GB589040A - Improvements in or relating to the production of sulphonamides - Google Patents

Abstract

Sulphonamide derivatives are produced by heating together in the liquid phase an aryl sulphonamide containing at least one free hydrogen atom in the sulphonamide grouping and a thioether of the general formula R2SR3 wherein R2 is an alkyl or aralkyl group and R3 is a heterocyclic group containing at least one nuclear nitrogen atom. Reaction may be effected in the presence of a basic metal oxide or hydroxide, particularly those of Groups Ia, IIa and IVb of the Periodic Table, or of a salt thereof with an acid replaceable by a sulphonamido group, or of a strong organic base. Specified compounds are sodium and potassium hydroxides, magnesium oxide, barium hydroxide, sodium, potassium and lead carbonates and acetates, triethanolamine, trimethylamine and sodium ethoxide. A high-boiling solvent, e.g. phenol, the alkylated phenols, and the naphthols or mixtures thereof may be present. The groups R2 and R3 are preferably so chosen that the mercaptan obtained as a by-product or the sulphonamide produced is progressively removed from the reaction zone, and R2 represents preferably an alkyl group containing not more than six carbon atoms, advantageously methyl, ethyl, propyl or isopropyl. The sulphonamide may be unsubstituted, e.g. benzene- or p-toluene sulphonamide, or monosubstituted, having the general formula R.SO2NHR1, wherein R1 is an alkyl, aryl, acyl, aralkyl or heterocyclic group. Specified as mono-alkylated compounds are N-methyl and N-ethyl sulphonamides, and as monoacyl compounds, a sulphonacetamide or a sulphonpropionamide. When R1 represents a heterocyclic group a sulphonamide derivative may be produced containing two like or unlike heterocyclic groups, e.g. a thiazole with a pyrimidine group. R3 may be a pyridine, diazine (e.g. a pyrimidine), thiazole, thiazoline, or oxazole group, optionally containing substituents. The group R in the sulphonamide may represent phenyl containing as a p-substituent an amino group, free or protected, i.e. an acylamino or alkylamino group, or a group readily convertible to amino, i.e. a nitro or azo group, or a halogen atom. The thioether may be produced in situ either prior to or simultaneously with the desired sulphonamide derivative, e.g. by interacting an alkali metal mercaptan derivative with a halogen derivative of the appropriate heterocyclic compound, or, in the case of a pyrimidine thioether, from an S-alkyl isothiourea and an appropriately substituted diketone. Numerous examples are given. Lead sulphanilamide is prepared by the interaction of sulphanilamide and lead acetate.