THE ORIGIN OF THE ANOMERIC EFFECT - CONFORMATIONAL-ANALYSIS OF 2-METHOXY-1,3-DIMETHYLHEXAHYDROPYRIMIDINE

The anomeric effect is thought to be the result of either molecular orbital interactions, which stabilize the axial conformer, or electrostatic interactions, which destabilize the equatorial. To test which of these is more important, it is proposed to determine the change in the anomeric effect on replacing the oxygen of an anomeric molecule by nitrogen. Nitrogen is less electronegative than oxygen, leading to weaker electrostatic interactions and stronger molecular orbital interactions, so the two interactions act in opposite directions. Accordingly, the conformational equilibrium of 2-methoxy-1,3-dimethylhexahydropyrimidine (3) was measured by H-1 and C-13 NMR. The proportion of axial conformer is almost the same as in 2-methoxy-1,3-dioxane. Corrections for steric effects, supported by AMI and MMX calculations, indicate that the anomeric effect is weaker in the nitrogen analog, suggesting that electrostatic interactions predominate. We therefore conclude that in nonpolar solvents n-sigma* interactions are not primarily responsible for the anomeric effect. Moreover, it is shown that the bond length changes that have long been considered as strong evidence for n-sigma* interactions can be accounted for on the basis of dipole-dipole interactions.