RESOLUTION OF CHLOROSULPHOACETIC ACID ETC. 233 XXXIX.-Resolution of Chlorosulphoacetic Acid into its Optically Active Components. By HILMAR JOHANNES BACKER and WILHELM GERARD BURGERS. CHLOROSULPHOACETIC acid SO,EI*CHCl*CO,H one of the simplest compounds with an asymmetric carbon atom has hitherto resisted all attempts at optical resolution. Porcher stated (Bull. SOC. cJzi?n. 1902 [iii] 27 438) that resolution is possible but Pope and T 234 BACKER AND BURGERS RESOLUTION OF CHLOROSULPHOACETIC Read repeating his experiments did not confirm his results and were led " to dismiss them as not in accordance with experiment " (J. 1908 93 794; 1914 105 811). We have resolved the racemic acid by a method which apparently had not previously been applied to such purposes namely by slow crystallisation of alkaloidal salts in the cold.After a preliminary examination of their solubility the alkaloid salts of chlorosulphoacetic acid were prepared by treating the sodium salt at room temperature with a soluble salt of the alkaloid in such dilutioii that crystallisation of the product did not start at once and only a small part was subsequently deposited. Since the solubility of the alkaloid salts was so small that the effect of the active chlorosulphoacetic acid on the rotation was inappreciable the sodium and ammonium salts were examined. For purification the same " cold crystallisation " was used. The alkaloid salt was therefore converted a t 0" into the ammonium salt by means of the theoretical quantity of dilute ammonia the alkaloid was filtered off and the solution of the ammonium salt was mixed with the alkaloid (as acetate) in such concentration that again only a part of the alkaloid salt crystallised.By means of yohimbine a dextrorotatory ammonium salt was obtained and an acid of nearly twice the rotation. I-Sjtrychnine gave fhe dextro-rotatory acid whilst d-cinchonine furnished the laevo-component, so that the small rotation we first obtained could not be ascribed to the presence of traces of the alkaloids. The highest constant value of the molecular rotation was for the acid [MI = & 39" and for the neutral ammonium salt [MI = & 20". The acids and their salts gradually racemise in solution a t room temperature. Bases accelerate racemisation of the salts. On evaporation the solutions lose their activity completely.These active acids therefore are more stable than fluorochlorobromo-acetic acid which shows activity only in its alkaloidal salts (Swarts, Bull. roy. Be@. 1896 [iii] 31 25) but they do not attain the high stability of chloroiodomethanesulphonic acid which is not racemised by any of the usual methods (Pope and Read loc. cit.).* E X P E R I M E N T A L . Preparation of Chlorosulphoacetic Acid .-The method used for the preparation of other sulphocarboxylic acids (Rec. trav. chim. , 1920 39 694; 1924 43 297) gives a good yield and a pure product. * This research is being continued and the method will be applied to other resolutions. The present results are published because of the departure of Mr. Burgers.