2156 FORSTER AND ZJMMERLI !CCXXV.-Studies in the Camphane Se.ries. PartStereoisomeric Hydrazones and Semi- X X VIII.cai-baxones of Carnphorquinone.By MARTIN ONSLOW FORSTER and ADOLF ZIMMERLI.THE expectation of stereoisomerism among semicarbazones is anatural corollary of the Hantzsch-Werner hypothesis, Up to thepresent time, however, it does not appear that any systematicattempt has been made to place the question of semicarbazone-isomerism on the basis occupied by that of the oximes, Apart fromthe distrust with which the hypothesis in question is stiIl viewed insome quarters, the principal reason for this omission to bring thesemicarbazones into Iine with oximes is the scattered and ill-definednature of the evidence relating to the occurrence of isomerism inthe former class.The cases of isothujone, carvenone, and tetra-hydrocarvone appear to have been established by Wallach (Ber.,1895, 28, 1955), but the isomeric semicarbazones of citral and ofionone owe their formation to the existence of each ketonein two isomeric forms. Wallach has also shown that syn-thetical pulegone, obtained by condensation of methylhexanonewith acetone, yields two semicarbazonea (Ber., 1896, 29, 2955 ;also AnnaEen, 1898, 300, 269), from both of which the ketone isregenerated by acid, but a claim for the production of isomeridesfrom phenyl-l-methyl-A6-cycZohexen-5-one (Knoevenagel and GoldSTUDlES IN THE CAMPHANE SERIES. PART XXVIII. 2151smith, Ber., 1898, 31, 2465) is not based on strong evidence.Benzoylmethylthiodiazole, on the other hand, gives rise t o twoderivatives (Wolff, Annulert, 1902, 325, 173), but the supposedexistence of two benzilnionosemicarbazones (Posner, Ber., 1901, 34,3979) was shown to be fallacious by Biltz and Arnd (Ber., 1902,35, 344; compare also Biltz, Annulen, 1905, 339, 243), the secondsubstance being 5 : 6-diphenyl-3-oxy-1 : 2 : 4-triazineY prepared byThiele and Stange (Annalen, 1894, 283, 27).Nef has recordedthe production of two semicarbazones from propaldehyde (Annulen,1904, 335, 202), whilst Knoevenagel and Same1 (Ber., 1906, 39,681), and later Rupe and Dorschky ( B e y . , 1906, 39, 2112),found that when semicarbazide acts on carvone in the cold, theproduct is distinct from that described by von Baeyer, into which,however, it is convertible at raised temperatures.I n reviewing the foregoing evidence relating to the existence ofisomeric semicarbazones, we have not encountered any systematicattempt to explain the phenomenon, but the experiments describedin this paper lead us to express the opinion that stereoisomerism ofthe type displayed by oximes must now be regarded as existing inthis class also.Our attention was drawn to the subject by an observation madein connexion with camphorquinonesemicarbazone (Lapworth andChapman, Trans., 1901, 79, 381), and our thanks are due toDr.Lapworth for his consent t o our using this material. I npreparing it by the slightly modified process of Diels and vom Dorp(Ber., 1903, 36, 3190), we noticed that the mother liquor containeda more soluble isomeride melting a t a lower temperature thanthe modification already described, and calling the latter thea-derivative, we refer to the new compound as the 8-semicarbazone.When this is heated above its melting point, it is converted intothe a-semicarbazone, and the latter, under the influence of hotaniline, undergoes the change described by Borsche ( B e y ., 1901,34, 4297 ; 1904, 37, 3177), giving rise to camphorquinonephenyl-carbamylhydrazone, with liberation of ammonia :The product, however, is an equilibrium mixture of two isomerides,related to one another in a manner similar t o the connexionbetween the semicarbazones. Both camphorquinonephenylcarbamyl-hydrazones are produced, also, when the B-semicarbltzone is heate2158 FORSTER AND ZIMMERLI :with aniline, and by the condensation of camphorquinone withphenylcarbamylhydrazide :and they may be obtained separately by the action of phenyl-carbimide on two new hydrazones of camphorquinone.The action of hydrazine on camphorquinone is stated by Odd0(Gazzetta, 1897, 27, ii, 117) to yield " biscamphanonazine," identicalwith Angeli's azocamphanone (Gazzetta, 1894, 24, ii, 44), producedin association with camphenone by heating diazocamphor.Asrepresented by Angeli, the formation of azocamphanone :CsH,,<?:N":(?>C H co oc 14'obviousIy depends on the condensation of hydrazine with twomolecules of the diketone, but we find that if the substances interactin molecular proportion, two new derivatives of ca.mphorquinone areproduced; these, being isomeric, are referred to as the a- andP-hydrazones, and it is by the action of phenylcarbirnide on thesetwo substances that the above-mentioned a- and P-phenylcarbamyl-hydrazones are respectively obtainable :Thus, the isomeric hydrazones (m.p. 206O and 1 0 2 O ) are con-nected through the isomeric phenylcarbamylhydrazones (m. p. 21 loand 161O) with the isomeric semicarbazones (m. p. 2 3 6 O and 147O)respectively, and the members of each pair bear to one another thesame relation in respect of solubility, fusibility, and inter-convertibility by heat, A further connexion between the hydrazonesand semicarbazones is established by the fact that whilst aceticanhydride converts the hydrazones into acetyl derivatives (m.p.239O and 150°), of which the 8-compound is transformed into thea-modification by heat, an equilibrium mixture of these isomericace.tyl derivatives follows the action of hot acetic anhydride onthe isomeric semicarbazones :+ CH,*CO*NH, + CO,. C:N*NH-CO*CH, cs %<b*These reactions are summarised in the diagram on p. 2159.It now becomes necessary to explain our grounds for ascribingthe present case of isomerism to stereochemical rather than strucHea2160 FORSTER A N D ZIMMERLI :tural considerations, a.nd since the only justification for a stereo-chemical explanation is the exclusion of structural differences, weproceed to deal with the possible causes of the foregoing relation-ships. These are:1. Dimorphism, condemned by the distinct differences in opticalactivity which solutions of the respective pairs display undercomparable conditions.2.Polymerism, which might be suspected from the higher meltingpoint and sparing solubility of the a-compounds. The latterproperty has precluded application of the freezing-point method ofmolecular-weight determination except in the case of the a-phenyl-carbamylhydrazone ; this is normal, and so is the a-semicarbazonein boiling chloroform, whilst for other reasons which becomeapparent later in this paper it is difficult to believe that theIess fusible member of each pair is merely a polymeride of thecorresponding &modification.3. The structural difference which, depending on the asymmetryof the camphane molecule, renders the types,C , H , , < ~ ~ 2 and C,H,,<?’ cx,’distinct from one another.The principal objection to thisexplanation is one which is familiar to all workers with camphorderivatives, namely, the immensely superior reactivity of thea-position. But it is excluded also by the formation of thehydrazones on reducing diazocamphor, supported by the improba-bility of the above types undergoing interconversion by merelyheating the substances at 100-200°.4. cis-trans-Isomerism, also depending on the asymmetry of thecamphane nucleus, as represented by the formulae:NX NHC8€Xl,(C<hH and C8Hl,(Y<kx ,‘co ‘cothe possibility of which has been indicated by Armstrong andRobertson (Trans., 1905, 87, 1278). This point would be difficultto argue in the case of the semicarbazones and phenylcarbamyl-hydrazones if these had the constitution :respectively, but is simplified by their experimental relation to thehydrazones, because it is obvious that cis-trans-isomerism of theorder shown above could not occur in the case of the lattersubstancesSTUDIES IN THE CAMPHANE SERIES.PART XXVIII. 21615. The structural difference arising from enolisation, namely :as suggested by Betti in connexion with the phenylhydrazones( B e y . , 1899, 32, 1995). Here again the test is furnished by thesimple hydrazones, which would be represented as :But this enolic formula represents the nitrogen in a conditionhopelessly unprotected and quite incompatible with stability, whilstthe alternative cycloid could not reasonably be expected to displaychemical behaviour practically identical with the azethenoid com-pound represented by the first of the above expressions.The latterremark applies also to the formula:suggested by analogy to Hantzsch's representation of the alkaliderivatives from oximinoketones. Thus the keystone of thediscussion is the constitutdon of the simple hydrazones.6. The structural difference of compounds derived from theazethenoid and cyclic hydrazones :respectively. The discussion of this possibility involves a referenceto the early work of Curtius on the interaction of hydrazine hydrateand ketonic substances. I n dealing with the constitution ofhydrazine derivatives from benzil and benzophenone, Curtius andThun (J.pr. Chem., 1891, [ii], 44, 161) and, later, Curtius andRauterberg (Zoc. cit., p. 192) distinguish the products by theformulz :N €3'GH5' and (C6H5\,C: N *NH,,C,H5-C0respectively. Their principal reasons for doing so were the superiorreactivity of the benzophenone derivative towards benzaldehyde,although the benzilhydrazone also condenses with that substance,and the oxidation of the benzilhydrazone to the correspondingderivative of diazomethane by the actsion of mercuric oxide :NH N C6H5*CO*CPh<hH -+ C,H,*CO*CPh<#2168 FORSTER AND ZLMMERLI :the benzophenonehydrazone being stated to yield a tetrazone bythis treatment :(C,H,),C:N*NH, --+ (C,H,),C: N*N:N*N : C( C61T5),.The evidence of tetrazone-formation will be found on examination,however, to be noticeably slender, and in the light of our ownexperiments we suggest that the “ tetrazones ” derived from benzo-phenonehydrazone (Curtius and Rauterberg, Zoc.cit.), benzylidene-hydrazone (Curtius and Pflug, Zoc. cit., p. 535), and acetophenone-hydrazone (Curtius and Pflug, Zoc. cit.) are unstable derivatives ofdiazomethane, corresponding with that obtained from benzil-hydrazone.I f this suggestion is justified it would, a t first sight, appear toconfirm the cyclic representation of the hydrazones. But it hasbeen already pointed out that cis-trans-isomerism of an unsub-stituted cyclic hydrazone does not seem possible, and the directconsequence of revealing isomerism in a simple hydrazone istherefore to discredit the cyclic structure for at least one member ofthe pair in favour of the azethenoid representation.How, then,is the formation of a diazomethane derivative from an szethenoidhydrazone to be explained ? We suggest the following inter-pretation, first pointing out that it is probably the self-evidence ofthe conclusion that a hydrazone, convertible into a diazomethanederivative by mercuric oxide, must be derived from a cyclic type,which has obscured the possibility of an alternative explanation.It seems to us most likely that the cause of this change is to befound in the Hofmann-Curtius reaction, which, without quotingother examples (Trans., 1909, 95, 433; Schroeter, Ber., 1909, 42,2336) may be summarised in the equations:X*@O*NHBr - HBr =X*N:C:O.X*CO*N,- N,=X*N:C:O.Applying this t o the present question, we have to deal with acase of arrested transformation :X,C:N*NH, - H, = X,C:N*N --+ X,C<n ”it being impracticable for the denuded atom of nitrogen to displacecarbon from its position in the molecule, with the result that theazethenoid linking incurs a redistribution of valency.Although a superficial criticism of this explanation might dismissit as forced, and less probable than the one at present accepted, itis strongly supported by the following circumstances. As alreadypointed out, the isomeric camphorquinonehydraones cannot bothhave the cyclic structure; if, on the other hand, one were cyclicand the other azethenoid, some difference in bebaviour towards anoxidising agent should evince itself.But there is none. ThSTUDIES IN THE CAMPHAKE SERIES. P m r XXVIII. 