AM1 study of proton-transfer reactions of barbituric acid

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 possi bilities, although thermodynamic factors favor the migration of a methylene proton to a neighboring oxygen, kinetic effects favor proton transfers fro m imine nitrogens. The intervention of a single water molecule has a dramat ic effect on the activation barrier, bringing it down significantly, partic ularly for the methylene proton transfer. Several factors, including the re duction in the strain in the transition state, charge-transfer effects, ion ic resonance, and solvent effects were analyzed to explain this. Bulk diele ctric effects further reduce the activation energies for the proton transfe rs. Substituents at the 5-position,however, do not seem to have much effect on the activation barriers. (C) 1999 John Wiley & Sons, Inc.