [C] are equilibrium concentrations ofacceptor (CAN) donor (PEG) and complex respectivelyFor the above equilibrium concentration of [PEG-CAN]complex ([C]) can be correlated to the formation constant (119870)
by the following relationship If [CAN]0and [PEG]
0represent
initial concentrations of CAN and PEG respectively then
[C] =119870[CAN]0[PEG]0
1 + 119870[PEG]0 (2)
But according to Lambert-Beerrsquos law absorbance (119860) = 120598119888119897In the above equations 119897 is path length 119889 is absorbance
120598 is the molar extinction coefficient and 119870 is formationconstant of the complex respectively For one cmpath lengthabove equation can be written as (119860) = 120598119888
[C] =119860
120598119897=
119870[CAN]0[PEG]0
1 + 119870[PEG]0 (3)
Further taking the reciprocals to the above equation it rear-ranges to
[CAN]0
119860=
1
119870[PEG]0120598+
1
120598 (4)
However the absorbance of CAN and [CAN-PEG] absorbin the same region significantly therefore the observedabsorbance (119860) could be written as
119860 = 119860(CAN) + 119860
(Complex)
119860(Complex) = Δ119860 = 119860 sim 119860
(CAN)(5)
Therefore a plot of ([CAN]0Δ119860) versus 1[PEG]
0should
give a straight line according to the above equation Theseplots have been realized in the present study (Figure 4)Formation constant (119870) has been calculated from the ratioof intercept to slope while inverse of the intercept gave molarextinction coefficient (120598) and is represented in Table 1
3 Results and Discussion
31 Mechanism of CAN Oxidation of Xanthine Alkaloids inMeCN Medium Earlier reports on CAN oxidation stud-ies from our laboratory and elsewhere show that a vari-ety of CAN species such as Ce(NO
3)6
2minus Ce(NO3)5
minusCe(OH)(NO
3)4
minus Ce(NO3)4 and Ce(OH)
3+ may exist innitric acidmedium [39ndash43] However CAN species inMeCNmedium could be entirely different Since MeCN is large
Advances in Physical Chemistry 5
Table 4 Activation parameters of hypoxanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
Benesi-Hildebrand plot of ([CAN]Δ119860) versus (1[PEG-200])
Figure 4 Benesi-Hildebrand plot of CAN-PEG-200
excess over [CAN] MeCN may penetrate into the coordi-nation spheres of Ce(IV) and form solvated CAN speciesaccording to the following equilibrium
(NH4)2Ce(NO
3)6+ CH
3CN
(CAN)
999445999468 [(NH4)Ce(NO
3)5(CH3CN)] + NH
4NO3
(SolvatedCAN)
(6)
31 315 32 325 33 335
119910 = minus44045119909 + 77753
1198772 = 09999
103119879
minus58
minus6
minus62
minus64
minus66
minus68
minus7
ln(119896
998400998400119879
)
Eyringrsquos plot ln(119896998400998400119879) versus (103119879)
Figure 5 Eyringrsquos plot PEG-300 catalysed oxidation of caffeine byCAN
Solvated CAN may be able to oxidize the substrate to afforduric acid as product when Xanthine alkaloid is added to thereaction mixture (see Scheme 2)
32 Mechanism of Oxidation in PEG Media Progress ofthe reaction has been studied in the presence of a set ofpoly oxy ethylene compounds (PEGs) with varied molec-ular weights ranging from 200 to 6000 units and it was
6 Advances in Physical Chemistry
O
O
NN
N
H
O
O
N
NN
N
O
O
N
NN
N
OH
N
O
O
NH
NN
N
H
H
Slow
O
O
NH
NN
N
O
O NO
O
+
(CAN)
R3
R3
R3
R3 R3
R2
R2R2R2
R2
R1
R1 R1 R1
R1
∙ONO2
[Ce(III)ACN]
minusNO2
(Uric acid derivatives)
(Ce(III) nitrate) HNO3NO2minus + +CAN
NH4Ce(NO3)4(ACN)
minus
+
(NH4)[Ce(NO3)5(ACN)]
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
