RELATION OF POSITION lSOMERlSM TO OPTICAL ACTIVITY. 47 VIL-Thc: Relation oj* Positiou Isomerism to O p t i d Activity. V. The Rotcttioib of the iVenthyl Estew of the Isome I& Diby-omobenao ic: Acids. By JUL~US BEREND COIIEN and ISRAEL HYMAN ZORTMAN. THE present paper is a continuation of previous investigations on this subject (Trans., 1903, 83, 1213; 1904, 85, 1262, 1271; 1905, 87, 1190) and contains an account of certain physical constants of the menthyl esters of the six isomeric dibromobenzoic acids and the products formed in their preparation. The esters were prepared by methods already described (Zoc. cit.), namely, by oxidising the six dibromotoluenes to the corresponding acids, which were then converted into the acid chlorides, and the latter into the esters by heating with menthol.The following tables contain the physical constants of the acids, acid chlorides, and esters. The details of their preparation are given in the experimental part. TABLE I. RI. p. of highest m. p. 11. 1). of i~ure acid, recorded by acid Substance. C. a i d Z.. previous obee~vers. chloride. 2 : 9- 2 ; 4- 168-169 149-150" (153 f 147" (Claus Hubner) and Lade)j60-62* 1 1 169 (Miller) I 166.5 (Claus and Weil) 47-49 151-152 { 153 (Claus a,ld wei1),-39--41 158 (Hdbner) 1 189 (Claus and Weil) 136-137" (Meyer and Sudborough) 229-230" (Hiibner) stadt) 232-233" (Halber- 209" (Claus and Weil) stein) 228-227" (Anger- 2 : 5- l'res- BI. 1). of IE. p. ul' sure 52-43" - - ester. ester. iu 111111. 242-2.15 16 - 48-14 238--240 16 - 151-152 - 41-42 241-244 15 - 245-250 20 Tho same relation subsists between the melting points of the acids and esters as was observed in the case of the dichloro- and chloro- bromo-benzoic acids and esters, namely, the lower the melting point of the acid the higher that of the ester.Table 11 contains the densities and specific rotations of the inenthyl esters, together with the molecular rotations of the three series of dihalogen esters.48 COHEN AND ZORTMAN: THE RELATION OF TABLE I1 Menthyl \ [ A l ] ~ o o . ester of Density at 20". [4F. Chlorobromo- dibromo- Dibrorno- ester, Dichloro- beuz- Before dis- After dis- Before dis- After dis- ester, C1 : BY, ester, oic acid. tillation. tillation. tillation. tillation. Br : Rr. Br : C1. C1 : el. 2 : 3- 1.4189 1'4170 - 41.41" - 39'79"" - 173.2" { - 172.9" 2 : 4- 1.4007 1.4060 -51.49 -51.62 - 215.8 { 1:;:; } -209.6 193 5 - - 2 : 6 - .f i n be1 3 : 4 - - 1 *4'L58 - -55.18" -230'7 { )- -227.5 8 : 5- 1'4114 1'4150 -54'57 -53'79 * -228'2 -235.9 -233.2 Menthyl - - - 90.92 { i%k;:;e) - 236'3 - - benzoate} * In the case of the 2 : 3- and 3 : 5-estersY a little acid separated on distillation, The rotation I n all other cases, and the product was probably less pure than the undistilled material. is therefore calculated from observations on the undistilled ester. the rotation is that of the distilled product, which is assumed to be purer. With the single exception of the 2 : 6-ester, the effect of the substi- tution of two bromine atoms is less than that of the substitution of two chlorine or one chlorine and one bromine atom. This result was anticipated from the relation which subsists between the monochloro- and monobromo-derivatives (Trans., 1903, 83, 121 6).The magnitude of the deviation beginning with the ester OF smallest rotation is as follows : 2:6-; 2 : 3 - ; 2 : 5 - ; 2:4; 3:5-; 3 : 4 - ; phenyl. The order is the same as that of the dichloro- and chlorobromo- esters with the exception of the 3 : 4- and 3 : 5-esters, the positions of which are reversed in the present case. The influence of the ortho- bromine atom in depressing the rotation is very clearly indicated in all cases, but most strikingly in that of the 2 : 6-ester. The steadily and rapidly