Oxane anomeric equilibrium

The electronegativity of the substituent on C-4 also influences the anomeric equilibrium. Consequently, 2,4-dimethoxyoxane exists in methanol as an equilibrium mixture containing 80% of the isomer having an axial methoxyl group on C-2, compared with 67-69% for 2-methoxy-4-methyl-oxane. ... 

In summary, experimental data on the isomeric abundances at anomeric equilibrium reveal that the preference for the axial position depends on several, interconnected factors which were clarified in surveys on carbohydrate stereochemistry, and these provided a background for ensuing theoretical studies. The elucidation of this relationship in complex carbohydrates is greatly facilitated by measurements on the simple derivatives of oxane, and qualitative trends have already been established. Table II illustrates sever possibilities of the quantification of the energetic aspect of the anomeric effect. The procedure most frequently used, based on Eq. 7, suffers from the ambiguity of the A values for the oxane ring and by their presumed variation with solvent. 

If we now replace the anomeric halogen by an acetoxy group, the equilibrium position is inverted, the weak anomeric effect not being able to compensate for two diaxial interactions at room temperature. The per-O-benzoylated derivative, however, leads to a 1 1 equilibrium. Here we recognize the limits of these analyses, as they only take into account the oxane part. With benzoate substituents, the essential point is no doubt elsewhere. Another aspect of the problem is that the conformational energy differences can appear weak as compared to the stacking forces in crystals. In crystalline form, per-(9-acetylated -D-xylo chloride adopts an all-equatorial conformation, just as the peracetylated fluoride, 85% tetraaxial in solution, crystallizes in the tetraequatorial form. In these cases where there is equilibrium in solution, conesponding to free enthalpy differences close to... 

Fig. 5.—The Standard Equilibrium in (a) Substituted Oxanes and (b) Substituted Cyclohexanes Used in the Definition of the Anomeric Effect by Eq. I.

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