ORGANIC CHEMISTRY -HETEROCY CLIC DIVISION.IN reviewing the chemistry of heterocyclic compounds for the pastyear, the writer of this Report has been struck chiefly by the largeamount of attention given a t the present time to compounds occurringnaturally or forming essential portions of material obtained fromliving matter. Besides the important work which is at present beingcarried on with respect to the fats, the carbohydrates, the fate of theamino-acids1 in metabolic changes, and the general question of enzymeaction, amongst heterocyclic compounds we notice more particularlythe work on the fission products of the nucleic acids, which belong to thepyrimidine series, the pyrrole and indole compoiinds resulting fromthe hydrolysis of proteins, natural organic dye-stuff s, and more especiallythe alkaloids.Other matters of prime importance which are now engaging con-siderable attention are spacial questions as they affect the formationand stability of rings, and the relationships between the constitutionof cyclic compounds and their ability for salt formation, the latterquestion being intimately bound up with the connexion between coloiirand constitution, and, one may add, other optical properties such asmagnetic rotation.2Xpacia I Considwations.Baeyer’s strain hypothesis first gave a rational explanation of theobserved fact that rings of five or six members mere most easilyproduced, and when formed exhibited the greatest stability; it istherefore a matter of some interest to record observed cases whererings containing less than five or more than six atoms have beenproduced.A ring containing one atom each of carbon, nitrogen, and oxygen issupposed by Wieland to exist in the nitrile-oxides, the first of whichseries was obtained by Werner5 by removal of hydrogen chlorideF.Ehrlich, Abstr., 1907, ii, 44.Compare especially Sir W. H. Perkin, Trans., 1907, 91, 806.3 Ber., 1885, 18, 2277. Abstr., 1907, i, 527.l b i d . , 1894, i, 585ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 139from benzhydroxamic chloride ; since these compounds show no greattendency to form additive products, Wieland replaces the generalformula :0Several four-membered heterocyclic compounds are described.M. Kohn 6 has eliminated hydrogen bromide from 8-bromo-p-methyl-amino-P-methylpentane hydrobromide and obtained a tertiarysaturated base, representing the change in the following manner :-+ (CH,),F--~*CH, (CH,),Q*NH*CH,CH2*CHBr *CH, CH,* CH*CH3The parent substance, trimethyleneimine, was described some yearsDiels and Stein ti regard the termolecular benzoyl cyanide describedback by Howard and Marckwald."C,H,*CO*N: $! *Y:N*CO*C,H,N:C*CO*C,H, ' by Nefg as possessing the structure:.I -but, on the other hand, W.Meister lo offers evidence against the ringstructure assigned by Dunstan and Goulding to methazonic acid,ll andconsiders that it has the open-chain constitution :OH*NO:CH*CH:N*OH.Blaise and Gaultll consider that the product obtained fromhydrazine and diketopimelic acid contains a seven-membered ring ;the writer would suggest that the substance may quite possibly be1 -aminodihydropyridine-2 : 6-dicarboxylic acid, and a similar criticismmay be applicable to the substance obtained by Ciusa13 by thereduction with sodium and amyl alcohol of the hydrazino-oxime fromcinnamylideneacetophenone.Leach l4 finds that pinene nitrosochloride reacts with twomolecules of potassium cyanate, giving a compound CI2HI7O3N3, towhich he assigns a cyclic structure involving an eight-memberedr i n g : v>NH.C=K-o-COC 7 H 4 ( C H , ) *NH* COThe formula is based on the fact that the subsbnnce exhibits thefeebly acidic properties usually associated with an imide, and whenreduced by zinc dust and acetic acid gives a very stable +-carbamide,Abstr., 1907, i, 338.Ibid., 1907, i, 528.lo Ibid., 1907, i, 885.l2 Absty., 1907, i, 280.l4 Trans., 1907, 91, 10.Ibid., 1899, i, 749.Ibid., 1896, i, 71.l1 TTans., 1900, 77, 1262.l3 Ibid., 62140 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.H-NH C7H14(CH3)=NH >CO, whilst cyanic acid is liberated as carbondioxiae and ammonia.Schroeter 15 in preparing benzenesulphonylanthranilic acid hasobserved a by-product insoluble in alkalis and evidently a bimolecularanhydride of the constitution :Whilst an eight-membered ring is involved in this case, Schroeterconsiders that the uoimolecuIar “acylanthranils” obtained in many casesduring the acylntion of nnthranilic acid are metoxazones of thetvDe : J JGabriel assumed l6 the intermediate formation of a nine-memberedring in the transformation of y-bromopropylphthalimide intoy-hydroxypropylphtbalimide, and, in carrying out corresponding reac-tions with /3-bromopropylphthalimide, Bartholdy l 7 has succeeded inactually isolating the corresponding compound :containing an eight-membered ring.Spallino’s 1* assumption that the internal anhydride, C1,HgO,N,obtained from phthalonic acid and anthranilic acid contains a nine-membered ring has some justification from the results of analyses andthe molecular weight determination.Bischoff and E. Frahlich l9 have examined the action of halogenisedncetylhalides on the sodium salts of dihydric phenols in the hope ofobtaining lactones of the formula :Whilst positive results were obtained in the case of cntechol,resorcinol and quinol did not give compounds of the desired type;although i t is possible that a two-fold polymerideis formed in the caseof resorcinol, such a compound would involve a fourteen-memberedring.When one comes to the question of actually realising any givencyclic formula, one needs to know the conditions under which ringl5 Abstr., 1907, i, 529.I7 lbid., 1907, i, 1043.l9 ]bid., 696, 697.l6 Jbid., 1905, i, 649.]bid., 872ORGANIC CHEMISTRY-HETEROCYCLIC DIVISlON 241closing is possible.There are evidently other factors at work besidesthose indicated in Baeyer’s original strain theory. Where a portionof the new cyclic structure is built up with two ortho-carbon atoms ofan aromatic nucleus, there is the possibility OF building a larger ringthan if one starts with two carbon atoms of aliphatic function.Thispoint is drawn attention to by J. v. Brdiin,20 who rinds that o-amino-phenylbutyric acid cannot be isolated in the free condition, but whenliberated from its salts passes immediately into an elactam, the ringhomologue of oxindol and hydrocar bostyril.Kaufler 21 introduces a somewhat novel conception in supposing that,where a substance contains two aromatic nuclei in its molecule, theseare frequently inclined towards one another, so bringing reactive groupsinto sufficient proximity to make ring formation possible. Thefollowing formulae :are assigned to benxidine, p-diaminostil bene,diamine respectively, and may account f u r thean azimide according to Vaubel and Schenerand 2 : 7-naphthylene-fact that the first gives22 and a unimolecularphthalglbenzidine,23 whilst a unimolecular phthalyl derivative maybe obtained from 2 : ?‘-naphthylenediamine, which is insoluble bothin acids and alkalis.Kaufler and Karrer also find that, when7-amino-2-naphthol is diaxotised, the diazonium salt couples withitself to a bimolecular compound, which is probablyBut special conditions may prevent ring formation by what isusually known as “steric hindrance,” and so Scholtz and Wasser-mann 24 in continvation of earlier work find that, whilst arylaminesand ae-dibromopentane usually give N-arylated piperidines, the sameresult cannot be obtained with o-toluidine or a-naphthylamine. Azo Abstr., 1907, i, 524.22 Ibid., 1906, i, 323.23 Koller, ibid., 1904, i, 778.Ibid., 307, 776, 794, 795, 799.Abstr., 1907, i, 339.The mol. wt.is unknown142 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.somewhat similar case of steric hindrance bas been observed byJiirgen~.~5Willstatter's researches on aniline- black have induced Bucherer 26 tobring all syntheses of indamines and azines by the oxidation of mono-or di-amines under one common point of view. A diamine (ortho orpara) is oxidised to a di-imide, and this will unite with a compound whichmay be represented by HR, giving a second diamine differing from thatoriginally employed by having one of its hydrogen atoms replacedby the group R. The process can then be repeated, and even thesynthesis of such a complex compound as safranine can be quiteeasily brought into the scheme.Methods for opening rings also deserve notice, and J.v. Braun27finds that, in addition to the treatment of benzoyl derivatives of cyclicsecondary amines with phosphorus pentahalides, cyanogen bromidefrequently gives satisfactory results, Thus the reagent unites withl-phenylpiperidine, giving phenyl-o-bromoamylcyanamide, which canafterwards be hydrolysed to the bromoamylaniline.The part played by the " keten " group, CH,*CO, in the synthesis ofa large number of compounds of entirely different series, some open-chain, some homocyclic, others heterocyclic, occurring in nature hasbeen discussed by Collie.28The application of heterocyclic structure to the compounds formedby many metals with amino-acids, Werner's co-ordination number beingemployed, is due in the first place to Ley,29 and has been enthusias-tically adopted by Ts~hugaeff.3~ I n this scheme, copper glycine isrepresented as (I) :80 fiCR,*CR,(I.1 (11.)and Tschugaeff extends the idea to certain compounds of cobalt, itsderivatives with the oximes of