Synthesis and redox properties of ferrocenylquinoxalines

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Pergamon PII]

Polyhedron Vol[ 06\ No[ 12Ð13\ pp[ 3044Ð3051\ 0887 Þ 0887 Elsevier Science Ltd All rights reserved[ Printed in Great Britain 9166Ð4276:87 ,08[99¦9[99 S9166!4276"87#99112!X

Synthesis and redox properties of ferrocenylquinoxalines Piero Zanelloa\ Marco Fontania\ S[ Zaka Ahmed b and Christopher Glidewellb a

Dipartimento di Chimica dell|Universita di Siena\ Pian dei Mantellini\ 33\ 42099 Siena\ Italy b

School of Chemistry\ University of St[ Andrews\ St[ Andrews\ Fife KY05 8ST\ U[K[ "Received 29 March 0887^ accepted 0 June 0887#

Abstract*The ferrocenyl 0\1!diketone ð"C4H4#Fe"C4H3#COCOPhŁ when condensed with aromatic 0\1!diamines forms a range of ferrocenyl!substituted quinoxalines] when the diamine is unsymmetrically substituted the quinoxaline is formed as a mixture of two regio!isomers\ which can in some cases be separated by careful chromatography[ Electrochemical studies show that these present ferrocenylquinoxalines undergo the expected reversible one!electron oxidation centred on the ferrocenyl moiety and a two!electron reduction process centred on the quinoxalyl fragment\ which is accompanied by chemical complications[ The oxidation of the ferrocenyl group occurs at potentials slightly higher than that of unsubstituted ferrocene "by about 099Ð049 mV\ depending on the substituents# indicating that the quinoxalyl substituent is slightly electron!withdrawing with respect to ferrocene[ Þ 0887 Elsevier Science Ltd[ All rights reserved Keywords] cyclic voltammetry^ electrochemistry^ ferrocene^ quinoxaline[ ———————————————————————————————————————————————

INTRODUCTION The reaction between 0\1!diketones and 0\1!diamines to form quinoxalines\ well!known as a characteristic reaction for both components\ has been successfully exploited as a polymer!forming process when applied to combinations of bis"0\1!diketones# and bis"0\1! diamines# ð0Ð2Ł[ For polymer synthesis\ the reaction can generally be performed under solvent!free "melt! phase# conditions\ when the sole by!product is water which distills from the reaction mixture at the melting temperature of the components[ It is the removal of the water by!product\ along with the in situ formation of new heteroaromatic rings\ which drives the process to completion[ The e}ectiveness of this reaction ð0Ð 2Ł makes it an attractive route for the synthesis of organometallic polymers\ for example by reaction of 0\0?!ferrocenediylbis"0\1!diketones# with bis"0\1! diamines#[ We have recently described e}ective routes to a range of ferrocenyl 0\1!diketones ð3\ 4Ł and here we present the results of a study of reactions of a representative ferrocenyl diketone\ FcCOCOPh ð3\ 5Ł ðFc"C4H4#Fe"C4H3#Ł with a range of 0\1!diamines\

 Author to whom correspondence should be addressed[

to form the corresponding ferrocenylquinoxalines\ along with an electrochemical study of their redox properties[ Monomeric ferrocenylquinoxalines are themselves potentially of interest and importance] a number of quinoxalines are powerful antibiotics and some examples show potential as anti!cancer drugs ð6Ł and their action in this respect is dependent on their binding to DNA by intercalation ð7Ł[ At the same time\ some rather simple ferricinium salts have been shown to exhibit powerful anti!tumour activity against a range of human tumour types ð8Ł] the intro! duction of ferrocenyl substituents onto the quin! oxaline framework could perhaps provide\ in a single molecular species\ a powerful combination of these two actions[

RESULTS AND DISCUSSION Syntheses of ferrocenylquinoxalines Reaction of 0!ferrocenyl!1!phenylethanedione\ FcCOCOPh\ 0\ with 0\1!diaminobenzene\ 1\ yields the corresponding 1!ferrocenyl!2!phenylquinoxaline\ 2[ When the reaction is conducted in the absence of solvent by melting together the two components under

