GB512145A - The preparation of new therapeutically useful heterocyclic compounds - Google Patents

Abstract

512,145. Sulphonamide compounds. MAY & BAKER, Ltd., EWINS, A. J., and PHILLIPS, M. A. Nov. 29, 1937, Nos. 32925/37, 14197/38 and 17042/38. [Class 2 (iii)] p-Aminobenzenesulphonamido derivatives of the pyridine, quinoline and isoquinoline series, which possess therapeutic properties, are prepared by (1) reacting a benzenesulphonyl halide containing an acylamino, nitro,' azo or halogen substituent in the p-position with a pyridine, quinoline or isoquinoline compound containing an amino substituent having at least one reactive hydrogen ; the acylamino group in the product may then be hydrolyzed, the nitro and azo groups are reduced and the halogen atom is converted into an amino or substituted group by treatment with ammonia or a primary or secondary amine; (2) reacting a benzenesulphonamide containing an acylamino, nitro, azo or halogen substituent in the p-position with a pyridine, quinoline or isoquinoline compound containing a reactive halogen substituent, and the resulting compound then treated as in (1). The products, in so far as they contain a reactive hydrogen, may be treated with an acyl, alkyl, aryl or aralkyl halide or an alkyl sulphate. Examples are given of the condensation of (1) p-acetylaminobenzenesulphonyl chloride with 2-aminopyridine, 6-aminoquinaldine, 5-amino-8- methoxyquinoline, 2-hydroxy-4-methyl-7- aminoquinoline, 2-aminopyridine-3-carboxylic acid, 2-amino-6-methylpyridine, 6-aminoquinoline, 4-aminopyridine, 1-aminoisoquinoline, 5-iodo-2-aminopyridine and 2- methylaminopyridine, followed in each case by treatment with caustic soda solution to split off the acetyl group ; (2) p-acetylaminobenzenesulphonyl chloride with 2-aminopyridine; (3) p-acetylaminobenzenesulphonyl chloride (2 mols.) with 2:6-diaminopyridine (1 mol.), followed by hydrolysis with caustic soda ; (4) p-nitrobenzenesulphonyl chloride with 2-aminopyridine and reduction of the product with ferrous hydroxide ; (5) p-nitrobenzenesulphonic acid anhydride with 2-aminopyridine and 6-aminoquinine, aldand subsequent reduction of the nitro group using ferrous hydroxide ; (6) p<1>-diethylaminoazobenzene-p-sulphonyl chloride with 2-aminopyridine, followed by reduction with sodium hydrosulphite to give 2-(p-aminobenzenesulphonamido)-pyridine ; (7) p-chlorobenzenesulphonyl chloride. with 2-aminopyridine and heating the 2-(p-chlorobenzenesulphonamido)- pyridine in an autoclave with aqueous ammonia ; (8) p-acetylaminobenzenesulphonamide with 2-bromopyridine and 2-chloroquinoline in the presence of copper powder, followed by alkaline hydrolysis ; (9) p-acetylaminobenzenesulphonamide with 5-nitro-2-chloropyridine; (10) p-acetylaminobenzenesulphonmethylamide, prepared from the sulphonyl chloride and methylamine, with 2-bromopyridine in the presence of copper powder, and hydrolyzing the product; (11) 2-(p-chloro or bromo-benzenesulphonamido )-pyridine, prepared from p-chloro or bromobenzenesulphonyl chloride and 2- aminopyridine, with methylamine or dimethylamine in an autoclave in the presence of cuprous chloride ; (12) p-acetylbenzylaminobenzenesulphonyl chloride (see Specification 483,945) with 2-aminopyridine, followed by hydrolysis with caustic soda solution ; (13) p-acetylaminobenzenesulphonyl chloride with phenyl 2-aminopyridine-5-sulphonate and hydrolysis with caustic soda solution to give 2 - (p - aminobenzenesulphonamido) - pyridine - 5 - sulphonic acid ; (14) 2 : 4-dinitrodiphenylamine-41-sulphonyl chloride with 2-aminopyridine. Further examples describe the treatment of (15) 2-(p-aminobenzenesulphonamido)-pyridine with p-nitrobenzoyl chloride to give the p<1>-nitrobenzoylamino compound ; (16) 2-(p-amino- and dimethylamino-benzenesulphonamido)-pyridines with dimethyl sulphate to form the corresponding sulphonmethylamido products; (17) 2-(p-aminobenzenesulphonamido)-pyridine with benzyl chloride to yield the sulphonbenzylamido body; (18) 2-(p-aminobenzenesulphonmethylamido)- pyridine with acetic anhydride to form the p-acetylamino compound. p-Nitrobenzenesulphonic acid anhydride is prepared by the action of thionyl chloride on p-nitrobenzenesulphonic acid dihydrate. 2 : 4 - Dinitrodiphenylamine - 4<1> - sulphonyl chloride is obtained by reacting the sodium salt of the. sulphonic acid with phosphorus pentachloride. p<1> - Diethylaminoazobenzene - p - sulphonyl chloride is prepared by the action of phosphorus pentachloride on the sodium salt of the sulphonic acid.