1134 LAPWORTH : ACTION OF CXVI.-Action of Hydro7ytic Agents o n a-Dibromo- C'oizstitut ion of BI.o?,aoccci~a~)7Lol.enic Acid. campho~. By ARTHUR LAPWORTH. WHEN P-dibromocamphor is warmed with strong aqueous alkalis, i t dissolves, and acid products are obtained; these do not appear to have been examined, bnt their formation indicates that hydrolysis of the dibromocamphor has occurred, and if is probable that they in- clude derivatives of a-cnmpholenic acid. This acid has been isolated from the product of the actior! of moist sodium amalgam on P-dibromo- camphor (Kachler and Spitzer, M o ~ t t s l ~ , 188.2, 3, 216 ; 1583, 4, 643), and its presence is doubtless due to the occurrence of combined reduction and hydrolysis. The formation of a-campholenic acid by two different reactions, from P-clibromocamphor on the one hand, and from camphoroxime on the other, would certainly seem to indicate that the substance is related to camphor in a simple manner.I n the present paper, how- ever, evidence is brought forward which shows that obscure changes in structure may occur under conditions which cannot be regarded as violent, and it is of especial interest that a change of this kind occurs in a reaction almost exactly analogous to that whereby P-dibromo- camphor affords a-crtmpholenic acid. Action of Silveq* Conzpounds on a-D ~bro~szocnvzpho~*. a-Dibromocamphor, unlike the P-derivative, when treated with alkalis, or with sodium amalgtm, is merely reduced, and hitherto no hydrolytic effect appears to have been observed. It mas in the hope of producing such an effect that the following experiment was made, A solution of a-dibromocamphor in alcohol was warmed on the water- bath in a reflux apparatus, and to the hot solution small quantities of finely powdered silver nitrate were added.After each addition cloudiness ensued, and was followed by a copious deposition of silver bromide, the rtddit,ion of silver salt being interrupted when this cloudiness was no longer produced. The whole was heated for about an hour, and after the addition of hydrochloric mid, in amount sufficient to precipitate the excess of silver, the liquid was filtered, . evaporated a t a low temperature, and then distilled in steam; a solid product, smelling strongly of camphor, passed over, le ving an oily residue. The solid product in the distillate was collected an carefully fractionated, when it resolved itself for the most part into camphor and monobromocamphor.The less volatile portion, on examination,HYDROLYTIC AGlENTS ON a-DIBROMOCAMPHOR. 1135 was found t o contain monobromocamphor and unaltered dibromo- camphor. The oily residue in the distilling flask could be separated into two portions by means of sodium carbonate solution ; the portion insoluble in sodium carbonate was for the most part unaltered dibromocamphor, but contained a small quantity of nitrogenous substance soluble in hot caustic potash. The portion dissolved by sodium carbonate separated on the addition of an acid as a brown, apparently amor- phous precipitate, and after purification by dissolving in sodium carbonate and reprecipitating with acid, was crystallised from alcohol.This acidic substance separated from alcohol in beautiful, white needles, and from ethylic acetate in large, transparent, monoclinic plates; it melted at 159'. It dissolved Elowly in cold dilute sodium carbonate with effervescence, and the solution a t once discharged the colour of dilute potassium permangannte. On treatment with bromine, i t evolved hydrogen bromide, and yielded a neutral substance which separated from alcohol in needles and melted at 152'. The substance obtained by the action of silver nitrate on a-dibromocamphor had therefore the properties of an unsaturated Py- or @-acid. It contained bromine, and gave the following results on analysis : 0,2073 gave 0.3701 CO, and 0.1110 H,O.C=48*7; H=6*0. CloHl,O,Br requkes C = 48.6 ; 13 = 6.1 per cent. It was finally found by direct comparison to be identical in all respects with bromocamphorenic acid, first obtained by Forster from dibromocamphor in an indirect manner (Trans., 1896, 69, 46). This action of silver nitrate appears a t first sight to be merely one of hydrolysis in accordance with the equation C,oH1,OBr, + H,O = CloHl,O,Br + I-TBr, and