Electrostatic analysis, anomeric effect

The balance of electrostatic and delocalization interactions in an isolated molecule may be perturbed by the influence of the solvent. In calculations based on Eq. 7, the analysis of solvation-energy terms suggested that the electrostatic contribution stabilizing the ap orientation of the acetal s ment is the conformationally dominant term. For example, in 2-methoxyoxane, the difference in energy of the (ap, ap) and (ap, sc) conformers in water, compared to that in the isolated molecule, caused by solute-solvent electrostatic interactions alone, amounts to 4 kJ.mor. Accordingly, the inter-and intra-molecular, electrostatic interactions operate in reverse directions in acetals. Whereas the intramolecular, electrostatic interactions are responsible, together with delocalization interactions, for the aiq)earance of the anomeric, reverse anomeric, and exo-anomeric effects, the solute-solvent electrostatic interactions lessen their im nitude, and may even cancel them. Of course, the solvent may also influence the electron distribution and energy of MO s in a molecule. In this way, the orbital interactions of lone-pairs and delocalization contributions to the anomeric effect may be scaled by the solvent, but this mechanism of the environmental effect is, in most cases, of only minor importance. 

In addition to steric effects and electrostatic effects, the conformational analysis of carbohydrates requires two stereoelectronic effects to be taken into consideration the gauche effect and the anomeric effect, in its various manifestations. Both of these effects can be considered as aspects of no-bond resonance. 

The initially proposed explanation for the anomeric effect as a simple dipole-dipole interaction [12] therefore accounts for only a part of the effect, but it does not represent the whole story. If one calculates the electrostatic interaction energy in frans-2,5-dichloro-l,4-dioxane (Fig. 2.9) (the molecular geometry is known from X-ray analysis) using the values of ji = 2.2 and 1.4 D for the dipole moments of C-Cl and C-0 bonds and e = 2.3 for the dielectric constant, one arrives at the energy difference of about 1 kcal/mol in favor of the diaxial form [36]. This difference is clearly too small to account for a strong preference for the diaxial conformation [37]. 

The concept of hyperconjugation relies on a local orbital picture of quantum chemistry that is consistent with the common chemist s view of Lewis structures. Natural bond orbital (NBO) analysis [30] has been used to explain the anomeric effect by showing a favorable interaction between the heteroatom lone pair and the ct orbital of the substituent bonded to the anomeric carbon [16, 31, 32]. This was done most recently by Freitas [33] for a series of 2-substituted tetrahydropyrans, who found that NBO analysis provides a coherent framework in which to analyze the results, as we do in this report. Freitas points out that steric, electrostatic, and hyperconjugative effects play a role whether or not the anomeric effect is observed in his calculations, and sometimes the hypercongjugative effect is not the dominate factor in the preference of one isomer over the other. 

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