Patent GB-662798-A (GB)
Title: Improvements in or relating to the production of sulphonamides and intermediates thereof
IPC: C07D277/56
Filed: 1949-05-05
Abstract: p - Hydroxybenzenesulphonamido - heterocyclic compounds of the general formula <FORM:0662798/IV (b)/1> in which R is hydrogen or an aliphatic, aralkyl or heterocyclic residue, are prepared by condensing a p-acyloxybenzenesulphonyl halide with an amino heterocyclic compound having the formula NHR-Het, and hydrolyzing the p - acyloxybenzenesulphonamido - heterocyclic compound so formed until the acyl group is replaced by hydrogen.  The hydrolysis preferably takes place in the presence of an aqueous solvent and at a temperature between 0 DEG  and 150 DEG  C. using either acidic or alkaline agents.  In examples: (1) 2-aminothiazole is condensed with 1 - benzoyloxybenzene - 4-sulphonyl chloride in pyridine and the product hydrolysed by heating with aqueous sodium hydroxide; (2) 2-aminothiazole is condensed with 1 - carbethoxyoxybenzene - 4 - sulphonyl chloride in pyridine and the product hydrolysed; (3) 2 - amino - 5 - carbethoxy - thiazole is condensed with 1-carbethoxyoxybenzene-4-sulphonyl chloride and the product hydrolysed; (4) 2-aminopyrazine is condensed with 1-carbethoxyoxybenzene - 4 - sulphonyl chloride and the product hydrolysed, and in an analogous manner there is obtained (5) N-(2-pyridyl)-1-phenol - 4 - sulphonamide from 1 - carbethoxyoxybenzene - 4 - sulphonamide; (6) N - (2-pyridyl) - 1 - phenol - 4 - sulphonamide from 4 - (p - toluenesulphonyloxy) - benzene - 1 - sulphonyl chloride-itself obtained by reacting phosphorus pentachloride with the sodium salt of 1-(p-toluene-sulphonyloxy)-benzene-4-sulphonic acid; (7) N-(2-pyridyl)-1-phenol-4-sulphonamide from 1 - acetoxybenzene - 4-sulphonyl halide; (8) N-(2-pyrimidyl)-1-phenol-4 - sulphonamide; (9) N - (4 - methoxy - 2-pyrimidyl) - 1 - phenol - 4 - sulphonamide, and (10) N - (4 - methyl - 2 - pyrimidyl) - 1 - phenol-4-sulphonamide from 1-carbethoxyoxybenzene-4-sulphonylchloride; (11) N-(4,6-dimethyl-2-pyrimidyl) - 1 - phenol - 4 - sulphonamide from 1 - (p - toluenesulphonyloxy) - benzene - 4-sulphonyl chloride; (12) N - (5 - methyl - 2-thiadiazolyl) - 1 - phenyl - 4 - sulphonamide from 1 - benzoyloxybenzene - 4 - sulphonyl chloride; (13) N - (2 - quinolyl) - 1 - phenol - 4-sulphonyl chloride; (14) N-(2-thiazolyl)-1-phenol-4-sulphonamide from N-(2-thiazolyl)-1-carbethoxyoyxbenzene - 4 - sulphonamide using aqueous sulphuric acid, and (15) N-(2-pyridyl - 1 - (p - toluenesulphonyloxy) - benzene-4 - sulphonamide from N - (2 - pyridyl) - 1 - (p-toluenesulphonyloxy) - benzene - 4 - sulphonyl chloride.  Other heterocyclic residues referred to are those of pyridazine, imidazoline, thiophene, pyrrole, pyrazole, purine, iso-oxazole, thiazolidine, oxazine, acridine, benzothiazole, quinoxaline and pteridine.  Substituent groups such as alkyl, alkoxy, hydroxyalkyl, carboxyl, halo, carbalkoxy, nitro and amino groups may be present.  Where R in the general formula is an organic radical, secondary amines such as 2 - N - (b  - hydroxyethyl) - amino thiazole, bis - 2 - pyridyl amine, 2 - (N - methylamino)-pyridine and 2 - (N - methylamino) - benzothiazole may be used.