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P[ Zanello et al[

an inert atmosphere\ the yield of the deep!purple prod! uct is generally somewhat less than 49)\ after chro! matographic puri_cation[ However\ if the two reactants are _rst mixed in dioxan solution and then slowly heated _rst in solution and\ subsequently\ after all the solvent has evaporated\ as a melt\ the yield of puri_ed product is consistently around 54)[ The product 2 is readily characterised by its ana! lytical data and its 0 H and 02 C NMR spectra[ The 0 H NMR spectrum contains\ as well as characteristic signals from the monosubstituted ferrocenyl frag! ment\ well!separated resonances arising from the phe! nyl and quinoxalyl fragments] the 02 C spectrum again shows the characteristic resonances from the fer! rocenyl fragment\ together with seven CH and _ve quaternary resonances in the aromatic region[ A sin! gle!crystal X!ray di}raction analysis of 2\ prepared in this manner\ has been published ð09Ł[ Because of the signi_cantly enhanced yield obtained when the reac! tants were _rst heated in dioxan "b[p[ 090>C# prior to the melt!phase condensation\ the reactions of 0 with other aromatic 0\1!diamines were all conducted under similar conditions^ in all these reactions\ the choice of solvent was in~uenced by a combination of reactant solubility and solvent volatility[ As with compound 2\ nearly all the resulting quinoxalines were isolated after chromatography on silica or alumina as hydrates\ either monohydrates or hemihydrates[ Thus\ when the ferrocenyl diketone 0 was reacted with 2\3!diaminobenzoic acid 3\ initially in chlo! robenzene "b[p[ 021>C#\ the quinoxaline 4 was obtained in ca[ 79) yield after chromatographic puri! _cation[ However\ both the 0 H and 02 C NMR spectra indicated the presence of the two regio!isomers 4a and 4b\ arising from the alternative orientations of the reactants in the condensation process] integration of the 0 H spectrum in the ferrocenyl region indicated a major]minor isomer ratio of 1]0[ No chromatographic conditions could be found under which the isomers were separable and conse! quently the assignment of the major and minor iso! mers as either 4a or 4b was not possible[ However\ it was possible\ despite some peak overlap\ to analyse completely for each isomer the quinoxalyl region of

the 0 H NMR spectrum in terms of an ABX pattern having a JAX " 4 JHH# of zero[ Similarly\ with the 3! nitrodiamine 5\ the two regio!isomers 6a and 6b of the corresponding nitroquinoxaline are formed\ with in this case a major]minor isomer ratio of 2]0^ again\ the quinoxalyl region of the 0 H NMR spectrum was ana! lysed in terms of two ABX patterns each with a JAX of zero[ From the condensation of the diketone 0 with 1\2! diaminotoluene\ again a mixture of two regio!isomers 7a and 7b was formed\ with a major]minor ratio of 2]1 as judged from the 0 H NMR spectrum\ but on this occasion the two isomers were separable by care! ful chromatography on silica[ On the other hand\ the two regio!isomers 8a and 8b obtained using 1\2!diam! inopyridine were not separable on silica\ but were found to be separable on alumina provided that pure dichloromethane was employed as eluent] even the slightest increase in the polarity of the mobile phase caused the isomers to elute together[ In the quinoxaline!forming condensations involv! ing substituted diamines\ the modest regio!selectivity is determined by the relative nucleophilicities of the two amino groups in the diamine component\ and the relative electrophilicities of the two carbonyl carbon atoms in the diketone 0[ It is assumed that the more nucleophilic amino group reacts faster with the more electrophilic carbonyl[ In diamines 3 and 5\ in which the substituent R is electron!withdrawing\ the amino group meta to R will be the more nucleophilic\ while the carbonyl adjacent to the phenyl ring in 0 will be the more electrophilic\ because of the strong electron! donating character of the ferrocenyl fragment[ Hence\ it is to be expected that 4b is the more abundant isomer of 4^ similarly for 6\ the ferrocenyl fragment is preferentially para to the deactivating substituent[ In 1\2!diaminotoluene\ the amino group ortho to methyl is the more nucleophilic\ so that 7b is expected to predominate\ while the strong deactivation of the 1! amino group in 1\2!diaminopyridine leads to the expectation of 8a as the major isomer[ Use of the bis!0\1!diamine\ 09\ under the reaction conditions employed for the formation of quin! oxalines 2\ 4\ 6\ 7 and 8 and using dioxan as solvent