u-diketones (for example, nitroso-p-naphthol) being represented by the general formula (11). A matteraffecting heterocyclic compounds in general is discussed by B~-iihl,~lwho shows that, whilst the molecular refraction and dispersion ofsaturated heterocyclic compounds are normal (that is, correspond withthe values reckoned in the ordinary manner), the values obtained forunsaturated heterocyclic compounds point to optical depression.25 Abstr., 1907, i, 1036.27 Ibid., 960.'L8 Trans., 1907, 91, 1806.Ibid., 1907, i, 392, 830.2Q Ibid., 981.29 Abstr., 1905, i, 175.Compare ibid., 1900, i, 430.Trans., 1907, 91, 115ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION.143Onium ” Salts and Pseudo-bases.The relationships existing between cyclic ammonium, thiouium, andoxonium salts and the pseudo- (carbinol) bases obtained from them haveonce more attracted considerable attention. It is now a well-recognised fact that in those cases where the carbinol group (oroximido-group in case of azines) is in the para-position to a hydroxylor amino-group, water is removed with greater or less ease, in fact, inthe case of azines such removal of the elements of water isspontaneous, and the hydroxylated azonium salts are hydrolyticallydissociated.Thus whilst safranine and aposafranine salts are derived frompowerful bases, the corresponding hydroxylated azonium salts arecharacterised by extreme instability, and pass spontaneously on treat-ment with water by loss of acid into aposafranone or hydroxyapo-safranone.For aposafranone, two formulae have been proposed, thepara-quinonoid and the ortho-quinonoid :N Neither of which would correspond with the salt :N N/\CGH5 C1/\C,H5 C1The second formula representing aposafranone as an internal salt ofthe phenolic and quaternary ammonium functions is due t o Kehrmann,and is in many respects at variance with the properties exhibited bythe substance, for one would expect such a compound to add on theelements of water and give a strongly basic ammonium hydroxide.This, as we have seen, is not the case, any more than it is with thesimilarly constituted substances derived from dihydroxyphenylacridi’ne.An example in the latter series is given by A.E. Dunstan andMiss Cleaverley,32 who have obtained 2 : 8-dihydroxy-5-phenyl-3 : 7-di-methylacridine from the commercial dye-stuff, benzoflavinb, by heating32 Trms., 1907, 91, 1619144 ANNUAL kEPOltTS ON TBE PROGRESS OF CHEMISTRY.the base under pressure with diluted sulphuric acid. The hydroxylgroups were acetylated, methyl iodide then added, and the resultingquaternary ammonium salt hydrolysed. When alkali is added to asalt of the dihydroxyacridinium compound (I), a carbinol base doesnot separate (11), but in its place the corresponding anhydro-compound (111) :Considerations of this character make one somewhat critical asto whether the pyrines obtained by A.Michaelis, Rademacher, andSchmiedekampf 33 from bis-l-phenyl-3-methyl-5-pyrazolone are reallyto be represented structurally as the authors do by formula (I) andnot rather by formula (XI) :N*C,H5 N*C,H5 N*C6H, N*C,H5CH3*N/\C C/\N* CH, C H , * N A C : X X1:C'\C*CH3CH3*C-C--C--C*CH3 CH,*C= C-- C==C*CH3(1.) (11.1I l'x'l I I l'x(l I I I I IThey are obtained by acting on the corresponding bis-quaternaryammonium compounds with alkalis, hydrogen (or other) sulphide,primary bases, &c., so that X and X1, which may be the same, ordifferent, are either 0, 8, Se, NH, N*C,H,, &c.In fact, Michaelisand Hillmann34 themselves prefer the formula of an ammoniumhydroxide (I) to that of a bridged-ring compound (11) for the productof the, action of aniline on 4-chloro-2 : 6-lutidine methochloride :33 Abstr., 1907, i, 731. 34 Ibid., 726ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION, 145C6H3(IV.)although formula (111) is accepted for the product from aniline and5-chloroacridine methochloride when (IV) is available.Kehrmann 36 seems, however, prepared to admit the possibility ofpara-quinonoid structure in some cases. The condensation productfrom 6-amino-1 : 2-naphthaquinone and o-aminodiphenylamine differsso markedly from its isomerides in its properties that, in view of theisolation of 2 : 6-naphthaquinone by Willstatter and Parnas,37Kehrmann is quite inclined to admit the substance having theformula (I) instead of (11) :(111.)whilst formula (111) is suggested for the oxazine from 6-amino-1 : 2-naphthaquinone and o-aminophenol on account of its resemblanceto Meldola's blue.Ann. Report, 1906, 157.36 Abstr., 1907, i, 563.37 Ibid.? 425.REP.-VOL. 1V. r146 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.Corresponding compounds are obtained with 6-hydroxy-1 : %naphtha-quinone ; the 7-hydroxyphenylisonaphthaphenazoniurn salts are orange-red, but the anhydro-base is dark blue, and the relationship can beexpressed by the formulae :It may be noted that a very similar constitution (derived from a1 : 7-naphthaquinone) was suggested in last year’s Report 38 for a darkblue anhydro-base derived from phenonaphthacridine.One of the most interesting contributions of the past year to theconstitution of oxonium salts is the work of A.G. Green and King 39on the halide salts of the quinonoid esters of phenol- and quinol-phthaleins. I n addition to the isolation of the free quinonoid mono-methyl ester of phenolphthalein from the hydrochloride mentioned inlast year’s Report,40 the new compounds derived from quinolphthalein,represented by formulae (I), (11), and (111), have been prepared andexamined :v6H4 CO,HCvGH4* CO,*CH,C(111. ) UV.1The free base corresponding to the second formula is represented bythe authors as possessing structure (IV), but from their paper it seemsdoubtful if it has been isolated, since whilst the chloride itself issoluble in water with an orangeared colour, it does not dissolve inaqueous alkalis, and if warmed with them hydrolyses, forming theoriginal lactoid monomethyl ether from which it was produced withmethyl alcohol and hydrogen chloride.58 Anic.&port, 1906, 172.40 Ann. Report, 1906, 179.39 Abstr., 1907, i, 933ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 14’7Another very important paper on phenopyrylium compounds is dueto Decker and von Fellenberg,41 in which a large number of substances,the oxygen analogues of quaternayy quinolinium and acridiniurn com-pounds, are described. The coeroxonium and coerthionium compoundsare further studied,42 and the theory connected with the conjugatedouble linkings in application of Thiele’s theory undergoes furtherex tension.A few more papers on oxonium salts may be mentioned : Hantzschand Denstorff 43 and Feist 44 continue the discussion on the hydro-perbromides of negatively subst i t t i ted pyrones, whilst Faworsky 45 findsthat ethylene ether, O < ~ ~ ~ : ~ ~ ~ > O , readily forms oxonium salts.Finally, we may note that a cyclic, basic iodonium compound,I*OHdiphenyleneiodonium hydroxide, (\/\/\ has been prepared by I I I’\/-\/Mnscarelli46 by the action of moist silver oxide on di-iodoxy- or di-iodoso-diphenyl ; its acetate and oxalate are described.Pive-membered Rings.Amongst syntheses of pyrrole derivatives may be noted Clarkeand Lxpworth’s 47 production of Smith’s tetraphenylpyrrole 48 by theaction of heat on y-cyano-a-benzoyl-y-anilino-py-diphenylpropane,and the preparation of eeveral pyrroles of high molecular weightby J.Schmidt and R. Scha11,4Q who have employed aminodiphenylderivatives in conjunction with acetonylacetone. Ethyl phenacyl-acetate condenses readily with the three nitroanilines to give theesters of the 5-phenyl- l-nitrophenyl-3-methylpyrrole-3-carboxylic acids,Borsche and Titsingh 5O observing no steric hindrance even witho-nitroaniline, although it is incapable of giving piperazine derivativeswhen heated with ethylene dibromide and sodium acetate to 150’.Pyrrolidone, being now easily obtained by the electrolytic reduc-tion of succinimide,f~l bas been further studied by Tafel andWas~muth,5~ whilst the thiopyrrolidone, obtained from it by means ofphosphorus pentasulphide, is found by Tafel and Lawaczeck 53 to givea strong base on methylation, the methyl group becoming attached tothe sulphur atoms.Absts.., 1907, i, 950, 1064.AIL~L. Uepo~~t, 1906, 153.33 d b s l r . , 19.37, i, 283.45 Ibid., 274.dl Am., 949.4 Rd*) 1021.47 Trans., 1907, 91, 704.49 Abstr., 1907, i, 724.51 Abstr., 1900, i, 557.53 Ibid., 720.48 Ibid., 1890, 57, 646.50 Ibid., 1908, i, 103.p2 Ibid., 1907, i, 719.L 148 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.Other pyrrolidone syntheses have been effected by H. Weber,54whilst Zelinsky and Schlesinger b5 have condensed acetonylacetone,ammonium chloride, and potassium cyanide to an amino-nitrile, which,when heated with hydrochloric acid, passes over into 2 : 5-dimethyl-pyrroline-5-carboxylic acid :CH,*C(CN)(NH,)*CH2*CH2*COoCH3 -+ CH==== I C(CHJ>NH,CH,*C(CH,)(CO,H)Markwalder 56 finds that methyl y-anilinopropyl ketone gives thehydrobromide of 1 -phenyl-2-methyl-4 : 5-dihydropyrrole when treatedwith hydrochloric acid, but on attempting to liberate the base theanilino-ketone is regenerated.I n addition to the synthesis by Emmert 57 of 1-phenyl-5-methyl-pyrrolidines by simultaneous electrolytic reduction of Isvulic acid andnitrobenzene, a general reaction discovered by L.J. Simon andConduche 58 is of interest, aldehydes readily condensing with ethyloxalacetate in