Tautomeric equilibria in 3- and 5-hydroxyisoxazole in the gas phase and in aqueous solution: a test of molecular dynamics and continuum models of solvation

Abstract

The keto–enol tautomerism of 3- and 5-hydroxyisoxazole in the gas phase and in aqueous solution has been investigated by a range of theoretical methods. In the gas phase, ab initio studies using basis sets with polarisation functions, and the inclusion of electron correlation at the MP4 level, predict that the hydroxy form of 3-hydroxyisoxazole, and the 4H-oxo form of 5-hydroxyisoxazole are the only forms that will be observed. Free energies of hydration, predicted by free energy perturbation studies using molecular dynamics, and by the polarisable continuum model due to Tomasi et al. yield consistent results which differ from those predicted by the self-consistent reaction field (SCRF) model. All methods studied here predict that the enol form of 3-hydroxyisox-azole is dominant in aqueous solution, in agreement with experiment, whilst it is only the SCRF model that correctly predicts that the 2H-oxo form of 5-hydroxyisoxazole is observed in aqueous solution.