2163a- and /3-hydrazones, dissolved in cold pyridine, have been oxidisedwith aqueous mercury acetamide to diazocamphor, and the pre-cipitation of mercury takes place instantaneously in both cases.Moreover, by reducing diazocamphor in cold alcohol with ammoniumsulphide, both hydrazones have been regenerated. It appears tous that these experiments point incontestably t o stereoisomerismof the Hantzsch-Werner type. Theoretical considerations make itclear that at least one of the hydrazones must be azethenoid, andsince oxidation of both leads to diazocamphor, the production of adiazomethane derivative from a hydrazone by this step cannot beaccepted any longer as evidence of the cyclic structure.Further-more, the fact that diazocamphor yields both hydrazones onreduction vitiates the conclusion that because diazomethane iscycloid, a hydrogenised diazocamphor must be a cyclic hydrazone.On the other hand, formation of both hydrazones on reducing diazo-camphor gives colour to our hypothesis, because if it be admittedthat ring-scission occurs on reduction, anti- and syn-modificationswould be produced simultaneously :Moreover, from relationships developed recently between structureand optical activity in the camphane series (Trans., 1909, 95, 942),it is to be exjected that a substance derived from diazocamphor inthe manner indicated by the formuls:would display lower rotatory power than diazocamphor itself,whereas the a- and B-hydrazones of camphorquinone both havedistinctly higher molecular rotation.Furthermore, they do notdiffer greatly from one another in respect of this property, althougha, considerable difference might be anticipated between an azethenoidand a. cyclic hydrazone.The second chemical distinction which has been mentioned asleading Curtius to differentiate between cyclic and azethenoidhydrazones, namely, condensation with benzaldehyde, corroboratesthe evidence from oxidation. When suspended in cold water andshaken with this agent, both hydrazones undergo immediate con-densation, indicated by a change of colour, since the benzylidenederivative is deep yellow. The final product is the same whetherthe a- or the 8-hydrazone is employed as starting-material, but th2164 FORSTEB AND ZIMMERLI :deeper colour generated by the latter substance, and the delay insolidification shown by the product, suggest the preliminaryformation of an unstable P-benzylidene compound.Before concluding, we ought to mention that there is one dis-tinction existing between the members of each pair which willdoubtless be quoted as evidence in conflict with our explanation.Itis a fact that whilst the a-hydrazone, a-semicarbazone, and a-phenyl-carbamylhydrazone are colourless, the P-modifications are faintlyyellow. It was by a distinction of this order that Armstrong andRobertson (Zoc. c i t . ) attempted to justify their representation of thephenylmethylhydrazone and phenylbenzylhydrazone of camphor-quinone as " phanes," whilst retaining the azethenoid structure forthe diphenylhydrazone, and if the same principle were applied tothe substances described herein, the colourless a-hydrazone and itsderivatives would be represented as cycloid, whilst the yellowfl-compounds would be labelled azethenoid.I n the foregoingremarks we have endeavoured to show that this cannot be accepted,but even if that evidence could be swept aside, we still hold thatthe conclusion from colour is in support of our hypothesis, whichregards the a- and /3-derivatives as anti- and syn-carbonylic respec-tively :FHXa-Hydrazone, a-semicarbazone, &Hydrazone, B-semicarbazone,For it cannot be denied that from the conflict of views as to therelation between colour and constitution there does emerge thisprinciple, that colour appears to be associated with a concentrationof unsaturated atoms.Clearly there is a more intimate massing ofsuch atoms in the P-compounds as represented above than in theirisomerides, and it is fair t o claim this point as favouring the stereo-chemical hypothesis. I n further support of the latter, it may bestated that the only chemical distinction between the members ofeach pair which has yet come to light is to be found in the behaviourof the semicarbazones towards aqueous alkali. Whilst the a-semi-carbazone forms a yellow solution which does not undergo spon-taneous alteration, the dissolved 8-semicarbazone quickly loses itsand a-phenylcarbamylhydrazone.and 8-ph enylcarbamy lhy drazone.colour, and on acidifying the liquid there is liberatedoxyt,riazine :thSTUDIES IN THE CAMPHANE SERIES. PART XXVIlI. 2165production of which is obviously more favoured by the s y ~carbonylic configuration than by the alternative one.These, then, are our principal reasons for inclining to the stereo-chemical representation of the camphorquiponehydrazones and theirderivatives described in this paper. If this interpretation findsacceptance, it carries with it fresh evidence in support of theHan tzsc h-Werner hypothesis ,EXPERIMENTAL.A ction of Hydraaine Hydrate on Camphorpinone.A zocamphanone.-Twelve grams of hydrazine hydrochloride, dis-solved in 100 c . ~ . of water, were treated with 12 grams of potassiumhydroxide, and, when cold, mixed with 33 grams of camphor-quinone in 100 C.C.of hot alcohol. During one hour at 40° theappearance of the liquid had completely changed, owing to theseparation of a bulky, pale yellow precipitate; this was collected,washed with 50 per cent. alcohol, and found to weigh 29 grams.The product was dissolved in 400 C.C. of boiling alcohol, whichdeposited lustrous, six-sided, transparent plates, almost rhombo-hedral in form; becoming deep yellow at 195O, it melted anddecomposed at 218O. (Found, N = 8.75 ; C,,H,,0,N2 requiresN =8.53 per cent.) This compound is the ‘‘ azocamphanone ” ofAngeli (Zoc. cit.), who records 222O as the melting point, whilstOdd0 gives 217-218O. It does not reduce hot Fehling’s solution,and is not hydrolysed by a hot 20 per cent;.solution of alcoholicpotassium hydroxide ; concentrated hydrochloric acid, however,when mixed with an alcoholic solution and boiled, eliminateshydrazine, but cold concentrated sulphuric acid, although forminga deep yellow solution, does not resolve azwamphanone int’ohydrazine and camphorquinone. An alcoholic solution does notchange when heated with an aqueous solution of mercury acetamide.When powdered or in separate crystals, azocamphanone appearscolourless, but when viewed in bulk it has a, yellow tinge, andsolutions are deep yellow ; 0-3104 gram, dissolved in chloroformand made up t o 25 c.c., gave a, 4O20’ in a 2-dcm. tube, whence[a]D 174’5O and [MI, 571°J not 790°J as previously stated in error(Trans., 1909,95, 948).C‘:N*NH,Cc)T h e Isomeric Camphorquinonehydrazones, C,H,,< I .