presence of ammonia or primary arnines to give2 : 3-diketopyrrolidinecarboxylic esters := C,H,*OH + H,O + NH,R C,H,*O,C-YOCH, .GO, *C,H, + + RWHOSeveral interesting reactions of pyrrole and its derivatives havebeen studied, Pictet and Rilliet 59 finding that pyrrole and formaldehyde yield under suitable conditions a solid product, Cl,H1,ON,,which, when distilled, gives some a-methylpyrrole, but on distillationwith zinc dust furnishes a-picoline.Further, when methylene chlorideis heated to 120--130° with potassium pyrrole, two dipyridylmethanesare produced, one, melting at 11 2 O , is evidently linked by the nitrogenatoms, as it will not react with potassium, whilst the other, melting a t66", is probably a transformation product of the first compound andlinked by carbon in the a-position, as it reacts vigorously with potass-ium.The hope that either of these might furnish pyridylpyrrole onpassage through a red-hot tube and 80 lead to another synthesis ofnicotine was not realised.Pyrrole compounds, in which the hydrogen of the imino-group isreplaced by hydroxyl or an amino-group, behave frequently in aninteresting manner. Angeli and Marchetti 60 consider that the54 Abstr., 1900, i, 1071.56 Ibid., 1907, i, 639.58 Ibid., 963.Go Ibid., 1907, i, 436.55 Ibid., 720.57 Ibid., 339.59 Ibid., 445ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 149nitroso-derivative they have obtained from 1-hydroxy-2 : 5-dimethylpyrrole probably possesses the second of the two formulie :C( CH,):QH C( C H3) : YHHoN<C(CH,):C*NO o:N'C(CH3)*C:NOHfor, when bydrolysed in presence of hydroxylamine, it yields the tri-oxime of hexane-2 : 3 : 5-trione,CH,*C(:NOH)*C(:NOH)*CH,*C(:NOH)*CH,.Bulow and KlemannGf have examined the action of nitrous acidon amino-compounds in a number of cases, and find that, whilstthe amino-group is diazotised when attached to carbon, be the com-pound carbocyclic or heterocyclic, amino-groups attached to nitrogenin a ring are removed in the form of nitrous oxide :>N*NH, + HNO, = H20 + N20 + >NH.The reaction is of considerable importance, as we shall see in thecase of the N-aminotriazoles.The occurrence of pyrrole groupings in various proteins is now wellrecognised, and papers on chlorophyll have appeared by Koiniewskiand Marchlewski,62 and Willstatter, in con junction with H~cheder,~,and Mieg.64 Willstitter and Hocheder have isolated and characterisedseveral hydrolytic products f rpm chlorophyll, most of which containnitrogen ; they also isolated phytol, C,,H,,O, a thick, oily, unsaturatedprimary alcohol boiling at 1 4 5 O under a pressure of 0*03-0.04 mm.Kuster 65 has oxidised the '( acid )' and " basic '' hsmopyrroles, andfinds that both of them give methyl ethylmaleinimide on oxidation.The haemopyrrole of weak acid function is the one most easily,oxidised, and it is probably 3-methyl-4-ethylpyrrole, whilst the otherI' basic " haemopyrrole is either 3-methyl-4-ethylpyrroline or perhaps2 : 4-dimethyl-3-ethylpyrroline, one of the methyl groups being lost inthe oxidation.Carrasco and Padoa66 find that 1-methylindole may be producedfrom dimethyl-o-toluidine by passing it over reduced nickel at 300° to330°, whilst the following syntheses lead to isatin and its derivatives.Rudolf BauerG7 finds that if oxanilide be treated with phosphoruspentachloride, diphen yloxalimino-chloride is formed, whieh ifheated on the water-bath and poured into water furnishes isatin :N N/\A + 2H20 = C6H5*NH2 + 2HCI + 1' /\/\CCl\ h / C * O H .I I ' C1.C N*C6H,COAbstr., 1908, i, 54.(13 Ibid., 784.65 Ibid., 572.]bid., 603,G2 Ibid., 1907, i, 866.tx Ibid., 865.Ibid., 1521-50 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.The reaction, discovered by P.J. MeyerjGS of producing p-tolly-p-methylimesatin by the action of dichloroacetic acid on p-toluidinebas been examined by Ostromisslensky.~~ I n trying the reaction withaniline, Hellerr0 obtained a substance to which he assigned theconstitution of a disminostilbenedicarboxylic acid, but the presentauthor finds that a portion of the reaction product (about 24 per cent.)does consist of phenylimesatin.W.Peters 71 finds that many of the metallic derivatives of isatinare nitrogen derivatives, and the sodium oxygen salt could not beisolated, and Deussen, G . Heller, and Notze172 have followed thegradual change of sodium N-isatin to sodium isatate, and of the latterback to isatin under the influence of hydrochloric acid by conduc-tivity determinations.Heller73 has further followed the colour changes of these com-pounds, and observes that sodium N-isatin dissolves in water with thosame violet-red shade that isatin gives at first in dilute alkali; thechange to yellow is due to the formation of sodium isatate, but theaci-isatin salt is probably formed intermediately ; the silver derivativecertainly behaves as an oxygen salt and gives an O-ether74 withmethyl iodide, whilst the sodium derivative furnishes N-methyl-isatin.This O-ether is very reactive, giving a stable dianil with aiiiline anda-isatinphenyl hydrazone with phenylhydrazine, the latter beingidentical with Baeyer’s ben~eneazoindoxyl.~~ The latter substance byreduction and subsequent oxidation passes into indigo.Condensation products of isatin have been studied by C.Liebermannand R.Krauss76 and C. H a ~ l i n g e r . ~ ~ I n the former papers, theindigo-like colouring matters, of which indophenine, pyrrole-blue, andisatin-blue may be taken as typical, are submitted to a lengthyexamination, and in some cases provisional formuls are assigned ; threesuch formuls may be given here :CH:CHN d I6870727475171 >NHCH:CHDichloropyrrole-blue B.Ber., 1883, 16, 925, 926, 2261.Abstr., 1904, i, 730.lbid., 442. 73 ]bid., 442.Baeyer and Oeconomides, Abstr., 1883, 201.Abstr., 1884, 74.Ibid., 975.B i d . , 1907, 40, 4972.71 Ibid., 1907, i, 239.76 Ibid., 1907, i, 657ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 151&HBlue from i~atindipiperidide.~~C. Liebermann and Danaila 79 have also oxidised the phenolisatins,whilst Haslinger has examined the action of ethylamine on isatin andits derivatives.He finds that three classes of derivatives may beproduced, of which the following may be taken as typical :N N'C,€€,, NC , H , ~ C * O H c H /\GO C,H,Br20C*NH*C2H,.c:o 4v C : N*C2H, C:( N H*C,H,),Yellow. Colourless. Green.An indole derivative whicb has aroused considerable interest in thelast few years is tryptophan, a product of the hydrolysisof manyproteins. Neuberg and Popowsky80 have worked out a method forobtaining the substance from fibrin, and prepared and analysed severalcoloured halogen derivatives, whilst A bderhalden and Kempe haveprepared several polypeptides from tryptophan, incidentally discoveringthat the violet coloration with bromine or chlorine water is peculiar t otryptophan itself, since the reaction is not given by its polypeptidesuntil after pancreatic digestion,Finally, the synthesis of racemic tryptophan has been effected byEllinger and Flamand.82 Indole-aldehyde and benzoylglycine condenseto an azlactone, which hydrolyses to a-benzoylaminoindolylacrylicacid.The latter compound by reduction and hydrolysis givestryptophan :78 Schotten, Abstr., 1891, 928, 1491.79 Abstr., 1907, i, 976.81 Ibid., 652.80 Ibid., 263.g2 lbid., 727152 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.C*CHO NC*CH2* CH (NH,) C0,HC8H6N* CH:C( C0,H) * NH*CO* C,H, -+ G x > H .NHM. Freund and Wirsing 83 have described di-p-dimethylamino-indigotin; they start with p-arninodimethyianiline, convert this into di-methylaminophenylglycine, fuse with sodamide, dissolve the productin water, and oxidise.The substance is easily soluble in organicsolvents with a green colour, and dyes wool a light green shade froman acetic acid solution. The solution in hydrochloric and sulphuricacids is blue, but will not dye wool.A. G. Perkin and Bloxam 84 have investigated the constituents ofnatural indigo, and find that indigo-brown contains at least threeconstituents, to which the formuh Cl6HI1O3N2, C16H1404N2, andC2,H2,0,N, are assigned. They are probably complex indoxylderivatives, since they yield anthranilic acid when digested with 50per cent. potash solution. Besides these substances, A. G. Perkin hasisolated a rhamnoside of kaernpfe1-01,~~ (r27H3001r, from the indigo ofIndigofeva arrecta, but it is improbable that the kaempferol is identicalwith the ( { Indigo-yellow " obtained by Bolley and Crinsoz 86 fromBengal indigo.A.Q. Perkin and Bloxams7 have so improved the method ofisolating indican, Cl4Hl7O6N,3 H20, from indigo leaves by extractionwith acetone that they can obtain more than 30 grams per kilo.Dextrose is obtained by hydrolysis, but by carrying out t h i s operationwith hot dilute sulphuric acid the indoxyl is converted into a brownsubstance ; nevertheless, its estimation has been effected by conversioninto indirubin by isatin. This is the basis of a quantitative processfor indoxyl devised by Orchardson, Wood, and Blosam.88Closely connected with indigo is the sulphur analogue, thio-indigo, which is obtained from carboxyphenylthioglycollic acid.P.Friedlander and Chwala describe methods for obtaining arylthio-glycollic acids ; 89 it may be noted that the amino-compounds are not83 Abstr., 1907, i, 254.85 Ibid., 435.87 Trans., 1907, 91, 1715.b Abstr., 1907, i. 525.tu Trms., 1907, 91, 279.86 Jahresb., 1866, 573.88 Abstr., 1907, ii, 203ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 153obtained from the nitro-derivatives by reduction, since ring formationoccurs :SThe so-called thionaphthen derivatives form the subject of anThionaphtben, C,H,<-s->CH, has been described by Gattermannand Lockhart and by Komppa; it shows the grea ost analogy toimportant paper by F r i e d l a ~ d e r .