The equilibrium constant 119870 = [C][CAN][PEG] where[CAN] [PEG] and [C] are equilibrium concentrations ofacceptor (CAN) donor (PEG) and complex respectivelyFor the above equilibrium concentration of [PEG-CAN]complex ([C]) can be correlated to the formation constant (119870)
by the following relationship If [CAN]0and [PEG]
0represent
initial concentrations of CAN and PEG respectively then
[C] =119870[CAN]0[PEG]0
1 + 119870[PEG]0 (2)
But according to Lambert-Beerrsquos law absorbance (119860) = 120598119888119897In the above equations 119897 is path length 119889 is absorbance
120598 is the molar extinction coefficient and 119870 is formationconstant of the complex respectively For one cmpath lengthabove equation can be written as (119860) = 120598119888
[C] =119860
120598119897=
119870[CAN]0[PEG]0
1 + 119870[PEG]0 (3)
Further taking the reciprocals to the above equation it rear-ranges to
[CAN]0
119860=
1
119870[PEG]0120598+
1
120598 (4)
However the absorbance of CAN and [CAN-PEG] absorbin the same region significantly therefore the observedabsorbance (119860) could be written as
119860 = 119860(CAN) + 119860
(Complex)
119860(Complex) = Δ119860 = 119860 sim 119860
(CAN)(5)
Therefore a plot of ([CAN]0Δ119860) versus 1[PEG]
0should
give a straight line according to the above equation Theseplots have been realized in the present study (Figure 4)Formation constant (119870) has been calculated from the ratioof intercept to slope while inverse of the intercept gave molarextinction coefficient (120598) and is represented in Table 1
3 Results and Discussion
31 Mechanism of CAN Oxidation of Xanthine Alkaloids inMeCN Medium Earlier reports on CAN oxidation stud-ies from our laboratory and elsewhere show that a vari-ety of CAN species such as Ce(NO
3)6
2minus Ce(NO3)5
minusCe(OH)(NO
3)4
minus Ce(NO3)4 and Ce(OH)
3+ may exist innitric acidmedium [39ndash43] However CAN species inMeCNmedium could be entirely different Since MeCN is large
Advances in Physical Chemistry 5
Table 4 Activation parameters of hypoxanthine in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
Benesi-Hildebrand plot of ([CAN]Δ119860) versus (1[PEG-200])
Figure 4 Benesi-Hildebrand plot of CAN-PEG-200
excess over [CAN] MeCN may penetrate into the coordi-nation spheres of Ce(IV) and form solvated CAN speciesaccording to the following equilibrium
(NH4)2Ce(NO
3)6+ CH
3CN
(CAN)
999445999468 [(NH4)Ce(NO
3)5(CH3CN)] + NH
4NO3
(SolvatedCAN)
(6)
31 315 32 325 33 335
119910 = minus44045119909 + 77753
1198772 = 09999
103119879
minus58
minus6
minus62
minus64
minus66
minus68
minus7
ln(119896
998400998400119879
)
Eyringrsquos plot ln(119896998400998400119879) versus (103119879)
Figure 5 Eyringrsquos plot PEG-300 catalysed oxidation of caffeine byCAN
Solvated CAN may be able to oxidize the substrate to afforduric acid as product when Xanthine alkaloid is added to thereaction mixture (see Scheme 2)
32 Mechanism of Oxidation in PEG Media Progress ofthe reaction has been studied in the presence of a set ofpoly oxy ethylene compounds (PEGs) with varied molec-ular weights ranging from 200 to 6000 units and it was
6 Advances in Physical Chemistry
O
O
NN
N
H
O
O
N
NN
N
O
O
N
NN
N
OH
N
O
O
NH
NN
N
H
H
Slow
O
O
NH
NN
N
O
O NO
O
+
(CAN)
R3
R3
R3
R3 R3
R2
R2R2R2
R2
R1
R1 R1 R1
R1
∙ONO2
[Ce(III)ACN]
minusNO2
(Uric acid derivatives)
(Ce(III) nitrate) HNO3NO2minus + +CAN
NH4Ce(NO3)4(ACN)
minus
+
(NH4)[Ce(NO3)5(ACN)]
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
Benesi-Hildebrand plot of ([CAN]Δ119860) versus (1[PEG-200])
Figure 4 Benesi-Hildebrand plot of CAN-PEG-200