-H. J. B ACID INTO ITS OPTICALLY ACTIVE COXPONENTS .235 To 94 g. (1 mol.) of freshly distilled chloroacetic acid cooled with ice are gradually added SO g. (1 mol.) of sulphur trioxide with constant shaking. A viscous nearly colourless syrup of the mixed anhydride of sulphuric and chloroacetic acids is formed (Found by titration after decomposition with water equiv. = 57. CH,Cl*CO*O*SO,H decomposed by water into CH,Cl*CO,H + H,SO,, requires a mean equivalent weight of 174.513 = 58.2). The anhydride is converted into the sulphonic acid by warming: CH,C1*C0*O*SO3H -+ SO,H*CHCl*CO,H. At 70" the external heating is discontinued; the heat of reaction causes the tem-perature to rise to about 140" the liquid becoming coloured towards 100" and a feeble evolution of gas (CO and SO,) setting in.The product is a brown syrup consisting mainly of chlorosulphoacetic acid (Found equiv. = 84. Calc. equiv. = 174.32 = 87.2). When kept over-night the acid may crystallise. A solutim of the syrup or crystallised mass in 5 litres of water is t'reated with barium carbonate in excess (200 g.). The filtrate, evaporated to 250 C.C. and cooled deposits 270 g. of pure crystalline barium chlorosulphoacetate (yield more than 80%) (Found : Ea = 41.83 41.84. On concentration the mother-liquor gives as in Andreasch's preparation (Monatsh., 1 SS6 7 158) crystals of barium chloromethanedisulphonate (about 1.5 g.) (Found H20 = 17-37; Ba = 32.56 32.54. Calc. for CIE0,ClS,Ba,4H20 H,O = 17.24; Ba = 32.860/). Chlorosulphoacetic acid was prepared by shaking its barium salt rrzechanically for 1 hour with the calculated quantity of 2AT-sulphuric acid.The filtrate which was free from sulphuric acid and barium was concentrated fist by distillation under reduced pressure then in a desiccator over sulphuric acid and finally over phosphorus pentoxide until crystallisation set in. Chlorosulphoacetic acid forms very hygroscopic crystals containing 1H,O (Found Jl = 191.8. Calc. for C,H,05C1S,H,0 X = 192-56). The melting point determined in an apparatus for hygroscqpic substances (Chem. TYeelcblad 1919 16 1564) was 83". Sormal Alkaloidal Xalts .-The normal salts of chlorosulpho-acetic acid with various alkaloids were prepared either by dissolving the bases in the equivalent quantity of the acid or by double decomposition from sodium chlorosulphoacetate with a soluble salt, usually the acetate or phosphate of the alkaloid.The salts all of which were obtained in the crystalline state,* were titrated with sodium hydroxide in presence of phenolphthalein or thyrnol-p ht halein. Calc. Ba = 41.89y0). * Pope and Read state that the quinine and cinchonine salts were not obtained crystalline. Their strychnine salt contained 1H,O. I" 236 BACKER AND BURGERS RESOLUTION OF CRLOROSULPHOACETIC The normal quinine salt forms a felted mass of small needles containing 4H20 (Found H20 = 8-03 M = 894. requires H20 = 8.05%; M = 895.0). The normal cinchonine salt crystallises with 1H20 in silky needles, concentrically arranged in dense globules (Found H20 = 2.36; M = 780. C2H,0SClS,2C1,H220N2,H20 requires H20 = 2.31% ; M = 780.9).The normal strychnine salt when crystallised from a dilute solution forms needles about & inch long containing 3H20 (Found H20 = 6.08 6.15; M = 896.7 897-2 895.8. C2H,06C1S,2C~,02N2,4H,0 requires H,O = 6.03%; M = 897). d-Chlorosulphoacetic Acid.-Sodium chlorosulphoacetate (0.05 mol.) in 1150 C.C. of water was treated with 33.4 g. (0.1 mol.) of strychnine dissolved in the same volume of water containing 11 g. of acetic acid. Slender needles began to separate within 1 hour and after 10 hours a t 20° 9 g. of strychnine salt were collected corresponding to 20% of the quantity formed (44-8 g.). For polarimetric examination weighed quantities of the strych-nine salt (06-2 g.) were shaken a t 0" with the theoretical quantity of dilute ammonia the volume was brought to 20 c.c.and the solution of the ammonium salt after being extracted four times with half its volume of chloroform was examined by means of a polarimeter (Schmidt and Haensch) with monochromator. In some cases the concentration of the ammonium salt was verified by evaporation of the solution. The rotatory power was measured for X = 589 pp (D) and for two arbitrary wave-lengths in the green (A = 533 pp) and blue (A = 494 pp). The ammonium salt pre-pared from the strychnine salt mentioned above gave the following figures Concentration 0.00480 g.