-Anaqueous solution of hydrazine hydrate prepared from 30 gramsof hydrazine sulphate and 24 grams of potassium hydroxide in150 C.C.of water was mixed with 33 grams of camphorquinone,dissolved in 150 C.C. of hot alcohol. After three hours at 40°2166 FORSTER AND ZTMMERLI :23 grams of pale brown crystals had separated, quite distinct irlappearance from the bulky precipitate of azocamphanone, and acurrent of steam having been passed through the filtrate until allvolatile matter was removed, a further 2 grams crystallised fromthe hot liquid, so that under these conditions the yield ofa-hydrazone amounted to 75 per cent. There was not any azo-camphanone or camphorquinone, and after recrystallisation fromabout 400 C.C.of boiling alcohol, the a-hydrazone separated in long,lustrous, transparent prisms, melting and evolving gas at 206O :0-2538 gave 0.6189 CO, and 0.2037 H20. C = 66.51 ; H = 8.98.0.1418C,,H,,ON, requires C = 66-66 ; H = 8.88 ; N = 15.55 per cent.The a-hydrazone and its solutions are colourless, but large crystdsfrequently have a brown tinge; 0.3110 gram, dissolved in chloroformand made up to 25 c.c., gave a, 7 O 9 ’ in a 2-dcm. tube, whence[a]= 287-4O. The compound is insoluble in petroleum, and is notreadily soluble in other media even when these are boiled; acetoneor benzene is a convenient solvent from which to obtain it incolourless crystals, but upwards of 100 C.C. of the latter solvent atthe boiling point are required to dissolve 1 gram of the substance.It is readily soluble, however, in warm phenol, and sparingly so incold pyridine.A solution in chloroform decolorises bromine immediately, andammoniacal silver oxide is reduced when warmed with the alcoholicsolution. On adding solid sodium nitrite to a cold suspension of thea-hydrazone in glacial acetic acid, the salt assumed a transientpurple tint, whilst the liquid became yellow and evolved gas; ondiluting the acetic acid with water, azocamphanone was precipitated,On passing a current of steam through the filtrate from thea-hydrazone as prepared under the foregoing conditions, 3 gramsof a straw-yellow, crystalline material were carried over.The yieldof this compound, however, was trebled by adding 40 grams ofhydrazine hydrate to 50 grams of camphorquinone dissolved in75 C.C. of alcohol, when the deep yellow colour changed immediatelyto pale brown; copious precipitation of the a-hydrazone took placeafter a very short interval, and at the end of half an hour theliquid was filtered and subjected to a current of steam, The soliddistillate, consisting of P-hydrazone, weighed 12.5 grams, whilst2 grams more were obtained by extracting the distilled water(1200 c.c.) with ether ; the yield of accompanying a-hydrazone wm66.6 per cent., and if both compounds are required, the aboveconditions of procedure are the most economical. The P-hydrazonewas recrystallised twice from boiling petroleum (b.p. 60--80°),12 grams requiring 120 C.C. of the solvent, which deposited long,,, 18.9 C.C. N, at 1 5 O and 751.5 mm. N=15*43STUDIES IN THE CAMPHANE SERIES. PART XXVIII. 2167lustrous, straw-yellow needles or transparent prisms, melting at102O :0.2038 gave 0.4975 CO, and 0.1632 H,O.0.1864The substance has a faint odour suggesting that of bornylamine;it is readily soluble in organic media, excepting petroleum. Asolution containing 0.3134 gram, made up to 25 C.C. with chloroform,gave a, 5O48' in a 2-dcm. tube, whence [a], 231'3O. An alcoholicsolution reduces cold ammoniacal silver oxide, and a solution inchloroform decolorises bromine immediately.C = 66.59 ; H = 8.96.C,,H,,ON, requires C = 66.66 ; H= 8.88 ; N= 15.55 per cent.?, 26.6 C.C.N, a t 25O and 754 mm. N=15.79.Interconversion of the Hydrazones.On melting the &hydrazone, it was noticed that if the temperatureof the bath is raised to 150-160° the liquid solidifies, and thischange was found to be due to conversion into the isomeride, whichis readily isolated by recrystallisation from hot alcohol. Theconverse transformation cannot be brought about by merely meltingthe a-hydrazone, because this modification slowly loses nitrogen at205-210°, yielding camphor :If, however, the a-hydrazone is dissolved in molten paraffin wax,and maintained at 180° during a few minutes, it is a simple matterto demonstrate the formation of the P-hydrazone by suspendingthe product in hot water, and passing a current of steam throughthe liquid, when the volatile modification is carried into thecondenser.Action of Sulphuric Acid on the Hydrazones.The hydrazonss behave exactly alike towards sulphuric acid.When covered with the warm agent of 30 per cent.strength, aclear solution is formed almost immediately, and this a t oncebecomes turbid, setting to a paste of azocamphanone in the courseof a few minutes; on extracting the filtered product with boilingalcohol, crystals of hydrazine sulphate remain undissolved. With10 per cent. acid, a clear solution is not produced, because thedissolution of the hydrazone is overtaken by the separation ofazocamphanone2168 FORSTER AND ZIMMERLI :Acyt Derivativee of the HydrazonesC: N *NH*CHO The a-Formyl .Derivative, CsH,,<&O .