CAMPHORSULPHONIC ACID (REYCHLER). 1441 CXLI1.-Studies of the Terpenes and Allied Compounds. The Sulphonation of Cumphor. I. Camphor- sulphonic Acid (Reychler): the Formation of An- h ydramides. By HENRY E. ARMSTRONG and T. MARTIN LOWRY. ALTHOUGH in determining the structure of camphor to be that repre- sented by the formula chosen, with remarkable felicity, 6y Bredt, in 1893, chemists have decided an issue which had long engaged attention, the problems offered by camphor and allied compounds are still many and intricate. No substance known t o us suffers rearrangement of its parts and undergoes a complete change of type more readily than does camphor-for example, under the influence of dehydrating agents. Such changes appear the more remarkable when it is remembered that it is but a mono-ketone derived from a ‘ phane ’ or saturated cycloid hydro- carbon : indeed, no better illustration can be given than that which camphor affords of the extraordinary effect exercised by oxygen in promoting change. There can be little doubt that the ketonic group is the centre from which the primary influence proceeds in all cases.But great as is the advance in our knowledge, the ‘‘ mechanism ” of many of the changes involved in the passage from camphor to com- pounds of other types is still far from being understood, and we are1442 ARMSTRONQ AND rAowRty : SOLPHONATION OF without any clue as to the manner in which it is formed, and as to the part which camphor and compounds such as the terpenes play in nature : in this connection, the fact that camphor is so rarely met with whilst terpenes are of universal occurrence is in itself remarkable.The problems which the substitution derivatives of camphor offer are in some respects peculiar. Usually the hydrogen atoms of the CH, group contiguous with the CO group are first affected ; in fact., nearly all the known substitution derivatives are of this type. It is only on sulphonation that camphor behaves “ abnormally,” the sulphonic group entering one of the median methyl groups in the so-called Ir-position; and not only is the action abnormal in respect of the position occupied by the sulphonic group, but it also involves the ‘‘ optical inversion” of the camphor. It is therefore obvious that the sul- phonation either involves, or is attendant on, changes in the molecular structure of the camphor other than those which ordinarily accompany the process.On this account, the further study of the action of sul- phuric acid on camphor became desirable ; the discovery made by Reychler in 1898 (BUZZ. SOC. Chim., [iii], 19, 120) that camphor can be easily sulphonated in another manner, and without undergoing inversion, accentuated the importance of extending the inquiry. Reychler’s method consists in merely adding camphor (3 parts) to a mixture of acetic anhydride (4 parts) with ordinary concentrated sulphuric acid (2 parts) ; the sulphonic acid gradually crystallises out a t the ordinary temperature, the greater part separating within two or three days. The extreme ease with which the camphor is sulphonated is altogether remarkable, but the most noteworthy circumstance in connection with the acid is that whereas only a single series of salts and a single sulphochloride were obtained by Reychler, he described two distinct compounds formed by the action of ammonia on the sulpho- chloride-the one melting at 223’ and the other a t 132’.These he regarded as camphorsulphonamides of the formula C,oH,,O(SO,*NH,), and the analytical results which he quoted are in accordance with this conclusion. As determinations of molecular weight made by the boil- ing point method-with the object of ascertaining whether perhaps the two compounds were not polymerides-gave similar values ap- proximating to the formula C,oH,70,NS, we were content at first to accept Reychler’s view, especially as on substituting piperidine for ammonia we obtained two undoubtedly isomeric piperidides of normal composition’. It appeared to be not improbable, in fact, that the crude sulphonic acid was a mixture of stereoisomeridea, and that Reychler had succeeded in separating the isomerides only in the case of the amides (compare Lowry, Trans., 1898,’73, 569, 986).But we were obliged to abandon this explanation on finding that the properties of the sulpho- chloride were unaffected by recrystallising it repeatedly. Ultimately,CAMPHOR. I. CAMPHORSULPHONIC ACID (REPCHLER). 1443 observations were made which led to the discovery that either of the compounds could be obtained at will. It was found that by making use of a dilute solution of ammonia, only the compound of higher melting point-which is apparently the normal product -was formed ; whereas if a concentrated solution of ammonia were used and the interaction allowed t o proceed unchecked, the compound of lower melt- ing point was obtained, but in admixture with a greater or less propor- tion of the compound of higher melting point, Precisely similar results were obtained with the sulphobramide which we prepared from the acid.But no variation in the proportion in which the two piper- idides were produced was noticed on varying the conditiuns of inter- action ; and in conformity with Reycbler’s statement, we could obtain only a single anilide. As the compounds formed by the action of ammonia answered to the descriptions given by Reychler, i t did not seem necessary to analyse them.Bearing in mind the ease with which the sulphonation is effected, it was not unnatural to suppose that the camphor had undergone sul- phonation in the a-position, and that we were dealing with stereoiso- meric a- and a’-sulphonamides, the formation of which from a single acid could be accounted for on the assumption that the ketonic group took part in the interaction. This view received support from the observation made at an early stage of the inquiry that the supposed amide of lower melt- ing point was converted into that of higher melting point by merely warming it either with a mineral acid or with bromine-the very agents which are most frequently active in bringing