-mol. in 100 c.c.; Z = 2; aD = + 0.18"; [MI = + 18.7". For recrystallisation 4-48 g. (0.005 mol.) of the active strychnine salt were decomposed by ammonia.The separated strychnine was dissolved in dilute acetic acid and added to the solution of the ammonium salt. The total volume being 230 c.c. the concentra-tion was the same as above. 1.3 Grams or nearly 30% separated. Rotation of the ammonium salt Conc. 0.01115 g.-mol. in 100 C.C. ; 1 = 2 ; tcD = + 0*45" as33 = + 0*58" aqD4 = + 0.74" ; [MID = + 20.2" = + 26-0" [MI,, = + 33.2". Conc. 0.00560 g.-mol. in 100 c.c.; I = 2; C C ~ = + 0-23" a533 = + 0*30" a4D4 = + 0.37"; [MID = + 20.5" [M],, = + 26-8" [M'J,, = $- 33.0". Addition of sulphuric acid to liberate the acid (2 mols. for 1 mol. of ammonium salt) increased the rotatory power but this did not chang ACID IKTO ITS OPTICALLY ACTIVE COMPONENTS. 237 further on addition of more sulphuric acid. Rotation of the free acid : C'OnC.0.005 g.-mol. in 100 C.C. ; ,! = 2 ; a = + o.40°,a533 = + o.5?o, 1 - Chlorosulphoacetic Acid .-Sodium c hlorosulp hoac et a t e (0 -0 5 mol.) was mixed with 30 g. (0.1 mol.) of cinchonine dissolved in water containing 9 g . of acetic acid. The total volume was 1150 C.C. After 2 days 5-5 g. of the cinchonine salt or 14% of the total amount (39 g.) had separated. The product was decomposed with ammonia like the strychnine salt the only differeme being that the alkaloid was filtered off before extraction of the solution with chloroform. Rotation of the ammonium salt Conc. 0.00278 g.-mol. in 100 c.c.; I = 2 : The active cinchonine salt (3.9 g.; 0.005 mol.) was recrystallised in the same way as the strychnine salt. From 115 c.c. the same concentration as above there separated 0.95 g.or 257;. Rotatory power of the ammonium salt Conc. 0.00324 g.-mol. in 100 c.c.; I = 2 ; aD = - 0.12" = - 0*17" agg4 = - 0.23"; [AM] = The acid liberated by an excess of sulphuric acid gave the figures : Conc. 0.00305 g.-mol. in 100 c.c.; mD = - 0.23" c1333 = - 0*29", c1494 = -/- 0.62"; [Jf] = + 40" [A$f]533 = + 52" [l!f]gg4 = $- 62". aD = - 0.08" ; f i t l ] D == - 14.4". - 18*5" [ill]533 == - 26.2") [Jf],g4 = - 35.5". aqg4 = - 0.38" ; pi], = - 37-70 [ J ~ I ~ ~ ~ = - 47.50 [N],g = - 62-30. Thus the mean values for the rotatory power are : Chlorosulphoacetic acid [MI = zfr 39" = & 50", h'eutral ammonium salt [il.i'] = & 20" = 36", [MI494 = Zt 62". [&!]494 = & 34". Xacenzisntioiz. The rotation of a neutral solution of the d-ammonium salt contain-ing 0.1 mol.per litre had fallen in a fortnight to half its value. The rotation of a solution containing 0.05 11101. of the d-acid per litre and an excess of sulphuric acid diminished in 10 days by one-fourth. A solution of 0.05 mol. of the ammonium salt per litre containing 0.1 mol. of free ammonia had lost one-third of its rotatory power within 24 hours. The d-acid and the d-ammonium salt each in a solution containing 0.05 mol. per litre were rapidly heated boiled for 1 minute and immediately cooled. Their rotatory powers had decreased by about 5%. The same solutions evaporated on a water-bath and diluted to the original volume racemised completely. Examined a week later it m-as inactive. ORGANIC CHEMICAL LABORATORY, (HOLLAXD ).UNIVERSITY OF GRONINGEN [Received September 8th. 1924. RESOLUTION OF CHLOROSULPHOACETIC ACID ETC. 233 XXXIX.