Theoretical investigation of tautomerism of 2- and 4-pyridones: origin, substituent and solvent effects

Abstract

Computational investigationattheBHandHLYP/6-311+G(d,p) leveloftheoryofthegas-phasetautomerismof2-and4-pyridonesconfirmedtheslightprevalenceof lactiminthecaseof theformer,but its dominance inthecaseof the latter, asshownpreviously. Examinationof aromaticitybyusingHOMA, EDDB, NBOdel, NICSandAICD led to theconclusion that tautomerizationof 4-pyridone results in greateraromaticitygain. ItisalsodrivenbythePaulirepulsionrelief,whichwasrevealedbythetautomerizationenergydecompositionanalysis.Bycontrast, inthecaseof2-pyridone, lactimisfavouredbyorbital andelectrostatic interactions anddisfavouredby thePauli repulsion. Aromaticitygain in this case is smaller.Thepositionofthetautomericequilibriumcanbemodulatedbysubstituent inductiveeffects(Cl andF), inductiveandresonanceeffects (NH2andNO2),hydrogenbonding(NO2),andmediumpolarity, theincreaseofwhichincreaseslactampopulation.