about stereo- isomeric change. We therefore continued to accept Reychler’s con- clusion that the two compounds were isomeric, and referred to the compounds as stereoisomerides in our preliminary communication (Proc., 1901, 17, 182).On applying Reychler’s method to a-chloro- and a-bromo-camphor, i t was found that although these were sulphonated somewhat less readiIy than camphor, they gave rise to acids isomeric with those described by Kipping and Pope ; these were obviously derivatives of the Reychler acid, as they could be converted into derivatives of this acid by reduction. Each of the acids gave but a single sulphonamide. Whereas, however, the bromosulphonamide gave on reduction the labile camphorsulphon- amide (m. p. 132’), the chlorosulphonamide-which was much less readily reduced-gave the stable compound melting at 223’. On attempting to prepare the bromo-acid by the reversed method from camphorsulphonamide and bromine, two brominated compounds were obtained, the one melting at 166’, the other a t 186’.Neither OF these was identical with the amide prepared directly from bromo- camphorsulphonic acid, but as both, on reduction, gave the supposed ‘‘ camphorsulphonamide ” melting at 2234 they were obviously related1444 ARMSTRONG AND LOWRP: SULPHONATION OF to it in some simple way. Eventually they were found to be anhydr- ides formed by the withdrawal of the elements of a single molecule of water from the bromosulphonamide. The one melting at 186' was readily obtained from the a-bromocamphorsulphonamide by merely boiling this with acetic anhydride, whilst both were formed on digest- ing the amide with bromhydric acid.Bearing in mind the manner in which they are prepared and their behaviour on reduction, it is probable that the anhydride melting at 186' is directly derived from dibromo- camphorsulphonamide, whilst that melting at 166' is the stereoisomeric a'-bromo-compound. As the two compounds described by Reychler as camphorsulphon- amides were both found to be unaffected by acetic anhydride, our belief in the existence of two isomeric amides derived from the acid remained for some time undisturbed, especially as we had been able to prepare two undoubtedly isomeric piperidides. The formation from camphor- sulphonic acid of two isomeric SuIphonamides could not well be explained unless they were regarded as stereoisomeric a- and a'-compounds, but as the investigation proceeded, we were impressed by the difficulty of ob- taining direct proof that the Reychler acid was in reality an a-derivative of camphor, particularly after we had discovered that its sulphobromide was converted into P-bromocamphor and sulphur dioxide when decom- posed by heat.Eventually we were led to take the step of controlling the statements put forward by Reychler. It was then discovered that whilst the compound melting at 132' had the composition of camphor- sulphonamide, the supposed amide melting at 223O was not an isomeric substance but the anhydride of which we had previously obtained stereoisomeric bromo-derivatives ; and that although it could not be obtained by means of acetic anhydride, it was readily prepared by heating the sulphonamide above its molting point.Whilst i t affords proof that Reychler's acid is a single substance, the evidence thus far adduced throws no light on the nature of the acid, and is compatible with the view that it is an a-derivative: in other words, that sulphuric acid behaves, under certain conditions, in what may be said to be a normal manner towards camphor. The sulphonatiori is effected with remarkable readiness, almost more readily than bromination, and it might therefore be anticipated that the action would proceed in the same manner in the two cases. But as no trace of camphoric acid is formed on oxidising Reychler's acid with nitric acid, it is difficult to believe that the acid can be an a-derivative. It may be mentioned here, as an indication that the in- troduction of the S0,H group increases the stability of the molecule, that a-bromocamphorsulphonic acid is only very slowly oxidised when boiled with nitric acid-even in presence of silver nitrate.Passing to the positive evidence as to the nature of the acid, atCAMPHOR. I. CAMPHORSULPHONIC ACID (REYCHLER). l4+5 present we have but one fact, namely, that P-bromocamphor is readily obtained by decomposing its sulphobromide. Hitherto, it has always been found that the chloro- and bromo-compounds prepared by decom- posing sulpho-chlorides and -bromides contain the halogen in the posi- tion originally occupied by the sulphonic group, even in the cases in which the sulphonic acid is capable of undergoing isomeric change. There would be no reason to doubt this in the case of camphor were it not that the /I-bromo-derivatives have been prepared by a process of isomeric change from the a-derivatives, and it would therefore not be surprising if a similar transfer were to take place under thesomewhat drastic conditions involved in the formation of a simple bromo-deriva- tive by the decomposition of a sulphobromide.Evidence that the two a-positions are free in Reychler’s acid is afforded, however, by the fact that what appear to be isomorphous mixtures of chlorobromosulphonamides are obtained by the action of bromine on a-chlorocamphorsulphonamide, and of chlorine on the a-bromamide, whilst the a-bromo-compound appears to give only a single substance when brominated, and the a-chloro-compound but a single dichloro-derivative.But this evidence is of a much less striking character than that obtained in the case of the chlorobromocamphors (Lowry, Trans., 1898, 73, 569), and cannot be regarded as affording any conclusive proof of the position of the sulphonic group. A second argument to the same effect is afforded by the fact that P-bromocamphor cannot be sulphonated to any appreciable extent under conditions which determine the sulphonation of a-bromocamphor, which is especially remarkable when it is borne in mind how easily camphor is sulphonated and that a-bromocamphor is sulphonated with- out difficulty; there is no