2524 TUTIN AND CATON: THE ABSORPTION SPECTRA OFCCLVIIL-The Absorption Spectra of Some SubstitutedPyraziaes and thew Salts.By FRANK TUTIN and FREDERIC WILLIAM CATON.IN the preceding paper, the preparation of 2 : 5- and 2 : 6-diphenyl-pyrazine, pp’-dimethoxy-2 : 5- and -2 : 6-diphenylpyrazine, andmm’pp’-tetramet%hoxy-Z : 5- and -2 : 6-diphenylpyrazine is described.During the course of this work, certain remarka.ble colour changeswere observed on treating these bases with acids, which suggestedto us that a fuller investigation of the subject might lead tointeresting results. Thus, whilst trhe hydrochloride of 2 : 6-di-phenylpyrazine appeared colourless, the corresponding salts of theanalogous pp’-dimethoxy- and mm’pp’-tetramethoxy-bases werebright yellow and orange-coloured respectively.Furthermore, onadding sulphuric acid to a chloroform solution of pp/-dimethoxy-2 : 5-diphenylpyrazineY a yellow liquid which exhibited an intense,green fluorescence was first produced, whilst on the addition ofan excess of the acid a very deep violet-coloured solution resulted.The further investigation of the bases in question rendered itevident that pyra.zine derivatives, which have hitherto been statedto be monoacidic bases, in reality yield two series of salts, thedi-acid salts being in all cases much more highly coloured thanthe corresponding derivatives containing but one equivalent ofacid. The depth of colour of corresponding salts of analogous baseswas found to increase with the accumulation of methoxyl groups,and to be somewhat greater in compounds of the 2: 5-series thanin the corresponding members of the 2 : 6-series.The colours of the salts obtained will be seen on reference to thefollowing table MOUO-hydrocbioride.Very pale yellowsolution.Practicallycolourlesscry st als.Bright yellowcrystals.Mono-hydrobromide.Pale yellowsolution.Dihydro-chloride.Bright yellowsolution.Yellow solution.Base,2 : 5-Diphenylpyrazine.Monosulphate.( 1 )Palo yellowcrystals.Colourlesscrys tals.2 : 6-Diphenylpyrazine.pp'-Dimethoxy-2 : 5-diphenylpyrazine.Orange-colouredcrystals.Yellow crystals.pp'-Diniethoxy-2 : 6-diphen ylpyrazine.Yellow crystals.Deep yellowcrystals.-Pale yellowcrystals.(Could notformed.Orange-redcrystals.mm'pp'-Te tramethoxy-2 : 5-diphenylpyrazine.snm'pp'-Tetranietlioxy-2 : 6-diphenylpyraziiie.Deep yellowcrystals.Orange-colourodcrystals.Yellow crystals.(Could notformed2526 TUTIN AND CATON: THE ABSORPTION SPECTRA OFd 5 2000X ! 1800*-2 1600 s2N 3 14002kq 1200 s s2Y*+-- 8 1000800I n order therefore t o throw some light on the nature of thesecolour changes, some of the above-mentioned bases and certain oftheir salts have been examined spectroscopically in chloroformsolution. This solvent was chosen as both the bases and their saltsare sufficiently soluble in it, and, although it has a, certain amountof general absorption in the extreme ultra-violet region of thespectrum, it was thought that it would not interfere appreciablywith the results.Moreover, the sa.lts of the pyrazines have muchless tendency to hydrolyse when dissolved in chloroform than inalcoholic solution.*The curves obtained from 2 : 6-diphenylpyrazine, pp’-dimethoxy-‘t ‘ P C!- ’FIU. 1.Oscillation frequencies.2000 2500 3000 3500 40002 : 6-Diphenylpyrazine2 : ti-Diphenylpyrazine hydrocldoride.2 : 6- Dipl~enylpyrazii~e hydrobroinide.- - - - - -- - _2 : 6-diphenylpyrazine, and nznt’pp’-tetramethoxy-2 : 6-diphenyl-pyrazine are shown in Figs. 1, 2, and 3 respectively. From these itis seen that each of the bases shows absorption in the ultra-violetpart of the spectrum, and that salt-formation is accompanied by aconsiderable shift of the bands towards the red end, thus accountingfor the development of colour on treatment with acids.I n thecase of 2 : 6-dipheiiylpyrazine hydrochloride, which is practicaJlycolourless, the absorption bands still lie within the ultra-violet,have a certain excess of the respective acid in the solution.