Anomeric effect magnitude

It IS not possible to tell by inspection whether the a or p pyranose form of a par ticular carbohydrate predominates at equilibrium As just described the p pyranose form IS the major species present m an aqueous solution of d glucose whereas the a pyranose form predominates m a solution of d mannose (Problem 25 8) The relative abundance of a and p pyranose forms m solution depends on two factors The first is solvation of the anomeric hydroxyl group An equatorial OH is less crowded and better solvated by water than an axial one This effect stabilizes the p pyranose form m aqueous solution The other factor called the anomeric effect, involves an electronic interaction between the nng oxygen and the anomeric substituent and preferentially stabilizes the axial OH of the a pyranose form Because the two effects operate m different directions but are com parable m magnitude m aqueous solution the a pyranose form is more abundant for some carbohydrates and the p pyranose form for others... 

The magnitude of the anomeric effect depends on the nature of the substituent and decreases with increasing dielectric constant of the medium. The effect of the substituent can be seen by comparing the related 2-chloro- and 2-methoxy-substituted tetrahydropy-rans in entries 2 apd 3. The 2-chloro compound exhibits a significantly greater preference for the axial orientation than the 2-methoxy compound. Entry 3 also provides data relative to the effect of solvent polarity it is observed that the equilibrium constant is larger in carbon tetrachloride (e = 2.2) than in acetonitrile (e = 37.5). 

In the case of 2-hydroxytetrahydropyran, the axial conformer 22 is calculated to be more stable than its equatorial conformer 23 in vacuum (Fig. 12). Solvent effects change the equilibrium constant and the equatorial form 23 is favored in aqueous solution, in agreement with data. The magnitude of the conformational endo-anomeric effect in 22 is estimated to 2.0 kcal/mol (gas phase stereoelectronic effects overwhelming the steric... 

OH group in an axial alignment which, assuming that the anomeric effect in keto-hexoses is of the same magnitude as in aldoses (5), supplements the conformational impact of the equatorial 1-carbinol group.)... 

In an extensive, comparative study of a range of glycosyl halide derivatives in their thermodynamically more-stable forms, it was uniformly found that the conformation adopted in solution is the one having the halogen group axial, suggesting that the anomeric effect must be of considerable magnitude (29, 30). 

On the basis of the above results and discussion, the glycosides can now be considered. Efforts have been made previously to evaluate the magnitude of the anomeric effect by undertaking equilibration studies between equatorial and axial isomers at the anomeric center in carbohydrates (48), in monosubstituted 2-alkoxytetrahydropyrans (49, 50) and in more rigid systems (51). The anomeric effect has been evaluated to be of the order of 1.2 to 1.8 kcal/mol from these studies. In these evaluations, the conformation of the OR group in the axial and in the equatorial isomer was not considered the influence of the exo-anomeric effect was therefore neglected (3). Nevertheless, these studies demonstrated the importance of the anomeric effect. 

The magnitude of the anomeric effect depends on the substituent with the effect decreasing with increasing dielectric constant of the environment. 

Anomeric effects were first demonstrated in furanosides by means of X-ray diffraction [61,68, 294]. The importance of the anomeric effect for furanosides in solution was shown by studies of fused ring systems [295,296], from studies of nucleosides [297,298], and by comparing C-, N-, and 0-furanosyl glycosides in the solid state and solution [299]. Interestingly, the magnitude of the anomeric effect for nucleosides is pH dependent with the largest effect being observed under the most acidic conditions [300]. 

When the substituent in 54 or 55 is axial, and also in the case of the a-anomer of a sugar, it is clear that the destabilizing C-O dipole effects, present when oxygen of OMe is equatorial, are minimized when this oxygen becomes axial. The absence of any significant dipolar repulsions in the latter case has been proposed as the cause of the anomeric effect (see Perrin et al.1). Though its cause is still uncertain the anomeric effect is well documented and it commonly has a magnitude of ca. 8-10 kJ mol, and is solvent dependent. 

The resonance frequency of the axial chlorine is always lower than that of the equatorial chlorine (David 1979). Figure 2.6 suggests another point of view the dispersion of equatorial resonances, close to 0.5 Hz, has an order of magnitude, called the crystal effect by the specialists, of intermolecular origin. When first analysed, they should not be considered significant. On the other hand, the variation range of the axial resonances, 1.7 MHz, is quite superior to the crystal effects. This dispersion expresses the before-mentioned fact that the anomeric effect of chlorine (as with any other substituent) in a pyranose is not independent of the configuration of the rest of the molecule. Thus, the resonance of the axial D-manno chloride is by far the lowest and it is well known that the anomeric effect is intensified in a-D-manno derivatives. 

Stable than the anomer. The experimentally observed Gibbs energy difference in water is 1.5 kJ.mol . The difference of 2.3 kJ.mol between the two values represents the magnitude of the anomeric effect AG(AEl). 

For solutions, the data for the various ring-forms of the axial 2-methoxyoxane given in Table XVII show that AG(EAEl) for the exo-anomeric effect is minimal in water, and higher in less-polar media. The results for the model of o ,a-trehalose, namely, the a, a) form of 2-(oxan-2-yloxy)oxane, indicate a different behavior.The magnitude of the exo-anomeric effect calculated for this compound is 15 kJ.moC, and is not sensitive to solva-... 

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