reason to suppose that a bromine atom in the P-position would exercise so complete a n inhibiting influence as to prevent all action if the a-position be that attacked on sulphonation.In further support of this argument, it may be pointed out that whilst a-bromocamphor is not attacked by hydroxylamine, a hydroxime is ob- tained without difficulty, not only from p-bromocamphor (Forster), but also from camphorsulphonic acid. Assuming the foregoing arguments to be sound, the only conclusion we can draw is that the Reychler acid is a /I-derivative of camphor, The anhydrosulphonamides,” to which reference has frequently been made, are compounds of considerable interest if the lesson which their formadion conveys b3 considered. I n ordinary cases, the sulphon- amide is formed directly from the sulphochIoride, and there is no extraneous group which can come into play, but in camphor the CO group must also be considered. If it be supposed that, instead oE the interaction taking place ‘‘ normally ’’ between ammonia and the S0,Cl group, the CO group is affected and unites with the ammonia,1446 ARMSTROKG AND LOWRY : SULPHONATION OF and that subsequently hydrogen chloride and water are eliminated, a closed chain would be formed in the following manner : *?*OH --f *?*OH + 4 .*SO,CI NH, *SO,*NH *SO,*N The tendency of the ammonia to combine with the ketonic group would be less, it may be supposed, the higher the temperature, and the S0,Cl group would therefore exercise the superior attraotion at higher temperatures. I n point of fact, the amide is only formed from camphorsulpho-chloride and -bromide when the action is allowed to proceed uncontrolled ; the more carefully the operation is conducted, the greater is the amount of anhydro-compound formed ; and this may easily be made the sole product, but the amide is never obtainedalane.This argument finds further support in the fact that the bromo- and chloro-sulphochlorides yield only the amide. It may be supposed that the introduction of the halogen leads to a considerable reduction of the attractive power of the ketonic group ; and it may be noted incident- ally that the non-formation of a hydroxime from a-bromocamphor affords direct evidence that the a-halogen atom does exercise such an inhibiting influence. An explanation of the action of acids, which are far more active as ‘I dehydrating agents ” than even acetic anhydride, is easily given on the assumption that the first product is an additive compound, thus : I n a similar manner, when acetic anhydride is used as dehydrating agent, the action may be supposed to involve the formation of an intermediate additive compound of the acetal type.It remains only to refer to the two camphorsulphopiperidides. It does not seem probable that these are stereoisomerides, as all attempts to convert them into one another by the action of mineral acids have been unsuccessful. I t appears to us that their formation is most satis- factorily explained by assuming that a series of changes takes place similar to that involved in the formation of the anhydramides. The piperidide melting at 140°, which can also be prepared by reducing a-bromocamphorsulphopiperidide, is probably a piperidide of the normal type, C,,H,,O*SO,*NC,H,,, formed in the normal manner.The forma- tion of an isomeride may be accounted for on the assumption that an additive compound of ths aldehyde-ammonia type is formed, which is converted into a sulpholactone by the subsequent elimination of hydrogen chloride ; thus :CAMPHOR. I. CAMPHORSULPHONIC ACID (REYCHLER). 1447 A t present, however, no proof of the correctness of such an explan- ation can be given. CamphorsuZphonic Acid (Reychler). In preparing the acid, either ordinary concentrated sulphuric acid or the monohydrate may be used; but acid containing 10 per cent. of sulphuric anhydride gives less satisfactory results than the weaker acid. For most purposes, it is sufficient to allow the liquid to drain away from the crystalline magma and then to wash the crystals with acetic acid until they are nearly free from colour ; but the acid can be further purified by recrystallising i t either from acetic acid or from ethyl acetate; it separates from the latter solvent in large, trans- parent prisms.Our observations serve to confirm Reychler's state- ments as to the physical properties of the acid. CamphorsuZphochZoride.--TnTe have found that the melting point and rotatory power of this compound are not altered by repeatedly recrys- tallising it from ether, chloroform, and light petroleum ; nor were they different when the acid used in preparing i t was recrystallised four times alternately from acetic acid and ethyl acetate. Constants.-[ u?: + 31 -1' (Solv. - chloroform ; c - 10 grams per CarnphwsuZpho6romide (n. sp.").-In preparing this, it is necessary to work with moderately small quantities, t o use a slight excess of the potassium salt rather than of the pentabromide, to leave the liquid pro- duct until firm and solid, and to avoid all local heating when the product is ultimately ground up with crushed ice; if these precautions be not observed, and especially if excess of pentabromide be used, the yield is very small and the product impure.The sulphobromide can be purified by recrystallising it from dry ether, from which it separates in large, four-sided tablets. I n working with large quantities, the wet substance may be dissolved in chloroform, and the solution having been dried by means of calcium chloride, the sulphobromide is pre- cipitated by adding light petroleum after distilling off as much as possible of the chloroform.Constants.-M. p. 9 3 O [ u]F + 26.0' (Solv. - chloroform ; c - 10 grams per 100 c.c.). * These letters are affixed so as to indicate the new compounds deecribed in the paper. All the compounds which are described were analysed : the results which were obtained are expressed by the formuls which are given. As the substances are all well defined, and are related t o each other in a very simple manner, no question can arise as to the interpretation which should be given to the results, and the numbers are of no independent value: to aave space, therefore, the analytical values are omitted.