* Even when employing chloroform as a solvent for the salts it was iiecessary tSOME SUBSTITUTED PYRAZINES AND THEIR SALTS. 2527FIG. 2.Oscillation f ~e p uencies.2000 2500 3000 3500 400000 2 2000X% g 1200$10003 -*Y800pp'-Dimethoxy-2 : 6-diphenylpyraxine.- - - - - - pp'-Dimathozy-2 : 6-diphenylpyrzine hydrochloride._ - - pp'-Dimthoxy-2 ; 6-diphe~nylpyrxine hydrobromide.FIG. 3.Oscillation f repuencies.2000 2500 3000 3500 40000 0" 20004Xc;) -f 3 140020 0860 C !z3s40800m dpp'- Tetrccmet hoxtj - 2 ; 6 -diphe?Lylpyrazinc.- - - - - - mm'pp'-Tetru.~tethoxy-2 : 6-diphenylpyrzine hydrochloride.--- nim'pp'- Tetramcthoxy-2 : 6-diphenylpyrazine hydrobromide2528 TUTIN AND CATON: THE ABSORPTION SPECTRA OFregion, but one band shown by the corresponding hydrobromide justextends into the visible part of the spectrum, thus explaining thepale yellow colour of the salt in question. The shift of the absorp-tion bands towards the red end of the spectrum caused by thesubstitution of hydrobromic for hydrochloric acid is not nearly sogreat as that caused by the conversion of the base into its hydr*chloride, thus indicating that the alteration in position of the bandsin the latter case must be due chiefly to salt-formation, and only ina minor degree to the weight or nature of the acid radicle attached.The di- and tetra-methoxy-bases of the 2 : 6-series, and all ofthe salts show two absorption bands, but in the case of 2 : 6-diphenyl-FIG.4.Oscillation frequencies.2000 2500 3000 3500 400000 2 20003 1800 z% 2 1600$ 1400Xm.u-* uh332 12003 1000‘r)Y8002 : 5-Diphenylpyrazine.2 : 5-Diplienylpyrazine hydrochloride. - - - - - -pyrazine only one band is seen. Nevertheless, it is considered mostprobable that the absorption of all three 2: 6-substituted bases is,in reality, similar, the second absorption band of the last-mentionedbase being lost owing to the absorption shown by the chloroformwhich was used as a solvent.The curves yielded by 2 : 5-diphenylpyrazine and its monohydro-chloride, and by pp’-dimethoxy-Z : 5-diphenylpyrazine and the corre-sponding salt of this base, are shown in Figs.4 and 5 respectively.It will be observed in the case of these 2 : 5-substftated bases thatthe curves show only one absorption band, whilst two such areexhibited by the curves obtained from t,he salts. One possiblSOME SUBS'I'I'TUTED PYRBZINES AND THEIR SALTS. 2529explanation of this is that the second absorption band of the2 : 5-substituted bases has been lost owing to the absorption causedby the chloroform, just as is thought likely t o be the case with2 : 6-diphenylpyrazine, as already mentioned. On the other hand,t'he fact .that the band shown by the 2 : 5-substituted bases is muchbroader than either of the bands in any of the other curves obtainedwould suggest that in the bases of the 2 : 5-series the two absorptionbands may have become merged into one.Certain general conclusions may be drawn from the absorptioncurves given, namely, the following: (1) The similarity of theFIG.5.Oscillation frequencies.2000 2500 3000 3500 4000py'-Dimethoxy-2 : 5-diphenylnjrxine.pp'-DimeMoq1-2 : 5-dipkenylpyrclxi.nz hyldTochloride. - - - - - -curves given by the bases and their salts, particularly in the2 : 6-series, indicates that no change other than the rearrangementof valencies necessitated by the change N"' -+ NV occiirs on treatingthe bases in question with acids.(2) That salt-formation causesan increased persistency of the bands, together with a v@ry largeshift towards the red end of the spectrum. This result is similarto, but very much greater than, that which has previously beenobserved in the case of pyridine and its homologues (Hartley, Trans.,1885, 47, 685; Baker and Baly, ibid., 1907, 91, 1122; and Purvis,Proc. Camb. Phil. Soc., 1908, 14, 436). (3) The introduction ofmethoxyl groups causes a shift of the absorption bands towards thered end of the spectrum-an effect which has several times pre2530 TUTIN AND CATON: THE ABSORPTION SPECTRA OFviously been noted by other workers. (4) The position of thesubstituent groups in the pyrazine