~ ~OHnaphthalene. The hydroxylic derivative, C,H,<-s>CH, C W ) re-sembles a-naphthol in odour ; it is volatile with steam, and the methylethers of the two substances smell alike and have nearly the sameboiling point. The O-carboxylic acids are equally unstable, and theamderivatives have the same shade. Similar resemblances areobserved for the amino-compounds.Two methods for passing from anthranilic acid to cnrboxyphenyl-thioglycollic acid can be represented by the following scheme :/\NH, '\N2C1 (KCu[CNS]z) (NdzS) OSH 1 b02H --+ QO,H \/ I /CO,H -+ I )CO,H -.-+ \ \/ $1m "1 w_(Heat) /\S*CH,* C0,H -+ I ICO,H \/When the carboxyphenylthioglycollic acid is heated with sodiumhydroxide t o 150-160°, it passes into sodium hydroxythionaphthen-carboxylate (analogue of indoxylcarboxylic acid), the aqueous solutionof which is readily oxidised to thioindigo :From o-aminothiophonol, o-cyanophenylthioglycollic acid may beprepared, which ivomerises when warmed with dilute alkali to amino-thionaphthencarboxylic acid ; from the latter compound, carbondioxide may be removed by boiling with water, and the analogue ofa-naphthylamine produced.Abstr., 1907, i, 334154 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.Kespecting indigo and thioindigo, Falk and Nelson 91 speculate onthe stereochemistry of these substances, and think it likely that,whilst indigo is a &-compound, its diacetyl derivative as well as thio-indigo belongs to the trans-series.Other work on complex derivatives containing the pyrrole nucleusmay be briefly mentioned, new carbazole derivatives having been pre-pared by Borsche and F e i ~ e , ~ ~ J.Schmidt and R. S~ha11,~3 and G.Schultz and H a ~ e n s t e i n , ~ ~ whilst Fichter and Probst have continuedthe work on quindoline derivative^.^^Pyraxoles and Iminaxoles.Pyrazole derivatives have been prepared by Biilow and D e s ~ n i s s , ~ ~St0ermer,~7 Franz Bachs and A l ~ l e b e n , ~ ~ A. Michaelis with Mielecke,99and Klopstock,l whilst the formation of ethyl l-phenylpyrazole-3-itcetate-4-carboxylate and ethyl l-phenylpyrazole-4-carboxylate ob-served by W. Wislicenus and Breit2 in the condensation of ethylformylglutaconate with phenylhydrazine is notable in that the pro-duction of the latter ester involves the scission of ethyl acetate (assuch) from the molecule.Pellizzari and Roncagliolo have examined the condensation productsof aminocarb~carbazide,~ NH,*CO-NH*N H*CO*NH*NH,, finding thatit loses ammonia on heating, giving urazine (see triazoles), whilst itcondenses as a primary hydrazine with acetylacetone to give a derii-ative of dimethylpyrazole.Ethyl ethoxymethylenemalonate has beenemployed by A. Michaelis and Remy in the synthesis of pyrazolones ;A. R. Smith and J. F. Thorpe obtain 4-cyano-l-phenyl-3-benzyl-4-ethylpyrazolone from phenylhydrazine and the ethyl derivatives ofethyl a-cyano-y-phenylacetoacetate,6 and Ruhemann 7 has preparedmonornet h p 1 1 -phen yl- 5 -p yrazolonedicarboxy late, starting with themethyl dicarboxyaconitate of Anschutz.Pyrazolonimines have been prepared by Moureu and Lazennec,* whocondense acetylenic or P-ketonic nitriles 9 with hydrazines ; where thelatter reagents are replaced by hydroxylamine, iaooxazolones result.I n addition to other pgrazolone syntheses by Michaelislo and Schenk,ll91 Abslr., 1908, i, 107.93 Ibid., 792.96 Ibid., 977.97 Ibid., 252.99 Ibid., 1908, i, 61.Ibid., 967.Ibid., 1905, i, 576.Trans., 1907, 91, 1891.8 Abstr., 1907, i, 159.l o Ibid., 716.92 Ibid., 1907, i, 242.94 ]bid., 1074.96 Ibid., 252.98 Ibid., 356.ZbicE., 1907, i, 735.Ibid., 833.Ibid., 1907, i, 445.7 I b i d ., 1359.Ibid., 397.l1 Ibid., 966ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 155Stoermer and Johannsen,l2 Biilow,13 and Michaelis,l4 the paper byStoermer and Martinsen 15 is worthy of attention.on the conversion of pyrazolones into pyrazoles by phosphorus tri-bromide has shown that deoxybenzoin is reduced to stilbene andcarbostyril to quinoline by the same reagent, and the present worktends to show that the reaction is due to the replacement of hydroxylby bromine and reaction of the bromine atoms so introduced withhydrogen bromide and excess of phosphorus tribromide.A synthesis in the related indazole group is given by Freundler,lrwho acts on benzene-2-azobenzoic acid successively with phosphorustrichloride and water.Previous workbut the way in which he explains the mechanism of the reaction isdisputed by Tiff eneau.lsWindaus 19 has continued his study of the action of ammoniacal zinchydroxide solution on sugars, and a?-glucose, d-mannose, &fructose,d-sorbose, Larabinose, and Z-xylose have all been found to act in muchthe same way as glucose, whilst maltose and lactose give smaller yieldsof a glyoxaline.Rhamnose gives 2 : 4-dimethylglyoxaline in additionto 4-methylglyoxaline, showing that it furnishes acetaldehyde as wellas methylglyoxal and formaldehyde on decomposition.The formulation of histidine as iminazolylalanine is confirmed byWindaus and Vogt,20 who find that by elimination of the amino-group it is converted into a product identical with a synthesisedglyoxaline-4-propionic acid, the latter compound furnishing 4-/3-amino-ethylglyoxaline when the carboxyl is replaced by the amino-group ;Knoop 21 gives a further confir mation of the assigned structure bydegradation to glyoxaline.H.Biltz 92 finds that diphenylglyoxaline is oxidised by potassiumpermanganate to dibenzoylcarbamide, whilst Bonn 23 has effected asynthesis of benzylmethylglyoxaline, using benzylacetoacetic ester as astarting point.Amongst keto-derivatives of iminazole, the base prepared by Finger24by the interaction of acetiminoethyl ether and glycine ethyl ester,l2 Abstr., 1907, i, 966.l4 Ibid., 246.' 6 Ibid., 1904, i, 181.2o Ibid., 978.2.3 lbid., 646.Ibid., 986.l5 Zbid., 446.I7 Ibid., 1907, i, 158.l9 Abslr., 1907, i, 288.21 Iblbid., 788.2y Ibid., 1908, i, 55.BzJ2. SOC. chim., 1907, [iv], 1, 1201.lbid., 1907, i, 876156 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.is peculiar, inasmuch as it reacts with two molecules of benzaldehyde,the methyl as well as the methylene group taking part in thereaction.H, Biltz has studied the glyoxalones obtained by the condensation ofbenzoin with ~ a r b a m i d e , ~ ~ and also the acetylenediureine,26 firstobtained by S ~ h i f f , ~ ~ from glyoxal and carbamide.This substance, aswell as derivatives which have been described by seem>COYN H ~ ~ R ~ N HNH*CR*NH undoubtedly to possess the constitution, CO<originally assigned to them.Dieckmann and Kammerer z9 have obtained derivatives of thenearly allied parabanic acid in examining the action of hydrocyanicacid in phenylthiocarbimide, and of ethyl oxalate on phenylcarb-amide.0. Fischer3O thinks that theexplanation of the second Z-methylnaphth-iminazole obtained by Meldola, Eyre, and Lane 31 is given in that thesupposed molecule of water of crystallisation is really an oxygen atomwhich has not been removed during the reduction.This would makethe compound possess the constitution :Franzen describes the production of N-diaminonaphthiminazolefrom 2 : 3-naphthalenedihydra~ine,~~ and his observation of theformation of 2-phenylbenziminazole by warming benzaldehyde-o-aminoyhenylhydrazone with dilute mineral acids,33calls to mind the indole syntheses of Emil Fischer.Kym34 and Brand.S50 ther papers on benziminazole derivatives have appeared from25 Abstr., 1908, i, 56.27 Bid., 1878, 287.29 Ibid., 1907, i, 979.Ibid., 352.Trans., 1903, 83, 1185.Jbid., 321. 34 Ibid., 560.26 Ibid., 62.28 Ibid., 1890, 1290.32 Abstr., 1907, i, 880.35 I b i d . , 800ORGANIC CHEMISTRY -HETEROCY CLIC DIVISION. 1571 : 2 : 3-Triazoles have been obtained by Peratoner and Azzarello 313and Tamburello and Milazzo37 by tohe action of diazomethane and itshomologues on cyanogen and its chloride. The reactions are of the ~ ..N:YHN H < ~ : ~ * ~ ~ (or CI>’ and if typa CH2N2 + C2N2 (or CNC1) =suitable precautions are not taken the diazo-hydrocarbon reactsfurther, alkylating the imino-group.2-Substituted benzotriazoles have been obtained by Grandmouginand Guisan 38 by the reduction of o-nitroazo-compounds,Nand the azimidols, producedNby the action of alkali on o-nitro-sub-stituted phenylhydrazines, have been examined by Curtius and hisp ~ p i l s .3 ~ The first member of this series, benzazimidol,was described by Nietzki and Brauns~hweig.~OThe vexed question of the constitution of the products obtainedby the transformation of ethyl diazoacetate seems to be finallysettled by the work of Curtius, Darapsky, and Ernst MUller.*1 Bulowfirst pointed out the great probability of the so-called “dihydro-tetrazine” being N-sminotriazole, and this is definitely confirmed by theabove-named authors, who also show that the bisdiazomethane ofHantzsch and Silberrad is really C-aminotriazole, and that thetrue tetrazine series is represented by the so-called “ bisazoxy ”-com-pounds of Hantzsch and Lebmann.The relationships of the differentcompounds are well shown by a chart given in the second paper quotedabove, and the names in brackets are those by which the compoundshave been known at various times :36 Abstr., 1907, i, 979.a* Ibid., 1092.4o I t i d . , 1895, i, 135.37 Ibid. , 1088.3y Ibid., 969, 1078.41 Ibid., 1907, i, 262, 359, 450, 451158 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.