-Resolution of Chlorosulphoacetic Acid into its Optically Active Components. By HILMAR JOHANNES BACKER and WILHELM GERARD BURGERS. CHLOROSULPHOACETIC acid SO,EI*CHCl*CO,H one of the simplest compounds with an asymmetric carbon atom has hitherto resisted all attempts at optical resolution. Porcher stated (Bull. SOC. cJzi?n. 1902 [iii] 27 438) that resolution is possible but Pope and T 234 BACKER AND BURGERS RESOLUTION OF CHLOROSULPHOACETIC Read repeating his experiments did not confirm his results and were led " to dismiss them as not in accordance with experiment " (J. 1908 93 794; 1914 105 811). We have resolved the racemic acid by a method which apparently had not previously been applied to such purposes namely by slow crystallisation of alkaloidal salts in the cold.After a preliminary examination of their solubility the alkaloid salts of chlorosulphoacetic acid were prepared by treating the sodium salt at room temperature with a soluble salt of the alkaloid in such dilutioii that crystallisation of the product did not start at once and only a small part was subsequently deposited. Since the solubility of the alkaloid salts was so small that the effect of the active chlorosulphoacetic acid on the rotation was inappreciable the sodium and ammonium salts were examined. For purification the same " cold crystallisation " was used. The alkaloid salt was therefore converted a t 0" into the ammonium salt by means of the theoretical quantity of dilute ammonia the alkaloid was filtered off and the solution of the ammonium salt was mixed with the alkaloid (as acetate) in such concentration that again only a part of the alkaloid salt crystallised.By means of yohimbine a dextrorotatory ammonium salt was obtained and an acid of nearly twice the rotation. I-Sjtrychnine gave fhe dextro-rotatory acid whilst d-cinchonine furnished the laevo-component, so that the small rotation we first obtained could not be ascribed to the presence of traces of the alkaloids. The highest constant value of the molecular rotation was for the acid [MI = & 39" and for the neutral ammonium salt [MI = & 20". The acids and their salts gradually racemise in solution a t room temperature.Bases accelerate racemisation of the salts. On evaporation the solutions lose their activity completely. These active acids therefore are more stable than fluorochlorobromo-acetic acid which shows activity only in its alkaloidal salts (Swarts, Bull. roy. Be@. 1896 [iii] 31 25) but they do not attain the high stability of chloroiodomethanesulphonic acid which is not racemised by any of the usual methods (Pope and Read loc. cit.).* E X P E R I M E N T A L . Preparation of Chlorosulphoacetic Acid .-The method used for the preparation of other sulphocarboxylic acids (Rec. trav. chim. , 1920 39 694; 1924 43 297) gives a good yield and a pure product. * This research is being continued and the method will be applied to other resolutions.The present results are published because of the departure of Mr. Burgers.-H. J. B ACID INTO ITS OPTICALLY ACTIVE COXPONENTS . 