Synthesis and redox properties of ferrocenylquinoxalines

gave\ as a mixture of regio!isomers\ the expected bis! product 00[ However\ when the ferrocenyl diketone 0 and the bis!diamine 09 were reacted together in alka! line aqueous solution ð00Ł\ the predominant product was the monoquinoxaline 01\ accompanied by only a trace of 00[ Electrochemistry Figure 0\ which refers to compound 2\ shows the typical cyclic voltammogram exhibited by the present compounds in dichloromethane solution[ Both an oxi! dation process possessing features of chemical reversi! bility and an apparently irreversible reduction process\ which is about twice greater in height than the oxi! dation step\ are apparent[ Controlled!potential coulometric investigation of the anodic process "Ew¦9[6 V# show the con! sumption of one electron:molecule[ Upon exhaustive one!electron oxidation the original ruby!red solution of 2 turns jade!green and displays an absorption in the visible region at lmax581 nm[ In con_rmation of the chemical reversibility of the ferrocene:ferricenium oxidation\ cyclic!voltammetric tests performed on the oxidised green solution display voltammetric pro_les entirely complementary to that shown in Fig[ 0[ Analysis ð01Ł of the cyclic!voltammetric anodic responses with scan rates varying from 9[91 to 0[99 V s−0 show parameters which are diagnostic of a one!electron removal which is essentially reversible from the electrochemical viewpoint[ As a matter of fact\ the ipc:ipa ratio is constantly equal to unity\ the

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current function ipa:v0:1 remains constant and the peak!to!peak separation progressively increases from 69 to 069 mV[ Such a slight departure from the con! stant value of 48 mV expected for an elec! trochemically!reversible one!electron process neatly parallels that observed for the one!electron oxidation of unsubstituted ferrocene\ so that it may be attributed to uncompensated solution resistances[ So far as the reduction process is concerned\ it was not possible to perform macroelectrolysis inves! tigations because of the closeness of the solvent reduction[ Based on the relative heights\ we assign it to a single two!reduction process\ which is however complicated by subsequent reactions\ as yet uncharac! terised[ As the inset of Fig[ 0 shows\ when the scan rate was increased beyond 1[99 V s−0\ a reoxidation appears directly associated to the reduction process[ This means that the rate of the chemical complication falls within the cyclic voltammetry time window\ allowing estimation of ca[ 9[94 s as the half!life of the electrogenerable ð2Ł1− anion ð02Ł[ Table 0 presents for all the compounds studied the formal electrode potentials of the redox changes dis! cussed above and\ for comparison\ the corresponding data for the unsubstituted 1!ferrocenylquinoxaline "02# are also reported[ The electrogenerated fer! ricenium species ð4Ł¦\ ð8Ł¦ and ð02Ł¦ proved to be not fully stable and to undergo slow decomposition[ In comparison with unsubstituted ferrocene itself\ the ferrocenylquinoxalines oxidise at potential values some 099Ð049 mV higher\ thus indicating that the quinoxaline exerts a signi_cant electron!withdrawing

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P[ Zanello et al[

e}ect[ However\ the e}ects of the substituents on the quinoxaline ring are always readily interpreted[ Com! parison between 02 and 2\ indicates that the 2!phenyl substituent\ which might have been expected to make the oxidation more di.cult\ in fact makes the oxi! dation slightly easier\ suggesting that resonance e}ects predominate over inductive e}ects[ This could also explain the absence of inductive e}ects exerted by the methyl group in 7\ or the carboxyl group in 4\

compared with 2[ On the other hand\ the strongly electron!withdrawing NO1 group in 6 generates its expected e}ect[ The redox behaviour of the biferrocene complex 00 merits comment[ It exhibits a single oxidation process\ but unfortunately\ because of its very low solubility satisfactory controlled!potential coulometry was not possible[ However\ in view of the absence of further oxidation processes up to ¦0[1 V\ it may be specu!

