AM1 study of proton-transfer reactions of barbituric acid

Abstract

The AM1 method is used to study the mechanisms of intra- and intermolecular proton transfer in barbituric acid. In the vapor phase, of the three possibilities, although thermodynamic factors favor the migration of a methylene proton to a neighboring oxygen, kinetic effects favor proton transfers from imine nitrogens. The intervention of a single water molecule has a dramatic effect on the activation barrier, bringing it down significantly, particularly for the methylene proton transfer. Several factors, including the reduction in the strain in the transition state, charge-transfer effects, ionic resonance, and solvent effects were analyzed to explain this. Bulk dielectric effects further reduce the activation energies for the proton transfers. Substituents at the 5-position, however, do not seem to have much effect on the activation barriers. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 74: 327–336, 1999