CAMPHOR. III. OPTICAL INVERSION OF CAMPHOR. 1469 CXLIV.-Studies of the Teq-penes and Allied Compounds. The Xulphonation of Camphor. 111. The Optical Inversion of Ccmnphor und the Mechanism of Betem- and Meso- sulphoiaation, of Homo- and Hetero-brornanation, and of Dehydration. By HENRY E. ARMSTRONG and MARTIN T. LOWRY. THE formation of isocamphoronic acid, CH,X*CH(CMe,X)*CH,X (X = C02H), on oxidising P-bromocamphor, would appear t o be almost conclusive proof that the bromine atom is not present in a methyl group; consequently, of the two formulae which, as Forster has pointed out (this vol., 267), account for the conversion of P-bromo- camphor into campholenic acid by the action of alcoholic potash, that which he preferred is to be regarded as highly probable, namely : CH,-YH-CH, CHBr-CMe-CO I p 2 1 .It is improbable that both of the c 6 pentaphane ’ I rings (Armstrong, Proc., 1890, 6, 227) in P-bromocamphor would be broken if the bromine were present in a methyl group-especially in view of the results obtained by Kipping on oxidising the rr-derivative. Until proof to the contrary be given, it may therefore be assumed that, of the three series of derivatives of camphor now known : the a- or homo-ketonic series is that in which hydrogen is displaced in the methylene group next the CO group ; the p- or hetero-ketonic series, that in which hydrogen is displaced in the methylene group next the ‘‘ mono-methylated ” carbon atom ; and the X-or meso-series, that in which hydrogen is displaced in one of the median methyl groups. There can be little doubt that the Reychler sulphonic acid belongs to the p- or hetero-ketonic series; were it an a-compound, it can scarcely be doubted that i t would yield some camphoric acid on oxidation.The manner in which the p- and rr-derivatives are formed merits special consideration. As we have previously remarked, the ketonic group is probably in all cases the “centre of attraction,” the point of departure of all changes. The formation of the homo-ketonic a-derivatives-alpha-1470 ARMSTRONG AND LOWRY : SULPHOKATION OF brornination, for example-may be pictured as taking place in the following manner : I n discussing the conversion of aa'-dibromocamphor into up-dibromo- camphor, and similar changes, under the influence of hydrogen bromide (Swarts), it is important to take into account the evidence recently brought forward by Forster favouring the conclusion that the carbon atoms in camphor are so situated that a trimethylene ring or triphane is easily formed by the union of the two carbon atoms on either side of the monornethylated carbon atom in camphor.The introduction of the bromine into the P-position, in fact, may be pictured as involving the following changes in the CH*CHMe*CO group: CH,*CMe*C(OH)Br -+ CMe< ?*OH CH CMe<X(?" + Br, -+ CHBr*CMe-CO + HBr. A similar explanation may be given of the formation of the P-sulphonic acid, The sulphonatiug agent is apparently a n acetyl- sulphuric acid whicb on combining with the ketonic group mould give rise to a compound containing the group CH,*CMe C( OAc)( 0 *SO,H), convertible by loss of sulphuric acid into the triphane derivative: By a reversible process, the latter might pass over into the &acid, becoming first CH(SO,H)*CMe*C(OAc), and then CH(SO,H)*CMe*CO.I n undergoing conversion into up-dibromocamphor, aa'-dibromo- camphor must obviously be reduced by the hydrogen bromide a t some stage in the process and tbe CBr, group converted into the CHBr group of a-bromocamphor ; the change may be pictured as taking place in the following manner : Y B r 2 + ~ ~ r --3 CBr, I YEr2 +H -+ yBrH+Br,+HEr. co C(0H)Br C(0H)Br Br co Whether this change occurs initally or whether-and to what extent-tribromination precedes reduction is open to question, but the latter is perhaps the more probable, inasmuch as camphor cannot be directly tribrominated in any complete manner although tribromo- camphor is readily formed as a bye-product on oxidising up-dibromo-CAMPHOR.III. OPTICAL INVERSION OF CAMPHOR. 