Synthesis and redox properties of ferrocenylquinoxalines

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Fig[ 0[ Cyclic voltammogram recorded at a platinum electrode on a CH1Cl1 solution containing 2 "0[2×09−2 mol dm−2# and ðNBu3ŁðPF5Ł "9[1 mol dm−2#[ Scan rates] main _gure\ 9[19 V s−0^ inset\ 1[99 V s−0[

Table 0[ Formal electrode potentials "in V\ vs S[C[E[#\ peak! to!peak separations "in mV# and spectroscopic data "in nm# for the redox changes exhibited by the present fer! rocenylquinoxalines in dichloromethane solution[ Complex

E99:0¦?

DEpa

lmax b

E99:1−?

2 4 6 7 8 00 02 FcH

¦9[36 ¦9[38 ¦9[44 ¦9[38 ¦9[44 ¦9[35f ¦9[42 ¦9[28

79 86 64 68 64 69 84 73

581 579 559 694 570 − 564 519

−0[79c − −0[44d\e −0[79d −0[40c − −0[68d −

a

Measured at 9[0 V s−0[ Absorption band of the oxidized species[ c Measured at 1[9 V s−0[ d Peak potential value[ e A preceding reduction centred on the NO1 group is pre! sent at E9?−9[84 V[ f Two!electron step[ b

lated that this is due to a single two!electron step[ Were this to be so\ it would imply that no electronic communication occurs between the two quinoxalyl units[ Finally\ as far as the presence of isomeric species is concerned\ as noted above for compounds 4\ 6\ 7\ 8 and 00\ it may be pointed out that only in the case of compound 4 was the presence of two almost over! lapping oxidation processes observed\ which could

account for the somewhat greater peak!to!peak sep! aration in 4 compared with the other species[

EXPERIMENTAL The diketone FcCOCOPh was prepared as pre! viously described ð3Ł[ Aromatic diamines were obtained from commercial sources and were puri_ed using published methods ð03Ł[ NMR spectra were rec! orded at ambient temperatures\ in CDCl2 solution unless stated otherwise\ on a Bruker AM!299 spec! trometer operating at 299[024 MHz for 0 H and 64[358 MHz for 02 C[ Diethyl ether and light pet! roleum "b[p[ 39Ð59>C# were dried over sodium wire[ Elemental analyses were by the Microanalytical Lab! oratory of this School[ Synthesis of 1!ferrocenyl!2!phenylquinoxaline Melt!phase reaction Ferrocenylphenylethanedione 0 "9[1 g\ 9[52 mmol# and 0\1!diaminobenzene 1 "9[0 g\ 9[82 mmol# were taken in a Pyrex glass test tube with a side arm and _tted with a bubbler[ The mixture was heated to melting in an oil bath at 039>C under nitrogen for 29 min\ water vapours were observed con! densing on the walls of tube[ After cooling the crude material was dissolved in dichloromethane and checked by TLC^ this showed one purplish!red spot almost at the same Rf value as fer! rocenylphenylethanedione[ This crude product was chromatographed on silica gel using dichloromethane as the eluting solvent\ concentrated and crystallised to