#>CH*CO;C,H,Ethyl ciiazoacetate.$NaOH)N-- N>C*CO,HCO,H*C<~~~>C.CO,H 3 C02H*C< NH-NHRisdiazoacetic acid. - ~ - I Tetrazinedicarboxylic acid.RONH,Tetrazine. iV- Aminotriazoledicarb-(Bisazoxymethane. ) oxylic acid.(Dihydrotetrazinedi -carboxylic acid.) +p 2 0 )N-N+(HzS) i j (o)I I (Heat)(Heat) H i C H f-I (Bisazoxyacetic acid.) I (Heat)#--V CO,H* C C *CO,HJ.HC<$;>CH \/fl-3 NH,*C C*CO,HN H\/C- Aminotriazolecarb-oxylic acid.(Tris- bisdiazome thane-tetracarboxylic acid )$(Heat)M--R\/NH,*C CHNHC- Aminotriazole.(Bisdiazomethane. fJ(HN02) M-”v *HC 8 HNHTriazole.M. Busch42 draws attention to the fact that he had recognised theso-called diphenylurazine as N-phen ylaminotriazole some years back,43and Pellizzari and Repetto44 now think it quite probable that thebase, C,N6H6, obtained by Pellizzari and Cantoni 45 by the action ofcysnogen bromide on aqueous hydrazine is not ‘‘ guanazine,” but4-aminonuanazole :Stoll6 has similarly recognised the supposed dihydrotetrazinesobtained by the action of primary hydrazines on dibenzoylhydrazidedichloride as N-arylaminotriazoles : 4GAbstr., 1907, i, 564.43 Ibid., 1901, i, 616.46 Ibid., 1907, i, 359, 654.u Ibid., 1908, i, 65.45 Ibid., 1905, i, 577ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 159The thiourets obtained by Fromm and Schneider 47 by oxidising thearyldithiobiurets with iodine :7-Y\/C,H,*NH*CS*NH*CS*NH, + I, = HI + CGH5*N:C C:NH,H1,NHhave been used by Fromm and Vetter 48 in the synthesis of triazoles andother ring compounds. Half the sulphur is eliminated by the actionof aromatic amines, open-chain compounds possessing the constitutionsC,H, *N: C( SH) *NH*C(: NH) * NH C,H,andrespectively being produced by the action of aniline and phenyl-hydrazine.The acetyl derivative of the first condensation product loses wateron boiling with alcohol and potash, and the resulting compound isformed according to the equation :CGH, N : C( SH) NH C( : NH) N H*NH* C6H,,VO*CH, VO*CH,BH YH C,H,*TH r;JHC,H,*N:C C:N*C,H, Or ( s:c c:N*c6H5) =\/NH\/NHThe compound produced from phenylhydrazine loses hydrogensulphide on heating, giving 3-amino-5-anilino-1 -phenyltriazole.Fromm and von Goncz 49 publish a further triazole synthesis,potassium cyanoiminodithiocarbonate, (KS},C:N.CN, being used asinitial material ; it may be converted into the corresponding dibenzylester, which then condenses with phenylhydrazine giving 5 (or 3)-amino-3(or 6)-thiobenzyl- 1 -phenyltriazole.An interesting study OF dynamic isomerism has been made byAcree5O in the case of phenylurazole and its 4-methyl derivative.Several tautomeric formulae are possible ; the substance behaves, how-ever, as if it had the structure (I) :(1.) (11.)47 Abstr., 1906, i, 714.4L) Ibid., 872.Ibid., 1907, i, 982.50 Ibid., 258, 796160 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.for the dissociation constants of the 2 : 3- and 4 : 5-amido-groups areK = 0.00001 and K=0.0000005 respectively, a result which is con-firmed by the conversion of the substance into a dimethyl ether ofstructure (11) by the action of diazomethane.Fetraxoles.Dimroth and Merzbacher 51 find that tetrazoles are producedby the interaction of arylazoimides and the phenylhydrazones ofaldehydes :and Wieland and Bsuer52 incidentally touch on the tetrazole andtetrazine groups in studying the action of alkalis on dihydroxy-guanidine.The reaction gives an ' I aminoazaurolic acid,"ON*C(NH,):N*NH*C(NH2):N*OH,the name calling to mind the " azaurolic acids " [for example,CH,*C(NO):N*NH*C( :N*OH)*CH,]obtained by Victor Meyer as reduction products of nitrolic acids.The aminoazaurolic acid yields isonitrosoaminodihydrotetrazinewhen boiled with 18 per cent. hydrochloric acid, and undergoes partialhydrolysis on reduction, hydrazodicarboxylamideoxime,NH,*CO.NH*NH*C(NH,):NOH,being produced. By the action of nitrous acid, a cyclic compound isformed, constituted probably as :When tetrazole itself is treated with benzoyl chloride in pyridinesolution, it undergoes fission, nitrogen is eliminated, and dibenzoyl-carbamide produced.Heller 53 further finds that, although no actiontakes place in the cold, when tetrazole and benzoyl chloride arewarmed, dibenzoylhydrazine is formed ; the same compound being alsoobtained from 1 : 2 : 4-triazole.Furan a d Erurazan.Very few syntheses are to be noted in this group, Ludwig5* hasobtained dialkyldihydrobenzof urans by the action of the Grignardreagent on phthalide; Fromherz and Meigen 55 have prepared andexamined the s p - and anti-oximes of methylfurfuraldehyde, whilst51 Abstr., 1907, i, 659.54 Ibid., 702.52 Ibid., 491.55 Iblbid., 232.53 Ibid., 261ORGANIC CHEMISTRY-HETEROCY CLlC DIVISION. 161diphenylene oxide (and carbazole) have been condensed with phthalicanhydride by Stummer.5Gvon Kostanecki and Lampe 57 find that reduction effects a fission ofthe furan ring in the tetramethyl ether of catechin, a reactioncorresponding with Alexander's 58 production of coumaran and o-ethyl-phenol by the reduction of coumarone with sodium and alcohol.Thet w o authors named have further examined the halogen substitutionproducts of the tetramethyl ether 59 and, con jointly with M a r s ~ h a l k , ~ ~synthesised some compounds which must be nearly related tocatechin,Tannin has formed the subject of further discussion, Nierenstein 6lconsidering that, as its acetyl derivative only contains five acyl groups,Dekker's formula,@ which corresponds with the possibility of a hepta-acetyl compound, cannot be coxrect.The hydrogenisation of the furan nucleus has been effected byPadoa and PontiF3 who passed furfuraldehyde vapour mixed withhydrogen over reduced nickel a t 2 2 5 O .The course of the reduction isillustrated by the following scheme :-+ EH-SH -+ C H C*CH, -+ gH-GH CH C*CH,*OH GH-GHv C H C*CHO v 0\/0 0CH2*YH, -+ CH2*FH2 I yH2'p% -+ I CH, CH*CH, CR, CH-CH, CH,C*CH, -\/ / //0 HO 0The methylfuran and secondary amyl alcohol were detected, thefury1 alcohol and methyltetrahydrofuran isolated and analysed, whilstthe methyl propyl ketone was separated as its semicarbazone.The furazan compounds may be mentioned here ; 64 Wielandsuggested some time back that the glyoxime peroxides, which havegenerally been represented as possessing structure (I), are moreprobably furazan oxides (XI) :R*;C;--8*R'b-o"I(1.)Quite recently,Gj he has56 Ahstr., 1907, i, 723.Ibid., 1908, i, 86.Ann.Report, 1906, 167.65 Zbid., 1908, i, 108.REP.-VOL. IV.\/0(111.)come to the conclusion that formula (111) is~57 Ibid., 334.60 Abstr., 1907, i, 950.m Abslr., 1907, i, 146.58 Ibid., 1892, 1318.Bid., 331.Zbid., 1904, i, 54.162 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.to be preferred, and shows that the ‘* glyoxime peroxides ” are convertedinto the corresponding furazans by the action of phosphorus penta-chloride.Thiophen and Thiusoles.By the action of mercuric acetate on thiophen, Dirnroth 66 obtaineda compound to which he gave the constitutionC,H2(Hg*O*CO* CH,)(HgOH)S ;this is corrected by P a ~ l i n i , ~ ~ who uses the substance for the isolationof thiophen, to C4H,(HgO*C0.CH3),S.thionessal ”(tetraphenylthiophen) showing that it may be produced by the drydistillation of sodium thiobeuzoate, and Fromm and Holler 69 examinethe results obtained by Engler 70 from distillation of the product ofthe action of hydrogen sulphide on acetophenone.Fromm andHoller find that it is neither a thiopinacone nor disulphide, but amixture of sulphur and 2 : 4-diphenylthiophen.von Walther and Greifenhagen 71 have obtained substituted thiazo-lines by the interaction of bromoacetophenone and diary1 t hiocar bamides,thiocarbamides, or thiourethanes.Fromm and Schmoldt 6* describe several syntheses ofiso Oxuxolones.In addition to the work of Moureu and Lazennec already referredto under pyrazolones, we may note the production of oximinophenyl-isooxazolone by Wahl from ethyl isonitrosobenzoylacetate,72 andReissert’s production of anthranil by the decomposition of o-nitro-dimercaribenzylidene oxide, N0,*C6H,*CH:Hg,:0, with hydrochloricacid.73Pyridine and Piperidine.The behaviour of piperidine vapour and of pyridine vapour mixedwith hydrogen towards reduced nickel has been examined by Sabatierand Mailhe 74 as well as by P a d ~ a . ~ ~ The authors find that piperidinegives pyridine, but pyridine and hydrogen do not give piperidine ; in thedeviation from the behaviour of benzene, Sabatier and Mailhe see anargument against Korner’s pyridine formula.The wandering of alkyl groups in the pyridine series has engagedthe attention of H.Meyer the first observation that 4-methoxy-pyridine gave N-methylpyridone a t 220’ being due to Haitinger andLieben.66 Abstr., 1899, i, 428.63 Ibid., 702.7O Ber., 1895, 28, 895.T2 Ibid., 217.74 Ibid., 549. Ibid., 636.76 Ibid., 343,(i7 Ibid., 1907, i, 788.6g Ibid., 710.i1 Abstr., 1907, i, 349, 551.i 3 Ibid., 1103ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 163Somewhat similar changes with the esters of pyridinecarboxylicacids were observed by Kirpal ; 77 for instance, apophyllenic acid isproduced by the