Heterocyclic ambident nucleophiles: The alkylation of sodium N⁶-acyladenides

Abstract

In the alkylation of N⁶-acyladenines in dimethylformamide, changes in the site of alkylation caused by variations in the alkylating agent and the acyl group were investigated. Almost exclusive alkylation at the imidazole ring nitrogens, N7 and N9, was observed in all cases. The alkylation pattern, expressed as the N7 : N9 ratio was, however, found to vary widely, from 40 : 1 to 1 : 13, with changes in the alkylating agent. These divergent alkylating patterns are rationalized by considering the looseness or tightness of the S_N2 transition states involved for a particular alkylating agent; these considerations then allow the relative importance of the thermodynamic, charge density and, particularly, steric factors to be assessed. Cases of ?abnormally? high preference for alkylation at the hindered N7 position are explained in terms of a special hydrogen bonding association between the N⁶-acylamino NH group of the substrate and an acceptor group in the alkylating agent.