THE OPTICALbY ACTIVE NEOMETHYLHYDRINDAMINES. 61 V.-The Optically Active neo Methyl~~yd?,z'ndumines. By (the late) LT. J-OSEPH WALTER HARRIS.* THE reduction of 8-methyl-a-hydrindoxime CH2<yz$> C:NOH, with sodium amalgam and acetic acid leads to the formation of two * Lt. J. W. Harris B.Sc. was one of those who actuated by a high sense of patriotic duty joined the O.T.C. of the University College Nottingham. before there was any immediate prospect of a war and his efficiency and enthusiasm led to his promotion to the rank of colour sergeant. In the summer of 1914 he had just completed his first piece of research work and when war was declared he immediately volunteered for active service. Shortly after-wards he was given a commission in the 3rd Lincolns and went to the Western front where he was killed in action during the early part of the war.His death was a great blow to all who knew him whether in civilian or in military life ; he was a most promising chemist an ideal officer. The presen 62 HARRIS THE OPTICALLY ACTIVE dl-bases one of which may be isolated by the fractional crystal-lisation of the hydrochlorides prepared from the mixture (Kipping and Clarke T. 1903 83 913). The other base cannot be obtained, a t any rate easily in this way or by a similar treatment of the normal sulphates benzoates cinnamates or picrates but by frac-tionally crystallising the d-bromocamphorsulphonates and mechani-cally separating the obviously diff erent crystals both the dl-bases can be ultimately obtained in a state of purity (Tattersall and Kipping T.1903 83 918). As this method of separation was unsatisfactory the author of this paper a t the suggestion of Professor Kipping made some further experiments on the subject and found that the two &-bases in the crude product could be isolated in the manner described below. He then succeeded in resolving the dZ-neo-base into its optically active components both of which were obtained in a state of purity. All the four optically isomeric P-methylhydrindamines tlieref ore, have now been characterised ; the two neo-bases which form only abotlt 25 per cent. of the original mixture have very low molecular rotations cornparod with those of the other two methylhydrind-amines. Sepration of Methylhydrindamine and neoMethylhydrindamine b y means of their Hydrogen Oxalates.The aqueous solution of the mixed bases obtained by the reduc-tion of methylhydrindoxime was neutralised with finely divided oxalic acid and a further equal quantity of acid was added. This solution was then concentrated and cooled. The first fraction con-sisted of tufts of long silky needles and was nearly pure methyl-hydrindamine hydrogen oxalate. Subsequent fractions were simi-lar but the needles gradually became less well defined and when aboutl two-thirds of the total substance had been separated the deposits consisted of hard crystalline masses. The latter after several recrystallisations from water yielded tufts of needle-liks prisms which were neomethylhydrindamine 'hydrogen oxalate. Some ammonium salts separated in large transparent masses from time to time but these were easily removed by extracting the salt of the organic base with alcohol.By the above metho,d about fivesixths of the original mixture was separated into the two dl-salts the pro-paper is an account of his work which he handed to me before he went to the front and except the few lines of introduction and some immaterial alterations the matter is given in his own words.-F. S. K NEOMETHYLHY DBINDAMINES. 63 portion being about three to one rnet'liylliydrii~dttmine being present in the larger quantity. dl-~~et~~tylliydriizdamine hydrogen oxalat e , C1"H1l*NH, C,H,04,H207 crystallises froin water in which it is readily soluble in tufts of long silky needles melting a t 110-11lo. These are 'hydrated and lose water a t 70-80°; a t looo some decomposition is observed but this is not noticeable in the melting-point tube.The dehydrated salt melts at 143-145O with slight decomposition : 0.4338 lost 0.031 at 80°. H,O=7*14. The above formula requires H,O = 7.06 per cent. The benzoyl derivative of the base made in the usual way, crystallised from alcohol in needles melting a t 150° showing the base t o bme methylhydrindamine (Tattersall and Kipping Zoc. c i t . ) . dl-neoMet Jqlhydr.inda8mine hydrogen oxalnt e, C,,H,,*NH,,CzH20,,2H,O, in an impure condition crystallises iii compact masses. From water and alcohol the pure compound is obtained in tufts of neeldle-like prisms which partly liquefy a t about looo and finally melt a t 173-175*~which is the melting point of the anhydrous salt.When treated with benzoyl chloride the salt gave a benzoyl derivative, crystallising in needles and melting a t 169O wliich is the melting point of the benzoyl derivative of neomethylhydrindamine (Tatter-sall and Kipping Zoc. cit.) -% 0.4336 lost 0.0568 a t 903. 