isomerisation of either of the acid monoethyl esters-of cinchomeronic acid. Meyer has now examined several acids derivedfrom pyridine and quinoline containing alkyloxy-groups in the 2- andcarboxyl in the 3-, 4-, or 5-position, but in no case was a wandering of thealkyl to nitrogen observed, although where the carboxyl and methoxylgroups are in the meta-position relatively to one another the methylgroup wanders so as to give a carboxylic ester.Zincke publishes with Schreyer 78 a further communication on thetransformation products of dinitrophenylpyridinium chloride ; Barthe 79describes new mono- and tri-bromopyridines, whilst B.Oddo,80 inexamining the compounds of pyridine and quinoline with magnesiumphenyl bromide, finds that one molecular proportion of the latterunites with one, two, or three molecules of quinoline. New stilbazolesare described by Ahrens and Luthers1 and Lowensohn,S2 whilstOrtolevas3 continues his study of the substance obtained by theaction of iodine on a pyridine solution of benzaldehydephenyl-hydrazone.The physical properties of pyridine derivatives have engaged someattention.F. Baker and Balys4 find that introduction of methylgroups or chlorine atoms into the pyridine nucleus, whilst it reducesthe oscillation frequency, does not alter the type of the absorption.From the absorption spectra of the hydroxypyridines, it is concludedthat the P-compound is phenolic, but that the U- and y-derivatives arepyridones.Kirpal 85 has determined the dissociation contents of the isomericester-acids produced by quinolinic and cinchomeronic acids, and Kailan 8Bhas measured the velocity of esterification of pyridinemonocarboxylicacids by alcoholic hydrogen chloride.A number of tetrahydropyridine bases are described by W.Koenigs,Bernhart, and IbeleY87 whilst K. Lofflers8 has (in conjunction withPlocker, Grosse, and Grunert) prepared a number of conidine bases,the attempt a t synthesising conidine itself being unsuccessful.A piperidine synthesis from ethyl acetonedicarboxylate, aldehydes,and primary amines is given by Petrenko-Kritschenko and M. Lemin,sgand Gabriel and Colman find that, when the isomerisation product of1 -y-chloropropylpiperidine is distilled with potash, some I-y-hydroxy-77 Abstr., 1902, i, 564 ; 1903, i, 117, 852.Ibid., 792.*l Ibid., 965.s3 B i d . , 729.as Abstr., 1907, i, 722.s7 Ibid., 1907, i, 791.89 Ibid., 708. ]bid., 237.7a Ibid., 1907, i, 625.so Ibid., 549, 668.a2 Ibid., 1908, i, 51.Trans., 1907, 91, 1122.86 Ibid., ii, 678.88 Ibid., 437, 439, 440, 441.M 164 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.propylpiperidine is produced.In this, they see a further proof thatthe condensation product of 1 - y-propylpiperidine is unimolecular.Other work which bears on this question is contained in a paper byJ. von BraunQ1 on the action of piperazine on a€-dihalogenpentanes.Finally, Franchimont, van Rijn, and Friedmann 92 have studied theaction of nitric acid on various piperidides, and find that those ofsuccinic and sulyhuric acids give nitropiperidine.Quinoline.Blaise and Maire93 find that 4-alkylquinolines can be readilyprepared by heating aniline with ketones containing a P-chloroethylradicle; von Niementowski 94 finds 4-anilino-2-hydroxyquinoline amongstthe products of interaction of ethyl benzoylacetate and anthranilicacid, whilst 0.Stark,g5 in an attempt to dehydrate the oxime of3-acetyl-2-methylquinoline, obtained 3-amino-2-methylquinoline as theresult of a Beckmann transformat ion accompanied by hydrolysis of theacetyl groups.B. Odd096 finds that, not only does magnesium phenyl bromidecombine with different molecular proportions of quinoline, but that,when bromobenzene, quinoline, and magnesium are allowed t o interactin toluene solution, 2-phenylquinoline is produced.L,. J. Simon and M a ~ g u i n , ~ ~ examine the mechanism of Dobner’sreaction, and employ a-naphthylamine, pyruvic acid, and benzaldehydeas components ; H.Meyer and Turnau 9s give details of the preparationof quinoline-2-carboxylic chloride by means of thionyl chloride, whilstOmstein99 extends the work of Rlulert and Pfitzinger 2 on derivativesof 3-methylcinchonic acid. I n a paper on cases of steric hindranceamong alky 1 substituted cinchonic acids, Hans Meyer 3 incidentallycorrects a number of errors in the dissertations of Ornstein (Berlin,1904) and Mulert (Berlin, 1904).A cridirte.Senier, with A ~ s t i n , ~ has investigated the conditions under whichmixed phenonaphthacridines may be obtained by the methylene iodidemethod and, with C~mpton,~ the production of simpler substitutedacridines when methylene chloride is used. Bucherer and Seyde 69l Abstr., 1907, i, 728. Jbid., 842.93 Ibid., 241.95 Ibid., 973.Ibitl., 549.99 Jbid., 443.94 Ibid., 1081.g7 Ibid., 725. 98 Ibid., 344.Ibid., 1906, i, 534.Ibid., 1907, i, 342.Ibid., 1927.Ibid., 1903, i, 53.Trans., 1907, 91, 1233, 1240.6 Ahntr. 1907. i. 34.4ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 165employ formaldehyde and nitrous acid with diarylamines, and A. E.Dunstan and Hilditch have condensed diphenylamine with p-bromo-and chloro-benzoic acids.I n the production of acridones, aryl substituted anthranilic acidsare necessary, and the conditions under which the chlorine in o-chloro-benzoic acid may be replaced by arylamino-grmps have been studiedby Ullmann.7 The best catalyst is a small quantity of a copper salt,and Irma Goldberg and Marie Nimerovaky * find that the presence ofa small quantity of copper enables the further phenylation ofanthranilic acid to diphenylanthranilic acid.It is necessary, however,to use iodobenzene as bromobenzene is inactive.A number of acridones have been prepared from the arylaminobenzoicacids mentioned, and Ullmann (Zoc. cit.) finds that, whilst the introduc-tion of halogens into the acridone molecule has practically no effect onthe fluorescence, this property is nearly inhibited by nitro-groups. Ofthe aminoacridones, the 2- and 4-derivatives fluoresce strongly inalcoholic solution, whilst the l-amino-compound does not ; on additionof hydrochloric acid, the conditions are reversed, the 5uorescence of the2- and 4-compounds disappearing, whilst the l-aminoacridone hydro-chloride exhibits the property.Goldberg and Nimerovsky (Zoc.cit.) have obtained the hitherto un-known 1 O-phenylacridone from the dehydration of diphenylanthranilicacid, and Ullmann and Maag find that the substance gives a colourlesscarbinol base with magnesium phenyl bromide which dissolves in acids,giving solutions of acridinium salts; these possess a yellow colourand green fluorescence. In a later paper,lO Ullmann, Bader, andLabhard t find that acridine itself readily condenses with dimethyl-aniline in presence of phosphoryl chloride to furnish 5-p-dimethylamino-acridine.Diaxines.Paal and Kuhn l1 continue the synthesis of o-diazines, whilst thern diazines, since they include the pyrimidines, have engaged muchattention.The most important syntheses in the latter group are dueto T. B. Johnson, H. L. Wheeler, and their co-workers (F. W. Heyl,C. 0. Johns, and C. F. Speh),12 and an example of the methodemployed by these chemists was given in last year's Report (p. 173).Studies are being made of the behaviour of various carboxylic acids ofthe series towards hot 20 per cent. sulphuric acid with the view of ob-taining information as to the manner in which the pyrimidines arebound up to the nuclein molecules.7 Abstr., 1907, i, 842.l1 Zbid., 1908, i, 57.l2 Ibid., 1907, i, 559, 728, 877, 879, 972, 1083; 1908, i, 59.8 Ibid., 621.lo Ibid., 1908, i, 52. Ibid., 638166 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.As an example, cytosine-5-carboxylic acid is found to be convertedinto urscil-5-carboxylic acid by the treatment whereby cytosine isisolated from the nucleic acids.Evidently, then, the latter substancescannot contain the cytosine-5-carboxyl grouping.I n order to find out whether some of the pyrimidine derivatives ob-tained by the hydrolysis .of nucleic acids with moderately concentratedsulphuric acid may not be formed from purine bases by hydrolysis andreduction, Burian l 3 has heated dextrose with diluted sulphuric acid(30-40 per cent.), adenine, and guanine. The result is positive,6-aminopyrimidine being obtained from the first base, and 2-amino-6-oxypyrimidine (isocytosine of Wheeler and Johnson) from thesecond.The oxidation of uracil derivatives has been studied by Hoebell*and Offe,l5 the work being a continuation of that of Behrend.16The colours exhibited by the condensation products of aromaticaldehydes with diphenylbarbituric acid obtained by Miss Whiteley 17are striking, the benzylidene derivativo of 1 : 3-diphenylbarbituric acidoccurring in two forms, one yellow and the other colourless; the di-phenylmethylene derivative is yell0 w, whilst the product from cinnam-aldehyde is orange-yellow.Hantzsch assigns the respective formulae :NH--C---Y/C:NO*OM \ and GO\ / /C-NO OM \\NH*COto the colourless and coloured salts of nitrobarbituric acid.Tafel and H.B. Thompson l9 have submitted 5 : 5-diethylbarbituricacid (veronal) to electrolytic reduction; it is more difficult to reduce thanbarbituric acid itself, and, instead of giving a hydrouracil, furnishes 4 : 6-diketo-5 : 5-diethylhexahydropyrimidine.Einhorn and von Diesbach 2Ofind that veronal is not attacked by sodium amalgam, but the corre-sponding