N-Alkylation of nitriles—I : A general synthesis of substituted amidines

Abstract

A general synthesis of substituted amidines has been worked out starting from a nitrile compound, an alkyl halide, a Lewis acid and an amine. The method involves 4 steps: 1. formation of a nitrile-Lewis acid complex 2; 2. N-Alkylation of this complex 2 with an alkyl halide and formation of a nitrilium salt 3; 3. aminolysis of the nitrilium salt 3 with ammonia, a primary or a secondary aliphatic or aromatic amine to get the amidinium salt 4; 4. neutralization of the amidinium salt with a base yielding the substituted amidine 5. In practice, the amidine 5 is obtained in a one-pot synthesis and none of the intermediates 2, 3 or 4 needs to be isolated. Overall yields of 40–80% based on the nitrile 1 are obtained. More than twenty new mono-, di or trisubstituted amidines have been prepared by this procedure.