235 To 94 g. (1 mol.) of freshly distilled chloroacetic acid cooled with ice are gradually added SO g. (1 mol.) of sulphur trioxide with constant shaking. A viscous nearly colourless syrup of the mixed anhydride of sulphuric and chloroacetic acids is formed (Found by titration after decomposition with water equiv. = 57. CH,Cl*CO*O*SO,H decomposed by water into CH,Cl*CO,H + H,SO,, requires a mean equivalent weight of 174.513 = 58.2). The anhydride is converted into the sulphonic acid by warming: CH,C1*C0*O*SO3H -+ SO,H*CHCl*CO,H. At 70" the external heating is discontinued; the heat of reaction causes the tem-perature to rise to about 140" the liquid becoming coloured towards 100" and a feeble evolution of gas (CO and SO,) setting in.The product is a brown syrup consisting mainly of chlorosulphoacetic acid (Found equiv. = 84. Calc. equiv. = 174.32 = 87.2). When kept over-night the acid may crystallise. A solutim of the syrup or crystallised mass in 5 litres of water is t'reated with barium carbonate in excess (200 g.). The filtrate, evaporated to 250 C.C. and cooled deposits 270 g. of pure crystalline barium chlorosulphoacetate (yield more than 80%) (Found : Ea = 41.83 41.84. On concentration the mother-liquor gives as in Andreasch's preparation (Monatsh., 1 SS6 7 158) crystals of barium chloromethanedisulphonate (about 1.5 g.) (Found H20 = 17-37; Ba = 32.56 32.54. Calc. for CIE0,ClS,Ba,4H20 H,O = 17.24; Ba = 32.860/).Chlorosulphoacetic acid was prepared by shaking its barium salt rrzechanically for 1 hour with the calculated quantity of 2AT-sulphuric acid. The filtrate which was free from sulphuric acid and barium was concentrated fist by distillation under reduced pressure then in a desiccator over sulphuric acid and finally over phosphorus pentoxide until crystallisation set in. Chlorosulphoacetic acid forms very hygroscopic crystals containing 1H,O (Found Jl = 191.8. Calc. for C,H,05C1S,H,0 X = 192-56). The melting point determined in an apparatus for hygroscqpic substances (Chem. TYeelcblad 1919 16 1564) was 83". Sormal Alkaloidal Xalts .-The normal salts of chlorosulpho-acetic acid with various alkaloids were prepared either by dissolving the bases in the equivalent quantity of the acid or by double decomposition from sodium chlorosulphoacetate with a soluble salt, usually the acetate or phosphate of the alkaloid.The salts all of which were obtained in the crystalline state,* were titrated with sodium hydroxide in presence of phenolphthalein or thyrnol-p ht halein. Calc. Ba = 41.89y0). * Pope and Read state that the quinine and cinchonine salts were not obtained crystalline. Their strychnine salt contained 1H,O. I" 236 BACKER AND BURGERS RESOLUTION OF CRLOROSULPHOACETIC The normal quinine salt forms a felted mass of small needles containing 4H20 (Found H20 = 8-03 M = 894. requires H20 = 8.05%; M = 895.0). The normal cinchonine salt crystallises with 1H20 in silky needles, concentrically arranged in dense globules (Found H20 = 2.36; M = 780.C2H,0SClS,2C1,H220N2,H20 requires H20 = 2.31% ; M = 780.9). The normal strychnine salt when crystallised from a dilute solution forms needles about & inch long containing 3H20 (Found H20 = 6.08 6.15; M = 896.7 897-2 895.8. C2H,06C1S,2C~,02N2,4H,0 requires H,O = 6.03%; M = 897). d-Chlorosulphoacetic Acid.-Sodium chlorosulphoacetate (0.05 mol.) in 1150 C.C. of water was treated with 33.4 g. (0.1 mol.) of strychnine dissolved in the same volume of water containing 11 g. of acetic acid. Slender needles began to separate within 1 hour and after 10 hours a t 20° 9 g. of strychnine salt were collected corresponding to 20% of the quantity formed (44-8 g.). For polarimetric examination weighed quantities of the strych-nine salt (06-2 g.) were shaken a t 0" with the theoretical quantity of dilute ammonia the volume was brought to 20 c.c.and the solution of the ammonium salt after being extracted four times with half its volume of chloroform was examined by means of a polarimeter (Schmidt and Haensch) with monochromator. In some cases the concentration of the ammonium salt was verified by evaporation of the solution. The rotatory power was measured for X = 589 pp (D) and for two arbitrary wave-lengths in the green (A = 533 pp) and blue (A = 494 pp). The ammonium salt pre-pared from the strychnine salt mentioned above gave the following figures Concentration 0.00480 g.