GB642091A - Process for the production of substituted diphenylamine 2-monocarboxylic acids - Google Patents

Abstract

Substituted diphenylamine - 2 - carboxylic acids, useful for pharmaceutical purposes and of the general formula <FORM:0642091/IV (b)/1> wherein the phenyl nucleus II is free from additional substituents, are manufactured by condensing an o-halogenobenzoic acid (which may contain one or more further substituents, e.g. an additional halogen atom, in the benzene ring) with a p-aminodiphenyl sulphide in which the phenyl nucleus carrying the amino group is free from additional substituents but the other may be further substituted (e.g. by a protected amino group, such as an acylamino group, a nitro group or a halogen atom). The reaction is preferably carried out by heating in a suitable solvent (i.e. one which dissolves or partially dissolves one or both of the reactants, e.g. butyl or amyl alcohols) in the presence of an acid acceptor (e.g. an alkali metal carbonate) and of a source of copper (e.g. copper powder or a copper salt) as catalyst, and preferably in an inert atmosphere. When the phenyl nucleus I contains a group convertible to an amino group, this group may subsequently be so converted (e.g. an acylamino group hydrolysed or a nitro group reduced) and the product may be further reacted with an o-halogenobenzoic acid which may be the same as or different from that first employed. In an example, 4-amino-41-acetylaminodiphenyl sulphide, o-chlorobenzoic acid, potassium carbonate and copper powder are heated in amyl alcohol under reflux in an atmosphere of nitrogen to produce 4-(o-carboxyphenylamino)-41-acetamidodiphenyl sulphide, which may be hydrolysed with dilute alkali or acid to 4-(o-carboxyphenylamino)-41-aminodiphenyl sulphide Other o-halogenobenzoic acids specified are 2 : 3-, 2 : 4-, 2 : 5- and 2 : 6-dichloro- and 2-chloro-6-methoxy-benzoic acids. Specification 608,492 is referred to.