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give dark purple crystals of 1!ferrocenyl!2!phenyl! quinoxaline 2 "9[00 g\ 34)#[ Reaction in dioxan solution Ferrocenyl! phenylethanedione 0 "9[1 g\ 9[52 mmol#\ 0\1!diamino! benzene 1 "9[0 g\ 9[82 mmol# were dissolved in 0\3! dioxan "2 cm2# in a Pyrex glass test tube with a side arm and _tted with a bubbler[ This mixture was heated in an oil bath at 009>C under a gentle stream of nitro! gen until dryness[ The temperature of the bath was raised to 039>C and held at this temperature for 19 min[ The crude product was puri_ed as for the melt! phase reaction[ Weight of chromatographed product 9[05 g "54)#[ The products from these two processes were found to be identical by TLC and by 0 H and 02 C NMR[ Anal[ found C 61[1\ H 3[3\ N 5[8^ C13H07FeN1 requires C 62[8\ H 3[6\ N 6[1)^ C13H07FeN1[9[4H1O requires C 61[1\ H 3[7\ N 6[9)[ M[p[ 197Ð109>C "lit[ 197Ð 198>C ð3Ł#[ NMR d"H# 3[99[ "4H\ s\ C4H4#^ 3[24 "1H\ m# and 3[44 "1H\ m# "C4H3#^ 6[49Ð6[44 "4H\ m\ Ph#^ 6[61 "1H\ m# and 7[97 "1H\ m# "quinoxalyl#^ d"C# 58[8 "d\ C4H4#^ 69[0 "d#\ 69[7 "d# and 71[2 "s# "C4H3#^ 017[3 "d#\ 017[7 "d#\ 017[8 "d#\ 018[9 "d#\ 018[1 "d#\ 018[2 "d#\ 018[8 "d#\ 028[7 "s#\ 039[2 "s#\ 030[8 "s#\ 043[0 "s# and 043[0 "s# "phenyl and quinoxalyl#[

Synthesis of ferrocenylphenylquinoxalylcarboxylic acid In a similar manner\ ferrocenylphenylethanedione 0 "9[4 g\ 0[46 mmol#\ 2\3!diaminobenzoic acid 3 "9[15 g\ 0[6 mmol# and chlorobenzene "4 cm2# were heated in a silicone oil bath at 039>C under a gentle stream of nitrogen^ after 0 h[ TLC showed that no unreacted diketone remained[ During the reaction time the col! our of the mixture also changed from dark red to dark purple[ The mixture was then heated to dryness[ After cooling\ the solid residue was dissolved in dichlo! romethane\ _ltered\ washed with water\ dried "Na1SO3#\ concentrated and chromatographed over silica gel using diethyl ether as the mobile phase to yield ferrocenylphenylquinoxalylcarboxylic acid 4 "9[44 g\ 70)# as a dark purple solid[ The 0 H NMR spectrum showed the presence of two regio!isomers[ The relative yield of the regio!isomers as calculated from the 0 H NMR integration is 1]0[ Anal[ found C 55[8\ H 3[6\ N 4[6^ C14H07FeN1O1 requires C 58[0\ H 3[1\ N 5[4^ C14H07FeN1O1[H1O requires C 55[3\ H 3[4\ N 5[1)[ NMR d"H# "major isomer# 3[90 "4H\ s\ C4H4#^ 3[27 "1H\ m# and 3[47 "1H\ m# "C4H3#^ 6[3Ð6[6 "4H\ m\ Ph#^ 7[04 "0H\ d^ J\ 7[7#\ 7[24 "0H\ dd^ J\ 7[7 and 0[5# and 7[81 "0H\ d^ J\ 0[5# "quinoxalyl#^[ "minor isomer# 3[92 "4H\ s\ C4H4#^ 3[39 "1H\ m# and 3[59 "1H\ m# "C4H3#^ 6[3Ð6[6 "4H\ m\ Ph#^ 7[04 "0H\ d^ J\ 7[7#\ 7[27 "0H\ dd^ J\ 7[7 and 0[5# and 7[80 "0H\ d^ J\ 0[5# "quinoxalyl#^ d"C# "major isomer# 57[36 "d\ C4H4#^ 58[9 "d#\ 58[4 "d# and 79[0 "s# "C4H3#^ "minor isomer# 57[42 "d\ C4H4#^ 58[2 "d#\ 58[5 "d# and 79[3 "s# "C4H3#^ "both isomers# 015[82 "d#\ 015[85 "d#\ 016[94 "d#\ 016[05 "d#\ 016[52 "d#\ 016[61 "d#\ 016[67 "d#\ 017[2 "d#\ 018[5 "d#\

