Manufacture of new para-aminobenzene-sul honamide derivatives

摘要

p-Aminobenzene-sulphonamide derivatives are obtained by treating a p-aminobenzene-sulphonamide with an oxo-compound of general formula R1-CO-R2 wherein R1 represents H or an organic residue, and R2 represents H or a carboxyl or carbalkoxy group or a salt thereof, and a compound containing a reactive SH- group and also containing a salt-forming group when the oxo-compound does not carry such a group and, if required, converting the product into a water-soluble salt by treatment with a base or an acid the products carry in the amino radical of the benzene nucleus a substituent of the formula FORM:0584188/IV/1 wherein R1 and R2 have the meanings assigned above and wherein R3 represents an organic residue carrying a salt-forming group if neither R1 nor R2 contains such a group. Reaction is effected by (a) treating the starting-materials in admixture with one another; (b) condensing the p-aminobenzenesulphonamide with the oxo-compound followed by treatment with the compound containing a reactive-SH-group; (c) condensing the oxo-compound with that containing a reactive SH- group and treating with the p-aminobenzenesulphonamide. Any chemotherapeutically - active p - aminobenzenesulphonamide may be used as starting-material. Advantageously, such compounds contain a heterocyclic substituent in the sulphonamido group. Aliphatic, aromatic, alicyclic or heterocyclic aldehydes or a -keto-carboxylic acids are used as oxo - compounds. Advantageously, aliphatic aldehydes are used containing a small number of carbon atoms, e.g. formaldehyde or glyoxylic acid. Aliphatic, aromatic, alicyclic or heterocyclic compounds containing a reactive SH- group are used. If aldehydes containing salt-forming groups or keto-carboxylic acids are used, other SH- compounds may be used, e.g. ethyl mercaptan, thiophenol, thioglycollic acid ethyl ester, thioglycollic acid anilide, or thio-acid such as thioacetic- and thiobenzoic acids. Advantageously, the p-aminobenzene sulphonamide, oxo-compound and SH- compound are reacted in presence of an organic solvent such as ethanol, methanol, dioxan or acetic acid, optionally in presence of water. Salts are obtained from compounds carrying acid groups, e.g. by treating with organic bases, such as diethylamine, triethylamine or ethanolamine or with inorganic bases to obtain especially the sodium, calcium or ammonium salts, and in particular salts wherein the sulphonamido group resists salt-formation; salts with acids, e.g. hydrohalic acids are obtained from the final products of compounds carrying basic substituents. Numerous examples are given. Specifications 550,040 and 553,164 are referred to. The Specification as open to inspection under Sect. 91 includes treating (i) 2-(p-aminobenzenesulphonamido)-thiazole with aqueous formaldehyde and (a) thioglycollic acid, (b) thiosalicyclic acid, (c) thiolactic acid, and (d) b -thiolactic acid; and (ii) p-aminobenzenesulphonmethylamide with aqueous formaldehyde and thioglycollic acid. This subject-matter does not appear in the Specification as accepted.