therefore more or less analogous to the hydrolysis of /3-dibromo- camphor by sodium amalgam, and it is now clear that the production of this substance accounts for the formation of homocamyhoronic acid when a-dibromocamphor is oxidised in presence of silver nitrate (this vol., p. 992). When, in the above experiment, acetic acid is used instead of alcohol as a solvent, nitrous fumes are rapidly evolved, and the solution on cooling frequently deposits beautiful needles of bromo- camphorenic acid.The yield of this compound, although greater than in the former case, did not in any instance greatly exceed 15 per cent. of that theoretically possible. I n order to make certain that the nitric acid or nitrous fumes disengaged during the reaction played no part in the production of bromocamphorenic acid, the experiments were repeated with silver acetate instead of nitrate, but the results only differed as regards the 4 a 21136 LAPWORTH: ACTION OF length of time required to complete the reaction, and the proportion of acid produced. a-Dibromocamphor in alcoholic solution is rapidly attacked by moist silver oxide, and, in addition to the above products, a small quantity of a yellow, oily substance is formed; this is insoluble in alkalis, and, as it gives a crystalline compound on treatment with semicarbazide acetate, is probably a ketone : it is not camphorquinone, however, as it is not volatile in steam.Action of Mei*czC?y ccnd Lead Contpounds on a-Dibroi?~occ~ni~lor. Interesting results having been obtained with silver salts, i t was thought desirable to examine the action of other met.allic com- pounds on a-dibromocamphor. Mercurous nitrate was first chosen, as it resembles silver nitrate in yielding a very sparingly soluble bromide. On adding mercurous nitrate to a hot solution of a-dibromocamphor in acetic acid, nitrous fumes were at once evolved, and a precipitate of mercurous bromide was produced.If the action was interrupted after about 15 minutes, it was found that a small quantity of bromo- camphorenic acid could be isolated, but the amount formed was considerably smaller than when silver salts were used. It is interesting that lead salts and moist lead oxide seem to have little or no effect on a-dibromocamphor under conditions similar to the above. In order to induce any marked decomposition with lead oxide, it was necessary to heat the materials with water in sealed tubes a t 120-150°, and the experiments showed that when any appreciable action occurred, the orga.nic matter was almost entirely carbonised. I n one instance, however, the aqueous solution had acquired a distinct yellow colour, and on distilling the contents of the tube with steam, i t mas found that the first few drops of the distillate were bright yellow, and deposited a few yellow needles.Although the quantity was too small for analysis, the substance was easily identified, as it melted a t 196-198°, approxiuately the melting point of camphorquinone (Claisen, Bey., 1889, 22, 530). I t sublimed with great readiness, its aqueous solution was decolorised by sodium hydrogen sulphite, the colour being restored by means of acid, and, when examined in polarised light, the crystals could not be distinguished from those of camphorqninone prepared by the ordinary method. It may Be mentioned that from the same tube a consider- able quantity of monobromocamphor was obtained by continuing the steam distillation. I n order to determine whet her broinocamphorenic acid was pro- duced in the foregoing reaction, the csrbonised contents of four tubes were united and boiled with a solution of sodium carbonate.NoHYDROLY T1C AGENTB ON a-DIBROMOCAMPEOR, 1137 appreciable quantity of bromocamphorenic acid was obtained from the filtrate after aciditication, but on extracting the acid liquid with ethylic acetate and evaporating, a small quantity of a crystalline acid was ischtcd, which, after purification, melted with some effervescence at 1 8 4 O , but when allowed to solidify, melted again a t temperatures varying between 80' and 200'. It yielded an anhydride melting at about 2 1 5 O on treatment with acetyl chloride, and its whole be- haviour suggested that it was cainphoric mid.This was confirmed by analysis. 