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 or bital interactions, which stabilize the axial conformer, or electrosta tic interactions, which destabilize the equatorial. To test which of t hese is more important, it is proposed to determine the change in the anomeric effect on replacing the oxygen of an anomeric molecule by nit rogen. Nitrogen is less electronegative than oxygen, leading to weaker electrostatic interactions and stronger molecular orbital interaction s, so the two interactions act in opposite directions. Accordingly, th e conformational equilibrium of 2-methoxy-1,3-dimethylhexahydropyrimid ine (3) was measured by H-1 and C-13 NMR. The proportion of axial conf ormer is almost the same as in 2-methoxy-1,3-dioxane. Corrections for steric effects, supported by AMI and MMX calculations, indicate that t he anomeric effect is weaker in the nitrogen analog, suggesting that e lectrostatic interactions predominate. We therefore conclude that in n onpolar solvents n-sigma interactions are not primarily responsible f or the anomeric effect. Moreover, it is shown that the bond length cha nges that have long been considered as strong evidence for n-sigma in teractions can be accounted for on the basis of dipole-dipole interact ions.