The regiospecific alkylation of amides. MNDO SCF-MO calculations

Abstract

MNDO SCF-MO calculations are reported for neutral amides and the formamide anion. Consideration of the overall charge distribution and the atomic electron densities of the two highest MOs shows that frontier-orbital theory does not explain the known regiospecific alkylation of these compounds, but it can be rationalised in terms of a product-like transition state. Product control results from stabilisation by delocalisation of the nitrogen lone-pair electrons into the π-systems of the amide CO group. Significantly, in neutral amides where this is precluded, alkylation is calculated to occur on the nitrogen atom, in line with experiment.