A Mechanistic Study on the Amidation of Esters Mediated by Sodium Formamide

Kinetic and computational studies on the amidation of esters with mixtures of formamide and sodium methoxide are described. Rate studies are consistent with a fast deprotonation of formamide followed by two reversible acyl transfers affected by solvent participation. MP2 calculations suggest that the first acyl transfer between the ester and sodium formamide is rate-determining. The transition structures leading to the formation and collapse of the first tetrahedral intermediate are calculated to be isoenergetic.