diethylthiobarbituric acid is readily reduced by this reagent,a portion of the substance undergoing fission, and another portion givingthe hexahydropyrimidine compound described by Tafel and Thompson,whilst the remainder forms a condensation product which is probablybisdiethylmalonyltetraminoethane. A * 2-phenyl derivative of Tafeland Thompson's product has been produced by Burrows and Keane,21who condensed diethylmalonamide and benzaldehyde in presence ofhydrochloric acid.I3 Abstr., 1907, i, 735.l5 Ibid., 645.l9 Ibid., 1908, i, 58.21 Trans., 1907, 91, 269.l4 Ibid., 557.I6 Ibid., 1900, i, 120 ; 1903, i, 739 ; 1906, i, 310.Trans., 1907, 91, 1330.Abstr., 1907, i, 500.Ibid., 110ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 167Franchimont and Friedmann 22 find that hydrouracil and tri-methyleneureine yield mono- amd di-nitramines respectively, asupport of Franchimont's theory that the replacement of the hydrogenof an imino-group by the nitro-group is conditioned by the imino-groupbeing situated between a carboxyl and the residue of a saturatedhydrocarbon.Delepine 23 regards aldehyde-ammonia as the hydrate of a cycliccompound, t riet h y lid ene tria mi n e, and the hexaet h ylidene te tramine asalso possessing cyclic structure. The respective formulae are :CH2<cH(CH8)-NH N)CH*CH2\CH,*CH, .NH/CH--- >CH-NH/\cH(cH,): CH,.I n the purine group, Tafel's work on the electrolytic reduction ofuric acid (isopurone, jointly with Houseman 24), theophyllino, and para-xanthine (with Dodt 25) may be noted, whilst H.Schulze has studiedthe action of magnesium phenyl bromide on caffeine and certainderivatives. 26Hydurilic acid, which was discovered amongst the products of inter-action of nitric and uric acids by S~hiefer,~7 has finally beensynthesised by Conrad.28 The guanide obtained by condensation ofethyl ethanetotracarboxylate is the di-imide of hydurilic acid, which itfurnishes on heating to 156' with dilute hydrochloric acid :Amongst quinazolines, a number have been synthesised by Bogert z9and his co-workers, Wiggin, Sinclair, Seil, and Nelson.Parccdiazines.Pyrazine, C4H4N2, has been obtained from quinoxaline by Gabrieland Sonn,m the latter compound being oxidised by alkaline per-manganate to pyrazinedicarboxylic acid, from which carbon dioxide issubsequently removed.2j Absty., 1907, i, 877.23 Ibid., 484.24 Ibid., 984. 25 Ibid., 984.26 Ibid., 545. 27 Annnlcn, 1545, 55, 251 ; 1845, 56, 1.2i3 Abstr., 1907, i, 985. 29 Ibicl., 351, 560, 660.30 Ibid., 1908, i, 60168 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.Both oxalimide and the anilide of pyruvic acid have been referredto the piperlizine series, de Mouilpied and Rule 31 ascribing to theformer the constitution (I), whilst Wohl and Lipss2 give the latter,structure (11) :(1- ) (11.)Amongst the azine colouring matters, 0.Fischer and Romer33confirm Kehrmann and Prager's view s4 that, when hydroxylaminereacts with isorosindone, the amino-group enters the ortho-position tothe quinonoid oxygen of the benzene nucleus and not the naphthalenehalf of the molecule as at first supposed : 35Barbier and Sisley 36 prepare aposafranine by heating p-aminoazo-benzene hydrochloride with aniline, its hydrochloride, and water at160-170° ; they give the following explanation of the mechanism ofthe reaction :(I) C6H5*N:N*C,H,*NH2 -+ANR. Scholl h i s published several further papers on indanthrer1e,3~and has elucidated the structure of the flavanthrene discovered byR. Bohn amongst the products of fusion of /I-aminoanthraquinonewith potash, The probability of the substance possessing the con-stitution required by the equation :3l Trans., 1907, 91, 176.32 Abstr., 1907, i, 583.33 Ibid., 981.35 Ibid., 94.37 Ibid., 255, 256, 354.34 Ihid., 447.36 Ibid., 563ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION. 169has been confirmed by synthesis.Triccxines.Derivatives of 1 : 2 : 3-txiazines (triazones) have been produced byH. Meyer3s by the action of nitrous acid on the aromatic analogues ofpolypeptides. The latter subst,ances are prepared by the action ofo-nitrobenzoyl chloride on lithium rtnthranilate :NO,*C,H,*COCl+ NH,*C,H,*CO,Li =Licl+ NO2 c,H,* 00 *NH C,H,* C02H(repetition of the process if desired) and, finally, reduction of the nitro-to an arnino-group.The action of nitraus acid may be expressed by the equation :N/\ + HNO, = 2H20 + 1 A N H , /\I IC0"H-I I .,J,,,,!N--!,,~ \/ co CO,H\/C02HThis compound is ruptured by hydrogen chlonide to a dinzonium saltand, finally, salicylanthranilic acid, which condenses with aceticanhydride in the following manner :C02H 'w\O1 : 2 : 3-Triazine derivatives have been prepared by Bailey andKnox 39 and M.Busch and Meussdorffer 40 ; Ley and F. Muller 41 havesynthesised a dihydro-1 : 3 : 5-triazine derivative, and Finger 42 hasprepared the trihydrazide of cyanuric acid and some of its derivatives.Pyrone G~oup.Rlaise and Qeult43 publish several papers on pyran and pyroneThe attempt of Fleischmann 4433 Abdr., 1907, i, 317.41 l b i d . , 730. Bid., 298. 43 lbid, 148, 181, 332.44 Trans., 1907, 91, 250.derivatives from aediketopimelic acids,39 Ibid., 801.40 Ibid., 448170 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.to obtain a yy-dipyrone by condensation of triacetic lactone withacetoacetic ester or b-aminocrotonic ester proved unsuccessful, alactone being produced instead, whilst Collie and Hilditch 45 find thatwhen dehydracetic acid is heated with sulphuric acid of 85 instead of90 per cent. very little triacetic lactone is formed, but a substance,C8H804, which decomposes nearly quantitatively at 200' into dimethyl-pyrone and carbon dioxide is chiefly obtained. The formulaproposed by Collie for the product of the action of sulphuric acidon dehydracetic acid, which in its enolic form would bereceives confirmation from Tamburello and C a r a ~ e l l i , ~ ~ who haveconverted the substance by means of diazomethane into thecorresponding methoxymethylpyrone.Bain 47 has examined thebehaviour of the disodium derivative of diacetylacetone towardsethylene and propylene dibromides, thus extending his earlier ~ o r k . ~ 8Amongst chroman compounds, W. H. Perkin and R. Robinson49have made experiments on the synthesis of compounds nearly relatedt o trimethylbrazilin, which is possibly0CH~*O~\/\CH---/\O*CH,\/\/ \/\/ I ICH I IO*CH;CH*OH CH,Salicylaldehyde and 1 -hydrindone condense t o give 2'-hydroxy-2-benzylidene-1 -hydrindone, which is reduced then t o 1 : 2'-dihydroxy-2-benzylhydrindene. Loss of water furnishes 1 : 2-hydrindochroman, theseries of changes being represented by the scheme :0By replacing the salicylaldehyde with its p-methoxy-derivative andusing 5 : 6-dimethoxy-l-hydrindone in place of hydrindone itself, a45 Trans., 1907, 91, 787.47 Trans., 1907, 91, 544..m Ibid., 1907, 91, 1078.46 Gazxetta, 1907, 37, i, 561.Ibid., 1906, 89, 1224ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION.17 1substance was obtained which, if the above formula for trimethyl-brazilin is correct, merely differs from it by a hydrogen atom in placeof a hydroxyl group.von Kostanecki 5O publishes further syntheses in the flavane group,starting with cuminaldehyde, and C. Liebermann, S. Lindenba~ru,~~and Truchsiiss 52 continue the work on xanthophanic and glaucophanicacids.Further syntheses of xanthone derivatives, starting with o-chloro-benzoic acids, are published by Ullmann and C.Wagner,53 andWichelhaus 54 has examined the action of sulphur on fluorescein.The question of the constitution of phthalein salts has led R. Meyerand K. Marx55 to make a spectroscopic comparison of fluorescein andthe phthaleins of phenol and quinol in alkaline solution. It is foundthat the two latter substances are very similar, but differ markedlyfrom fluorescein. Further, Meyer and J. Stark 56 have compared thefluorescent spectra in alcoholic and sulphuric acid solution both in thecase of fluorescein and fluoran. With the first compound, the solventmakes little difference, with the second compound the influence of thesolvent is most marked, and the result is attributed to formation ofoxonium salts, a conclusion arrived a t by Hewitt some years back.57That apparently minor differences in constitution can have consider-able influence on fluorescent phenomena appears from the descriptionof a number of fluoresceins by Friedl, Weizmann, and W ~ l e r .~ ~Oxnxines.The labile changes occurring between 0- and N-acylsalicylamideshave been ascribed by McConnan and Titherley 59 to cyclic tautomerism,N-benzoylsalicylamide being represented in its labile form by thestructure :This view is controverted by Auwers,gO but Titherley 61 now showsthat the phenylbenzometoxasone obtained by Keane and Nichollsfrom salicylamide and benzaldehyde can be oxidised in sulphuric acidsolution to N-benzoylsalicylamide, a result which might be simplyexpressed by the equation :50 Abstr., 1907, i, 952.52 Ibid., 890.53 Ibid., 846. 54 lbid., 232. 55 Ibid., 932.56 Ibid., ii, 418. 