-[H. E. A.] 100 C.C.).1448 ARMSTRONG AND LOWRY : SULPHONATION OF Carnphorsulphoncide, C,,,H,,O*SO,-NH,, is only formed by the interaction of the siilphochloride and ammonia when a concentrated solution of the latter is used and the action is allowed to proceed violently; even then, the amide is always mixed with more or less of the anhydramide described below, from which it is distinguished by its moderate solubility in hot water.To separate the two compounds, the crude product is boiled with a little water ; the undissolved part is almost pure anhydramide, but the substance which separates from the aqueous solution as it cools is still impure and must be recrystallised at least twice. The amide is also produced when a-bromocamphorsulphonamide is reduced with zinc dust and acetic acid. Constants.-M. p. 132' (Reychler, 127'). [a]'D7" + 1 - 5 O (Solv. - chloroform, c - 10 grams per 100 c.c.).The b. p. of 7.099 grams of benzene was raised 0.158' by 0.1145 gram, 0.406' by 0.3795 gram, 0.588' by 0.6975 gram :. Mol. wt. 272, 352, 446; calc. 232. Ca~~~ol.su~~Lonunh~dramide, CloH,,NSO,, is the sole product of the interaction of ammonia and the sulphochloride when a dilute solution of ammonia is used, even when the mixture is heated in the water- bath. It crystallises well from a large bulk of boiling alcohol. The conversion of camphorsulphonamide into this compound takes place under somewhat remarkable conditions, being readily determined by acids, whilst ordinary dehydrating agents are relatively ineffective. When the amide is merely covered with concentrated chlorhydric, bromhydric, or sulphuric acid, it soon dissolves, but the anhydramide separates from the solution in the course of a few minutes; it is of interest, as an indication of the strength of the acid, that the conver- sion of the amide into the anhydramide may be brought about in the course of a few minutes by boiling it with a concentrated solution of camphorsulphonic acid.Camphorsulphonamide crystallises unchanged from acetic anhydride. If it be heated above its melting point, gas (water vapour) is given off at about 170', and the liquid solidifies at about 200' and again becomes liquid when the melting point of the anhydramide is reached. Constants.-M. p. 223' (Reychler 220'). [a]F - 33.5' (Solv. - chloroform ; c - 5 grams per 100 C.C. The b. p. of 7.130 grams of benzene was raised 0.543'by 0.324 gram, that oE 6.958 grams 0.560' by 0.4650 gram, and that of 7.130 grams 0.760° by 0.7070 gram :.Mol. wt = 265, 280, 348 ; calc. 214. Camp~orsul23honucnilide, C,oH,,O-SO,*NHPh.-Reychler's observa- tion that only one anilide is produced by the interaction of aniline andCAMPHOR. I. CAMPHORSULPHONIC AClD (REYCHI'ER). 14 49 camphorsulphochloride is confirmed by our experiments. substance is obtained on reducing a-bromocamphorsulphonanilide. Constants.-M. p. 1 1 9 O . [ a ] r + 67.3O (Solv. - chloroform, c - 10 grams per 100 c.c.). Cccmphorsulphon-p-bromccnilide (n. sp.).-This compound may be pre- pared either by brominating the anilide just referred to, or from p-bromaniline. It is only slightly soluble in spirit, from which it crys- tallises in flat needles, but somewhat more soluble in acetic acid.Constants.-M. p. 167'. [ a]1;' + 56.4' (Solv. - chloroform ; c - 10 grams per 100 c.c.). Camphorsulpho~iperid~d~$.--Of the two isomeric piperidides formed by the interaction of piperidine and camphorsulphochloride, the more soluble is produced only in small quantities, and we have not succeeded in altering the conditions so as t o effect any noticeable alteration in the proportions in which the two substances are formed. The less soluble-which is the principal product-can also be prepared by reducing a-bromocamphorsulphopiperidide, and on this account is prob- ably the normal piperidide, C,,H,,O~SO,-NC,H,,. As the tmo piper- idides do not undergo change into each other when digested with con- centrated chlorhydric acid, they cannot well be stereoisomerides.Carnphorsulphopiperidide ('2) (n. sp.).-Constants.-M. p. 140'. [ a ] : + 32.2 (Solv. - chloroform ; c - 5 grams per 100 c.c.). The piperidide crystallises from dilute spirit in long, glistening needles. It was obtained from a solution in acetone in stout, glistening crystals which were measured with the following results : The same System.-Orthorhombic. Axial ratios.-a : b : c = 1.1 722 : 1 : 0.8978. Poorrn8 present.-a{ loo), c{OOl}, p { 1 lo], r{ 1011, p{O1 l}. The form p(O11) was observed only twice and the form ~(001) is frequently missing. Ha6it.--Stout prisms, slightly elongated along the b-ixis and often flattened parallel to a face of the form ~(101). VOL. LXXXI.1450 ARMSTRONG AND LOWRY : SULPHONATION OF Angles observed. (CT =loo : l 0 j rr =I01 : 101 re =lo1 : 001 rr = l o 1 : I01 ac =100:001 ap =loo : I10 pp =110 : 110 pq = 110 : 011 r p = l o 1 : 110 rq = l o 1 : 011 r p = l o 1 : 110 Limits.Number of observations. ___ 30 6 10 15 6 26 14 24 2 2 19 ~ ~~ 1 52'18'- 52'55' 1 105 4-105 20 1 37 13- 37 42 I 74 17- 75 9 89 50- 90 7 I 49 15- 49 50 80 40- 81 5 66 27- 67 3 ~ 59 26- 59 40 ' 115 55 -113 33 j 53"48' Mean. 52'33' 105 12 37 27 74 46 89 58 49 32 80 50 66 45 53 48 59 33 113 15 Calculated. - 105" 6' 37 27 74 54 90 0 80 56 66 45 53 48 59 27 113 15 - isoCamphorszc~hopiperidide ( 1 ) (n. sp.).-Constants.-M. p. 56'. [ a]r + 3 3 . 6 O (Solv. -chloroform ; c - 10 grams per 100 c.c.). This compound is excessively soluble in almost all solvents; it can be obtained in large, transparent crystals by allowing its solution in dilute alcohol to evaporate slowly. Brilliant crystals were obtained from light petroleum which were measured with the following results : System,- Orthorhombic.Axial rcctios.-a : b : c = 1*1080 : 1 : 0.9814. Forms present.-af100), c(OOl), p(110), ~(101). The form ~~(100) Habit.