1852 FRANKLAND AND TWISS: THE INFLUENCE OF VARIOUS CLXX1X.-The Influence of Various Substituents on the By PERCY FARADAY FRANKLAND and DOUGLAS FRANK TWISS, M.Sc. IN a previous communication on the same subject, the optical activity of seventeen derivatives of tartramide has been described by one of us (P. F. Frankland and Slator, Trans., 1903, 83, 1349), but amongst these only the methylamide and ethylamide were derivatives of tartaric acid with aliphatic amines. I n the present communication we have confined our attention to the latter, having prepared and examined the normal and isopropylamides, the allylamide, the normal and iso- butylamides, and the normal heptylamide. The rotation of these compounds has, as before, been determined in pyridine, and, when possible, also in methyl alcohol, and in water solution.The amides described i n the present paper were prepared by the interaction in the cold of the amine with an alcoholic solution of methyl tartrate, and all were obtained as crystalline bodies of high melting point (183-216'). Excepting in the case of the isopropyl- amide, of which only 23 per cent, of the theoretical quantity was obtained, the yields were excellent, and in the case of the isopro- pylamide also a better yield would no doubt have resulted if the alcohol had been evaporated off after completion of the reaction. The results of our investigation are summarised in the following table : Optical Activity o f Tartramide. Part 11.SURSTITUEKTS ON THE OPTICAL ACTIVITY OF TARTHAMIDE. 1853 Tartaric di- Amide.................. Methylamide ......... n-Propylamide ...... isoPropylamide ...... E th ylamide ......... Allylamide .......... n-Butylamide.. ....... n-Heptj lamide ...... isoButylamide ...... Sunzrnary of Results : Py ridinc. Mc thy1 alcohol. Water. Melting b F-, point. p . p. [hl]?'. p. [w:oO. 195" - - 0.0807 -t208" 0'077 +160" - - 0-1797 213 1-305 158 189 0.684 +274" 4'998 266 0-994 255 7-679 279 4-986 262 10.350 242 210-211 1.049 277 4,997 282 1'390 262 5.030 2 i 9 5.001 281 i-468 256 216 2.196 289 2.019 290 1.808 264 4'741 287 4.857 290 2.717 260 189 1'654 272 1'910 273 1.398 247 4.665 272 4.867 272 4.682 247 183 2.528 251 2900 273 2.392 247 4.735 252 5.914 270 4.697 246 193 1.899 286 0.907 298 0.258 280 4.801 288 4'416 291 - - 183.5 1.753 295 1.007 306 0.549 275 5'064 294 5'432 305 - - 183 1'621 304 0.9951 303 - - 3.579 305 - - - - With the above may be compared the previously-determined rotations of the following substitution derivatives of tartramide : Tartaric di- Pyridine.Methyl alcohol. Piperidide * ................................ 0" - Phenylhydrazide .......................... < + 80 - Diacrtj lltartaricl-o-toluidide ............ + 80 - H ydrazide -- - nc-Tetrahydro-/3-naphth~lamide * ...... + 240 - Tartranil. ..................................... + 2 i 2 + 268" Benzylamide ................................ + 300 Furfurylaniide .............................. + 307 _- Tartaric-p-toluil ........................... + 366 + 280 Acetophenone- hydrazone .................. + 397 - a-Naphthylamide ...........................+ 400 - Benzylidene-hydrazide ..................... + 554 - o-Toluididc - ............................... + 667 ni-Toluidide - ................................. -t 730 Furfurylidene-hydrazidc ................ t 736 - Anilide + 739 - p.Toluidide ................................... + i 9 3 - nr-Tctrahydro-/3-naphthylamide * ...... + 840 - B-Naphthylamide .......................... + 1160 - Methyltartrimide t ...................... c - Ethyl tax t rimide t - - .................................... - ..................................... ........................... * Frankland and Ormerod, Trans., 1903, 83, 1342. t Ladenburg, Ber., 1896, 29, 2710. Water. + 281 *6 f 264 -3 The foregoing figures show that all the substituted tartramidcs, excepting the phenylhydrazide and piperidide, have a higher dext ro- 6 F 21854 FRANKLANn ANT) TWISS : TT-TE INFT,UENCE OF VARIOIJS rotation than tartramide itself, and that substitution by aromatic radicles leads to a dextrorotation of a much higher order than that resulting from substitution by aliphatic groups.The piperidide is inactive, at any rate in pyridine and in aniline solutions, which were the only ones in which it was examined, The benzylamide and fur- furylamide have about the same rotation in pyridine as the n-heptyl- amide, whilst the ac-tetrahydro-/I-naphthylamide has even a lower dextrorotation in pyridine than any of the alkyl-substituted tar- tramides. Taking the derivatives with the aliphatic amines of the normal series, it appears that the value of [MI, does not show any evidence of having reached a maximum within the range of the series of com- pounds prepared, for the n-heptylamide has a higher molecular rota- tion than any of the lower homologues.The isopropylamide has a lower rotation than the n-propylamide, whilst the rotation of the iso- butylamide is greater (excepting in water solution) than that of the 91-bntylamide. The rotatioh of the allylamide as compared with that of the n-pro- pylamide is particularly interesting, for it is now generally believed that the presence of a double bond in a carbon-chain leads to an increase in the optical activity (see P. Frankland and Slator, Trans., 1903, 83, 1351, where numerous references to this relationship are given). In the present case, however, the substitution of n-propyl by ally1 is attended by a marked diminution in the rotation, and the same exceptional relationship will be shown by one of us (P.Frankland and Done) to be exhibited in the case of the n-propylamide and allylamide of malic acid. The piperidide ig the only secondary amide hitherto examined, and, as indicated in the above table, it was found to be practically inactive ; this result naturally suggests that racemisation of the tartaric acid had taken place in the process of preparation, but it may also be due to the dextrorotation being depressed to about zero by the introduction of the piperidine group, and that this is perhaps the case is rendered less remotely possible since it has been found by one of us that in the malic series the piperidide has a much lower rotation than the un- substituted malamide in pyridine and methyl alcohol solutions, whilst in glacial acetic acid solution the sign of the rotation is actually reversed.EXPERIMENTAL. Tartaric Di-n-propylarnide. An excess of n-propylamine was added to a concentrated solution of methyl tartrate in absolute ethyl alcohol in the cold. The separation of amide commenced in the course of a few minutes j the crystalsSUBYTITUENTS ON THE OPTICAL ACTIVITY OF TARTRAMIDE. 1855 formed, after standing for two days, were filtered off, and a further crop was obtained by evaporating part of the alcohol. The yield was about 80 per cent. The product was purified by recrystallising from a mixture of equal parts of ethyl alcohol and ethyl acetate. 