decreasing rotation with the increasing atomic weight of the halogens in the di-ortho-positions induces one t o predict the almost complete annihilation of activity in compounds which contain iodine in place of the other halogens.The remarkably high melting point of the diortho-ester corresponds closely with the constants of the other 2 : 6-dihalogen compounds ; the dichloro-ester melts a t 134--135O, the chlorobromo-ester at 144-1 45", and the dibromo-ester at 151-152".POSITION ISOMERlSM TO OPTICAL ACTIVITY. V. 49 E x PER IMENTA L. Preparation of the Dibromohenxoic Acids, Acid Chlorides, and Menthy2 Esters. The method employed for obtaining the dibromobenzoic acids is pre- cisely that used in the former preparations of the dihalogen compounds (Zoc. cit.) and needs no general description. The acid chlorides were prepared and purified in the manner already described.As in former examples of diortho-acid chlorides, the 2 : 6-dibromobenzoyl chloride required a much higher temperature for esterification (I 75-180') than the isomeric acid chlorides, all of which react rapidly below 130' with menthol. The esters, with the exception of the 2 : 6-compound, were distilled under diminished pressure. The rotations before and after distillation varied slightly. I n the two cases already referred to, namely, those of the 2 : 3- and 3 : 5-esters, some decomposition occurred and a little free acid separated in the distillate. The effect was to lower the rotation slightly. It is evident that even a t this high temperature of distillation no racemisation occurs. Menthyl 2 : 3-Dibromoberzxoate.-The dibromobenzoic acid was pre- pared from 3-nitro-o-toluidine (obtained from aceto-o-toluidide by Reverdin and Crdpieux's method) (Bey., 1900, 33, 2498).The base was diazotised and converted into the bromonitro-compound, reduced to the bromoamine, and again diazotised as follows : This may serve to illustrate the series of reactions usually adopted in the preparation of the other dibromotoluenes. Sixty grams of nitro- toluidine gave nearly 20 grams of 2 : 3-dibromotoluene. The oxidation of the dibromotoluene was effected by heating in sealed tubes with dilute nitric acid (1 vol. of HNO,, sp. gr. 1.4, to 2 vols. of water) a t 130-135' for' five and a half hours. The acid which was separated from the product was very impure and, like the product of oxidation of the 3-chloro-2-bromotoluene (Trans., 1904, 85, 1266), contained a large quantity of a compound melting above 200' and also a substance melting below 135'.The crude material, amounting to 16 grams, was purified by repeated crystallisation from ligroin, in which the less fusible acid is nearly insoluble and the more fusible compound readily soluble, whilst the 2 : 3-acid dissolves in the boiling liquid, but is nearly insoluble in the cold. Eventually 4.2 grams of acid were obtained, which seemed to YOL. LXXXIX. E50 COHEN AND ZORTMAX: THE RELATION OF soften slightly a few degrees below 148' and then melted sharply. Recrystallisation did not seem to alter the melting point, but a small quantity of acid obtained a t a later stage on distilling the menthyl ester melted sharply a t 149-150', and may be taken as the true melting point.The acid was heated on the water-bath with an equal weight of phosphorus pentachloride and the product distilled under diminished pressure at 100" to remove most of the phosphorus oxy- chloride. The acid chloride, which solidified on cooling, was dissolved in benzene t o separate the insoluble phosphorus pentachloride and the benzene distilled off, the last traces being removed by heating to 100" in a vacuum. The residual solid cake was powdered and pressed on a porous plate and left in a vacuum desiccator to remove any remaining phosphorus