0.1454 anhydrous salt gave 0.3246 CO and 0.0834 H,O ; C = 60.8 ; H,0=13-1. The above forinula requires a loss of 13.2 per cent. H= 6.4. C,,H,,04N r'equires C = 60.8 ; H = 6.33 per cent. Resolqr t i o t i of dl-neo36etB?/l~~yc~damin,e. dl-n~Met~~tylhycn~amine Itydrogcn ozalate (20 grams) was decomposed with sodium hydroxide the base distilled in steam and the distillat? neutralised wi,th tartaric acid a further equal quan-tity of the acid being added to form the1 hydrogen salt.The solu-tion was then concentrated to a small balk allowed to cool and a crystal of pure I-neomethylhydrindamine hydrogen tartrate intro-* Since the melting point of the A-base described by Kipping and CLrke (Zoc. c i t ) was 169O it is evident that by the fractional crystallisation of the hydrochlorides of the mixed bases the salt of dZ-neomethylhydrindamine is fist isolated whereas in the case of the d-bromocamphorsulphonates the salt of dl-methylhydrindamine forms the most sparingly soluble fraction.-F. S. K 64 HARRIS THE OPTICALLY ACTIVE duced. A deposit consisting of tufts of needles separated and was collected. 'The amount of this fraction was roughly a b u t one-third of the whole. I f the1 solution was allowed t o remain too long before it was filtered the needle-like crystals became covered with white =asses.This first fraction was recrystallised from water until its melting point became constant. and consisted of Z-neomethyl-hydrindamine hydrogen tartrate (about 8 grams). The mother liquors on further concentration and seeding gave deposits of white masses obviously a mixture and melting over a wide range. The last mother liquors gave long white needles melting a t 1 6 5 O . It was however found t o be impossible t o isolate a pure compound from these mother liquors owing t o the great solubility of the salt. The whole of the mother liquor was therefore decomposed with sodium hydroxide the base distilled in steam and the distillate neutralised with hydrochloric acid. On concentrating the solutioa, long needles of dl-nesmethylliydrindamine separated but the final mother liquor was found to contain a salt which was more readily soluble in water than that of the dl-base and the solution of this salt showed dextrorotation.To obtain this dextro'rotatory base the active mother liquor was decomposeld with sodium hydroxide the base distilled in !team and the solution neutralised with d-bromocamphorsulphonic acid. The solution was conoentrated until it became turbid and allowed t o remain when a mass of needles separated. These were recrystal-lised from water until the melting point became constant at 229-230O. This substance was found to be d-neomethylhydrind-amine d'bromocamp horsulphona t e. 1-nedfe t hylhydrindarnine hydrogen tarrtra t e, Cl,Hll*NH,,C,H,O,,H,O, the salt which forms the most sparingly solible portion described above crystallises from water or alcohol' in large vitreous prisms, often growing together in leaf-like' masses.It is hydrated and when heated in a melting-point tube it partly liquefies a t about looo and finally melts a t 1 7 3 O . It is readily soluble in water less so in alcohol and practically insoluble in ethyl acetate acetone, benzene or chloroform : 0.3522 lost 0.0204 a t 100'. H,O=5*71. The above formula requires H,O=5*71 per cent. Samples dried a t looo gave in a 200 mm. tube in aqueous solution the following results : Wt. of salt. Vol. of solution. a. [aILl. [MIIJ. 0-7 11 6 gram . . . . . . . . . 26 C.C. 0.65" 11-4" 34" 0.4600 , . . . . . . . . . 9 9 0.42 11.4 3 NEOMETHYLHYDRINDAMES.65 As the molecular rotation of the tartaric acid ion in its metallic hydrogen salts is [MI1 4Z0 that of the base is [MI - 8 O . 1-neoMe t h y Zh ydrindaniine d- b romocamphorsulphmat e, C,oH,l~NH2,Cl,Hl,0Br*S03H, is moderately soluble in water and crystallises from the warm solu-tion in aggregates of needles the solution first becoming milky if the salt is not free from the optically active isomeric base. These needles are hydrated but lose all their water on exposure to the air. The freshly crystallised substance when heated in a melting-point tube partly liquefies a t about 80° and finally melts a t 214O It is mom readily soluble in alcohol than in water and easily dissolves in ethyl acetate chloroform or acetone but is insoluble in ether.The anhydrous salt was examined in aqueous solution in a 200 mm. tube. Wt. of salt. Vol. of solution. a. [.ID* [MI,. 0.5068 ......... 