nucleus affects the position ofthe absorption bands shown by the bases and their salts, the bandsshown by the 2 : 5-substituted compounds being nearer the red endof the spectrum than those shown by their 2 : 6-substitutedisomerides (compare Purvis, Zoc.cit.).The absorption curves given also appear to indicate that theweight of the acid radicle present in a given salt had an effect onthe position of the bands, the hydrobromides being more deeplycoloured than the corresponding hydrochlorides. It would appearpremature, however, to consider this conclusion as proved, withoutconsiderable further evidence obtained by the study of a varietyof salts, for, in every case where the sulphates could be obtained,they were found t o be less deeply coloured than even the corre-sponding hydrochlorides, but their absorption spectra were notexamined.It thus appears that the nature of the acid employedmay have a greater effect than its molecular weight on the colourof the resulting salt.The formation and properties of the salts which were obtainedfrom the pyrazine derivatives under consideration are describedbelow. I n most cases the melting points of these derivatives wereindefinite, and of no value for the purpose of characterisation.Salts of 2 : 5-Diphenyl~raaine.-No salt of this base with oneequivalent of an acid could be obtained in the solid state, but thedihydrobromide and disulphate crystallised readily. On passinghydrogen chloride into a chloroform solution of the base, a yellowliquid was obtained, which doubtless contained the dihydrochloride.Dry hydrogen bromide was passed into a solution of 2: 5-di-phenylpyrazine in glacial acetic acid, and the mixture kept a fewhours.Golden-yellow crystals then separated, which were foundto be 2 : 5-diphenylpyrazine dihydrobromide, C4H,N,(C6H,),,2HBr :0.1527 gave 0.1435 AgBr.C16H,,N2,2HBr requires HBr = 41.1 per cent.This salt was readily dissociated by water, alcohol, or moist air.On heating it with ethyl acetate, it dissolved and partly dissociated,and, on cooling the solution, it mixture of dihydrobromide andbase separated, but no monohydrobromide was obtained.2 : 5-Diphenylpyrazine disulphat e, C4H2N,(C6H,)2,2H,S04, re-sulted on the addition of concentrated sulphuric acid to a solutionof the respective base in ethyl acetate or glacial acetic acid; themonosulphate could not be obtained.2 : 5-Diphenylpyrazine di-sulphate forms yellow plates, which, when exposed to moist air,readily dissociate, yielding the colourless base :HBr = 40-5SOME SUBSTITUTED PYRAZINES AND THEIR SALTS. 25310.2417 gave 0-2570 BaSO,. H2S04=44.7.C16H12~,,2H,S0, requires H,S04 = 45.8 per cent.Although the result of this analysis is not in very close agreementwith the theoretical figures, owing to the readiness with which thesalt dissociates, it nevertheless proves conclusively that the salt hasthe formula indicated above.Salts of 2 : 6-Diphenylpyrazine.--The monohydrochloride of thisbase is described in the preceding paper (p. 2501). It is a prac-tically colourless, crystalline solid.The monohydrobromae, how-ever, is pale yellow, whilst the monosulphate is quite colourless.The dihydrochloride and d'isulphate were obtained in the form ofsolutions, both of which were yellow, but no positive indication ofthe formation of a dihydrobromide could be obtained.2 : 6-Dph en ylpyrasine mono h ydro b romid e, C4H,N, ( C6H 5)2,HBr,separated in pale yellow needles on passing hydrogen bromide intoa solution of the respective base in a mixture of ethyl acetate andalcohol, Like the previously described salts, it readily dissociated :0.1408 gave 0.0840 AgBr.C,,H,,N,,HBr requires HBr = 25.9 per cent.2 : 6-Diphenylpyrazine monosulphat e, C4H,N,(C6H,)2,H2S04,crystallised in quite colourless needles on adding concentratedsulphuric acid to a solution of 2 : 6-diphenylpyrazine in glacialacetic acid:HBr = 25.7.0.1316 gave 0'0934 BaSO,.Cl6H,,N2,H,SO4 requires H,SO, = 29.7 per cent.Salts of ppl-Dimethoxy-2 : 5-diphenylpyrazine.