018[7 "d#\ 029[0 "d#\ 020[0 "d#\ 026[2 "s#\ 027[06 "s#\ 027[13 "s#\ 028[3 "s#\ 039[9 "s#\ 031[9 "s#\ 041[3 "s#\ 042[9 "s#\ 042[5 "s# and 043[5 "s# "phenyl and quinoxalyl#^ 055[1 "s# COOH[ The resolution of the aromatic res! onances requires resolution enhancement[ Both the carboxyl carbons appear at the same position\ and two of the quaternary carbons of the aromatic:quinoxaline moieties are superimpose on other peaks in that region and hence are not visible in the spectrum[ Synthesis of ferrocenylphenylnitroquinoxaline Ferrocenylphenylethanedione 0 "9[11 g\ 9[58 mmol#\ 3!nitro!0\1!diaminobenzene 5 "9[01 g\ 9[65 mmol# and toluene "4 cm2# were re~uxed\ as above\ under a gentle stream of nitrogen for 2 h^ the reaction was monitored by TLC[ The solvent was evaporated after this time[ After cooling\ the solid residue was redissolved in dichloromethane\ _ltered\ concentrated and chromatographed over silica gel using dichloromethane as the mobile phase to yield ferrocenylphenylnitroquinoxaline 6 "9[11 g\ 62)# as a dark purple solid[ The compound crystallises as a hemi!hydrate as shown by the elemental analysis and integration of the 0 H NMR spectrum gave an isomer ratio of 2]0[ An attempt to separate the two isomers on silica using dichloromethane as eluent yielded a pure fraction of the more abundant isomer\ together with a mixture of both the isomers[ Anal[ found "iso! mer mixture# C 54[0\ H 2[8\ N 8[0^ C13H06FeN2O1 requires C 55[1\ H 2[8\ N 8[5^ C13H06FeN2O1[9[4H1O requires C 53[8\ H 3[0\ N\ 8[3)[ NMR "major isomer pure\ minor isomer from spectrum of mixture# d"H# "major isomer# 3[90 "4H\ s\ C4H4#^ 3[39 "1H\ m# and 3[46 "1H\ m# "C4H3#^ 6[4Ð6[5 "4H\ m\ Ph#^ 7[07 "0H\ d^ J\ 8[4#\ 7[33 "0H\ dd^ J\ 8[4 and 1[3# and 7[87 "0H\ d^ J\ 1[3# "quinoxalyl#^ "minor isomer# 3[99 "4H\ s\ C4H4#^ 3[32 "1H\ m# and 3[59 "1H\ m# "C4H3#^ 6[4Ð6[5 "4H\ m\ Ph#^ 7[05 "0H\ d^ J\ 8[3#\ 7[37 "0H\ dd^ J\ 8[3 and 1[3# and 7[87 "0H\ d^ J\ 1[3# "quinoxalyl#^ d"C# "major isomer# 58[8 "d\ C4H4#^ 69[7 "d#\ 60[0 "d# and 79[7 "s# "C4H3#^ 010[7 "d#\ 013[6 "d#\ 017[3 "d#\ 017[89 "d#\ 018[4 "d#\ 029[4 "d#\ 027[8 "s#\ 039[3 "s#\ 031[9 "s#\ 036[8 "s#\ 033[7 "s# and 046[0 "s# "phenyl and quinoxalyl#^ "minor isomer# 69[9 "d\ C4H4#^ 60[14 "d#\ 60[17 "d# and 79[6 "s# "C4H3#^ 012[1 "d#\ 014[5 "d#\ 017[1 "d#\ 017[76 "d#\ 018[3 "d#\ 018[5 "d#\ 027[9 "s#\ 027[8 "s#\ 033[0 "s#\ 035[6 "s#\ 034[1 "s# and 047[0 "s# "phenyl and quinoxalyl#[ Synthesis of ferrocenylphenylmethylquinoxaline In a similar manner\ ferrocenylphenylethanedione 0 "9[4 g\ 0[46 mmol#\ 1\2!diaminotoluene "9[11 g\ 0[7 mmol# and chlorobenzene "4 cm2# were re~uxed in an oil bath at 049>C under a gentle stream of nitrogen[ The reaction was monitored by TLC and after 3 h the reaction was complete[ The two regio!isomers had distinguishable Rf values\ but the less polar isomer