58 Yrarbs., 1907, 91, 1584.59 Ibid., 1906, 89, 1318. Yrans., 1907, 91, 1419.6‘2 Ibid., 264.51 lbid., 889.57 Ibid., 1900, ii, 318.6O Abstr., 1907, i, 928172 AKNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.Other p-oxazines and azoxonium salts are described by Kehrmannand Albert Winkelmann 63 and Nietzki and V. Be~ker.6~ J. F. Thorpe 65finds that dye-stuffs of the general formula (I) lose NHR,R, on pro-longed boiling with dilute acids, furnishing dialkylaminophenonaphth-oxazones (11) :0Meldola’s blue gives the same product, but the reaction in this casenecessitates simultaneous oxidation.Amongst the allied thiazine compounds, h e h m 66 has studied theaction of nitric acid on methylsne-blue and its homologues, the tetra-ethylthionine being far more reactive than the tetramethyl com-pound (met hylene-blue).Vuriouus Rings.Amongst unclassified cyclic structures, we may note the constitutionassigned by \Vieland 67 t o ‘‘ hydroxyleucazone,”the thianthrene compounds of J.Frohlich,6s which are derived fromS o-diphenylenedisulphide, C,H,<s>C6H,, and the continuation of thework on oxadiazines by Diels and Sa~se.6~Alkaloids.A control of the constitutions of tropine, ecgonine, cocaine, andbenzoylecgonine has been effected by G a u d e ~ h o n , ~ ~ who finds that theheats of formation of the alkaloids correspond with the constitutionsassigned to them.Ldger 71 has confirmed the constitution of hordenine as p-hydroxy-phenylethyldimethylamine, for the methiodide of its methyl ether givesp-vinylanisole when heated with alkalis, and Willstatter and €€eubnerT2find that tetramethyl-as-diaminobutane accompanies hyoscyamine inHyoscyamus muticus.63 Aktr., 1907, i, 345, 554.65 Ibid., 978.67 Ibid., 1907, i, 494.70 ]bid., ii, 738.64 Trans., 1907, 91, 324.66 Abstr., 1908, i, 63, 110.6* Ibid., 632.71 Ibid., i, 234, 336.69 Ibid., 1086.‘i2 Ibid., 959ORGANIC CHEMISTRY --HETEROCYCLIC DIVISION. 173Barger and Carr 73 have confirmed as a fact the suggestion of Kraff t 74that ergotinine is derived from ergotoxine by removal of the elementsof water, and assigns t o the two alkaloids the respective formulEe~,,J339O,N, and C,,H, 106%.About two years ago, Pictet made the suggestion that the vegetablealkaloids owe their formation to the following processes :1.The complex tissue materials, albumin, nucleins, chlorophyll, &c.,break down, giving relatively simple products.2. These simple bases then condense with other materials to formthe more complicated alkaloids.A systematic examination of various plants with a view of sup-porting this hypothesis has led to the isolation of pyrrolidine andN-methylpyrroline from tobacco, a base, C,H,N (probably a C-methyl-pyrroline), from pepper, pyrrolidine and a base, CllHI8N2, from carrotleaves, and a base, C,H,,ON, from coca, which is, however, notidentical with Liebermann’s hygrine.The knowledge of the betel-nut alkaloids has been materiallyextended by Wohl’s researches on amino-acetals and amino-aldeh~des.7~Ammonia reacts with chloropropalde hy de acetal,giving a mixture of primary, secondary, and tertiary bases.Thesecondary base by hydrolysis with hydrochloric acid furnishes thehydrochloride of A3-tetrahydropyridine-aldehyde, and if the corre-sponding N-methyl-A3-tetrahydropyridine-aldehyde (obtained by sub-stitution of methylamine for ammonia in the first reaction) is convertedinto the corresponding carboxylic acid,CHit is found to be identical with arecaidine. This alkaloid (and arecoline,its methyl ester) had been previously synthesised by Jahns,76 but theposition of the double linking was unknown.A.Ladenburg 77 now finds [aJD 17.85’ for pure isoconiine; thevalue previously obtained (19.2’) was too high, and probable due toadmixed allylpiperidine.Ladenburg states that for a tropeine to possess mydriatic properties,it must contain an acyl group attached to the benzene nucleus, and73 Trans., 1907, 91, 337.77 162.’ 1907, i, 956.7J Abs.fr., 1906, i, 979.75 Ibid., 1908, i, 46. 76 md., 1892, 737174 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.have an aliphatic hydroxyl in the side-chain.have synthesised a compound of the structure :Jowett and Pymm 75? /\CO--j J C H ( o ~ ) * C H * C O * c ~ H , , O N ’but its physiological action is feeble.Rabe’s formula for cinchotoxine bas received ample confirmation,two posthumous papers of W.Koenigs 79 definitely proving the hydro-lytic products required Iny the formula C,H6N*CO* CH2*CH,*C7H,,Nare obtained when Beckmann’s transformation is applied to the oximeof Rahe’s l-methylcinchotoxine.80Though the cinchotoxine formula is settled, it should be noted thattwo possible formuls remain for cinchonine itself, namely :CH-/?H-.y 3 2 ?%7H2 / 7H2 ’ ‘CH*CH:CH, I\CH*CH:CH~ CH, CH2and YH\’ / QHzYH2 t‘H, N-- HO* ?--N-- / CH-OHIC A N C9H6NP. Rabe 8J finds that when isonitrosomethylcinchotoxine is submittedto the Beckmann reaction, methylcincholeupone nitrile and cinchoninicacid result, whilst he has further investigated the behaviour ofcinchonine towards nitric ** and chromic 83 acids. The substanceobtained in the second case is apparently a ketone derived from analcohol (the cinchonine) by removal of two hydrogen atoms, so thatit would appear that the second formula given above for cinchonine isreally correct.Rate 84 gives us further evidence in favour of this formula, namely,the conversion of narcotine and gnoscopine (racemic narcotine) into aketone-base, nornarceine, by heating with dilute acetic acid ; hydrolysisalso occurs with formation of cotarnine and meconine, but the change tonornarceine may be represented as follows :CH,788083O*CH,CO/\CO,H (/o*cH,0.CH,.Trans., 1907, 91, 92.Ibid., 71. 8l Ibid., 546. 82 Ibid., 546.Ibid., 954. Ibid., 790.T9 Bernhart and Ibele, Abstr., 1997, i, 345, 717ORGANIC CHEMISTRY-HETEROCYCLIC DIVISION.175The analogy to the conversion of cinchonine into cinchotoxine isapparent when one compares the narcotine lactone formula with thesecondary alcohol formula for cinchonine.Rohde and Antonaz s5 find that the sodium derivative of methyl-cinchotoxine is readily oxidised (by nitrobenzene in alcoholic solution),giving a quinoline-y-carboxylic acid ; the meroquinenine half of themolecule appears, however, in an unworkable condition.Pictet and Jenny have examined the amine-oxide,C23H&5N2,4& H,O,from brucine and hydrogen peroxide; Pavesi 87 has found a newalkaloid, aporeine, in the latex of Papaver dubizcrn, and M. Freund 88 hasrevised Tambach and Jager’s work on n a r ~ e i n e . ~ ~M. Freund and F. Mayergo adopt Gadamer’sgl modification ofPerkin’s formula for berberit~e,~~ which makes the free base an aldehyde,but the berberine salts as of quaternary isoquinolinium type. Theformula of Gadamer would necessitate two asymmetric carbon atoms inan alkyltetrahydroberberine, and Freund and Mayer actually find that,when propyldihydroberberine is reduced, t w o racemic propyltetra-hydroberberines are formed.The morphine group of alkaloids has been the subject of extensiveinvestigations during the past year by LeesYg3 Knorr and Horleinyg4Pschorr,gS and Vongeri~hten.9~A certain amount of uncertainty as to isomorphine (and isocodeine),P-isomorphine (and P-isocodeine), and neo-iso- (or y-iso-) morphine (andpseudo-codeine) is cleared up by Lees’ classification of the geneticrelationships :P-isoMorphine f- Chloromorphide -+ Neo-isomorphine.1J. .5.I I + Chlorocodide -+ Neo-isoCodeine.J.P-is0 CodeineP-isoMorphine +- Bromomorphide -+ isoMorphineP-isoCodeine f- Bromocodide -+ isocodeine.I I +The nomenclature in the scheme is that used by Lees; in readingKnorr and Horlein’s papers it must be remembered that isomorphineis referred to as a-isomorphine, P-isocodeine as allo-$-codeine, neo-iso-morphine as y-isomorphine, and neo-isocodeine as +codeine.Whilst codeine and isocodeine both give codeinone on oxidation,a5 Abstr., 1907, i, 634.a8 Ibbid., 235.Ibid., 1902, i, 555.93 Ibid., 1907, 91, 1408.91 Abstr., 1907, i, 235, 547, 548, 789, 956, 957 ; 1908, i, 41, 4‘2.95 Ibid., 1907, i, 547, 635, 636, 958.86 Ibid., 436. 87 Ibid., 870.d9 Ibid., 1906, i, 879.y2 TTans., 1889, 55, 63 ; 1890, 57, 991.Ibid., 1907, i, 632.Ibid., 718, 1068176 ANNUAL REPORTS ON THE PROGRESS OF CHEMISTRY.p-iso- and neo-iso-codeines give q-codeinone, the two isomeric ketonesdiffering in melting point (1S7O and 174’ respectively) and values ofaD ( - 2 0 5 O and - 25O). Vl’hilst the isomerism of codeine to isocodeineis sterical, the same being true of the other pair of (p- and neo-) iso-codeines, oxidation of the secondary alcoholic grouping to a ketonemakes this form of isomerism disappear, and hence only twocodeinones are produced from the four codeines. The codeinones are,however, structurally different, codeinone can be degraded to 3 : 4 : 6-trimethoxyphenanthrene and the 3 : 4 : S-isomeride being obtained fromq-codeinone. Evidently some deep-seated change occurs during theformation or hydrolysis of chloro- and bromo-morphides.Hitherto both Knorr and Pschorr have been in substantial agree-ment as to an oxide-bridge between positions 4 and 5 of thephenanthrene nucleus, and the attachment of the nitrogen atom of thechain CH,*N*C*C* to position 9, but quite recently Bucherer97 hasproposed an entirely novel formula. The three proposed coustitutionsfor morphine are as follows :C H CH CHH O ~ \ \ C H/\/\/CH, C H CHI ’ I IN-CH CH”I I \ /CH, OHCH,Pschorr. Knorr. Bucherer.Bucherer’s formula has not yet been thoroughly discussed, butKnorr in a footnote to his last papergS thinks that in a modifiedform (as below) it may be worth considering. Unmodified, it requiresCH, C H0 C Hthat codeinone and thebainone should be secondary bases, which is atvariance with the facts of the case. J. T. HEWITT.97 Abstr., 1908, i, 43. 93 Ibid., 42