-The monohydro-chloride, monohydrobromide, and monosulphate of ppl-dimethoxy-2 : 5-diphenylpyrazine crystallised readily, and the disulphate wasalso obtained in crystals, although it was very unstable. A solutionof the dihydrobromide was obtained as a deep violet-coloured liquidby saturating a solution of ppl-dimethoxy-2 : 5-diphenylpyrazine inglacial acetic acid with hydrogen bromide; and this salt alsoappeared to be formed on passing dry hydrogen bromide over thesolid base.No positive evidence of the formation of a dihydro-chloride could be obtained.H2S04 = 29.8.p p I- Dim e tho x y-2 : 5-dip h erqlpprazine mono 12 y d ro c hl or id e,C4HBN,(C6H,=OMe),,HC1,was formed by saturating a warm solution of the pyrazine derivativein glacial acetic acid with hydrogen chloride.On cooling, the saltseparated in bright yellow needles :C,,H1602N2,HC1 requires HC1= 11.1 per cent.0.3191 gave 0.1374 AgC1. HC1= 10.9.This salt dissociated much more readily than the correspondin2532 TUTIN AND CATON: THE ABSORPTION SPECTRA OFderivative of the 2 : 6-substituted base, and, when dissolved inchloroform, oxhibits an intense green fluorescence.pp'-Dzm e t hoxy-2 : 5-dipZi enylpyraaine monoliydro b romid e,was prepared in a manner similar to the salt last described.formed orange-coloured needles :C4H,N2( C,H,*'OMe),,HBr,It0.2781 gave 0.1373 AgBr.C,,HIGO2N,,HBr requires HBr = 21.7 per cent.pp'-Dimethoxy-Z : 5-diphenylpyrazine monohydrobromide, likethe corresponding hydrochloride, is fluorescent in chloroformsolutdon.HBr = 21.3.p p -Dim e t h o xy- 2 : 5-diph eny lp y ra zine monosu Zpha t e,C4H2N, ( c,H4 0Me)2,H,S047separated in yellow needles on adding sulphuric acid to a warmsolution of the respective base in glacial acetic acid, and coolingthe mixture.It dissociates readily, and, like the last-mentionedtwo salts, is fluorescent in chloroform solution:0.2700 gave 0.1581 BaS04. HaSO4 = 24.6.C,8H,602N,,H2S0, requires H2W4 = 25.1 per cent.When to a, solution of pp'-dimethoxy-Z : 5-diphenylpyrazine inchloroform, concentrated sulphuric acid was added, a yellowsolution of the monosulphate was first formed, which ex-hibited a brilliant green fluorescence, but on introducing anexcess of the acid the base was dissolved by the latter, yieldingan intensely violet-coloured liquid below the chloroform. Sufficientethyl acetate was then added to render the mixture homogeneous,and the liquid kept a few hours, when pp'-&imethoccy-2 : 5-diphenyl-pgrazine disulphate, C4H,N2(C,H4*OMe),,2H,S04, separated insmall prisms, resembling in colour crystals of potassium per-manganate.This disulphate is very unstable; it dissociates inordinary air, yielding the yellow monosulphate, and, if the air beunusually damp, complete dissociation ensues. The dissociatedmixture may, however, be successively reconverted into the yellowmonosulphate and the deep violet-coloured disulphate by desic-cation :0.1224 gave 0.1200 BaSO,.C,8H1602N2,2H2S04 requires H2S04 = 40.2 per cent.This disulphate dissociated so readily that it could not be washedwith any solvent, and it is owing to this fact that the analysisindicated a, somewhat high percentage of sulphuric acid.Sults of pp'-Dimethoxy-Z : 6-dip,henylpyrazine.--This base readilyyielded a crystalline monohydrochloride, monohydrobromide, andmonosulphate, the first of which has been described in the precedingH,SO, =41*1SOME SUBSTITUTED PYRAZINES AND THEIR SALTS.2533paper (p. 2506). No indication of the formation of a dihydrechloride could be obtained, but the dihydrobromide was obtainedas a very deep violetrcoloured solid by passing dry hydrogen bromideover the solid base.A deep violetrcoloured solution of thedisulphate in concentrated sulphuric acid was formed, but this saltcould not be crystallised.ppl-Dimethoxy-2 : 6-diphenylpyrazine monohydrobromide,C4H,N2(C,H4-OMe)2,HBr,crystallised in deep yellow needles on the addition of a little con-centrated hydrobromic acid to a solution of the base in a mixtureof ethyl acetate and alcohol:0.1685 gave 0.0832 AgBr.This