GB896720A - Improvements in methods of preparing ortho-disubstituted ú=-aminobenzoic acid derivatives - Google Patents

Abstract

Compounds of the formula <FORM:0896720/IV (b)/1> (wherein R1 is hydrogen or alkyl, R2 is hydrogen or acetyl, R3 is halogen or alkyl, R4 is alkyl, Y is -NH- or -O-, n is 2 or 3 and R is a tertiary amino radical) are prepared by reduction of compounds of the formula <FORM:0896720/IV (b)/2> followed, when required, by alkylation and/or acetylation, and also, if desired, by the formation of acid-addition salts or quaternary ammonium derivatives of the products. These processes may be combined, in turn, with the preparation of the compounds of the second general formula above by heating a 1-bromo-2-R3-4-nitro-6-R4-benzene with a cuprous cyanide-pyridine (1 : 1) complex salt to give a 1-cyano-2-R3-4-nitro-6-R4-benzene hydrolysing this to the corresponding amide and thence to the corresponding acid, converting this to the acid halide (e.g. by the use of an inorganic halide such as thionyl chloride), and reacting this with the appropriate diamine or amino-alcohol HY(CH2)n-R. The reduction process of the invention is desirably accomplished either by catalytic hydrogenation using Raney nickel, or, when R3 is a halogen, by the use of powdered iron and hydrochloric acid. The subsequent alkylation may be effected with an aliphatic aldehyde with subsequent catalytic hydrogenation of the Schiff's base at first produced, and the acetylation of the free or mono-alkylated amino compounds may be effected with acetic anhydride or acetyl chloride. Hydrolysis of the substituted p-nitro-benzonitriles to the amides and then the acids may be effected with sulphuric acid and nitrous acid respectively. Examples are given. 1 - Bromo - 2 - R3 - 4 - nitro - 6 - R4 - benzenes are prepared from the corresponding p-nitroanilines, by diazotization and reaction with cuprous bromide. Specifications 768,770 and 791,599 are referred to.