Acid, base, and uncatalysed isomerisation of Z-to E-amidine. A mechanistic study

Abstract

The Z-amidines (2Z) have been prepared by stereospecific reaction of nitrilium ion intermediates and the kinetics of interconversion into the E-amidines (2E) studied in aqueous solution at 25 °C. The interconversion is strongly catalysed by acid, so that at all pH values < 11, the acid-catalysed pathway (C–N bond rotation in the protonated species) dominates. A pH-independent reaction (uncatalysed nitrogen inversion) is observed over a narrow range at high pH while with one amidine (5aZ) carrying the most electron-withdrawing substituent, base catalysis (probably reversible addition of HO^–) is unexpectedly observed. The more reactive amidines [e.g.(5c)] were formed and their isomerisations studied in situ; however, introduction of electron withdrawal in the substituent on the imino nitrogen [such as (5a)] or on the amino nitrogen [such as (2d)] permitted the isolation of pure Z-isomers.