-Usually stout crystals flattened parallel to a face of the is always small and frequently absent. form ~ ( 1 1 0 ) . Number of observed* 1 I cr = O O l : lo! rr =I01 : 101 ar = l o 0 : A01 rr =lo1 :A01 i p p = 110 : 110 p p =110 : 110 cp =001: 110 p r =110 : J O l pr = 110 : 101 24 11 8 12 8 8 16 32 20 Limits. ~ 41" 2'- 41O.58' 82 47 - 83 20 47 59 - 48 52 96 48- 97 16 84 5 - 84 22 63 27- 63 52 95 42- 95 55 116 0-116 37 89 50- 90 12 Mean. 41"32' 83 0 48 26 97 0 84 10 95 50 63 38 116 20 89 59 Calculated.I 83" 4' 48 28 96 56 84 8 95 52 116 22 90 0 -CAMPHOR. I. CAMPHORSULFHONIC ACID (REYCHLER). 1451 a-~1.oniocamp?~orsuZ~~onic Acid (n. sp.). a-Bromocamphor and a-chlorocamphor are readily sulphonated by means of a mixture of acetic anhydride (4 mols.) and sulphuric acid (1 mol.). The best results have been obtained by keeping the mixture duringa day or two at, atmospheric temperature, and then heating during two hours on a water-bath. Under these conditions, 80 or 90 per cent. of the material is sulphonated, but if the heating be prolonged, a large amount of insoluble matter is produced, and it is very difficult to purify the product. When sulphonation is effected, the cold mix- ture is poured into water, the solution then filtered and boiled for several hours with animal charcoal until the greater part of the acetic acid has been volatilised, when the liquid is again filtered%d neutralised with lime.The calcium salt separates from the properly concentrated solution ; if the product be brown in colour, the colour may be partially removed by washing the salt with spirit before recrystallising it. CuZciurn a-6romocumphorsuZpAonnte, (C,oH1404SBr),Ca + 6H,O, crys- tallises from hot water in pearly scales or in flat, transparent plates; it dissolves readily in hot, but only sparingly in cold water. Potassium a-brornocamp?~orsuZp?~onucte, C,,H,,OBr *SO,K + 4H20, crys- tallises from water in transparent, efflorescent tablets, and is more soluble than the calcium salt. a-Brornocu~pl~o~suZp~oc~Zo~ide, C,,,H,,OBr*SO,CI, dissolves readily i n chloroform and ethyl acetate, but less readily in ether and benzene ; it separates from these solvents in large, transparent prisms.It is an exceedingly stable substance, which can be kept during several months without undergoing change. Constants.-M. p. 65'. [u]: + 104" (Solv. - chloroform ; c - 10 grams per 100 c.c.). a-Bromoc~rnphorsuZphobrornide.-This compound is less stable than the chloride, undergoing hydrolysis slowly when exposed t o the air. If it be heated above 130°, it decomposes into sulphur dioxide and ap-dibromocamphor (m. p. 11 5O). Constants.-M. p. 61'. [a]? + 119" (Solv. - chloroform; c - 4 grams per 100 c.c.). a-BromocclcmioirorezlZphonarnide.-This compound crystallises from hot water or spirit in needles.When reduced by means of zinc dust and acetic acid, it yields camphorsulphonamide (m. p. 132'). When boiled with acetic anhydride, it is converted into the anhydramide ; a dibromo-derivative of the anhydramide is obtained when it is sub- jected to the action of bromine. 5 ~ 21452 ARMSTRONG AND LOWRY : SULPHONATION OF Constants.--M. p. 156O. [ U]T + 106' (Solv. - acetone ; c - 5,grams a-Brornoc~~phorsulp~anilide dissolves very readily in spirit, from Constants.-M. p. 106". [a]: + 177" (Solv. -chloroform ; c - 4.2 a-Bromocam~horsu~ho~ipe~id~~e separates from spirit in prismatic Constants.-M. p. 123'. [ u]F + 1 11' (Solv. - chloroform ; c - 3 per 100 c.c.). which i t crystallises in minute, felted needles. grams per 100 c.c.). crystals. grams per 100 c.c.). On reduction, it yields the piperidide melting at 140'.a- Chlorocanap~~su123T~onic Acid (n. sp,), Calcium a-Chlorocamphorsulphonate, (C,oH,404SC11),Ca t GH,O.-This salt crystallises from hot water in pearly scales. The barium salt, which is less soluble than the calcium salt, crystal- lises from hot water in minute, white scales. The potassium salt re- sembles that of the bromo-acid. The ammonium salt, although very soluble in water, may be obtained in large, glistening, transparent plates by allowing the solution to evaporate spontaneously. a-Chlorocam~hol.sul?~ochloride separates from ether in large, trans- parent crystals, which remain unchanged on exposure to the air. Constants.-M. p. 60". [a]:'" + 80.8O (Solv. - chloroform ; c - 5 grams per 100 c.c.).a-~~~orocam~horsu~~~~o~rorn~de,--Th~s compound was but partially examined. I t decomposes, when heated, into sulphur dioxide and a chZorobromocamp?kor melting a t 9s" ([.ID + 69*7'), agreeing in its pro- perties with that obtained by crgst,allising until the melting point and rotatory power were unchanged the pa-bromocblorocamphor pre- pared by heating a-chlorocamphor with bromine in sealed tubes (Lowry, Trans., 1898, 588). a-ChEorocnmphorsu123E.onccmide crystallises from hot water or spirit in needles. On reduction, by means of zinc dust and acetic acid, i t yields camphorsulphonanhydramide (ni. p. 223'). It is converted into the chloranhydramide by acetic anhydride, and on chlorination affords the dichlori-tnhydramide. Conetants.-BL p. 141". [a]F -+ 83.2' (Sdv.- acetone ; c - 6 grams per 100 c,c.),CAMPHOR. 1. CAMPHORSULPHONIC ACID (REYCHLER). 1453 Derivatives of Cumphorsul~~honan~ydrtcmitle contnining IIdogen (n. sp. >. The anhydride of camphorsulphonamide, described on p. 14-18, is the parent member of a series of compounds of which no fewer than eight have been isolated; in the majority of cases, the sulphonamides and the sulphonic acids from which these are derived are unknown, the anhydramide being the only derivative which has been prepared. The anhydramides are invariably produced when the sulphonamides are acted on by halogens, the substitution being accompanied by loss of the elements of a molecule of water. In the cases in which stereo- isomerism is possible, two compounds are usually produced ; in other cases, but one is formed, and whilst only one compound is produced when the anhydrides are made from the sulphonamides by the action of acetic anhydride, when t h e dehydration is effected by mineral acids, a mixture of stereoisomerides may be formed. Stereoisomerides con- taining two different halogen atoms are obtained as isomorphous mixtures, but those containing a single halogen atom are not iso- morphous, and can be separated in the ordinary way by fractional cry stallisation, a-Bromocc~mphorsulphonunh?