Proton inventory study of the base-catalyzed hydrolysis of formamide. Consideration of the nucleophilic and general base mechanisms.

An NMR study of the rates of hydroxide-promoted hydrolysis of formamide in aqueous media of varying mole fraction D(2)O (n) was performed at [LO(-)] = 1.42 M, T = 25 degrees C, to shed light on whether the mechanism involves a nucleophilic attack of HO(-) on the C=O or HO(-) acting as a general base to remove a proton from an attacking water. The solvent deuterium kinetic isotope effect under these conditions is inverse, k(OH)/k(OD) = 0.77 +/- 0.02 or k(OD)/k(OH) = 1.30 +/- 0.03. Proton inventory analysis of the k(n)() versus n data was undertaken through NLLSQ fits to equations representing four possible mechanisms encompassing nucleophilic and general base ones with waters of solvation on the attacking hydroxide, and with or without waters of solvation on the developing amide hydrate oxyanion. Both nucleophilic and general base mechanisms can be accommodated, but there are restraints on each that are discussed. The preferred mechanism is a nucleophilic one proceeding through a transition state having two solvating waters remaining on the attacking hydroxide and three additional waters attached to the developing amide hydrate oxyanion.