Patent GB-676037-A (GB)
Title: Splitting of sulphonamides
Inventor: WEISBLAT DAVID IRWIN
IPC: C07D475/04
Filed: 1950-01-27
Abstract: <FORM:0676037/IV (b)/1> Aromatic amines are prepared by splitting a sulphonyl radical from an aryl sulphonamide by means of hydrogen bromide in the presence of an aliphatic acid and a phenol or unsaturated compound which absorbs bromine more readily than the amine.  Suitable phenols are phenol itself, catechol, resorcinol, naphthol and monochlorophenol, and suitable unsaturated compounds are amylene and cyclohexene.  Preferably the reaction is carried out under anhydrous conditions at temperatures from 0 DEG  to 100 DEG  C. and with a ratio of hydrogen bromide to aryl where R1 is hydrogen and n is 1; (14) ethyl N-([2 - amino - 4 - hydroxy - 6 - pteridyl] methyl) - p - toluenesulphonyl-p-aminobenzoate is heated as in (7) to yield N-([2-amino-4-hydroxy-6-pteridyl]-methyl)-p-aminobenzoic acid; (15) N-([2-amino-4-hydroxy-6-pteridyl] methyl)-p-toluenesulphonyl-p-aminobenzoic acid is treated as in (14) and yields the same product; and (16) N-(2,3-diacetoxypropyl)-p-toluenesulphonyl-p-aminobenzoic acid is treated as in (7) to give N-(2,3-diacetoxypropyl)-p-aminobenzoic acid hydrobromide.  Ethyl N - (3 - chloro - 3 - ketopropyl) - p - toluenesulphonyl-p-aminobenzoate is obtained by treating ethyl p - toluenesulphonyl - p - aminosulphonamide of at least 2.1 to 1. In a particular form of the invention an aromatic amine HNYW may be prepared from a sulphonamide M-SO2-NYW in which M is an alkyl, aryl, aralkyl or cycloalkyl radical or substitution derivative thereof, and W is an aromatic radical.  Many suitable such radicals are specified. In examples: (1) p-toluenesulphonanilide, hydrogen bromide, glacial acetic acid and phenol are reacted to yield aniline hydrobromide; (2) p-toluenesulphonanilide, hydrogen bromide, pelargonic acid and phenol are reacted to yield aniline hydrobromide; (3) ethyl N-(p-toluenesulphonyl)-p-aminobenzoate, hydrogen bromide, acetic acid and phenol are reacted to yield ethyl p-aminobenzoate hydrobromide; (4), (5) and (6), N-methyl-p-toluenesulphonanilide, hydrogen bromide, acetic acid and phenol, betanaphthol or catechol are reacted to yield N-methylaniline hydrobromide; (7) meta-nitrobenzenesulphonanilide is reacted with hydrogen bromide, acetic acid and phenol to yield aniline hydrobromide; (8) beta-naphthalenesulphonanilide is reacted as in (7) to yield aniline hydrobromide; (9) methanesulphonanilide, and (10) p-nitrobenzenesulphonanilide are reacted as in (7) to yield aniline hydrobromide; (11) ethyl N - (3 - chloro - 2 - ketopropyl - N - p - toluenesulphonyl)-p-aminobenzoate is reacted as in (7) to yield N-(3-chloro-2-ketopropyl)-p-aminobenzoate hydrobromide; (12) diethyl N1-(p-toluenesulphonyl-p-aminobenzoyl)-glutamate is treated as in (7) to yield diethyl N1-(p-aminobenzoyl)-glutamate; (13) diethyl-N1-(NN-[(2-amino - 4 - hydroxy - 6 - pteridyl) methyl]-p-toluenesulphonyl - p - aminobenzoyl) - glutamate is reacted as in (7) to yield diethyl N1-(N-[(2-amino - 4 - hydroxy - 6 - pteridyl) methyl] - p - aminobenzoyl)-glutamate which is then hydrolysed to give N1-(N-[(2-amino-4-hydroxy-6-pteridyl) methyl] - p - aminobenzoyl) - glutamic acid benzoate with epichlorohydrin and oxidizing the ethyl N - (3 - chloro - 2 - hydroxypropyl) - p - toluenesulphonyl-p-aminobenzoate formed with sodium dichromate. Diethyl N1 - (p - toluenesulphonyl - p - aminobenzoyl)-l-glutamate is obtained from p-toluenesulphonyl-p-aminobenzoic acid by treatment with thionyl chloride to give the acid chloride which is then reacted with diethyl l-glutamate hydrochloride.  Diethyl N1 - (N - [3 - chloro - 2 - hydroxypropyl] - p -toluenesulphonyl - p - aminobenzoyl)-glutamate is made from diethyl N1-(p-toluenesulphonyl-p-aminobenzoyl)-glutamate and epichlorohydrin and is converted to diethyl N1-(N-[3 - chloro - 2 - ketopropyl) - p - toluenesulphonyl - p-aminobenzoyl)-glutamate by oxidation with chromic anhydride which is then treated with 2,4,5 - triamino - 6 - hydroxy - pyrimidine to yield diethyl N1 - (N - [(2 - amino - 4 - hydroxy - 6 - pteridyl] methyl) - p - toluenesulphonyl - p - aminobenzoyl) - l - glutamate.