Synthesis and redox properties of ferrocenylquinoxalines had almost the same value as the diketone\ so that it was sometimes di.cult to di}erentiate between dike! tone and this isomer of the product[ When the reaction was complete\ the solvent was removed and the solid residue was redissolved in dichloromethane\ _ltered\ concentrated and chromatographed over silica gel using dichloromethane:petrol as the mobile phase to yield ferrocenylphenylmethylquinoxaline 7 "9[5 g\ 84)# as a dark purple solid[ The relative yield of the regioisomers as calculated from the 0 H NMR inte! gration is 2]1[ Another column was run to separate the two isomers from each other^ this yielded _rst the pure less!polar isomer\ then the mixture of two isomers and _nally a small portion of the more!polar isomer[ Anal[ found C 63[9\ H 4[9\ N 5[6^ C14H19FeN1 requires C 63[2\ H 4[9\ N 5[8)[ NMR d"H# "major isomer# 1[84 "2H\ s\ CH2#^ 3[91 "4H\ s\ C4H4#^ 3[21 "1H\ m# and 3[44 "1H\ m# "C4H3#^ 6[3Ð6[6 "6H\ m# and 6[83 "0H\ d# "phenyl and quinoxalyl#^ "minor isomer# 1[71 "2H\ s\ CH2#^ 3[99 "4H\ s\ C4H4#^ 3[21 "1H\ m# and 3[44 "1H\ m# "C4H3#^ 6[3Ð6[6 "6H\ m# and 6[83 "0H\ d# "phenyl and quinoxalyl#^ d"C# "major isomer# 06[0 "q\ CH2#^ 58[6 "d\ C4H4#^ 58[6 "d#\ 69[7 "d# and 71[8 "s# "C4H3#^ 015[7 "d#\ 017[0 "d#\ 017[49 "d#\ 017[44 "d#\ 018[0 "d#\ 018[4 "d#\ 025[4 "s#\ 028[5 "s#\ 028[7 "s#\ 039[7 "s#\ 041[0 "s# and 041[3 "s# "phenyl and quinoxalyl#^ "minor isomer# 06[9 "q\ CH2#^ 58[5 "d\ C4H4#^ 58[5 "d#\ 69[6 "d# and 71[6 "s# "C4H3#^ 015[1 "d#\ 016[8 "d#\ 017[3 "d#\ 017[5 "d#\ 018[1 "d#\ 018[3 "d#\ 026[2 "s#\ 027[7 "s#\ 039[1 "s#\ 030[3 "s#\ 040[3 "s# and 041[8 "s# "phenyl and quinoxalyl#[

Synthesis of 1!ferrocenyl!2!phenyl!4!azaquinoxaline Ferrocenylphenylethanedione 0 "9[21 g\ 0[9 mmol#\ 1\2!diaminopyridine "9[11 g\ 1[9 mmol# and 0\3! dioxan "1 cm2# were heated\ as above\ in an oil bath at 009>C under a slow stream of nitrogen until dryness[ The temperature was then increased to 049>C and held for 29 min[ After cooling\ the mixture was dissolved in dichloromethane\ _ltered\ concentrated and chro! matographed on silica gel to give pure ferro! cenylphenylazaquinoxaline 8 "9[15 g\ 56)# as a dark purple solid[ The product contained both regio!iso! mers of the azaquinoxaline\ con_rmed by 0 H and 02 C NMR[ The two isomers which were not separable on silica gel were found to be separable on alumina by very careful elution using dichloromethane as eluting solvent[ Any slight increase in the polarity of the mobile phase "e[g[ one drop of methanol in 099 cm2 of dichloromethane# elutes both the isomers at the same time[ Integration of the 0 H NMR spectrum gave an isomer ratio of ca[ 2]1[ Anal[ found C 58[7\ H 3[5\ N 09[0^ C12H06FeN2 requires C 69[5\ H 3[3\ N 09[6)[ NMR d"H# "major isomer# 3[91 "4H\ s\ C4H4#^ 3[27 "1H\ m# and 3[51 "1H\ m# "C4H3#^ 6[3Ð6[6 "5H\ m\ phenyl and quinoxalyl#\ 7[31 "0H\ d×d# and 8[09 "0H\ d# "quinoxalyl#^ "minor isomer# 3[95 "4H\ s\ C4H4#^ 3[39 "1H\ m# and 3[57 "1H\ m# "C4H3#^ 6[3Ð6[7 "5H\