0.1014 gave 0.8216 CO, and 0.0760 II,O. C: = 59.6 ; I3 = 8.3. CloH1604 requires C: = 60.0 ; I€ = S.0 per cent. I t is possible, of course, that the formation of cainphoric acid from dibromocamphor in this way is due to the oxidation of camphor or monobromocamphor produced a t an intermediate stage, but, it seems more probable that hydrolysis ,bas taken place, with the production of camphorquinone, which would readily yield camphoric acid under the above conditions. Oxidcct ion of Derivatives of B?.o?nocc~?~~2,~orenic Acid. I n the endeavour to obtain fairly large quantities of homocamphor- onic acid by a convenient method, a large number of experiments were made with derivatives of bromocamphorenic acid, and a brief account of the results may be given.The method used by Forster (Zoc. cit.), namely, oxidation of bromo- camphorenic acid with ice-cold permanganate, was found to give very poor yields of the desired product, and was inconvenient on account of the large quantity of liquid necessarily involved. Oxidation of bromocamphorenic acid with dilute nitric acid, even in presence of silver nitrate, also gave poor results, as it was almost impossible to avoid the formation of a stable nitro-derivative, and the substance itself is so sparingly soluble in the nitric acid that the action is excessively slow. I n every case, however, some small quantity of homocamphoronic acid was obtained. Chromic acid was found to be quite useless as an oxidising agent. Dibromocampholid was next tried, and was oxidised in various ways.With dilute nitric acid and silver nitrate, fairly good results were obtained, but the action was slow ; on evaporating the filtrate after several days treatment with tho oxidising mixture, homo- camphoronic acid was at once obtained, apparently uncontaminated with any secondary product. The yield was in each case about 15-20 per cent. of that theoretically possible. a-Monobromocampholid, the lactone obtained by treating bromo-1138 LAPWORTH: ACTION OF camphorenic acid with sulphuric acid (Forster, Zoc. cit,) was found to be the most suitable substance for the purpose. It is rapidlyattacked bya solution of silver nitrate i n dilute nitric acid (1 vol. of nitric acid of sp. gr. 1.42, and 1 i vols. of water), and if the mixture is heated on the water-bath for about 60 hours, homocamphoronic acid, sometimes amounting to more than 60 per cent.of the bromocampholid used, may be readily obtained. I n this case also, the resulting homo- camphoronic acid seems to be practically pure, and only very small quantities of any secondary products are present, A miuute quantity of an acid which did not yield an anhydride when heated at 180' was observed, but the amount was less than 1 per cent. of that of the homocamphoronic acid obtained. Constitution of Brollzoca~~t~~AoreiLiC Acid. Sufficient is now known of the properties of bromocamphorenic acid and its derivatives to warrant a discussion of the probable structural formula of this substance. It has been shown by Forster that the acid is unsaturated and that it contains one closed chain (Zoc.cit.). It is practically certain, moreover, that the grouping *CH:CBr* forms a portion of the closed cliain, as the substance, when treated with ice- cold permanganate, rapidly loses bromine, and is subsequently con- verted into hornocamphoronic acid, an open-chain tricarboxylic acid. This view represents the oxidation as resulting iu the conversion of an acid COOH. C H <EB1' into UOOH*CiH1,<COOH, 'OH and the fact l3 CH that bromine is a t once eliminated receives explanation in the circum- stance that the glycol produced as the first step in the oxidation would contain the radicle >CBr*OI-I, from which hydrogen bromide would be split off immediately with formation of the >CO group. This also supplies a simple explanation of the fact, among others, that a-mono- bromocampholid, when hydrolysed, yields an acid having the formula C,oH160, (Forster, Zoc.cit.). It was at one time thought possible that homocamphoronic acid might be formed from an intermediate &ketonic acid by hydrolysis, but a number of important considerations ha.ve led to the rejection of this view. Of the formulze containing the radicle *CH:CBr*, which can be devised to represent bromocamphorenic acid, in view of its simple relationship to homocamphoronic acid, only two, ;cI! Br YNe, f/'H QMe*COOH GH ?file* COOH, CH2*CH, CBr*CH, I. 11. $XI2* ?Ale,HYDROLYTIC AGENTS ON a-DIBROMOCAMPHOR. 