0,0946 gave 10.0 C.C.moist nitrogen at 16.5Oand 761 mm. N = 12.30. Tartaric di-n-propylcmi& crystallises in colourless, flat, elongated plates, or fiat needles, melting at 216' with slight decomposition. It is easily soluble in pyridine, or hot alcohol, less so in ethyl acetate, whilst in cold water the strongest obtainable solution was about 2.4 per cent. C,oH,,04N, requires N = 12-07 per cent. Rotation of l'ccrturic Di-n-popyEanLide. 2). cl 20"/4". 4.741 0-9867 2.196 0.9817 4.857 0.8083 2'019 0-7991 2'717 1.0029 1 '808 1'0014 1. ay. [a]?. " 1 5 Ppaidine Solution. 0.999 +5.79" +123'9" +287'4" 1 *998 5 *37 124'7 289'2 Methyl Alcol~ol Solution. 1 '998 + 9 -79" -I- 124 '8" + 289 *5" 1.998 4-03 124'9 289.7 TVater Solution. 0.999 + 3.05' + 112.1" + 260.0" 1 -998 4-11 113'6 263-6 Turta ric Diisoprop y la~nide.The theoretical quantity of i8opropylamine was added to ' a solution of methyl tartrate in absolute ethyl alcohol. After standing two days the liquid became viscid and yellow ; the amide separated from this on cooling with ice or adding a crystal as nucleus. After standing two more days the crystals were filtered off, but only a 23 per cent. yield was obtained. The product was recrystallised from ethyl acetate to which a little alcohol had been added. N = 12.03. 0.1130 gave 12.1 C.C. moist nitrogen at 17Oand 737 mm. Tartaric di-isopropylamide crystallises in slightly flattened needles, I t s solubility in the ordinary C,,H,o04N, requires N = 12-07 per cent. melting at 189' without decomposition. solvents is rather greater than that of the normal propylamide.1856 FRANKLAND AND TWISS: THE INFLUENCE OF VARIOUS Pa 1.654 4-665 1910 4-867 1 '398 4 -682 Rotation of Tartaric Diisopropylamide.d 20"/43 0.9806 0.9858 0.79iO 0 8058 1 '0003 1 -0059 1. Qpidine Solution. 1.998 +3$Oo 3-117.3" 0.999 5 -38 117.1 Jlethpl Alcolml Solutiow. 1'998 + 3-59O + 117%" 0'999 4 -60 117'4 Water Solution. 1 '998 4- 2.98" + 106.7" 0.999 5 -00 106-3 Taqstaric Diallylantide. This was similarly prepared by mixture of theoretical of allylamine and methyl tartrate in alcoholic solution. [M]",". + 272 *Oa 271 *7 1- 273'3" 272'4 + 247-4" 246.6 proportions The amide already began to separate after an hour, and by filtering off the crystals after twenty-four hours' contact, a yield of 62 per cent. was obtained. The product was purified by recrystallisation from a mixture of equal parts of ethyl alcohol and ethyl acetate.0,0997 gave 10.84 C.C. moist nitrogen at 15Oand 745 mm. N= 12.48. CloH160,N, requires N = 12.28 per cent. Tartaric diaZZyZamide crystallises in flat, thin, colourless plates Its solubility in the common melting at 1 8 3 O to a pale yellow liquid. solvents is about the same as that of the n-propylamide. IZotatio~t of Tartayic Diallylamide. P. d 20"/4". 2.528 0'9838 4.735 0'9896 8'900 0'8023 5'914 0'8092 2'392 1'0036 4-697 1 'ooa6 I?. U","". [4y. [MI?. Pyridine Solution. 1 -998 +5*48" 4-110-3" +%51'4" 0'999 5 -18 110.7 252.3 Methyl A lcohol Solution. 1.998 + 5 -5i" +119%" + 2 7 3 Y 0.999 5 -66 118'4 269.9 FVate?. Solutiooh. 1 -99a + 5-19' 3- 1082" + 246.7" 0'999 5-10 107'8 245-7SUBSTITVENTS ON THE OPTICAL ACTIVITY OF TARTRAMIDE 1857 Tartaric Di-n-butylamide.Butylamine was added in theoretical quantity to a cooled solution of methyl tartrate in ethyl alcohol. The separated amide was filtered off after themixture had stood f o r about thirteen hours, a 75 per cent. yield being obtained. The product mas purified by recrystallisation from a mixture of two parts of ethyl acetate to one of ethyl alcohol. 