-On dissolving1 gram of the a-hydrazone in 10 gra.ms of formic acid (D 1*2),the pale yellow solution remained clear during a few seconds,when a shower of crystals separated; the derivative wasrecrystallised from boiling alcohol, of which about 70 C.C.wererequired by 1 gram, and was deposited in colourless, lustrous, six-sided plates, which displayed frequent twinning. It melts at 234O :0.1240 gave 14.6 C.C. N, at 18O and 757 mm. N=13*54.CI,HIBO,N, requires N = 13.45 per cent.The formyl derivative is insoluble in boiling petroleum, anddissolves sparingly in methyl alcohol, benzene, acetone, and chloro-form unless these solvents are heated, 15 C.C. of the lasbnamed,for example, dissolving about one decigram until warmed; it ismore readily soluble in pyridine and glacial acetic acid.A solutioncontaining 0.1720 gram, made up to 25 C.C. with chloroform, gavea, 3O33’ in a 2-dcm. tube, whence [a], 258.0°. On adding ferricchloride to an alcoholic solution, a pale brown coloration isdeveloped, whilst that with copper acetate is grass-green. Aqueousalkalis dissolve the substance readily, producing a bright yellowsolution, and on adding ferrous sulphate to the diluted liquid adark bluish-green precipitate is formed ; when the alkaline solutionis left a t the laboratory temperature, the colour quickly fades, andthe a-hydrazone separates.The same formyl derivative was also produced by the action ofthe acid on the P-hydrazone. An attempt to prepare a benzoylderivative by the action of benzoyl chloride on the formyl compounddissolved in pyridine was not successful.C: N*NH*CO*CH, The a-Acety2 Deiiuatiue, C8H,,<),0 .-Althoughdissolving readily in cold formic acid, the a-hydrazone is onlymoderately soluble in cold glacial acetic acid ; it dissolves on warm-ing the liquid, but does not crystallise readily even on dilution,owing to partial acetylation.The substance was therefore warmedwith five parts of acetic anhydride, when the acetyl derivativeseparated as a paste of crystals at the moment of complete dis-solution in the hot liquid ; recrystallisation from a considerableproportion of boiling alcohol gave long, lustrous, snow-whiteneedles, melting and decomposing at 239O :0-1047 gave 11.8 C.C. N, at 17O and 760 mm.N=13*07.C12H1802Ng requires N = 12.61 per centSTUDIES IN THE CAMPHANE SERIES. PART xxvm. 2169A solution containing 0.2226 gram, made up to 20 C.C. withchloroform, gave a, 5O54' in a 2-dcm. tube, whence [a]= 265'5O.The compound dissolves freely in dilute aqueous alkali, developinga, bright yellow coloration, and the solution yields an intense bluish-green precipitate with ferrous sulphate; 0.2083 gram, dissolved in5 C.C. of 10 per cent. sodium hydroxide and diluted to 25 C.C. withwater, gave aD 4O121 in a 2-dcm. tube, whence [aJD 252*0°. I nprocess of time, the colour of the alkaline solution fades, and thea-hydrazone separates from the liquid.The B-A cetyl Derivative,--On dissolving the P-hydrazone in fiveparts of cold acetic anhydride, the temperature rose slightly, andlong, fiat, transparent prisms began to separate in the course of afew minutes; after recrystallisation from boiling petroleum, thesubstance was found to be pale yellow, and melted at 150O:0.1297 gave 14-5 C.C.N, at 1 8 O and 760 mm.C,,H,,O,N, requires N = 12.61 per cent.A solution containing 0.3890 gram, made up to 25 C.C. withchloroform, gave aD 6O58' in a 2-dcm. tube, whence [a], 223'8O.The solution in aqueous alkali has the same appearance as that ofthe a-acetyl derivative, developing a similar precipitate withferrous sulphate; in the course of some hours, the yellow colourfades, and the liquid deposits crystals of the a-hydrazone.When the P-acetyl derivative is heated at temperatures aboveits melting point, varying proportions of the a-acetyl compound areproduced, but the conversion is not complete; moreover, on heatingthe a-acetylhydrazone in acet'ic anhydride, a certain amount of theB-isomeride may be isolated from the product.The a-Benzoyl Derivative, C,H,,<CO .-Thea-hydrazone requires about 25 parts of pyridine to maintain a clearsolution at zero, and on adding the calculated amount of benzoylchloride, also dissolved in ice-cold pyridine, the hydrochloride ofthe base separated, the benzoyl derivative being precipitated ondilution with water j recrystallisation from boiling alcohol, inwhich it is sparingly soluble, gave tough, lustrous, snow-whiteneedles, becoming yellow above 200°, and melting at 219-222O,according t o the rate at which the temperature is raised:N = 10.01.N=12.91.7 : N N H*CO*C,H,0.1322 gave 11.4 C.C.N2 at 16O and 757 mm.CI7H2,O2N, requires N = 9-86 per cent.The substance is not readily soluble in chloroform, and a solutioncontaining 0.2135 gram, made up to 50 C.C. with this solvent, gaveU, 1°45/ in a, 2-dcm. tube, whence [a], 204.9O. Although in partdissolved by 2 per cent. aqueous sodium hydroxide, the benzoylderivative did not form a clear solution; 0.1904 pam, suspendedVOL. XCVJI. 7 2170 FORSTER AND ZIMMERLI :in about 20 C.C. of the agent, was made up to 50 C.C. with absolutealcohol, the clear, deep yellow liquid giving a, 1°50/ in a, 2-dcm.tube, whence [aID 240'7O.On attempting to prepare a benzoyl derivative of the B-hydrazone,the principal product wm found to consist of the substance justdescribed, but the residue from the mother liquor remained oilyduring many nionths, suggesting that both isomerides are formed.The a-benzoyl derivative was obtained also by mixing equalquantities of camphorquinone and benzoylhydrazine in dilutealcohol, crystals separating after two hours at 40°; in this case,also, the filtrate deposited an oil, indicating the presence of a,mixture.Benzytidene Derivative of Ca,mpF.orpuinonehydrazone,The a-hydrazme was finely powdered, mixed with the calculatedamount of benzaldehyde, and heated with a few C.C.of alcoholduring two or three minutes; crystals did not separate on cooling,but water precipitated a, yellow oil, which quickly became solid, andwas recrystallised from boiling petroleum (b.p. 60--80°). Themassive, yellow crystals melted at 109'5O :0.1253 gave 12.0 C.C. N, at 20-5O and 758 mm.C,,H,,ON, requires N = 10.44 per cent.The substance is freely soluble in chloroform, benzene, acetone,alcohol, and ethyl acetate, but only moderately so in warmpetroleum; a solution containing 0.3035 gram, made up to 20 C.C.with chloroform, gave a, 4O50' in a 2-dcm. tube, whence [a], 159'2O.It is also produced immediately on shaking the finely powderedhydrazone with water and benzaldehyde, but the method is notconvenient, as a portion of the hydrazone remains mechanicallyprotected.The same benzylidene derivative is produced on agitating theP-hydrazone suspended in water with the aldehyde, the deep yellowcolour of the condensation product becoming noticeable imme-diately. Owing to the solubility of the P-hydrazone in water, noneescapes combination, but the product remains liquid during manydays, although rapidly becoming solid when heated t o looo andscratched.Another example of the capacity of the hydrazones for takingpart in condensation changes was given by heating an alcoholicsolution of the a-hydrazone and camphorquinone in molecular pro-N = 10.90STUDIES IN THE CAMPHANE SEHIES.PART XXVlII. 21'71portion during twelve hours under reflux, when azocamphanonewas produced :Oxidation of the Hydrazones t o Diazocamphor.Since i t was desirable to study the oxidation of the hydrazonesunder conditions precluding the likelihood of preliminary inter-conversion, it occurred to us that mercury acetamide, owing to itssolubility in cold water, might be a more suitable agent thanmercuric oxide, a study of the acetamide compound having shownthat it acts rapidly on primary hydrazines with precipitation ofmercury (Trans., 1898, 73, 783).Experiment showed that thebehaviour of the isomeric hydrazones of camphorquinone towardsthis agent distinguishes itself sharply from the indifference of azo-camphanone. It having been first ascertained that the P-hydrazoneis not transformed into the isomeride by dissolution in pyridine,1 gram dissolved in 3 C.C. of the cold solvent was treated with2 grams of mercury acetamide in 3 C.C. of cold water, the meta.1being precipitated immediately.The production of the diazo-compound was indicated on extracting with ether, which becamedeep yellow, and, after evaporation, the pyridine residue yielded0.8 gram of diazocamphor on dilution with water; recrystallisationfrom petroleum (b. p. 40°) gave long, striated, yellow prisms,melting at 73-74O.Procedure in the case of the a-hydrazone was modified by thesparing solubility of the substance, 5 grams of which were dissolvedin 80 C.C. of hot pyridine, cooled to 50-60°, and treated with 10grams of mercury acetamide in 30 C.C. of warm water; mercury wasprecipitated immediately, and 4 grams of diazocamphor obtained.A solution containing 0.4605 gram of the diazo-compound, madeup to 25 C.C. with chloroform, gave a, 4 O 5 8 ' in a, 2-dcm.tube,whence [a'JD 134.8O.Reduction of Uiaxocamphor to the Hydrazones.A 20 per cent. solution of diazocamphor in absolute alcohol wassaturated with hydrogen sulphide without undergoing any changein appearance, but on adding a few drops of dilute ammonia andagain passing the gas, the liquid became pale brown, and gradualseparation of the a-hydrazone took place; on subjecting the filtrateto steam distillation, a small proportion of the P-hydrazone wascarried over. As it is a matter of importance to establish theproduction of both compounds without question, the experiment7 c 2172 FORSTER AND ZIMMERLI !was repeated at zero, when it was found that the precipitation ofthe a-hydrazone was diminished, and the yield of P-hydrazone wasproportiona.tely increased.Reduction of t h e a-Hydrazone to a-Aminocamphor.Owing to the readiness with which the hydrazones undergoacetylation, a certain amount of the a-acetyl derivative is formedon attempting to reduce the a-hydrazone with zinc dust and aceticacid; it is precipitated, however, when the acid is neutralised.Onadding a further quantity of alkali to the filtrate, ammonia is setfree, and ether extracts aminocamphor, which may be identifiedby conversion into the oxime; a specimen of aminocamphoroximeobtained in this way melted a t 144-145O.T h e Isom,em'c Camphorquinonesemical.bazones,The discovery of a second camphorquinonesemicarbazone arosefrom the observation that on evaporating the filtrate from thesubstance described by Lapworth and Chapman, there is depositedan oil which, by treatment with very dilute aqueous alkali, isdivisible into two solids; one passes into solution, and consists ofthe derivative already known, whilst the new semicarbazone remainssuspended.A solution containing 33.2 grams of camphorquinone in 150 C.C.of alcohol was mixed with semicarbazide acetate prepared from22.2 grams of the hydrochloride and 27 grams of crystallisedsodium acetate in 100 C.C.of water; the liquid, from which crystalsof the a-semicarbazone quickly separated, was transferred to astoppered filtering flask connected with a water-pump, the alcoholbeing evaporated at the laboratory temperature during six to eighthours, when drops of oil became noticeable among the crystals.From the resulting sludge about 16 grams of the less soluble a-semi-carbazone were filtered, the mother liquor being poured into waterand treated with alkali hydroxide until a faint yellow colourpersisted ; the suspended oil became solid when stirred, and con-sisted of the more soluble P-semicarbazone mixed with a smallproportion of the isomeride. I n order to remove the latter, thefiltered product was ground three or four times with 10 C.C.of2 per cent. aqueous sodium hydroxide, the filtration necessary aftereach extraction being carried out as quickly as possible, becausealthough the a-semicarbazone dissolves in weak alkali without delay,the 8-modification is also soluble, but very slowly. The pale yellowpowder was then extracted twice with 300 C.C.of boiling water, thSTUDIES IN THE CAMPHAXE SERlES PART XXVIII. 