1189 correspond ih ahy simple way with any possible formula for a-dibromo- camphor. These, moreover, are the only expressions containing in addition the group :CNe*COOH, which is almost certainly present in bromocamphorenic acid for the following reasons, It is now scarcely open to question that camphoric acid contains the CMe complex : C<c- d>CXe*COOH present in camphononic acid, and .... consequently there are only three expressions possible for that sub- stance, namely, the Bredt, Perkin, and Porkin-Bouvesult formulae. No matter which of these be the correct one, it must be supposed that :C-CH-CH, camphor contains the group f I , in which the trsnsposi- :C-CNe CO tion of the *CH,* and *COO groups is not possible (compare Noyes, Ber., 1899, 32, 3289 and 2290). a-Dibromocamphor must therefore contain the group i I (compare Lowry, Trans., 1898, '73, 569, 1001).I n its transformation into brouiocamphorenic acid, it is at least certain that the *CO* group is converted into *COOH, and from what has been said i t must be clear that separation of the .CO* and *CBr,* groups has occurred. Although soine curious alter- ation in the structure of the molecule occurs, consisting evidently of the absorption into a ring of the carbon t o which the bromine atoms are attached, it is altogether unnecessary t o iimgine that the change has extended to the group :Cl\le*CC), which, i t is worthy of note, is present in hoinocamphoronic acid. We have now to choose between the formulle I and 11, and there can be little doubt which of thehe is to be preferred. The latter represents a y6-unsaturated acid, atlid in all probability an acid of this formula would be readily converted into the correspondiiig @y- or ap-acid, whilst such an occurrence is impossible with an acid represented by formula I.There are, inorever, a large number of facts which, taken together, speak in favour of formula I as against formula 11. Thus in the expressions for a-inonobromocampholid and for camphononic acid derived from formula, 11, namely : : C-UH-CBr, :C-CMe*C'O C Me2 CM e-C 0 I I UH, AH2 I and I I (a) CH,-CBr-O CH,-CO ( a ) (a) C&le,* CMe*COOH I (3 there is apparently no reason why oxidation should not take place at the points marked ( b ) as well as at those marked (a), whereas in fact only one product in each case can be isoltiteci.1140 ACTION OF HYDROLYTIC AGENTS ON a-DIBROMOCAMPHOR. All these difficulties disappear when formula I is used, and this expression explains in a most satisfactory manner all the facts bearing on the qriestion whieh have been observed by Forster and by the author.It is difficult t o understand the change which a-dibromocamphor undergoes in its conversion into bromocamphorenic acid, but it does not become easier if any of the other possible formulz for the latter substance be employed. The enlargement of a ring of car- bon atoms by the inclusion of a carbon atom hitherto outside the ring is by no means a n unknown phenomenon, and an assumption very similar to the one employed here, has been recently put forward by Wagner and Brickner t o explain the conversion of pinene into derivatives of camphene (Ber., 1890,32, 2323). ' It is worthy of remark that the formula above suggested as the most suitable for bromocamphorenic acid bears t o Ereclt's formula for dibromocamphor a relationship which could not, in the circumstances, be more simple. This relationship, as well as that connecting a number of important compounds the properties OC which have neces- sarily been cousidered in eliminating the improbable formuh, is exhibited in the following scheme : 1 1 /' 1 , CH,-CMe-COOII CH,*CRIe*COOH , I 1 p e 2 1 1p~e2 CH2*c!00H COOH UOOH COOH i~oiiiocaiiiphoroiiic Caiiigliorouic acid. ncid.FORSrER : CAMPHOROXIME. PART 111. 1141 It is hoped that the investigation, which is still being carried on, may elicit further evidence bearing on the question discussed in the paper. Much of the expense incurred during the work has been defrayed by a grant from the Research Fund of the Chemical Society, and for this help the author desires to express his indebtedness. CI1EMICAL DEPAI~TMENT, SCIIOOL OF PIIAliMACY, 17, BLOOMSBU~~Y SCJUARE, V. C.