ASYMMETRIC OPTICALLY ACTIVE NITROGEK COMPOUNDS. 1127 CXIV.-Asyrnwt ric OpticaUy Active Nitrogen Com- pounds. Dexts.0- uml L~~io-cL-l-renz?ll~~en~l~~nzethylammoniurrz Iodides and Bromides. By WILLIAM JACKSON POPE AND STANLEY JOHN PEACHEY. THE only direct evidence pointing t o the existence of asymmetric optically active nitrogen compounds is Le Bel’s observation (Compt. r e d . , 1891, 112, 784) that on cultivating Penicilliuna glccucunt in solutions of isobut,ylpropylethylmethylarnmonium chloride the liquid acquires a rotatory power of - 0’ 25’ or - Oo 30’ under favourable con- ditions. The value of this important observation is, however, con- siderably lessened by the fugitive nature of the opticid activity and by the failure of Marckwald and von Droste-Huelshoff (Bey., 1899, 32, 560) t o confirm Le Bel’s results.” Many futile attempts have been made to directly resolve quater- nary bases of the type N(OH)X,X,X,X, into optically active antipodes by means of optically active acids.Thus, Marckwald and von Droste-Huelshoff (loc. cit.) attempted to resolve Le Bel’s base by the aid of tartaric, camphoric, and mandelic acids whilst Wedekind (Be?..; 1899, 32, 51 7) ende:tvoured t o resolve a-benzylphenylallylmethyl- ammonium hydroxide by means of trtrtwic and camphoric acids; in no ca~e, however, was an optically active base obtsined. A consideration of the facts led us to the opinion that the failure of these and other attempts had its origin in tho facility with which tetralkylnmmonium salts are decomposed by water and converted into tertiary base and alcohol ; we therefore prepared a-benzyl- phenylallylmethylammonium iodide by M7edekind’s method (loc.c d . ) and were successful in resolving it into isomeric opticalIy active bases * Le Re1 has recently replied to IIarckwald and von Droste-Huelshoff‘s criticism (Compt. Tend,, 1899,129, 548), and has confirmed his previous results.1128 POPE AND PEACHEY: by using hydroxyl-free solvents containing only small quantities of water. A number of methods, differing in detail, were applied, but we ultimately adopted the following process as affording the best results. Carefully purified a-benzylphenylallylmethylammonium iodide was mixed with a molecular proportion of the anhydrous silver salt of Reychler's dextrocamphorsulphonic acid and boiled for an hour or so on the water-bath with a mixture of about equal parts of acetone and ethylic acetate, a few drops of water being added when necessary.After separating silver iodide from the gummy solution by filtration, the solvent was distilled off and, on cooling, the residue solidified to a crystalline mass consisting of a mixture of dextro- and laevo-benzyl- phenylallylmethylammooiuln dextrocamphorsulphonnte. Dextl.o-a-ben~~l?~en~~~il~~l~iretJ~yt(ci~z.iitoniui,t Dexlrocam~~?~o)~szc~~~?~onat~, C,H,* CH,* N(eGH,)(C,Hj)(CH,)*SO~* CloI!C150. By fractionally crystallising the mixture of dextrocamphorsulphon- ates from boiling acetone, the less soluble constituent, dextro-a-benzyl- phenylallylmethylammonium dextrocamphorsulpl~onnte wtts readily obtained in colourless, diamond-shaped plates melting a t 169-170".After drying a t looo, the salt gave the following results on analysis : 0.2005 gave 0.505s CO, and 0.1364 H,O. C,;H,,O,NS requires C = 69.0s ; 13 = 7-46. 