oxychloride. The crude acid chloride melted at 55-60" and after one crystallisation from ligroin a t 60-62". The product, amounting t o 3.5 grams, was heated in an oil-bath with 2.5 grams of pure menthol (Kahlbaum), the specific rotation of which had been ascertained, and gave the correct number.The reaction began at 100-105'. The mixture was maintained at 130' for an hour, water and a little sodium carbonate solution were then added, and the ester submitted to distillation in steam until all trace of free menthol had been removed. The residue was extracted with ether, dehydrated with fused calcium chloride, and the ether removed by distillation. The product solidified on cooling and melted sharply a t 52-53', The fused substance had an amber colour, which, however, did not interfere with the polarimeter readings : I = 0.303 dcm., d/30° = 1.4189, aD - 17.74". The ester, after distilling under reduced pressure, was colourless. A little free acid which separated in the process was removed by dissolv- ing in light petroleum, in which the acid is insoluble, and filtering.The distilled product melted a t 49-52?', which is lower than the original material, and was therefore less pure. A redetermination of the rotation and density confirmed this: 1=0*303 dcm., dj20°== 1.4170, a,, - 17.03'. The analyses of this and the other esters are recorded in a table a t the end of the paper. Jlenthyl 2 : 4-Dibronzohenxoate.-The dibromotoluene which served for the preparation of the acid was obtained from 2 : 4-nitrotoluidine by the usual series of operations. Sixty grams of the base gave 35 grams of dibromotoluene boiling at 152-158' under 80 mm. pressure. Twenty grams gave, on oxidation at 120-125" for five hours, 16 grams of crude acid (m.p. 145-152'), which were subjected t o steam-distillation to remove a small quantity of less fusible substance which was volatile in steam. After recrystallisation from benzene, 6 grams of acid were obtained melting a t 164-166'. ThisPOSITION ISOMERISM TO OPTICAL ACTIVITY. V. 51 was successively converted in the usual way into the acid chloride (m. p. 43-45') and the ester, which gave the following polarimeter readings : I = 0.302 dcm., d,'20°= 1.4023, a, - 21.94". The dibromo- toluene gave in succession 15 grams of acid (m. p. 165-167'), 13 grams of acid chloride (m. p. 47-49'), and 13.5 grams of ester. The polarimeter readings (u) before and ( b ) after distillation were as follows : a. E = 0.302 dcm. ; d/20' = 1.4007 ; aD - 21.78". A second preparation was made in a similar may.b. I = 0.302 dcm. ; d/20"= 1.4060 ; a D - 21.92". Menthyl 2 : 5-Bibromober~xoate.-The 2 : 5-dibromotoluene was ob- tained from 2 : 5-nitrotoluidine. Sixty grams of base gave 35 grams of dibromotoluene (b. p. 155-170°/120 mm.). The crude acid was crystallised repeatedly from alcohol and benzene, and finally from water after boiling with animal charcoal to remove colouring matter. About 26 grams of dibromotoluene yielded 9 grams of pure acid (m. p. 150-151"). The latter gave 6 grams of acid chloride (m. p. 39-41'> arid finally 7.3 grams of ester (m. p. 42-44'). The following are the polarimeter readings : ( u ) before and ( b ) after distillation : a. I = 0.302 dcm. ; d/20° = 1.3809 ; U D - 21.7". b. 1=0.302 dcm. ; d/20°= 1.3821 ; a , - 21.27".itfenthyl 2 : 6-Dibromobenxoate.