GB671939A - Diamidine salts and process for their manufacture - Google Patents

Abstract

The invention comprises diamidine salts of the general formula <FORM:0671939/IV (b)/1> (wherein each A represents an amidine salt grouping, that on the left being in the 5- or 6-position, and X represents S, O or NH), and their manufacture from the corresponding dinitriles by treating these with the oxonium halide of a heterocyclic compound containing "basic" oxygen in the ring, treating the resulting imino-ether hydrohalide with ammonia and converting the amidine formed to its salt with an acid, or by the Pinner method. The products are useful for therapeutic purposes, particularly as trypanocidal drugs. In examples: (1) 2-(p-cyanophenyl)-6-cyanobenzthiazole is treated with dioxane "hydrochloride" and ethyl alcohol, the resulting imino-ether hydrochloride is treated with ammonia, and the product is crystallized from hydrochloric acid to give 2-(p-amidinophenyl)-6 - amidinobenzthiazole dihydrochloride dihydrate; (2) and (3) 2-(p-cyanophenyl)-5- and 6-cyanobenzoxazole are similarly treated; (4) 2-(p - cyanophenyl) - 5(6) - cyanobenzimidazole is treated with ethanol and dry hydrogen chloride in nitrobenzene and the resulting imino-ether hydrochloride is further converted as in (1). Dinitriles of the general formula above, but in which each A represents a cyano group, are prepared as follows: (a) when X represents S, by condensing p-phenylenediamine monothiosulphuric acid with a p-acylaminobenzaldehyde (e.g. p - acetylaminobenzaldehyde), cyclizing the product (e.g. by refluxing with glacial acetic acid containing an alkali metal or ammonium acetate), converting the product by acid hydrolysis to the corresponding diamine and this to the dinitrile by the Sandmeyer reaction; or by condensing together o-aminothiophenols and aldehydes or acid chlorides, the reactants containing substituents (e.g. halogen atoms) subsequently replaced by nitrile groups (e.g. 5-bromo-2-aminothiophenol with p-bromobenzoyl chloride, with subsequent treatment with cuprous cyanide); (b) when X represents O or NH, by condensing together (with ring-closure by means of an oxidizing agent, e.g. lead tetracetate) o-aminophenols or o-phenylenediamines and benzaldehydes, acid chlorides or imino-ethers, the reactants being substituted by nitrile groups or substituents (e.g. NO2, NH2 or Br) subsequently replaced thereby (e.g. p p-cyanobenzaldehyde with 4-cyano-2-aminophenol, or with 5-bromo-2-aminophenol with subsequent treatment with cuprous cyanide, or with 4-cyano-o-phenylenediamine).