excess over [CAN] MeCN may penetrate into the coordi-nation spheres of Ce(IV) and form solvated CAN speciesaccording to the following equilibrium
(NH4)2Ce(NO
3)6+ CH
3CN
(CAN)
999445999468 [(NH4)Ce(NO
3)5(CH3CN)] + NH
4NO3
(SolvatedCAN)
(6)
31 315 32 325 33 335
119910 = minus44045119909 + 77753
1198772 = 09999
103119879
minus58
minus6
minus62
minus64
minus66
minus68
minus7
ln(119896
998400998400119879
)
Eyringrsquos plot ln(119896998400998400119879) versus (103119879)
Figure 5 Eyringrsquos plot PEG-300 catalysed oxidation of caffeine byCAN
Solvated CAN may be able to oxidize the substrate to afforduric acid as product when Xanthine alkaloid is added to thereaction mixture (see Scheme 2)
32 Mechanism of Oxidation in PEG Media Progress ofthe reaction has been studied in the presence of a set ofpoly oxy ethylene compounds (PEGs) with varied molec-ular weights ranging from 200 to 6000 units and it was
6 Advances in Physical Chemistry
O
O
NN
N
H
O
O
N
NN
N
O
O
N
NN
N
OH
N
O
O
NH
NN
N
H
H
Slow
O
O
NH
NN
N
O
O NO
O
+
(CAN)
R3
R3
R3
R3 R3
R2
R2R2R2
R2
R1
R1 R1 R1
R1
∙ONO2
[Ce(III)ACN]
minusNO2
(Uric acid derivatives)
(Ce(III) nitrate) HNO3NO2minus + +CAN
NH4Ce(NO3)4(ACN)
minus
+
(NH4)[Ce(NO3)5(ACN)]
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
Scheme 2 CAN oxidation of xanthine alkaloids in ACN medium
+
(PEG) (CAN) [PEG-CAN]
HHO
O HO
O119899119899
NH4[Ce(NO3)5(ACN)](NH4)[Ce(NO3)5(ACN)]
minusH+
119870
Figure 6
found that the reaction is enhanced remarkably in all PEGsReaction times were reduced from 24 hrs to few hours Thecatalytic activity was found to be in the decreasing orderPEG-200 gt PEG-300 gt PEG-400 gt PEG-600 UV-VisibleSpectroscopic results presented in Figure 5 clearly indicateda bathochromichypsochromic shift from 459 nm to around442 nm followed by hypochromic shift clearly indicate CANand PEG interactions to afford ldquoPEG bound CANrdquo [PEG-CAN] according to the following equilibrium (see Figure 6)
The plots of 119896119898
(rate constant of PEG reaction)versus 119862PEG (concentration of PEG) indicated a ratemaxima nearly in the vicinity of 150mol dmminus3 PEG-200 099mol dmminus3PEG-300 075mol dmminus3 PEG-4000500mol dmminus3 and PEG-600 Mechanism of PEGmediatedCAN-xanthine alkaloids reactions was explained in the linesof micellar catalysis because PEG resembles the structure ofnon-ionic micelles such as Triton-X Menger and Portnoymodel is used to explain PEG effects which closely resemblethat of an enzymatic catalysis [44ndash48] According to thismodel formation of PEG bound reagent (PEG-Ce(IV))could occur in the preequilibrium step due to the interactionof Ce(IV) with PEG The complex thus formed may possesshigher or lower reactivity to give products A general
[PEG-CAN]
Products
Xanthine alkaloid Xanthine alkaloid
CAN + PEG
119896119908 119896119898
119870
Scheme 3 CAN oxidation mechanism in presence of PEG
mechanism is proposed by considering the bulk phase andmicellar phase reactions as shown in Scheme 3 where 119896
119898
and 1198960or (119896119908) represent rate constants for PEG and bulk
phases respectively and 119870 is the [PEG-Ce(IV)] bindingconstant For the abovemechanism rate law could be derivedaccording to the following sequence of steps in the lines ofmicellar catalyzed reactions From Scheme 3 rate (119881) of thereaction comes out as
119881 = 1198960 [CAN] + 119896
119898 [PEG CAN] 119862S
119881
119862S= 1198961015840= 1198960 [CAN] + 119896
119898 [PEG CAN] (7)