-The 2 : 6-dibromotoluene used for oxidation was obtained from 2 : 6-dinitroluene by a series of alternate re- ductions and diazotisations. The yield from 150 grams of dinitro-corn- pound amounted to 50 grams of dibromotoluene (b. p. 110-130"/30 mm.). The 29 grams of crude acid obtained on oxidation were first purified by esterifying with methyl alcohol and hydrochloric acid, The 2:6-acid is not attacked, whereas other acids which may be present as by-products are esterified, and can be removed by shaking out the alkaline solution with ether. The crude acid was then recrystallised from benzene, when 11 grams of pure 2 : 6-acid were obtained, which crystallised in hexagonal plates and melted at 146-141". It was converted into the acid chloride (m.p. 35-39"), which, on crystallising from light petroleum, formed colourless needles (m. p. 39-42O). Seven grams of acid chloride gave, after crys- tallisation from alcohol, 5 grams of pure menthyl ester in colourless needles (m. p. 151-152'). The rotation was determined in benzene solution as follows : 3.9104 grams in 25.07 C.C. of benzene ; I = 2 dcm. ; uD - 1-46". 10 C.C. of above solution and 10 C.C. of benzene; E=2 dcm.; a D - 0.64". E 252 RELATION OF POSITfON 1SOMERISM TO OPTICAL ACTIVITY. 2.3760 grams in 13 C.C. of benzene ; I = 2 dcm. ; 1 *2798 grams in 13 C.C. of benzene; I = 2 dcm. ; Menthyl 3 : 4-Dibromobenxoate.-The aceto-p-toluidide used in the pre- paration of 3 : 4-dibromotoluene was brominated and then hy drolysed, and the 3-bromo-p-toluidide thus obtained was then diazotised in the usual way.Thirty-four grams of bromotoluidine gave 23 grams of 3 : 4-dibromotoluene (b. p. 160-165'/65 mm.). On oxidation in sealed tubes, 10 grams of acid (m. p. 215-225') were obtained which were recrystallised from dilute alcohol with the addition of animal charcoal and then gave a colourless product (m. p. 227-229'). About 7 grams of pure acid gave a n equal weight of acid chloride (m. p. 64-66') The ester amounted to 7.8 grams of a brown, viscid liquid which showed a rotation of - 33*5', but as the colour interfered with the reading, the ester was distilled under reduced pressure, and the colourless distillate then gave the following result : I = 0.302 dcm., d/20° = 1.4-258, a, - 23-76'.The liquid solidified on standing for some weeks and then melted at 41.43'. Menthyl 3 : 5-dibromobenxoccte.--The 3 : 5-dibromotoluene was obtained from 3-bromo-p-toluidine (b. p. 166'/50 mm.), described above, which was brominated and the amino-group replaced by hydrogen i n the usual way. Thirty-seven grams of bromotoluidine gave 34 grams of 3 : 5-dibromotoluene (m. p. 38-39'). Thirty grams of dibromotoluene gave 26 grams of crude acid, which, after recrystallisation from benzene, gave 18 grams of pure substance (m. p. 213-214'). From the acid were obtained 15.5 grams of pure acid chloride (m. p. 41-42'), and finally 20 grams of menthyl ester. The following polarimeter readings were made : ( a ) before and ( b ) after distillation : uD - 1 ~ 9 8 ~ . aD - 0-SO". (a) 1=0.302 dcm. ; d/2Oo= 1.4114; UD - 23.26". (b) I = 0.302 dcm. ; UD - 23.00". d/20' = 1.4159 ; As a little acid separated in the process of distillation, the un- distilled product probably gives the more trustworthy value. It should be added that although the melting points of several of the esters lie much above 20", a t which the densities and polarimeter readings were taken, they are easily supercooled and remain in a fused state a t 20' without showing any signs of solidification. The tendency to supercooling is rather remarkable, and it has been frequently observed that when the fused liquid has been cooled to the ordinary temperature in the pyknometer and crystallisation has begun a t the capillary end, the main portion will remain liquid for a considerable time.PRICE : CARO'S PERMONOSULPHURIC ACID. TABLE 111. Analyses of the Dibromobenxoic Esters. 2 : 3- 0.1476 0.1338 38.58 2 : 4- 0'2154 0.1920 37'98 2 : 5- 0 '1 338 0'1185 37.70 2 : 6- 0.1236 0'1114 38.34 3 : 4- 0'1208 0.1087 38'30 3 : 5 - 0.1552 0.1392 38.16 C,7H,0,Rr., requires Br = 38.27 per cent. Menthyl ester. Substance taken. AgBr. Per cent. THE UNIVERSITY, LEEDS. 53