A stepwise mechanism in the reaction of amines with carbodi-imides to form guanidines

Abstract

Reaction of amines with the water-soluble N-ethyl-N′-(3-trimethylammoniopropyl)carbodi-imide (ETC) perchlorate in aqueous solution is not catalysed by general acids or bases. Both acid and base forms of the amine may be involved in the kinetic expression; with weakly basic amines the former predominate whereas with strongly basic amines the latter do. Amines of intermediate basicity involve both acid and base forms. Guanidine formation is shown not to interfere with the synthesis of amides from relatively basic amines except at pH values above 8 where O-acylisourea formation is not efficient. On the contrary, guanidine formation will strongly compete with anilide synthesis in aqueous solution at acid pH.