Patent GB-556425-A (GB)
Title: Sulphanilamide derivative
IPC: C07C311/37
Filed: 1941-12-15
Abstract: 556,425. Benzene - sulphonyl - guanidines. HAWORTH, E., ROSE, F. L., and IMPERIAL CHEMICAL INDUSTRIES, Ltd. Dec. 15, 1941, Nos. 16146/41, 650/42, 5505/42 and 5506/42. [Class 2 iii)] p-Substituted benzenesulphonyl guanidines of the general formula X-C 6 H 4 -SO 2 .NH-C(NH)-NH 2  where X is an amino, nitro or acylamino group, are prepared by reacting a p-substituted benzene sulphonamide of the formula X-C 6 H 4 - SO 2 -NH 2  in the presence of an inorganic or a strong organic base with an isothiourea of the formula NH  2 .C(NH)-S.R where R is a saturated or unsaturated hydrocarbon radical which may bear hydroxy or etherified hydroxy groups as substituents and may also carry a second isothiourea group. If the base used is inorganic it may be the hydroxide of an alkali or an alkaline earth metal, or ammonia, and if an organic base it may be trimethylamine, triethylamine, triethanolamine or 2-aminopyridine. The base may be added in the form of a salt with a weak acid such as sodium carbonate, sodium acetate, borax, sodium ethylate or sodium phenate, or may also be added in the form of a salt of the sulphonamido compounds. The reaction is preferably carried out in the presence of a high boiling solvent such as phenol, ethylene glycol, xylene or o-dichlorbenzene. Nitro compounds may be reduced to the corresponding amino compounds, and acylamino-compounds may be hydrolysed to the amino compounds. The reaction should be carried out at a temperature above 90‹ C. and preferably in the range 120‹- 200‹ C. In examples (1) S-methyl-isothiourea sulphate is added to a phenol solution of the sodium salt of 4-aminobenzene sulphonamide and heated to 160‹ C., to give 4-aminobenzenesulphonylguanidine. (2) S-ethyl-isothiourea sulphate is added to a phenol solution of 4- aminobenzene sulphonamide to give 4-aminobenzenesulphonylguanidine. (3) S - methyl isothiourea sulphate is added to a solution of the sodium salt of 4-aminobenzenesulphonamide in the amide itself to give on working up 4- aminobenzenesulphonylguanidine. (4) S - allylisothiourea is added to a solution of the sodium salt of 4-aminobenzene-sulphonamide in phenol to give 4-aminobenzenesulphonylguanidine. (5) S-γ-hydroxypropyl isothiourea is added to a solution of the sodium salt of 4- aminobenzene sulphonamide in phenol to give 4 - aminobenzenesulphonyl guanidine. (6) S-cyclohexylisothiourea is added to a solution of the sodium salt of 4-aminobenzenesulphonamide in phenol to give 4-aminobenzene sulphonyl guanidine. (7) The bi-hydrochloride of the bis-isothiourea of the formula NH  2'  C(NH).S.CH 2 .CH 2 .O.CH 2 .CH 2 .S.C.(NH).NH 2  is added to a solution of the sodium salt of 4-aminobenzenesulphonamide to give 4-aminobenzene-sulphonylguanidine. (8) S-p-isotolylisothiourea nitrate is added to a solution of the sodium salt of 4-aminobenzenesulphonamide to give 4-aminobenzenesulphonylguanidine. (9) S-methylisothiourea sulphate is added to a phenol solution of 4-aminobenzenesulphonamide through which a stream of ammonia gas has been passed, the gas stream being continued during the addition. The product is as before: 4-aminobenzenesulphonylguanidine. (10) S - methyl-isothiourea sulphate is added to a solution of 4-aminobenzenesulphonamide in phenol to which magnesium oxide has been added. On working up 4-aminobenzenesulphonylguanidine is isolated. (11) S-methylisothiourea sulphate is added to a solution.of 4-aminobenzenesulphonamide to which sodium hydroxide has been added to produce 4-aminobenzenesulphonylguanidine. (12) S-methylisothiourea sulphate is added to a solution of 4-aminobenzenesulphonamide in phenol to which barium hydroxide has been added. 4- aminobenzenesulphonylguanidine is produced. (13) S-methyl-isothiourea sulphate is added to a mixture of 4-aminobenzenesulphonamide, sodium phenate and phenol to produce 4- aminobenzenesulphonylguanidine. (14) As in example (13) using potassium phenate instead of sodium phenate. (15) S-methyl-isothiourea sulphate is added to a solution of the sodium salt of 4-acetylaminobenzenesulphonamide in phenol to give 4-acetylaminobenzenesulphonylguandine. This may be hydrolysed with dilute hydrochloric acid. (16) S-methyl isothiourea sulphate is added to a mixture of 4-acetylaminobenzenesulphonamide, phenol and anhydrous sodium acetate to give 4-acetylaminobenzene-sulphonylguanidine, which may be hydrolysed as in example (15). (17) S-methyl - isothiourea sulphate is added to a mixture of 4-acetylaminobenzenesulphonamide, phenol and anhydrous sodium carbonate to give 4-acetylaminobenzenesulphonylguanidine. (18) S- methyl-isothiourea sulphate is added to a solution of 4-nitrobenzene-sulphonamide in phenol to produce 4-nitrobenzenesulphonylguanidine. This is reduced by treatment with iron filings and concentrated hydrochloric acid to 4- aminobenzenesulphonylguanidine. (19) S - allyl-isothiourea hydrochloride is added to a solution of 4-nitrobenzenesulphonamide in phenol to give 4-nitrobenzenesulphonylguanidine which may be reduced as in example (18). (20) S-cyclohexyl-isothiourea hydrobromide is added to a solution of the sodium salt of 4-nitrobenzene sulphonamide in phenol to give 4 - nitrobenzenesulphonylguanidine which may be reduced as in example (18). (21) S-methyl-isothiourea sulphate is added to a mixture of 4-nitrobenzenesulphonamide, phenol and triethanolamine to give 4-nitrobenzenesulphonylguanidine which is reduced as in example (18). (22) S-methyl-isothiourea sulphate is added to a solution of 4-nitrobenzenesulphonamide in phenol through which has been passed a stream of trimethylamine until the solution was saturated, the passage of the trimethylamine being continued during the addition. The product is 4-nitrobenzenesulphonylguanidine. It is reduced as in example (18). (23) S-methyl isothiourea sulphate is added to a mixture of 4-nitrobenzenesulphonamide, phenol and 2-aminopyridine to give 4-nitrobenzenesulphonylguanidine.