/drumide, CloH1,O,NSBr.-This compound is a very well-defined substance.It was first obtained by us by subject- ing camphorsulphonamide, dissolved in acetic acid, t o the action of bromine at about looo, and crystallising the product 15 times from spirit, acetic acid, and acetone.It was subsequently prepared by heat- i ng a-bromocamphorsulph onamid e wit h concentrated brom hyd ric acid. Theee methods usually give rise to a mixture of stereoisomerides ; t h e a-compound, however, is the sole product when a- bromocamphorsulphon- amide is heated with acetic anhydride. Jt separates from spirit and acetic acid in flat needles, and from acetone in orthorhombic prisms or tablets ; on reduction, i t yields camphorsulphonanhydramide(m. p. 2 2 3 O ) . [ u]gp + 99m30(Sol~. - acetone ; c - 5 grams per 100 c.c.).' This value is that obtained with the substance prepared by the third of the methods described above; that prepared by the first method gave [a]? + 97.8, and t h a t prepared by the second gave Constants.-M. p.186'. [ a ] F +9s*g0. The crystals were examined with the following results : System. -0rt horhom bic. Axial ratios.-a : b : c = 1.4659 : 1 : 2.1519 = 1 : 0.6821 : 1,4680. Porms p*ese.nt.-aflOO}, c(OOl}, q{O11}, r(101}, r'{ IOZ), p(1 lo}. Habit.-Usually prisms elongated along the a-axis, but sometimes tabular crystals in which the face q is largely developed, or in prisms1454 ARMSTRONG AND LOWBY: SULPHONATION OF elongated along the axis of 6. The dominant forms are c, p , and q ; the forms a and r are only occasionally observed. Angles observed. c : 'I (001) : ( O l l ) (7: q (011): (011) p : q (110) : (Oil) p: q (110) : (011) p : c (110):(001) q : T' (011) : (102) q:r'(Oll) :(l02) c : r' (001) : (102) r': r' (102) : (102) u : r' (100) : (102) T : r' (101) : (102) a : ?- (100) : (101) p : r (110 : (101) q : r (011) : (101) q : r (011) : (101) - Number I f obser- vations.24 14 2 .t 29 12 4 4 15 7 2 2 1 1 3 2 ~~ Limits. 64O49'- 65"19' 49 3 9 - 50 6 41 20- 41 36 138 24 -i38 41 89 52- 90 6 70 2 - 70 8 109 51-110 1 107 17 -107 31 53 31 -*53 46 19 27 - 1 9 40 34" 6' 62 17 36 5- 36 34 76" 8'- 76"20' 103 30 -103 47 Mean. 65" 44' 49 52 41 29 138 31 90 0 70 5 109 54 36 17 107 26 53 38 19 33 34 6 62 17 76 15 103 38 Calc. - 49'51' 138 31 90 0 70 8 109 52 36 17 107 26 53 43 19 27 34 16 62 15 76 16 103 44 - Angles of l,oH,,OCIBr, 64'53' 50 14 41 38 138 22 90 0 69 56 110 4 36 2 107 56 53 38 19 28 34 30 62 17 76 5 103 55 Optics; properties.-The plane of the optic axes is*(OlO), the axis of cc is the acute bisectrix, and the optic axial angle is large.An optic axis is seen emerging through each of the faces of the form ~'{102}. The crystals exhibit a very striking similarity t o those of &a'-di- bromochlorocamphors (Trans., 1898, '73, 585), as may be seen on com- paring the axial ratios and also the angular measurements in the last two columns of the above table. CloH,,O,NSBr, 1.4659 : 1 : 2.1519 = 1 : 016821 : 1.4680, C,oH,,C)CIBr,, 1.4661 : 1 : 2.3332 = 1 : 0.6821 : 1.4550. The resemblance is far closer than that which exists between com- pounds so closely related as aa'-dibromocamphor and aa'-bromochloro-CAMPHOR. I. CAMPHORSULPHONIC ACID (REYCHLER). 1455 camphor, and is all the more remarkable because there is no similarity of structure apparent in the compounds. The chief difference between the crystals is one of habit : the dibromochlorocamphors usually crys- tallise in prisms elongated along the b-axis, whilst the anhydramide is usually developed along the a-axis.It may also be pointed out that in these crystals the ratios a : b and c : a are almost identical, and that the c : a ratio agrees closely with that of the dichloranhydramide described on p. 1457, although the latter differs widely in the u : b ratio. C,,H,,O,NSBr, a : b = 1.4659 : 1. c : a = 1.4680 : 1. CloH,,OCIBr,, u : 6 = 1.466 1 : 1. C,,H,O,NSCI,, c : a = 1 *45 10 : 1. a'-B.).omocam~horsuZ~~onanhydrum~d~, -On one occasion, in attempt- ing t o prepare the compound just described by brominating camphorsul- phonamide, a product was obtained melting at 166O and of considerably lower rotatory power, [ a]y + 4 0 ~ 5 ~ (Solv.- acetone, c - 5 grams per 100 c.c.). A similar product was obtained by subjecting a-bromo- camphorsulphonamide to the action of bromhydric acid. The values obtained on analysing these products showed them to be identical in composition with the a-anhydramide, and there can be little doubt that i t is the stereoisomeride. Usually, when the second method is adopted, a mixture is obtained the melting point of which is near t o 166qalthough the compound melting a t 186'may be its chief constituent. The character of the product is easily ascertained by determining its rotatory power. a-Chlorocanaphorsulphonanhydramide, CloH,,O,NSC1, was first ob- tained on attempting to chlorinate chlorocamphorsulphonamide. It is readily formed on heating a-chlorocamphorsulphonamide either with acetic anhydride or with chlorhy dric acid.It crystallises from spirit or acetic acid in long, silky needles which are often several centimetres in length ; it is more soluble in acetone than the bromo-compound, and crystallises from this solvent in large, orthorhombic tablets. [ a]F + 59*5O (Solv. - acetone ; c - 5 grams per 100 c.c.) and 61.2'. The latter value is that found in the case of the substance prepared by the acid method, the former that of the product obtained on attempting to chlorinate the amide. The action of chlorine on camphorsulphonamide was not studied so fully as that of bramine, owing to the great difficulty of regulating the degree of chlorination, I n almost every case, the dichloranhydr- c : u = 1.4550 : 1.Constants.-M. p. 167O.1456 ARMSTRONG AND LOWHY: SULPHOlYATlON OF amide was produced ; but on one occasion a substance was separated by fractional cry stullisation, melting at 147O, of low rotatory power, [ a ] r + 16.9", which was probably an isomeride of the a-anhydramide. The crystah of a-chlorocamphorsulphonanhydramide were examined with the following results. Owing t o the small number of measure- ments made, the axial ratios may be incorrect to the extent of a few units in the third decimal place. A!ystem.