Ab Initio Study of the Axial/Equatorial Equilibrium in N- and O-Containing Rings in Gas Phase and Aqueous Solution: 1-Oxa-3-aza-, 1-Oxa-3,5-diaza-, 1,3-Dioxa-5-azacyclohexanes and N-Methyl Derivatives

Abstract

The axial and equatorial structures of 1-oxa-3-azacyclohexane, 1-oxa-3,5-diazacyclohexane, and 1,3-dioxa-5-azacyclohexane, which can show anomeric effect, were completely optimized at the HF/6-31G** level. The effects of polarization, diffuse functions, the ZPE, and the electronic correlation as considered at the MP2 level were also discussed. The HF/6-31G** wavefunctions were analyzed according to the NBO method, and it was found that the axial preferences of the R−N−C−O unit are due to hyperconjugation, this contribution being more important than steric effects. The N-methylation reduces the preference for the axial forms by approximately 3−3.5 kcal/mol because the delocalization is increased in the equatorial forms. By means of an ab initio method for the treatment of the solvent as a continuum (PCM), the influence of water on the conformational stability was estimated. It was found that the axial conformers reduce their energetic preference by between 1 and 3.5 kcal/mol mainly due to the interaction between the dipole moment of the solute and the reaction field of the solvent, although local dipolar interactions can also be important.