-mol. in 100 c.c.; Z = 2; aD = + 0.18"; [MI = + 18.7". For recrystallisation 4-48 g.(0.005 mol.) of the active strychnine salt were decomposed by ammonia. The separated strychnine was dissolved in dilute acetic acid and added to the solution of the ammonium salt. The total volume being 230 c.c. the concentra-tion was the same as above. 1.3 Grams or nearly 30% separated. Rotation of the ammonium salt Conc. 0.01115 g.-mol. in 100 C.C. ; 1 = 2 ; tcD = + 0*45" as33 = + 0*58" aqD4 = + 0.74" ; [MID = + 20.2" = + 26-0" [MI,, = + 33.2". Conc. 0.00560 g.-mol. in 100 c.c.; I = 2; C C ~ = + 0-23" a533 = + 0*30" a4D4 = + 0.37"; [MID = + 20.5" [M],, = + 26-8" [M'J,, = $- 33.0". Addition of sulphuric acid to liberate the acid (2 mols. for 1 mol. of ammonium salt) increased the rotatory power but this did not chang ACID IKTO ITS OPTICALLY ACTIVE COMPONENTS.237 further on addition of more sulphuric acid. Rotation of the free acid : C'OnC. 0.005 g.-mol. in 100 C.C. ; ,! = 2 ; a = + o.40°,a533 = + o.5?o, 1 - Chlorosulphoacetic Acid .-Sodium c hlorosulp hoac et a t e (0 -0 5 mol.) was mixed with 30 g. (0.1 mol.) of cinchonine dissolved in water containing 9 g . of acetic acid. The total volume was 1150 C.C. After 2 days 5-5 g. of the cinchonine salt or 14% of the total amount (39 g.) had separated. The product was decomposed with ammonia like the strychnine salt the only differeme being that the alkaloid was filtered off before extraction of the solution with chloroform. Rotation of the ammonium salt Conc. 0.00278 g.-mol. in 100 c.c.; I = 2 : The active cinchonine salt (3.9 g.; 0.005 mol.) was recrystallised in the same way as the strychnine salt.From 115 c.c. the same concentration as above there separated 0.95 g. or 257;. Rotatory power of the ammonium salt Conc. 0.00324 g.-mol. in 100 c.c.; I = 2 ; aD = - 0.12" = - 0*17" agg4 = - 0.23"; [AM] = The acid liberated by an excess of sulphuric acid gave the figures : Conc. 0.00305 g.-mol. in 100 c.c.; mD = - 0.23" c1333 = - 0*29", c1494 = -/- 0.62"; [Jf] = + 40" [A$f]533 = + 52" [l!f]gg4 = $- 62". aD = - 0.08" ; f i t l ] D == - 14.4". - 18*5" [ill]533 == - 26.2") [Jf],g4 = - 35.5". aqg4 = - 0.38" ; pi], = - 37-70 [ J ~ I ~ ~ ~ = - 47.50 [N],g = - 62-30. Thus the mean values for the rotatory power are : Chlorosulphoacetic acid [MI = zfr 39" = & 50", h'eutral ammonium salt [il.i'] = & 20" = 36", [MI494 = Zt 62". [&!]494 = & 34". Xacenzisntioiz. The rotation of a neutral solution of the d-ammonium salt contain-ing 0.1 mol. per litre had fallen in a fortnight to half its value. The rotation of a solution containing 0.05 11101. of the d-acid per litre and an excess of sulphuric acid diminished in 10 days by one-fourth. A solution of 0.05 mol. of the ammonium salt per litre containing 0.1 mol. of free ammonia had lost one-third of its rotatory power within 24 hours. The d-acid and the d-ammonium salt each in a solution containing 0.05 mol. per litre were rapidly heated boiled for 1 minute and immediately cooled. Their rotatory powers had decreased by about 5%. The same solutions evaporated on a water-bath and diluted to the original volume racemised completely. Examined a week later it m-as inactive. ORGANIC CHEMICAL LABORATORY, (HOLLAXD ). UNIVERSITY OF GRONINGEN [Received September 8th. 1924.