2173crystalline deposit (6 grams) from this being recrystallised from25 C.C. of warm benzene, to which the same volume of petroleumwas added. A t this stage the purification was complicated by thefact that following closely on the slender, yellow crystals of theP-semicarbazona there appeared opaque nodules containing theisomeride.Camplzorquino~ze-a-semicarbazone is the substance described byLapworth and Chapman (loc. cit.). It crystallises from alcohol inlustrous, colourless prisms, melting and evolving gas at 236O, aftersintering and becoming yellow at about 230O; it is much lessreadily soluble in organic niedia than the isomeride, and is insolublein petroleum.A solution containing 0.3152 gram, made up to20 C.C. with methyl alcohol, gave a, 8O45’ in a 2-dcm. tube, whence[a],, 277.6O. As distinguished from the P-compound, it dissolvesimmediately in dilute alkali, and 0.3344 gram in sufficient potassiumhydroxide, made up to 25 C.C. with water, gave a, 8O55‘ in a 2-dcm.tube, whence [aJD 333.3O ; this remained constant during six days,and the semicarbazone precipitated from the solution by aceticacid was unchanged material. Nevertheless, on heating with 10 percent. potassium hydroxide during three to four days, camphor wasgradually produced. Cold concentrated sulphuric acid dissolvesthe a-semicarbazone, and gradually changes it to azocamphanone,which is precipitated on pouring the liquid into water ; if, however,the hot acid is used, a certain amount of camphorquinone isproduced.An estimation of the molecular weight in boilingchloroform gave 236 instead of 223.Camp?borq uinone-P-semicar b azone cryst allises in pale yellowprisms, melts at 1 4 7 O , and is readily soluble in alcohol, acetone,ethyl acetate, chloroform, ether, or benzene, but dissolves onlysparingly in hot water or boiling petroleum :0.2328 gave 0.5037 CO, and 0.1539 HiO. C = 59.03 ; H = 7.66.0.3225 N=18*79.C,,H,,O,N, requires C = 59.19 ; €I = 7.62 ; N= 18.83 per cent.A solution containing 0.3152 gram, made up to 20 C.C. withmethyl alcohol, gave a, 6O20’ in a 2-dcm. tube, whence [a], 200-9O.When covered with aqueous alkali hydroxide, the P-semicarbazonedoes not appear to dissolve; if, however, the solid substance isthrown into hot 10 per cent.sodium hydroxide, there is producedimmediately a deep yellow solution, the colour of which graduallyfades, owing to the formation of the oxytriazine (see below), Onraising the temperature of the fused P-semicarbazone to about 190°,the substance became solid, and the a-semicarbazone wits found tohave been produced.,, 54.8 C.C. N, at 25O and 754 mm2174 FORSTER AND ZIMMERLI :Conversion of the Semicarbazones into the A cetylhydrazones.The semicarbazones were separately heated with boiling aceticanhydride during one hour, the solid product obtained in eachcase, on pouring the liquid into water, being found fa consist of amixture of the a- and P-acetyl derivatives of the hydrazones.Thetransformation was not easy to establish experimentally, becausethe relative solubility of the acetyl derivatives in alkali exactlyresembles that of the semicarbazones themselves, and as the meltingpoints of the latter differ from those of the respective acetylhydrazones by 3O only in each case, the preliminary experiments ledt o the supposition that the semicarbaxones are directly inter-convertible by tohe action of the agent in question.The Tsomeric Campho~~.uinonephenylcar6amylhydrazones,These derivatives were prepared by three different methods.(1) Action of hot aniline on the a- and P-semicarbazones, eachof which gave both phenylcarbamylhydrazones.(2) Condensation of camphorquinone with phenylcarbamyl-hydrazide, also yielding a mixture.(3) Interaction of phenylcarbimide and the a- and P-hydrazones,which led to the individual phenylcarbamylhydrazones, respectively.Camphorquinone-a-phenyl car6 amylh ydrazone.-Four grams ofthe a-semicarbazone were dissolved in 20 C.C.of aniline, and heatedten minutes a t the boiling point of the solvent, ammonia beingliberated freely before this temperature was reached ; the cooledliquid was diluted with its volume of alcohol, and poured into200 C.C. of 10 per cent, acetic acid at zero. The precipitated oilquickly hardened when scratched, and on dissolving the productin 80 C.C. of hot methyl alcohol, the a-phenylcarbamylhydrazonecrystallised in thick, colourless plates, melting at 21 lo, whilst theisomeride remained dissolved :0.2494 gave 0.6096 CO, and 0.1656 H,O.0-1660C,,H2,102N3,~CH,0 requires C = 66.64 ; H = 7.30 ; N = 13.33 per cent.The transparent crystals became opaque in the steam-oven, owingt o loss of crystal-alcohol :0.2462 gave 0.6158 CO, and 0.1546 H,O.C=68*23; H-7.03.C17H2102N3 requires C = 68.23 ; H = 7-03 per cent.Ordinary solvents, excepting petroleum, dissolve the substancereadily, but, unlike the a-semicarbazone, it is insoluble in coldC = 66.67 ; H= 7.43.N=13*75. ,, 20.3 C.C. N, at 24O and 761.5 mmSTUDIES I N THE CAMPHANE SERIES. PART XXVIII. 2175aqueous alkali hydroxide, although dissolving when heated, withdevelopment of a yellow coloration. A solution containing 0.2207gram, made up t o 25 C.C.with chloroform, gave a, 4’3‘ in a 2-dcm.tube, whence [a], 229’3O. An estimation of the molecular weightby depression of the melting point of benzene gave 327 insteadof 299.Camphorquinone-/3-p h e n ylcar b amylhydraaone.