1471 camphor with nitric acid, and a-chlorocamphor is convertible into a mixture of stereoisomeric pact'-chlorodibromocamphors. The process of rr-sulphonation must involve the opening of one of the rings a t an early stage. I f the rupture occur between the two methylated carbon atoms, everything is accounted for-including the optical inversion to which Kipping and Pope have directed attention as being so remarkable, and which, it is to be remembered, also takes place to a slight extent when bromocamphor is sulphonated (Kipping, Trans,, 1901, 79, 370). That such a rupture actually takes place, under certain conditions, follows necessarily from Bredt's proof (Annalen, 1901, 314, 369) that one of the products of the action of sulphuric acid on camphor is carvenone, which he regards as formed from dihydrocarvone : YHMe, Mey:CH, YH,mC--I-YH YH,*CH-$?H, CH,*CHMe* CO CH,*CHMe*CO Carvenone.Dihy drocarvone. The production of the latter compound is proof, not only that the ring is broken, but also that one of the methyls is attacked. This might well happen if, in the first instance, the ketonic group were t o combine with sulphuric acid, and then, by a reversal of the process, acid were to separate in such a manner that a n atom of hydrogen would be withdrawn from the contiguous methyl group, giving rise momentarily to a compound containing the group represented by the formula : 1 I CH;C*CH2 6H, I'U I .CRle-b*OH u Owing to the presence of two unsaturated carbon atoms, the molecule thus produced would be subjected to strains in two directions, both of which would tend-as shown by the arrows-to weaken the hold upon each other of the two methylated carbon atoms, and there- fore might well cause their separation, directly giving rise t o the dihydrocarvone postulated by Bredt. By combination with sulphuric acid, a compound might then be formed which, on being deprived of the elements of a molecule of water, would, by a reversal of the process, give rise t o camphorsulphonic acid. The process may be represented by the following scheme : H,C-YH--CH, Mey:CH, H,C'-CMe -CO CH,-CHMe-CO I MeQMe I 2 FH,-CH---~H, -+ f-1472 ARMSTRONG AND LOWRY : SULPHONATION OF CH2 PH Me$WH2*S0,H -+ H,C-CH-- I vH2* CH-YH, f- I MeF*CH2*S03H 1 .C.H,*CHMe* CO H,C-CMe-CO But an acid thus produced mould be optically active like camphor. To account for the racemisation, i t is necessary to postulate the occurrence of changes affecting both the asymmetric carbon atoms in camphor. The asymmetry of the carbon atom next the ketonic group might readily be reversed in sign by I‘ enolisation,” owing t o the presence of the hydrogen introduced in breaking the ring; but the “reversed ” compound could not take part in the re-formation of camphorsulphonic acid. On this account, and because the product of sulphonation is mainly racemic, i t is necessary t o suppose that a further change takes place involving the reversal of the asymmetry of the second carbon atom. This may be accounted for by supposing that, under the influence of the acid, dihydroeucarvone-or, more probably, the isodynamic dihydro- eucarvenol-is produced, and that equilibrium is established, not only between this compound and dihydrocarvone, but also with camphor, as shown in the following scheme : Camphor d - t 1.-+ f- - I @H /\ H27 QH2 H2C co \/ @HMe Me\/M6 y-0 SO,H Me\/Me c I1 C /\ 3 3 2 7 7H2 \/ H,C C*OH CiUe - ( d f I.) (d + I.) (Inactive.) Both the forms of dihydrocarvone required to give the two forms of camphor would then be present. I n justification of this argument, Butlerow’s experiments (Annulen, 1877, 189, 44) on the oxidation of isodibutylene may be quoted, in which i t was shown that under the influence of sulphuric acid i80- dibutylene is converted into an isomeride, an equilibrium being estab- lished between the two compounds, so that products of oxidation are obtained which are derived, not, merely from the hydrocarbon taken, but also from an isomeride.And not only was this the case, but evidence was also obtained of the presence of two alcohols in equilibrium with the hydrocarbons :CAMPHOR. III OPTICAL INVEBSION OF CAMPHOR. 1473 CH,\,CH, CH,\/CH, --+ ?*OH --+ g YH f- I .f- 3\/ 7% CH CH,*OH CH,. QH f- 7% -+ QH2 C Jle, CMe, CMe, CMe, Leading, as it does, to a highly racemised product, the sulphonation of camphor must therefore be regarded as a process involving a com- plex series of changes in which equilibrium is established between no less than three isomeric ketones, and the proportion of dihydroeucar- vone present must be the determining factor in regulating the extent to which racemisation takes place.It is of interest to note to how great an extent the presence of bromine in the a-position deter- mines the equilibrium in one direction, so that scarcely any racemisa- tion is effected when bromocamphor is sulphonated. The formation of acetyl-o-xylene (together with carvenone) by the action of sulphuric acid on camphor (Armstrong and Kipping) may almost be regarded as proof that the rupture of the median ring is accomplished through the intervention of the ketonic group. Whilst we did not think i t necessary t o postulate the formation of a direct linkage between the ketonic: carbon and a median methyl, such a linkage must evidently arise if the transference of a methyl group from the one position to the other is to be explained.The following scheme may serve in a measure to indicate the course of change : VOMe H2C!