Influence of solvent on the magnitude of the anomeric effect

Abstract

A novel application of 13C nuclear magnetic resonance provided the effects of solvent polarity and hydrogen-bond formation on the conformational equilibria for a range of 2-substituted tetrahydropyrans and the results are interpreted in terms of how solvent affects the competition between the endo- and exo-anomeric effects in determining the magnitude of the anomeric effect. In accord with the generally accepted origin of the endo- and exo-anomeric effects (anti-periplanar n–σ* interaction of the oxygen lone-pair orbital with the antibonding orbital of the adjacent C—O bond), the exo-anomeric effect for the α anomer is expected to be weaker because charge delocalization from the glycosidic oxygen to anomeric center is in competition with delocalization from the ring-oxygen atom. The effects of solvent on the relative magnitudes of the endo- and exo-anomeric effects are then considered to arise from the formation of specific complexes with the solvent, and the exo-anomeric effect of a β-glycoside is more strongly influenced. It is contended that hydrogen bonding of solvent to the ring oxygen increases the exo-anomeric effects. For this reason water is particularly effective for the strengthening of the exo-anomeric effect and, thereby, the conformational rigidity of glycosides. Experimental evidence is presented that indicates that the anomeric hydroxyl groups of free sugars dissolved in water tend to prefer the equatorial orientation because these provide stronger hydrogen bonds as proton donors to water.