Patent GB-554975-A (GB)
Title: Sulphanilamide derivatives
IPC: C07C311/37
Filed: 1941-11-19
Abstract: 554,975. Benzenesulphonyl isothioureas. HAWORTH, E., ROSE, F. L., SWAIN, G., and IMPERIAL CHEMICAL INDUSTRIES, Ltd. Nov. 19, 1941, No. 14859. [Class 2 (iii)] Para substituted benzene sulphonylisothioureas of the general formula X-C 6 H 4 -SO 2 -NH-C(NH)-S-R where X stands for nitro or acylamino are prepared by reacting a p-nitro-, or p-acylaminobenzene sulphonyl halide with an S-alkyl, S- cycloalkyl, or S-aralkyl-isothiourea. The reaction is preferably carried out in the presence of a solvent or diluent and in the presence of an acid binding agent preferably a base. Acid binding agents mentioned include inorganic materials such as caustic soda and sodium carbonate or organic compounds such as pyridine. When the p-nitro compounds are prepared these may be reduced to the corresponding p-amino compounds. The p-amino-, and p-acylamino-benzenesulphonyl-isothioureas so produced may if desired be treated with ammonia to produce p-amino-, and p-acylaminobenzenesulphonylguanidines, with the elimination of the mercaptan. This reaction is preferably carried out with phenol as a solvent. The ammonia may be passed in as a gas stream or generated in situ in which case it is preferred to work under pressure. In examples (1) 4- acetylaminobenzene sulphonyl chloride and S-methyl-isothiourea sulphate are reacted in acetone in the presence of caustic soda to produce N-(4-acetyl-aminobenzenesulphonyl) S- methyl isothiourea, as starting materials there may be used also the S-ethyl or the S-benzyl isothioureas. (2) S-cyclohexylisothiourea hydrobromide and p-nitrobenzenesulphonyl chloride are reacted in acetone solution in the presence of sodium hydroxide to give N(4- nitrobenzenesulphuryl) - S - cyclohexyl - isothiourea. (3) S-ethyl-isothiourea sulphate and p-nitrobenzenesulphonyl chloride are reacted as in example (2) to produce N (4-nitrobenzenesulphonyl) - S - ethyl - isothiourea. (4) S - benzyl - isothiourea hydrochloride and p-nitrobenzenesulphonyl chloride are reacted in pyridine solution to give N (4-nitrobenzene sulphonyl) - S - benzyl - isothiourea. (5) N- (4-nitrobenzenesulphonyl) - S - ethyl isothiourea is reduced in methanol solution with fine iron filings and concentrated hydrochloric acid to the corresponding 4-amino compound. (6) N- (4-nitrobenzene sulphonyl) S - benzyl - isothiourea is reduced to the 4-amino compound by treatment with a mixture of iron filings, aqueous ethanol, and calcium chloride. (7) Ammonia gas is passed into molten N-(4-aminobenzene-sulphonyl) - S - benzylisothiourea to give 4-amino-benzenesulphonyl-guanidine. (8) Dry ammonia is passed through melted N-(4- acetylaminobenzenesulphonyl) - S - methyl - - isothiourea to give 4 - (acetylaminobenzenesulphonyl) - guanidine. The acetyl group is then hydrolysed by refluxing with dilute hydrochloric acid. (9) Ammonia gas is passed into a molten mixture of N(4-acetylaminobenzenesulphonyl) - S - methyl - isothiourea and phenol. The product is extracted with water and the undissolved residue comprises 4 - acetylaminobenzenesulphonyl - guanidine. (10) Ammonia gas is passed into melted N - (4 - acetylaminobenzenesulphonyl) - S - ethyl - isothiourea to give 4 - acetyl - aminobenzenesulphonylguanidine. (11) Ammonia gas is passed into melted N(4-acetylaminobenzenesulphonyl) - S - benzylisothiourea to give 4-acetylaminobenzenesulphonylguanidine which is hydrolyzed as in example (8).