-Orthorhom bic. Axicd ratios.-a : b : c = 1.589 : 1 : 1.022. Fo~rns present.--Q(100}, b(0101, c(OOl}, r(101), pi1 10). Angles observed. ?lumber of observations. Mean. Calculated. a : r 1OO:lOl 9.: c 101 : 001 a : c 100 : 001 a : p 100 : 110 p : b 11O:OlO a : b 100:010 57"15' 32 43 90 0 57 49 32 11 90 0 - 32"45' 90 0 32 11 90 0 - Optical properties.-There is a good cleavage parallel to the form a{100), and an optic axial figure can be seen through the cleavage face.The optic axial plane is parallel to b(010), and the acute bisectrix is parallel to the axis of a. The optic axial angle is small and the double refraction positive. No very close relationship exists between the axial ratios of the chloro- and bromo-compounds. Most probably the value taken for the c-axis of the bromo-compound should be halved to render the measure- ments comparable, thus : a-Bromanhydramide ... ... .. 1.4659 : 1 : 1.076 a-Chloranhydramide ......... 1.589 : 1 : 1.022CAMPHOR. I. CAMPHORSULPHONIC ACID (REYCHLER). 14.57 l - 69" 9' 19 28 36 1 55 25 110 51 90 0 53 59 63 42 58 9 107 26 64 44 - Of the four anhydramides containing two halogen atoms, two aye ob- tained as isomorphous mixtures, two of the products appear to be single substances. aa'-Diclzlorocam~horszc~lzonccn~ydi.amide may be prepared by chlorin- ating either camphorsulphonamide, or a-chlorocamphorsulphonamide, or a-chlorocamphorsulphonanhydramide : the amide is dissolved in acetic acid and the liquid heated on a water-bath while a n excess of chlorine is passed into i t ; on allowing the solution to cool, the di- chlornn hydramide separates in large, transparent prisms or needles, n nd when recrystallised from spirit or acetic acid forms long, silky needles melting at 172'.When the substance is repeatedly recrystallised, the melting point rises to 1 7 6 O , but the rotatory power remains constant at [aID + 6 O ; the product is therefore t o be regarded as a single substance and not as an isomorphous mixture.The compound is reduced by zinc dust and acet'ic acid to camphorsulphonanhydramide (m. p. 223'). The following measurements were made of crystals of the dichlor- anhydramide deposited from acetone. System.-Orthorhombic. Axid rcctios.-a : b : c = 1,1096 : 1 : 1.6097. ~'ormspresent.-a(lOOt, c{OOl), r { l O l ) , r'{102), q = { O l l t . Hubit.-Prisms elongated along the b-axis. 110 46 90 0 53 58 63 40 5s l C 107 27 72 34 Limits. a : r 1OO:lOi r : r 101 : l o 1 I r : r' 101 : 102 c : r' 001 : 102 r : r 101 : l o 1 ~ n : c 100:001 :.I" 1TJO : 102 q : q 011 : o i i c : q 001:011 q : r 011:lOl q : r 011 : i o i q : r' 011 : 102 q : rr 011 : 102 a : q 1 O O : O l l , c : r 001 :I01 j I ' _ _ _ _ _ 27 13 15 21 , 8 I 19 1 2 24 11 1 9 ' I! 1 11 14 I 34"lgr- 34"53' 63 40- 69 31 19 1 3 - 19 31 35 48- 36 3 55 9 - 55 45 110 36 -110 53 89 25- 90 24 53 49 - 54 6 63 34 - 63 49 57 59 - 58 26 107 1 3 ---lo7 41 72 6 - 72 53 64 38 - 64 54 115 0-115 21 89 48- 90 8 Calculated.1458 AHMSTRONG AND LOWRY : SULPEONATION OF 0pticaZpoperties.-An optic axial figure can be seen through the faces of the form c{OOl).The optic axial plane is (010) and the axis of c is the acute bisectrix; the optic axial angle is small, the disper- sion is strong, u>p, and the double refraction is negative. aa'-Di bromoctLmphorszclphonanhyclranzide, C,,,H, ,02NSBr2, is best prepared by adding an excess of bromine t o a solution of cam- phorsulphonamide in acetic acid, and heating during several hours on the water-bath; it can also be prepared in a similar manner From a-bromocamphorsulphonamide and from the two isomeric brom- anhydramid es.It crystallises from acetic acid or spirit in long, silky needles. When reduced, i t yields camphorsulphonanhydramide. As specimens prepared by different methods had the same rotatory power, i t is probable that a single substance, not an isomorphous mixture, is produced. Constants.-M. p. 195'. [ a]r - '7.2" (Solv. - acetone ; c - 5 grams per 100 c.c). Dibromocamphorsulphonanhydramide crystallises from acetone in The following results were obtained in measur- transparent prisms.ing the crystals. 8ysfem.- Orthorhombic. Axicd vutios.-a : 6 : c = 1.8981 : 1 : 1.8202 = 1.0428 : 0.5494 : 1. ~ormspi.esent.--cc{lOO), c(OOl), q(O11 f , q'{Ol2),p(llO), o ( l l l ) , e.{101), The form o f l l l } , which is not shown in the figure, truncates Hubit.-Usually prisms elongated along the b axis, but also tabular r'{lO2}. the corners formed by the faces p (I r. crystals in which the form ~ ( 1 0 0 ) predominates.CAMPHOR, I. CAMPHORSULPHONIC ACID (REYCHLEK). 1459 Angles observed. Q : T (100) : (101) c : r (OOl):(lOl) r : r (101) : (101) a : T' (100) : (10'2) c : r' (001) : (102) r ' : r' (108) : (~102) r : r' (101) : (102) a: : e (100) : (001) c : q (001) : (011) q : q (01 1) : (011) c : q'(OO1) : (012) 2': 4' (012) : (012) q : 4' (011) : (012) a :p (100) : (110) p : p (110) : (110) p : p (110):(110) a : q (100):(011) a : q' (100) : (012) c : p (001) : (110) p : 0 (110) : (111) c : 0 (001) : (111) q : r (011) : (101) q : p (011) : (110) p : r (110):(101) r': q (102) : (011) p : 0 (011) : (111) o : r' (1 11) : (102) p : q' (110) : (012) T': 4' (102) : (012) r':p (102) : (110) q': 1' (012) : (101) 0 : q' (110) : (012) 0: T (111) : (101) 0:T'(lll):(lo2) 0 : T' (111) : (102) Number of observations.30 23 14 35 25 15 30 26 25 12 27 11 14 16 8 8 4 4 4 1 1 6 4 4 4 2 2 4 4 4 2 2 2 1 1 Limits. 30" 1'- 46"29' 43 33- 44 2 92 5- 92 44 64 8- 64 37 25 2t- 25 51 51 4- 51 24 17 58 - 18 26 89 48 - 90 11 61 5 - 61 17 57 32 - 57 41 42 10- 42 25 84 28- 84 42 18 47 - 18 59 62 5- 62 19 55 31 - 55 40 124 16 -124 32 89 5 5 - 90 6 89 59- 90 3 90 0 - 90 1 25'56' 64 4 69'30'- 69"40' 39 12 - 39 21 71 7- 71 15 64 10- 64 15 54 52- 54 56 60 54 - 60 59 53 23 - 53 27 48 6- 48 17 78 19- 78 30 57 44 - 57 46 30 44 - 30 51 91 34 - 91 37 77035' 102 23 Mean.46'12' 43 48 92 28 64 24 25 37 51 13 18 10 90 0 61 12 57 36 42 18 84 36 18 54 62 13 55 35 124 26 90 0 90 0 90 0 25 56 64 4 69 35 39 15 71 11 64 13 54 54 60 56 53 25 48 11 78 24 57 45 30 48 91 36 77 35 102 23 Calculated. - 43048' 92 24 64 23 25 37 51 14 18 11 90 0 61 13 57 34 84 36 18 55 62 13 55 34 124 26 PO 0 50 0 90 0 25 55 64 5 69 40 39 10 71 10 64 16 54 El 60 53 53 27 48 10 78 23 57 44 30 49 91 37 77 42 102 18 - OpticaE p.ope&es.