-From the motherliquor of the foregoing substance there gradually separated long,slender, silky needles, in which a few small crystals of thea-compound were embedded, and as the latter remained undissolvedon rapidly warming the liquid, it was possible to isolate theP-modification without much difficulty, the final recrysfallisationbeing effected by adding petroleum to a solution of the needles inbenzene. The substance is very pale yellow, and melts at 161O:0.2142 gave 0.5346 CO, and 0.1372 H,O. C = 68.10 ; H = 7.17.0.1062 ,, 13.9 C.C.N2 a t 24O and 754 mm.C,,H,,0,N3 requires C = 68.23 ; H = 7.03 ; N = 14-09 per cent.I n all common media the solubility of the P-phenylcarbamyl-hydrazone scarcely differs from that of the isomeride, but thetendency to form supersaturated solutions is much greater. Asolution containing 0.2128 gram, made up to 25 C.C. with chloro-form, gave a, 3O16’ in the 2-dcm. tube, whence [a], 191.9O.As in the case of the P-semicarbazone, transformation into thea-modification was readily accomplished by heating the P-phenyl-carbamylhydrazone above its melting point ; the clear liquid whichhad been carried to 200° remained vitreous on cooling, but imme-diately became crystalline on being scratched in presence of a smallquantity of methyl alcohol.In preparing the phenylcarbamylhydrazones by the foregoingmethod, it was noticed that the proportion of the two modificationsdepends on the duration of heating and on the temperaturereached.This is explained by the fact that either is convertibleinto the other isomeride by the action of hot aniline, eachindividual yielding an equilibrium mixture when a solution in thatbase is heated until the solvent boils; roughly speaking, the relationbetween the constituents of this mixture is a: B =2 : 1.The second process for obtaining the phenylcarbamylhydrazoneswas practised by mixing solutions containing 5 grams ofcamphorquinone and 4.5 grams of phenylcarbamylhydrazide,C,H5*NH*CO*NR*NH2, each in 15 C.C. of hot methyl alcohol, andheating the iiquid on the water-bath during a few minutaa;2.8 grams of the a-phenylcarbamylhydrazone separated on coolin:,whilst the mother liquor deposited a mixture of this with thecharacteristic, silky needles of the @modification,“~14.552176 FORSTER AND ZIMMERLI :The third method is the most convenient when the hydrazonesare available, because it leads to the individuals, and thus obviatesthe necessity of a tedious separation.The finely powdereda-hydrazone (1.8 gram), suspended in 250 C.C. of boiling benzene,in which it was not completely soluble, was heated with 3 gramsof phenylcarbimide on the water-bath during two hours, when theliquid did not deposit crystals on cooling. After distilling off thesolvent until only 30 C.C. remained, twice this volume of petroleumwas added, precipitating 2.7 grams of a crystalline powder, readilyidentified with the a-phenylcarbamylhydrazone on recrystallisation.I n preparing the &modification by this process, 0.9 gram of theP-hydrazone, dissolved in 10 C.C.of benzene, was treated with 0.7gram of phenylcarbimide, the mixture being left at the laboratorytemperature, and after the lapse of twelve hours diluted withpetroleum until pale yellow needles appeared ; after recrystallisationit melted at 161°, and did not depress the melting-point of theP-phenylcarbamylhydrazone prepared by the other methods.Camphane-oxytriuzine,Whilst the a-semicarbazone is dissolved immediately by aqueousalkali hydroxide, forming a permanent yellow solution, the&modification is transformed into the anhydride represented above,the conversion taking place at rates depending on the temperature.Camphorquinone-B-semicarbazone was covered with 10 parts of10 per cent.aqueous sodium hydroxide, and shaken at intervalsduring five hours, when the solid substance, at first coloured yellowby the agent, had passed into a colourless solution. After extractionwith ether, dilute sulphuric acid was added until the initial pre-cipitate was redissolved, when the liquid was shaken eight timeswith ether; the solvent deposited 85 per cent. of viscous residue,which quickly solidified. Recrystallisation from warm benzene, towhich petroleum was added, gave colourless, transparent pyramids,melting at 166-167O :0.2183 gave 0.5137 GO2 and 0.1406 H,O. C = 64.18 ; H = 7.21.0.1950 N=20.75.C,,H,,ON, requires C = 64-39 ; H = 7-31 ; N = 20.49 per cent.The substance is somewhat readily soluble in warm water, anddoes not crystallise completely on cooling ; alcohol, ether, chloroformand benzene dissolve it readily, but it is insoluble in petroleum. It,, 35.6 C.C. N, at 21° and 759 mmSTUDIES IN THE CAMPHBNE SERIES. PART XXVIII. 2177does not reduce Fehling’s solution, and when heated withammoniacal silver oxide yields a voluminous, white precipitate,freely soluble in ammonia,. A solution in sodium carbonate isstrongly alkaline, and gives a transient violet precipitate withferrous sulphate, becoming bright green when excess is added ;copper salts produce an apple-green precipitate, also formed bynickel sulphate, excess of which yields a clear solution. The opticalactivity of the oxytriazine and its derivatives is very much lowerthan that of the foregoing compounds of camphorquinone; a solutioncontaining 0.2855 gram, made up t o 25 C.C. with chloroform, gavea, 0°31/ in a, 2-dcm. tube, whence [aID 22*G0.The ucetyl derivative was readily formed on heating the oxy-triazine with a.cetic anhydride ; after recrystallisation from a,mixture of benzene and petroleum, it melted at 168-169O :0.1765 gave 0.4096 CO, and 0.1127 H,O.C,,H,,O,N, requires C = 63.16 ; H = 6-88 per cent.The substance dissolves freely in cold benzene, chloroform,acetone, or methyl alcohol, but is less readily soluble in ethylalcohol or ethyl acetate, from which it crystallises in lustrous,colourless needles. A solution containing 0.2444 gram, made up to20 C.C. with chloroform, gave a, 1°2/ in a 2-dcm. tube, whence[a], 42.2O.The benzoyl derivative, prepared by the action of benzoyl chloridein pyridine solution and purified by precipitation from acetic acid,followed by recrystallisation froin a mixture of benzene andpetroleum, melted at 193-194O :C=63*30; H=7.14.0.2021 gave 0.5150 CO, and 0.1108 H,O.C,8Hl,0,N, requires C = 69.90 ; H = 6-15 per cent.The compound is freely soluble in cold acetone or chloroform,but ethyl acetate, methyl alcohol, benzene, or ethyl alcohol dissolveit less readily, and it is very sparingly soluble in boiling petroleum.A solution containing 0.2808 gram, made up to 20 C.C. with chloro-form, gave only a, 0°13’ in a 2-dcm. tube, whence [a],, 7 ~ 7 ~ .C = 69.51 ; H=G.13.ROYAL COLLEGE OF SCIENCE, LONDON.SOUTH KENSINGTON, S.W