Tautomerism in 4-substituted 1-phenyl-3-methyl-pyrazolin-5-ones - a theoretical ab initio and C-13 NMR study

The tautomeric equilibria between the CH, OH and NH forms in a series of 4- substituted 1-phenyl-3-methyl-pyrazolin-5 -ones have been studied using ab initio calculations at various levels of theory and comparison made with th e experimental results obtained from NMR measurements. Quantitative compari son of both the relative energies and the C-13 chemical shifts of the tauto mers constituting the tautomeric equilibria were made by calculation of bot h sets of parameters. The influence of the solvent was included by employin g various models of the self-consistent reaction field theory. Initially. t he solvent was included in the calculations by applying a continuum of diff ering polarity over the surface of isolated tautomers (self-consistent isod ensity polarized continuum model method), then later by assuming formation of an adduct between the solute and the solvent (thereby simulating effecti vely the hydrogen bonding in the OH and NH tautomers) and finally by calcul ating dimer or trimer complexes of the various tautomers. In this manner, t he agreement between the theoretically calculated and the experimentally de termined tautomeric equilibria was improved significantly. The theoreticall y calculated C-13 chemical shifts of the tautomers were found to be viable for the assignment of the tautomers, particularly the preferred tautomer in the OH/NH equilibrium, which remains fast on the NMR time scale even at lo w temperatures. Copyright (C) 2001 John Wiley & Sons. Ltd.