-An optic axial figure can be seen through tbe faces of the form a(100). The optic axial plane is (010) and the axis of a is the acute bisectrix; the optic axial angle is large, the dis- persion small, and the double refraction positive, aa'-ChZorobromocampho~szcZphonanhydrccmides were prepared by the action of bromine on a-chlorocamphorsulphonamide and of chlorine on U-bromocamphorsulphonamide. The product obtained by the former method separated in crystals from the acetic acid used as solvent in the bromination process, and when recrystallised from acetic acid was obtained in long, silky needles, which melted a t 172' ; [a]E + 7.8" (Solv.-acetone ; c - 5 grams per 100 c.c.). After it had been recrys- tallised seven times, the melting point rose to 173', [ a l D falling to + 4*3', and after thirteen crystallisations the melting point was 1 7 4 O , Fa], + 2.4'.The product obtained by the action of chlmine on a-bromocamphor- sulphonamide cryfitallised well from the acetic acid, and when recrys-1460 ARMSTRONG AND LOWRY: SULPHONATION OF tallised from acetic acid was obtained in white needles, which melted at 192O, the value of [a]"" being - 38.3' ; after six crystallisations, the melting point was 194O, and [ It will be noticed that the products obtained in the two ways differ very considerably in their properties, and to a far greater extent than is observed in the case of the corresponding chlorobromocamphors. This may be accounted for on the assumption that as the anhydramides no longer contain the CO group, they are lees liable t o undergo stereoisomeric change than are the compounds in which this group is present.On this assumption, the product in each case consists mainly of the compound formed by direct substitution. A similar explanation may be given of the stability of the isomeric bromocamphorsulphon- an hydramides. The following results were obtained on measuring crystals of the bromochloranhydramide prepared by the action of bromine on a-chlorocamphorsulphonamide : - 42.2'. System.-Orthorhombic. Axial ratios.-a : b : c = 1.9014 : 1 : 1.8369 = 1,0351 : 05444 : 1. ~ormspresent.-a{lOO), c{OOl}, r{101), ~'{102}, q{o11}, q'{012}, ~ ( 1 1 0 ) . Habit.-From acetone prisms elongated along the b axis or stout tablets in which ~ ~ ( 1 0 0 ) is the dominant form. Angles observed. u : r 1 O O : l O l n : r' 100 : 102 c : T' 001 : 102 r:r'lOl :lo- q : p 011:011 c : q' 001 : 012 g : q' 011 : 012 p : p 110 : i i o a : p 100 : 110 Number of observations. 4 21 20 5 11 26 22 18 9 Limits.Mean. 45'49'-46" 1' 64 1 - 6 4 30 25 36-25 37 17 55 -18 41 42 17 -42 56 18 26-19 1 62 5-62 29 55 21 -55 37 57 8 - 5 i 21 ! 45"58' 64 13 25 47 18 11 57 13 42 34 18 48 62 16 55 29 Calculated. 45"59' 64 13 18 14 57 8 18 52 62 16 55 29 - -CAMPBOR. I. CAMPHORSULPHONIC ACID (REYCHLER). 1461 Optical popertie8.--dn optic axial figure can be seen through the form a(100), the acute bisectrix being parallel to the axis of a, and the optic axial plane perpendicular to the axis of b. The optic axial angle is very large, and the dispersion is too slight to be noticeable. The double refraction is positive in sign. The results obtained on measuring crystals of the isomeric chloro- bromanhydramide prepared by the action of chlorine on a-bromocamphor- sulphonamide were as follows : 8ystem.-Orthorhombic. Axial ratios.-a : b : c = 1.8873 : 1 : 1.8099 = 1.0506 : 0.5521 : 1. Rorms present.--a(1OO}, c(OO1}, r'(102}, p { l l O ) , q(O11}, q'iO12;. Habit.-From acetone brilliant prisms, elongated along the axis of b. Angles observed. a : T' 100 : 102 c : r' 001 : 102 q : p 011 : 011 c:q'001:012 q:p'011:012 a : p 1 0 0 : ~ l O p:p 110 :110 Number of observations. 26 22 3 12 9 21 12 Limits. 64"12'-64'31' 25 26 -25 43 57 49-58 2 4'2 1-42 14 18 45 -19 0 61 55 -62 30 55 313 -55 57 Mean. 64"22' 25 38 57 54 42 6 18 58 62 5 55 50 Calculated. - 25'38' 57 48 42 10 18 56 55 50 - Opticcd poperties.-An optic axis can be seen emerging through the faces of the form r'{102), the optic axial plane being perpendicular t o the axis oE b. The optic axial angle is very large, amd a complete optic axial figure was not observed ; the position of the acute bisectrix and the sign of the double refraction were therefore not determined. The optic axial dispersion is very slight. The properties of the four disubstituted anhydrnmides are summar- ised in the following table, a pair of values indicating the effects of fraet ional recrys tallisa t ion :1462 ARMSTRONG AND LOWRY: SULPHONATION OF Dibromo- ............... Chlorinated hromo- ... Brominated chloro- .. Dichloio- ............... Anhydramide. 1 M. p. [a], (Acetone). 1 Axial ratios. 195" - 7-20 1.8981 : 1 : 1'8202 192" t o 194" 1.8873 : 1 : 1'8090 172 to 174 +7*8" to +2'4" 1.9014 : 1 : 1'8369 172 t o 176 + 6" 1'1096 : 1 : 1.6097 -38'3" t o -42'2" It will be seen that the chlorination product melts at about the same temperature as the dibromanhydramide, whilst the bromination product resembles the dichloranhydramide. The rotatory powers of the chlorobromanhydramides lie outside the limits of the dichlor- and dibrom-anhydramides, an effect which may be ascribed to the asymmetry of the a-carbon atom when linked to two different radicles. The crystallographic data are somewhat striking : the first three members form a very close isomorphous series, the axial ratios of the dibrom- being intermediate between those of the chlorobrom-anhydramides, but the constants of the dichloranhydramide belong to an altogether different series, approaching somewhat to the monochlor- and mono- brom-anhydrsmides. It is not improbable that in this case we are dealing with an isodimorphous series.