'It is very soluble in alcohol or water, less so in acetone, and sparingly soluble in ethylic acetate. The thin, rhomboidal plates deposited from acetone shorn extinction bisecting the angles ; the bisectrix of a large optic axial angle emerges perpendicularly through the large face of the rhonib. The double refraction is positive in sign and the optic axial angle f o r blue is greater than that for red light. The rotatory power of the salt was determined in aqueous solution ; 0-5256 gram in 26 C.C. gave a,+ 1.87" in a 200 min. tube, whence [a]= + 44.4" and [ 111, + 208".As we have previously shown (this vol., p. 1086) that the molecular rotatory power of salts of destro- camphorsulphonic acid with inactive bases is [ XID + 51.7", it follows that the basic radicle in the salt now described has the molecular rotatory power of about + 150° in aqueous solution. C = 65-84 ; I3 = 7.56. ~ ; o e v o - a - 6 e l z x ? / l l ' ~ e ~ ~ l c i Z ~ Z ~ i ~ e t ~ ~ ~ t ~ ~ ~ ~ ~ i ~ ~ o n i z c n a Dextrocun~~~orsu~hoate. This salt is contained in the acetone mother liquors, and may be obtained as a granular, crystalline powder by distilling off the solvent and crystallising the residue from boiling ethylic acetate containing aASYMMETRIC OPTICALLY ACTIVE NITROGEN COMPOUNDS. 1129 little acetone ; after drying at looo, it gave the following analytical results : 0.1874 gave 0.4710 CO, and 0,1284 H,O.C = 68.55 ; H = 7.62. 0.1596 ,, 0.4016 CO, ,, 0.1099 H,O. C = 68.63 ; H = 7.64. C,7H,,0,NS requires C = 69.08 ; H = 7.46 per cent. An aqueous solution of 0.42'35 gram in 25 C.C. gave uD - 0.64" in a 200 mm. tube, whence [a],, - 18%' and [If], - 87". These numbers show that the substance still contained some of the salt of the dextro- base, because, when pure, its molecular rotatory power would be about [MIL, - 100'. Deztro-a-be~za~Z~~~~enyta~~~l~~iet~~~~~!ccl,tmoniunt Iodide, C,H,* CH,* N( C,H,)(C,H,)(CH,)I. On adding to an aqueous solution of dextro-a-benzylphenylallyl- methylammouium dextrocamphorsulplionate the equivalent quantity of potassium iodide dissolved in water, a white, crystalline precipitate immediately begins to separate.After remaining for half an hour, this is collected, well mashed with cold water, and purified by crystallising it several times from boiling 50 per cent. alcohol; it melts at 145-147'. The following analytical results mere obtained : 0.18116 gave 0.3864 CO, and 0.0962 H,O. C = 55.57 ; H = 6.63. 0.1460 ,, 0.2984 CO, ,, 0.0732 H,O. C = 55.74 ; H=5*57. 0.2561 ,, 0.1640 AgI. I = 34-61. C!,7H,,NI requires C! = 55.89 ; H = 5.48 ; I = 34.79 per cent, A solution of 0.1445 gram, made up to 15 C.C. with a mixture of equal parts of acetone and methylic alcohol, gave aD c 1*0lo in a 200 mm. tube, whence [.ID + 52.5' and [ATID + logo. This salt is much less soluble in hot ethylic alcohol than the ex- ternally compensated salt prepared by Wedekind.A hot alcoholic solution of a mixture of the dextro- and inactive iodides, when poured into a 200 mm. tube, gave uD + 0.25' whilst still warm ; on standing, however, crystals were deposited and the solution became inactive, all the dextrorotatory iodide having been deposited. These observations prove that Wedekind's externally compensated iodide is not a racemic compound but merely an ordinary or pseudoracemic mixture of the two antipodes. Corroborative evidence of this is obtained on examin- ing the small crystals of the dextro-iodide deposited from a cooling alcoholic solution ; these belong to the orthorhombic system, showing two forms of the kind (110) and (101). The microcrystallographic characters of the material are identical with those of the inactive iodide and agree with the data given for the latter by Fock (Bey.,1130 ASYMMETRIC OPTICALLY ACTIVE KITROGEN COMPOUNDS.1899, 32, 520) ; it follows that Fock actually measured crystals of the optically active iodides. Dextro-a- b e i a x ~ ~ ~ e n ~ l i t l l y l m e t 7 ~ y l ~ n z r n o l r i u l Bromide, C,H,* CH,* N( C,H,)( C,H,)( CH,) Br. On adding to an aqueous solution of dextro-a-benzylphenylallyl- methylammonium dextrocamphorsulphonate the equivalent proportion of potassium bromide dissolved in water, it precipitate of dextro-a- benzylphenylallglmethylammonium bromide was slowly formed ; after several recrystallisations from boiling alcohol, it melted at 147-1 49' and gave the following analytical results : 0.1027 gave 0.2409 CO, and 0.05SG H,O.0.1164 ,, 0.2731 CO, ,, 0.0676 H20. U=64*00 ; H=6*45. 