Advances in Physical Chemistry 7
Table 5 Activation parameters of theophylline in different PEG media
Type of PEG PEG (VV) 11989610158401015840 at 300K Equation 119877
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
term could be neglected in the above equation On the basisof the foregoing discussion themost plausiblemechanism forPEG catalysed reaction could be given as in Scheme 4 Therate law for Scheme 4 could then be considered as
119896120593=
119896119898119870 [PEG]
1 + 119870 [PEG] (17)
This rate law resembles Michaelis-Menten type rate law thatis used for enzyme kinetics Interestingly the plots of rateconstant (119896
120593) that is second order rate constant of PEG
mediated reaction versus [PEG] indicated Hill type curves(ie a gradual increase with an increase in [PEG] passingthrough a maximum point in the profile) This observationpoints out that beyond certain concentration PEG bound[CAN] inhibits the reaction rates This could be attributed tothe fact that [CAN] is tightly bound to PEG and surroundedby PEG environment giving less scope for rate accelerationsIn view of this reaction kinetics are studied in detail at variousPEG concentrations in order to have an insight into thevariation in the enthalpies and entropies of activation with[PEG]
33 Effect of Structure on Enthalpy and Entropy ChangesThe enthalpy and entropy of activation (Δ119867
and Δ119878) are
the two parameters typically obtained from the slope andintercepts of Eyringrsquos plot of ln(11989610158401015840119879) versus (1119879) as shownin Figure 5 The positive values for Δ119878
suggest a dissociativemechanism while negative Δ119878
values indicate an associativemechanism Values near zero are difficult to interpret [2649 50] Almost similar magnitude of Δ119866
in a series ofclosely related reactions generally indicates a similar typeof mechanism operative for closely related reactions understudy Overall free energy of reaction (Δ119866)may be consideredto be the driving force of a chemical reaction When Δ119866 lt 0
the reaction is spontaneous when Δ119866 = 0 the system isat equilibrium and no net change occurs and when Δ119866 gt
0 the reaction is not spontaneous Entropies of activationdata compiled in Tables 1 to 6 of the present study arehighly negative which are in accordance with an associativemechanism leading to awell-organized transition stateTheseresults probably support the association of PEG with CANwhich brings about changes in the transition state and causesimultaneous association and dissociation of species causingdisorderness in the transition state leading to a chemical
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
reaction Similar type of trends is recorded in all the PEGsused in this study
4 Conclusions
We have studied oxidation of Xanthine alkaloids such asXanthine (XAN) hypoxanthine (HXAN) caffeine (CAF)theophylline (TPL) and theobromine (TBR) by a commonlaboratory desktop reagent CAN in catalytic amounts Oxi-dation of xanthine derivatives afforded uric acid derivativesEven though the reaction is too sluggish in acetonitrilemedia even at reflux temperatures it underwent smoothlyin presence of Poly ethylene glycols (PEG) Reaction kineticsindicated first order in both [CAN] and [Xanthine alkaloid]Rate of oxidation is accelerated with an increase in [PEG]linearly Mechanism of oxidation in PEG media has beenexplained byMenger-Portnoy enzymatic model with the oxi-dation of PEG bound oxidant (PEG-CAN) as more reactivespecies than (CAN) itself