salt is not fluorescent, thus differing from its 2 : 5-substitutedpp f-Dimethoxy-2 : 6-diphenylpyrasine monosulphat e,HBr = 21.3.C18H,,0,N2,HBr requires HBr = 21.7 per cent.isomeride.C4H2~(C,H400Me),,H2s04,was obtained on adding concentrated sulphuric acid to a solutionof the respective base in ethyl acetate.It was not fluorescent, andformed pale yellow needles, which dissociated fairly readily :C18H,,02N2,H,S04 requires H2S04 = 25.1 per cent.mml p p f -T e t ramet hox y-2 : 5-diph eny Zpyrazline. - Theamount of this base available was very small, and therefore onlyits behaviour towards sulphuric acid was investigated. It wasmarkedly more basic than the previously mentioned bases. Whentreated with a small amount of sulphuric acid in glacial acetic acidsolution, it yielded mmfppf-tetramethoxy-2 : 5-diphenyllryrasinemonosulphate, C,H3(0Me),*C4H2N2*C6H3(0Me)z,HzS04, whichformed orange-red needles. If, however, the solution containedany excess of sulphuric acid, the orangecoloured crystals of themonosulphate soon gave place to small, jet-black prisms of the corresponding disulphate, C,H3(0Me),*C4H,N,*C,H~(0Me),,2H2S~~.These crystals possessed a brilliant metallic lustre, and were per-manent in the air, although they were dissociated fairly readily byalcohol.A dilute solution of mm1pp’-tetramethoxy-2 : 5-diphenyl-pyrazine disulphate in concentrated sulphuric acid had an intenselyblue colour. The amount of these salts was not sufficient foranalysis.Salts of mmlppl-T e trame t hoxy-2 : 6-dip~erryZpyrazine.-This basereadily yielded a crystalline monohydrochloride, monohydrobromide,and monosulphate, but no di-acid salt of it could be crystallised.No evidence of the existence of a dihydrochloride could be obtained,but a comppund of a bluish-black colour with a bronze lustre, which0-2635 gave 0.1549 BaSO,.SaltsH2S04 = 24.7.ofVOL.XCVII. 8 2534 ABSORPTION SPECTRA OF PYRAZINES.was doubtless the dihydrobromide, was obtained by passing dryhydrogen bromide over the crystalline base. A deep blue-colouredsolution of the disulphate in concentrated sulphuric acid was alsoobtained.mm'pp/-Tetramethoxy-2 : 6-diphenylpyrazine monohydrochloridehas been described in the preceding paper (p. 251 1). It is deepyellow, and does not dissociate so readily as the previously describedhydrochlorides.mm pp f -Te trame th oxy-2 : 6-diphen ylpy raaine monoh ydro b romide,C6H3(0Me)2*~4H2N20C6H3(0Me)B,HBr, was obtained in orange-coloured needles on passing hydrogen bromide into a solution ofthe respective base in warm ethyl acetate.The amount of productavailable was small, and it wits not analysed.mmfpp~-Tetrarnthoxy-2 : 6-diphenylpyrazke monosulphat e,CGH,( 0Me)2*C4H2N2*C6Hd oMe)z,HzSO&was prepared by adding Concentrated sulphuric acid to a solutionof the respective base in ethyl acetate. It formed yellow needles,which were stable in the air, but were dissociated by alcohol orwater.Two series of isomeric moneacid salts of the 2: 6-substitutedpyrazines are possible, which would be represented respectively bythe following formulce :H ,,CR:CH, ,CR:CH\. HX>N \CR.CH/ ---- N %CR:CH/N<X*(1.) (1Throughout the course of this work, however, no indication ofthe presence of isomerides was observed, and it is therefore probablethat the acid attaches itself to one of the nitrogen atoms morereadily than to the other. I f this be the case, the mono-acidic saltsof the 2: 6-substituted pyrazines are probably represented byformula 11. Furthermore, the fact that no di-acid salt of the last-mentioned bases could be crystallised may be due to these saltsbeing difficult of formation, owing to steric hindrance, but it isquite likely that it is due only to their being more soluble thantheir 2 : 5-substituted isomerides.In conclusion, the authors wish to acknowledge their indebtednessto Dr. J. T. Hewitt, who kindly placed at their disposal thespectroscope with which the curves given in this paper were obtained.THE WELLCOME CHEMICAL EAST LONDON COLLEGE.RESEARCH LABOKATORIEY, LONDON, E. C