0.3205 ,, 0,1923 AgBr. Br = 25.63. C17HJ?Br requires c1 = 64.15 ; 13 = 6-29 ; BY= 25.14 per cent. C = 63.97 ; H = 6.34. An ethylic alcoholic solution containing 0,1454 gram in 15 C.C. gave a,+1.33' in a 200 mm. tube, whence [a],+68*6 and [MID + 218O. Lcevo-a-benz?/l~~en?/~~lZ~~t~~et7~~Z([nz?iioniuna Iodide. On mixing the somewhat impure lsvo-a-benzylphenylallylmethyl- ammonium dextrocamphorsulphonate with potassium iodide as described above, a precipitate of the iodide is obtained from which Isevo-a-benzylphenylallylrnethylammonium iodide may be isolated by repeatedly crystallising the salt from boiling 50 per cent. alcohol, the active substance being less soluble than the inactive mixture. Its ordinary properties are identical with those of its dextro-isomeride ; it gave the following analytical results : 0.1335 gave 0.2'732 GO, and 0.0684 H,O.C= 55.Sl; IC=5.69. 0.1484 ,, 0,3032 UO, ,, 0.0739 H20, C=55.72; H=5.53. 0.2408 ,, 0.1539 AgI. I= 34.54. C17H,,NI requires U = 55.89 ; H = 5.48 ; I = 34.79 per cent. A solution of 0.3105 gram, made up to 15 C.C. with a mixture of equal parts of acetone and methylic alcohol, gave a,-2*13' in a 200 mm. tube, whence [ aID - 51 *4O. L ~ v o - a - ~ ~ ~ a ~ ~ Z ~ ? ~ ~ e n ? / l ( ~ l l ~ ~ ~ ~ ~ e t ~ ~ l ~ Bromide. This substance, prepared from its dextrocamphorsulphonate and purified by cry stallisation from boiling alcohol, has properties antipodal t o those of its dextro-isomeride. It gave the following results on analysis :RUHEMANN AND STAPLETON : TETRAZOLINE, 1131 0.1150 gave 0.2695 CO, and 0.0660 H,O.0.3447 ,, 0.2017 AgBr. Br= 24.90. A solution of 0.2240 gram, made up to 15 C.C. with absolute alcohol, gave aD-2*01” in a 900 mm. tube, whence [a], - 6 7 ~ 3 ~ . We have also succeeded in resolving the inactive iodide into its active components by digesting i t with the silver salt of dextro-a- bromocamphorsulphonic acid in acetone solution. C! = 63.92 ; H = 6-38, 0.1096 ,, 0.8566 CO, ,, 0.0632 H,O. C=63*85 j H ~ 6 . 4 1 , CI7H,,NBr requires C = 64.15 ; H= 6.29 ; Br = 35.14 per cent, The values of the melting points and rotatory powers given in this preliminary note are only provisional, and we shall subsequently determine them with greater accuracy, using more carefully purified materials. I n the present paper, it is proved that quaternary ammonium derivatives in which the five substituting groups are different, contain an asymmetric nitrogen atom, which gives rise to antipodal relation- ships of the same kind as those correlated with an asymmetric carbon atom. The method which has enabled UB to deal with quaternary bases is now being applied to various other types of substituted ammonium derivatives in order to ascertain the stereochemical nature of pentad nitrogen, We hope shortly to be in a position to publish results obtained with sulphonium derivatives of the type SX,X,X,T. Our thanks are due to the Government Grant Committee of the Royal Society and to the Kesearch Fund Committee of the Chemical Society for grants enabling us to purchase apparatus and materials used in this work. GOLDSMITHS’ INSTITUTE, NEW CEOSS.