References
[1] L Eberson Electron Transfer Reactions inOrganic ChemistrySpringer Berlin Germany 1987
[2] K B Wiberg Oxidations in Organic Chemistry (Part A) Aca-demic Press 1965
[3] W S Trahanosky Oxidations in Organic Chemistry (Part B)Academic Press 1968
[4] P Renaud and M P Sibi Radicals in Organic Synthesis vol 1Wiley-VCH Weinheim Germany 2001
[5] N L Bauld ldquoHole and electron transfer catalyzed pericyclicreactionsrdquo inAdvances in Electron Transfer Chemistry vol 2 pp1ndash66 1992
[6] M Chanon M Rajzmann and F Chanon ldquoOne electron moreone electron less What does it change Activations inducedby electron transfer The electron an activating messengerrdquoTetrahedron vol 46 no 18 pp 6193ndash6299 1990
[7] M Schmittel ldquoKetene-diene [4 + 2] cycloaddition productsvia cation radical initiated Diels-Alder reaction or vinylcy-clobutanone rearrangementrdquo Journal of the American ChemicalSociety vol 115 no 6 pp 2165ndash2177 1993
[8] M Schmittel and C Wohrle ldquoElectron transfer initiated Diels-Alder reaction with allenes as dienophilesrdquo Tetrahedron Lettersvol 34 no 52 pp 8431ndash8434 1993
[9] A Gieseler E Steckhan O Wiest and F Knoch ldquoPhotochem-ically induced radical cation Diels-Alder reaction of indole andelectron-rich dienesrdquo Journal of Organic Chemistry vol 56 no4 pp 1405ndash1411 1991
10 Advances in Physical Chemistry
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
[10] M Schmittel ldquoAmmoniumyl salt-induced Diels-Alder reactionof ketenes-control of [2 + 2] versus [4 + 2] selectivityrdquo Ange-wandte Chemie vol 30 no 8 pp 999ndash1001 1991
[11] N L Bauld ldquoCation radical cycloadditions and related sigmat-ropic reactionsrdquoTetrahedron vol 45 no 17 pp 5307ndash5363 1989
[12] P E Floreancig ldquoDevelopment and applications of electron-transfer-initiated cyclization reactionsrdquo Synlett no 2 pp 191ndash203 2007
[13] M Schmittel ldquoUmpolung of ketones via enol radical cationsrdquoin Topics in Current Chemistry vol 169 pp 183ndash230 1994
[14] M Schmittel and A Burghart ldquoUnderstanding reactivity pat-terns of radical cationsrdquoAngewandte Chemie vol 36 no 23 pp2550ndash2589 1997
[15] M Schmittel and A Langels ldquoA short-lived radical dicationas a key intermediate in the rearrangement of a persistentcation the oxidative cyclization of 22-dimesityl-1-(4-NN-dimethylaminophenyl)ethenolrdquo Angewandte Chemie vol 36no 4 pp 392ndash395 1997
[16] M Rock and M Schmittel ldquoControlled oxidation of enolatesto a-carbonyl radicals and a-carbonyl cationsrdquo Journal of theChemical Society Chemical Communicationspp no 23 pp1739ndash1741 1993
[17] V Nair L Balagopal R Rajan and JMathew ldquoRecent advancesin synthetic transformations mediated by Cerium(IV) ammo-nium nitraterdquo Accounts of Chemical Research vol 37 no 1 pp21ndash30 2004
[18] V Nair J Mathew and J Prabhakaran ldquoCarbon-carbon bondforming reactions mediated by cerium(IV) reagentsrdquo ChemicalSociety Reviews vol 26 no 2 pp 127ndash132 1997
[19] E Baciocchi andR Ruzziconi ldquo12- and 14-addition in the reac-tions of carbonyl compounds with 13-butadiene induced bycerium(IV) ammonium nitraterdquo Journal of Organic Chemistryvol 51 no 10 pp 1645ndash1649 1986
[20] A B Paolobelli P Ceccherelli F Pizzo and R J Ruzzi-coni ldquoRegio- and stereoselective synthesis of unsaturated car-bonyl compounds based on ceric ammonium nitrate-promotedoxidative addition of trimethylsilyl enol ethers to conjugateddienesrdquo The Journal of Organic Chemistry vol 60 no 15 pp4954ndash4958 1995