25 C.C. 2-32' 57.2' 262" 0-3856 9 9 1.75 57.1 261 ......... Taking the molecdar rotation of the bromocamphorsulphonic acid ion to be [MI 270° these results give a value of [MJD - 8 O ur -go for the base. 1-neoMethyZhydrindamine hydrochloride C,,H,,-NH,,HCl is much more readily soluble in water than the hydrochloride of the &base and crystallises from this solvent in long silky needles. It is very readily soluble in water or alcohol and also dissolves in ethyl acetate or chloroform but is practically insoluble1 in ether or carbon tetrachloride. When heated in a melting-point tube the substance begins to char at about 235O.The air-dried salt is anhydrous . The following results were obtained in aqueous solution in a 200 mm. tube : Wt. of salt. Vol.'of solution. a. [a]D. [ M I D . 0.5250 ............... 25 C.C. -0.130 -3.1" -5.70 0.7986 ............... 9 9 -0.23 -3.6 - 6.5 0.7754 ............... -0.21 -33.4 - 6.2 9 s l-neoMe t hylhydrindamine d-camphmsulphonate, C,oH,,-NH2,C,,H,SOe sop, is very readily soluble in water and crystallises in long vitreous prisms. The air-dried salt is anhydrous and when heated sinters at about 210° and finally melts a t 2 2 0 O . It is readily soluble in chloroform sparingly so in alcohol or acetone and practically insoluble in ether or ethyl acetate. VOL. cxv. 66 THE OPTICALLY ACTIVE NEOMETHYLHYDRINDAMINES. The following results were obtained in aqueous solution in a 200 rnm.tube: Wt. of salt. Vol. of solvent. a. I a]". 0.5898 ............... 25 C.C. 0.54" 11.4' 43.2' 04282 Y Y 0.50 11.8 44.7 Taking [MI for camphorsulphonic acid as 49O these results give for the base [MI - 5 ' 8 O and -4.3O respectively. The bemoyi derivative of I-meornethylhydrindamine crystallises from aqueous alcohol in long silky needles melting a t 171O. d-neoMethylh,,?/dmndamine d-bromocamphJorsulphonate, ............... CloHll*NHz,C,,H,,OBr*SO,H, is readily obtained in a pure condition from the active base con-tained in the mother liquors from the dl-hydrochloride (see above). It crystallises from warm water in tufts of fine silky needles and, as with many other bromocamphosrsulphonates the warm solution becomes milky when the salt separates unless it is free from its optical isomeride.The freshly crystallised salt contains water, probably one molecular proportion but it was impossible to obtain accurate determinations on this point since the salt rapidly loses water in the air and the air-dried salt is anhydrous. 1.69 of the salt roughly dried in the air lost 0.544 a t looo. Loss=3.2 whereas 1H,O requires a loss of 3.1 per cent. When the freshly crystallised salt is heated in a melting-point tvbe i t partly liquefies a t a b u t looo and finally melts a t 229-230°. It is moderately solubsle in water more readily so in alcohol; it is also soluble in acetone o r ethyl acetate but insoluble in carbon tetrachloride or ether. d-neoMe thy Zh ydninda min e hydrochloride Cl,Hl *NH,,HCl pre -pared from the pure bromocamphorsulphonate was dried a t looo and examined polarimetrically in aqueous solution in a 200 mm.tube. Wt. of salt. Vol. of solution. b a. 1.1". 0.5200 ............ 25 C.C. 0.13' 3.1' 5 . 7 O 0.4268 ............ 1 9 0.10 3-0 5.5 d-neo:Ue t h ylh ydriizdam ine hydrogen tart rate , C1,H1,'NH27@aH,0,,H207 is much mom readily soluble in water than the hydrogen tartrate of the 2-base and crystallises in aggregates of needle-like prisms : 1-2146 air-dried salt lost 0'0726 a t looo. When heated in a melting-pint tube the salt sinters a t about The following resu1t.s were I]I,o=5.9. The above formula requirm H,O=5*71 per cent. 900 and finally melts a t 166-167O BRIGGS CHROMATOCOBALTIAMMINES. 67 obtained with aqueous solutions of the anhydrous salt in a 200 mm. tube : Wt. of salt. Vol. of solution. a. [alD* 0.3122 ............ 26 C.C. 0.40' 16.0' 47.6' 0.3328 ............ 9 9 0.43 16.2 48.1 Taking the molecular rotation of the tartaric acid ion in its hydrogen salts as [MIL 42O these results give1 .[MI 5.5O and 6.1° respectively for the base. d-neoMe t h ylhydrindamin e d-camphorsulphonat e, Cl,Hll* NH,,Cl,,Hl,O S0,K crystallises from water in felted masses of needles which melt and decompose a t 195-205O. The salt is extremely readily soluble in water and readily so in alcohol or chloroform. It is sparingly soluble in ethyl acetate and practically insoluble in ether, A sample dried a t looo examined in aqueous solution in a 200 mm. tube gave the following result 0.6176 gram in 25 C.C. of solution gave a 0'73O [a], 14.8O [MI 56*1°. Taking the molecular rotation of the acid ion as 49O that of the base is [MI 7O. UNIVERSITY COLLEGE, NOTTINUHAM. [Received December 16th 1918.