Effects of Unshared Pairs of Electrons and Their Solyation on Conformational Equilibria

The empirical rules for estimating molar rotations of carbohydrate structures proposed by Whiffen and elaborated by Brewster provided interpretations of solvent effects on optical rotation with changes in conformational equilibria which in certain cases were confirmed by n.m.r. Conversely, it was found that only slight changes in rotation occur on changing the solvent for conformationally rigid molecules. Thus, studies involving optical rotations measured at the D-line of sodium and n.m.r. spectra provided the experimental support for the following solvation phenomena which are related to the role of unshared pairs of electrons in conformational equilibria. (a) The reverse anomeric effect was substantiated by the effect of introducing a positive charge on the imidazole ring of certain N-glycosides of imidazole. (b) The magnitude of the anomeric effect was influenced as expected by changes in the polarity of the solvent but hydrogen bonding of the solvent with the acetal oxygen atoms had a more pronounced effect. (c) The orientation of oxygen atoms in gauche relationship appears particularly favourable with water as solvent. (d) An intramolecular hydrogen bond between two hydroxyl groups is strengthened by hydrogen bonding of the free hydrogen to a basic solvent. le) The non-bonded interaction between two opposing axial oxygen atoms is dependent on the nature of the substituents. The repulsion is substantially greater when the oxygen atoms are either bonded to methyl groups or hydrogen-bonded to the solvent than when attached to acetyl, benzoyl or methane-sulphonyl groups. Tim first statement that unshared pairs of electrons may play an important role in establishing conformational preferences was made by Edward' with reference to the apparent stability of that anomeric form for a glycosyl halide which has the halogen in axial orientation. The statement made was, as seen in Figure 1, that by going axial the polar C, to X bond avoids an interaction with the axially oriented orbital of the ring oxygen. Later this was discussed by Kabayama and Patterson2 who pointed out that the unfavourable interactions could, indeed, involve repulsions between the orbitals occupied by lone pairs of electrons in the aglycon X with those of the ring oxygen. Such interactions equivalent to syn-axial interactions, would be released on passing from the equatorial to axial anomer.