-CB-CEJ2 H,C-CH-OH, CH 1 I Mel*OH I H2Q /'\ 5!H2 H,C CMe(0H) H,C'-CMe-C*OH H,C-Chle-UMe(OH) \ / It is well known that by the action of '' dehydrating " agents on camphor, a variety of benzenes are formed (compare Armstrong and Miller, Ber., 1883,16,2255), and that when care ia taken to carry outthe decomposition at as low a temperature as possible, the products appear to be practically all C,, derivatives-of which four are formed: cymene, metacymene, 1 : 2 : 4-dimethylethylbenzene, and 1 : 2 : 3 : 5- tetramethjlbenzene ; higher and lower benzenes are only formed when the conditions are such as to favour the occurrence of secondary changes.It is therefore probable that the transference of methyl groups involved in the production of several of the hydrocarbons may be conditioned by reversible intramoEecuZar changes such as are con- templated above, rather than by a succession of analytic and synthetic operations of the type determined by aluminium chloride, f o r example, VOL. LXXXI. 5 G1474 SULPHONATION OF CAMPHOR. 111. The production of mstacymene by means of phosphorus pentasul- phide and of zinc chloride may be accounted for if it be supposed that a triphane ring is first formed by the interaction of the ketonic group and the (ortho) methyl group attached to the contiguous carbon atom ; and that this ring is subsequently broken in such a manner that methyl becomes attached to the carbon atom of the ketonic group, meta t o the propyl group formed by scission of the linkage across the hexa- phane system.This argument is equally applicable in explanation of the oxidation OF the ortho-methyl group which is involved in the formation of ketopiaic acid from chlorocamphane (turpentine hydri- chloride), and of camphoic acid from camphene. To explain the formation of tetramethylbenzene, one of the chief products of the action of iodine, and which is also formed by the action of k n c chloride and of phosphorus pentasulphide on camphor, it is necessary to suppose that both the meso-methyls may be brought into connection with the hexaphane system.Assuming that one of the methyls were tranbferred t o the ‘ I keto- position ” in the manner shown above, in discussing the formation of acetyl-o-xylene, a compound would be formed from which the ele- ments of a molecule of water might be withdrawn in two ways : either in such a way as to give rise to the formation of the group CH,:C from the median *C*OH group, or in such a way as to involve the coupling of the ketonic group with the P-carbon atom. If, in either case, the change were to be reversed, hgdroxy-compounds would be formed (either T‘ or p), which would give rise, if deprived of the elements of water, t o a (r’P)-tetr.aphane derivative, corresponding t o the pp-corn- pound formulated on page 1473. If the tetraphane ring thus formed were subsequently broken, so as t o Sever the connection between the median carbon atom of camphor and that which had previously been associated with it in the form of methyl, the methyl group would be transferred t o the P-position ; three methyl groups would then bo con- The production of benzenes from camphor in the manner contem- plated involves the withdrawal of hydrogen at some stage in the pro- cess ; it is unnecessary to discuss the manner in which this may take place, but it may be pointed out that, however carefully the operation be conducted, a large proportion of resinous matter is always formed, and it may be that the withdrawal of hydrogen is in some way con- nected with the formation of this; it is noteworthy that even zinc chloride gives rise to the production of a not inconsiderable amount of the saturated hydrocarbon, C,,H,,.Lastly, it is of interest to note, as a further illustration of the influ- ence of bromine as a depressant of activity, that bromocamphor does tiguous.ACTION OF NITRIC ACID ON BROMOPHENOLIC COMPOUNDS. 1475 not give rise to hydrocarbons under the influence of dehydrating agents. We are inciined to think that the views advanced in this communi- cation may be of some value in arriving at the synthesis of camphor and that the recognition of reversible changes as playing a part in the formation of camphor and terpene derivatives generally may be of importance. CHEMICAL DEPARTMENT, CITY AND GUILDS OF LONDON INSTITUTE, CENTRAL TECHNICAL COLLEGE.