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m\ phenyl and quinoxalyl#\ 7[35 "0H\ d×d# and 8[04 "0H\ d# "quinoxalyl#^ d"C# "major isomer# 58[5 "d\ C4H4#^ 69[1 "d#\ 69[7 "d# and 70[7 "s# "C4H3#^ 013[7 "d#\ 016[7 "d#\ 017[8 "d#\ 018[1 "d#\ 025[1 "s#\ 025[7 "d#\ 027[7 "s#\ 037[3 "s#\ 041[4 "d#\ 044[2 "s# and 044[4 "s# "phenyl and quinoxalyl#^ "minor isomer# 58[7 "d\ C4H4#^ 69[6 "d#\ 60[9 "d# and 79[4 "s# "C4H3#^ 012[6 "d#\ 017[1 "d#\ 017[6 "d#\ 017[8 "d#\ 023[1 "s#\ 026[6 "d#\ 028[1 "s#\ 049[9 "s#\ 042[5 "d#\ 043[0 "s#\ 046[7 "s# "phe! nyl and quinoxalyl#[ Synthesis of di" ferrocenyl#diphenylbiquinoxaline In a similar manner\ ferrocenylphenylethanedione 0 "9[29 g\ 9[83 mmol#\ 2\2?\3\3?!biphenyltetramine 09 "9[39 g\ 0[76 mmol# and 0\3!dioxan "1 cm2# were heated in an oil bath at 009>C under a gentle stream of nitrogen until all the solvent had evaporated[ The temperature of the oil bath was then raised to 049>C and the mixture was kept at this temperature for 34 min[ After cooling\ the solid residue was dissolved in dichloromethane[ TLC analysis showed the pres! ence of two purple quinoxaline spots[ As three regioisomers of the product 00 could be formed in this reaction\ it is possible that the two of these isomers have virtually identical Rf values[ As the Rf values of the two distinguishable components are very closely similar\ attempts to separate the isomers have not so far been successful[ Synthesis of ferrocenyl!phenyl!5!"2?\3?!diamino! phenyl#quinoxaline Ferrocenylphenylethanedione 0 "9[09 g\ 9[203 mmol#\ 2\2?\3\3?!biphenyltetramine "9[02 g\ 9[50 mmol#\ sodium sul_te "9[95 g\ 9[37 mmol# and potassium carbonate "9[95 g\ 9[32 mmol# were dis! solved in 49) "v:v# aqueous ethanol "49 cm2#[ The mixture was re~uxed with stirring for 1 h[ After this time\ TLC of the organic extract showed two highly polar components of very similar Rf values\ in addition to traces of the bis!quinoxaline 00 and unre! acted biphenyltetramine[ During the course of the reaction some solid product precipitated out^ this was _ltered o} and the _ltrate extracted with diethyl ether[ The combined solids were puri_ed by chro! matography on neutral alumina using 19) "v:v# methanolic diethyl ether as eluent to yield ferrocenyl! phenyl!5!"2?\3?!diaminophenyl#quinoxaline 01 "9[01 g\ 66)#[ Anal[ found C 60[5\ H 3[7\ N 00[9^ C29H13FeN3 requires C 61[5\ H 3[8\ N 00[2)^ C29H13FeN3[9[4"H1O# requires C 60[2\ H 4[9\ N 00[0)[ Electrochemistry materials and apparatus for electrochemistry have been described elsewhere ð02\ 04Ł[ All the potential

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P[ Zanello et al[

values are referred to the saturated calomel electrode "S[C[E[#[ Acknowled`ements*P[ Z[ gratefully acknowledges the _n! ancial support of the University of Siena "ex quota 59)# and the technical assistance of Mrs Giuseppina Montomoli[ S[ Z[ A[ thanks the Committee of Vice!Chancellors and Prin! cipals "U[K[# and the University of St[ Andrews for _nancial support[

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