A Method for the Preparation of Substituted Biguanides

Abstract

It was found that amines added to the N-cyano group on cyanoguanidines in the presence of FeCl₃ or ZnCl₂ under mild conditions. For example, the reaction of cyanoguanidine [2a] with butylamine, proceeded at room temperature in the presence of FeCl₃ to give butylbiguanide [1a] in 99% yield. Similarly, [2a] or N-cyano-N'-phenylguanidine [2b] reacted with diethylamine, benzylamine, hexadecylamine, octadecylamine and aniline at room temperature or under reflux in dioxane or tetrahydrofuran to give the corresponding biguanides [1].
In the presence of ZnCl₂, [2] and two equivalents of amines were heated in refluxing dioxane. The initial products, biguanides [1]-ZnCl₂ complexes, were readily hydrolyzed by aqueous ammonia or amines to give hydropchlorides of [1].
When N-substituted-N'-cyano-S-methylisothioureas [3] reacted with primary amines in the presence of FeCl₃ or ZnCl₂ the addition to the cyano group and the substitution of the methylthio group with amines occurred at the same time to yield the corresponding [1].