[21] J R Hwu C N Chen and S S Shiao ldquoSilicon-controlledallylation of 13-dioxo compounds by use of allyltrimethylsilaneand ceric ammoniumnitraterdquoThe Journal of Organic Chemistryvol 60 no 4 pp 856ndash862 1995
[22] V Nair and J Mathew ldquoFacile synthesis of dihydrofurans bythe cerium(IV) ammonium nitratemediated oxidative additionof 13-dicarbonyl compounds to cyclic and acyclic alkenesRelative superiority over the manganese(III) acetaterdquo Journal ofthe Chemical Society Perkin Transactions 1 no 3 pp 187ndash1881995
[23] V Nair J Mathew and S Alexander ldquoSynthesis of spiroan-nulated dihydrofurans by cerium(IV) ammonium nitratemediated addition Of 13-dicarbonyl compounds to exocyclicalkenesrdquo Synthetic Communications vol 25 no 24 pp 3981ndash3991 1995
[24] B B Snider and T Kwon ldquoOxidative cyclization of deltaepsilon- and epsilonzeta-unsaturated enol silyl ethersand unsaturated siloxycyclopropanesrdquo The Journal of OrganicChemistry vol 57 no 8 pp 2399ndash2410 1992
[25] A J Clark C P Dell J M McDonagh J Geden and PMawdsley ldquoOxidative 5-endo cyclization of enamides mediatedby ceric ammonium nitraterdquo Organic Letters vol 5 no 12 pp2063ndash2066 2003
[26] M Schmittel G Gescheidt and M Rock ldquoThe first spectro-scopic identification of an enol radical cation in solution theanisyl-dimesitylethenol radical cationrdquo Angewandte Chemievol 33 no 19 pp 1961ndash1963 1994
[27] M Schmittel and A Langels ldquoEnol radical cations in solutionPart 12 synthesis and electrochemical investigations of a stableenol linked to a ferrocene redox centrerdquo Journal of the ChemicalSociety Perkin Transactions 2 no 3 pp 565ndash572 1998
[28] M Schmittel and A Langels ldquoEnol radical cations in solution13 First example of a radical dication rearrangement One-electron oxidation of dihydrobenzofuranyl cations leads todrastic rate enhancement in the oxidative benzofuran forma-tion from enolsrdquoThe Journal of Organic Chemistry vol 63 no21 pp 7328ndash7337 1998
[29] V N Vasudevan and S V Rajendra ldquoMicrowave-acceleratedSuzuki cross-coupling reaction in polyethylene glycol (PEG)rdquoGreen Chemistry no 3 pp 146ndash148 2001
[30] A Haimov and R Neumann ldquoPolyethylene glycol as a non-ionic liquid solvent for polyoxometalate catalyzed aerobicoxidationrdquo Chemical Communications no 8 pp 876ndash877 2002
[31] L Heiss andH J Gais ldquoPolyethylene glycol monomethyl ether-modified pig liver esterase preparation characterization andcatalysis of enantioselective hydrolysis in water and acylation inorganic solventsrdquo Tetrahedron Letters vol 36 no 22 pp 3833ndash3836 1995
[32] S Chandrasekar C Narsihmulu S S Shameem and N RReddy ldquoOsmium tetroxide in poly(ethylene glycol)(PEG) arecyclable reaction medium for rapid asymmetric dihydroxy-lation under Sharpless conditionsrdquo Chemical Communicationsno 14 pp 1716ndash1717 2003
[33] K Tanemura T Suzuki Y Nishida and T Horaguchi ldquoAldolcondensation in water using polyethylene glycol 400rdquo Chem-istry Letters vol 34 no 4 pp 576ndash577 2005
[34] R Kumar P Chaudhary S Nimesh and R Chandra ldquoPolyethy-lene glycol as a non-ionic liquid solvent for Michael additionreaction of amines to conjugated alkenesrdquoGreen Chemistry vol8 no 4 pp 356ndash358 2006
[35] K V Rao and S S Muhammed ldquoStudies in the two phasessystem sodium formate-yridine Extraction of nickel and sep-aration from chromiumrdquo Bulletin of the Chemical Society ofJapan vol 36 no 8 pp 941ndash943 1963