0,1482 gave 14.0 C.C. moist nitrogen at 17" and 737 mm. N = 10.84. Tartaric di-n-butylamide crystallises in beautiful, long, flat, needles melting at 193' without decomposition. Like the other amides described above, it is very soluble in pyridine or alcohol ; its solubility in water is, however, very small (only 0.3 per cent.).C12H2404N2 requires N = 10.77 per cent. Rotation of Turtcevic Di-n-butylamide. . d 20"/4". 1. a","", [a]ioo. Pyridine Soiution. 1'899 o-gaog 1-998 i- 4.10" + 110.2" + 286.4" 4.801 0.9849 0.999 5-23 110.7 287.8 Methyl Alcohol Solution. 0.907 0.7949 3.893 + 3.22" + 114-6" + 297.8" 4.416 0 *a033 0'999 3-97 112-0 291.3 Wuter Solution. 0.258 0.9989 3'899 + 1.08" + 107 '5" + 279 -5" Tartaric Diisobutylamide. i8oButylamine was added in theoretical quantity to a cooled solution of methyl tartrate in ethyl alcohol. After standing twelve hours, the amide which had separated was filtered off, the yield being about 70 per cent., whilst more was obtainable by evaporating the mother liquor. 0.1227 gave 11.8 C.C. moist nitrogen at 19"and 756.5 mm. N= 11.01. l'urturic diisobutylamide crystallises in small rhombic pJates melting at 183.5".It is more soluble in the ordinary organic solvents than the normal butyl- and propyl-amides, resembling the isopropylamide in this respect, but it is only very slightly so in water (0.8 per cent.). C!l,H,,O,N, requires N = 10.77 per cent.1858 P. 1 *753 5 '064 1 -007 5'432 0.549 OPTICAL ACTIVITY OF TARTRAMIDE. Rotation of Tuifuric Diisobutylamide. d 20"/4". I?. a:". [a]?. Pyridine So lution. 0.9805 1 '998 + 3.90" + 113.6" 0.9853 0'999 5.64 113.2 Methyl Alcohol Solution. 0-7949 3.899 + 3-67' + 117%" 0'8065 0 '999 5.13 117 -2 Wuter Solution. 0'9991 3.899 4- 2'26" d- 105.6" Tartaria Bi-n-hept ylumide. [ M]y. + 295.3" 894.3 + 305.7" 304.8 + 274.6" A theoretical quantity of n-heptylamine (Kahl baum) was added to a cold solution of methyl tartrate in absolute alcohol, The mixture became a solid mass i n the course of a few hours, and a theoretical yield of the amide was obtained.It was recrystallised from methylated spirit until of constant rotation. It forms elongated, flat plates melting at 183' without decomposition, and is much less soluble in most solvents than are the lower amides above mentioned. I t is insoluble in water, slightly soluble in cold alcohol, and at the ordinary temperature gives only about a 4 per cent. solution in pyridine. 0.2680 gave 19.4 C.C. moist nitrogen at 12' and 728 mm. ; N = 8.22. C,,H,,O,N, requires N = 8.14 per cent. Rotution of Taytaric Bi-n-?Leptylumide. P* d 20°/4". 1. a"," . [a]',"". [MIY. 1.621 0.9789 2.993 + 4.190 + 88-24" + 303.5" Pyridine Solution. 3.579 0'9805 0.999 3.11 88-72 305-2 Methyl Alcohol Solution. 0.9951 0.7955 3.899 + 2'72" t 88.14" + 303.2" Rotation of Tartayic BiphenyEhydrasiJe. Glacial Acetic Acid Solution. 0'5672 1.052 3.899 + 1'88" + 80'55" + 266.80'OPTICAL ACTIVITY OF MALAMIDE. 1859 Rotation of Tarturic Dinzethykamide. P. d 20"/4". 1. a:*'. [a]ioo. [ M]ioe. Nethyl Alcohol Xolution. 4.998 0.8147 3'899 + 23-97' + 151.0" + 265.8" 4.986 0.8147 1.998 12-08 148 *8 261.9 Rotation of Tartaric Diethylamide. MetAp 2 A Zcohol Xolution. 4'997 0'8117 1.998 $11'20" -1-138'1" +281'7" 5 '001 0-8127 1'998 11-21 137'9 251'3 CHEMICAL DEPARTMENT, UNIVERSITY OF BIRMINGHAM.