[36] S S Muhammed and B Sethuram ldquoUpper carboniferousflora from the Mecsek Mts (Southern Hungary)mdashsummarizedresultsrdquo Acta Geologica Hungarica vol 46 no 1 pp 115ndash1251965
[37] M Santappa and B Sethuram ldquoOxidation studies IV Kineticsof oxidation ofHCHOand some alcohols by ceric salts inHNO
3
mediumrdquo Proceedings of the Indian Academy of Sciences A vol67 pp 78ndash89 1968
[38] N Dutt R R Nagori and R N Mehrotra ldquoKinetics andmechanisms of oxidations by metal ions Part VI Oxidationof a-hydroxy acids by cerium(IV) in aqueous nitric acidrdquoCanadian Journal of Chemistry vol 64 no 1 pp 19ndash23 1986
[39] K C Rajanna Y R Rao and P K Saiprakash ldquoKinetic andmechanistic study of isopropanol and acetone by Ceric sulphatein aqueous sulphuric acidmediumrdquo Indian Journal of ChemistryA vol 17 p 270 1977
[40] J H Fendler and R J Fendler Catalysis in Micellar and Micro-Molecular Systems Academic Press New York NY USA 1975
[41] J Van Stam S Depaemelaere and F C De Schryver ldquoMicellaraggregation numbersmdasha fluorescence studyrdquo Journal of Chemi-cal Education vol 75 no 1 pp 93ndash98 1998
Advances in Physical Chemistry 11
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
[42] J H Fendler and W L Hinze ldquoReactivity control in micellesand surfactant vesicles Kinetics and mechanism of base-catalyzed hydrolysis of 55rsquo-dithiobis(2-nitrobenzoic acid) inwater hexadecyltrimethylammonium bromide micelles anddioctadecyldimethylammonium chloride surfactant vesiclesrdquoJournal of the American Chemical Society vol 103 no 18 pp5439ndash5447 1981
[43] L S Romsted ldquoA general kinetic theory of rate enhance-ments for reactions between organic substrates and hydrophilicions in micellar systemsrdquo in Micellization Solubilization andMicroemulsions K L Mittal Ed vol 2 pp 509ndash530 PlenumPress New York NY USA 1977
[44] F M Menger and C E Portnoy ldquoOn the chemistry of reactionsproceeding inside molecular aggregatesrdquo Journal of the Ameri-can Chemical Society vol 89 no 18 pp 4698ndash4703 1967
[45] F M Menger ldquoGroups of organic molecules that operatecollectivelyrdquo Angewandte Chemie vol 30 no 9 pp 1086ndash10991991
[46] K A Connors Chemical Kinetics The Study of Reaction Ratesin Solution VCH New York NY USA 1990
[47] J Espenson Chemical Kinetics and Reaction MechanismMcGraw-Hill 1981
[48] J E Leffler and E Grunwald Rates and Equilibria of OrganicReactions Wiley New York NY USA 1963
[49] H Maskill The Physical Basis of Organic Chemistry OxfordUniversity Press Oxford UK 1986
[50] V Jagannadham ldquoThe change in entropy of activation due tosolvationhydrationmdasha one hour graduate classroom lecturerdquoChemistry vol 18 no 4 p 89 2009
![Page 1: Research Article Polyethylene Glycols as Efficient ...downloads.hindawi.com/journals/apc/2013/835610.pdf · Under pseudo rst order conditions [CAF] [CAN] ... T : Activation parameters](https://reader042.documents.pub/reader042/viewer/2022031006/5b89f4807f8b9a9b7c8b482b/html5/page/1.jpg)
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![Page 4: Research Article Polyethylene Glycols as Efficient ...downloads.hindawi.com/journals/apc/2013/835610.pdf · Under pseudo rst order conditions [CAF] [CAN] ... T : Activation parameters](https://reader042.documents.pub/reader042/viewer/2022031006/5b89f4807f8b9a9b7c8b482b/html5/page/4.jpg)
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