Hydroxymethyl groups solvent effects

The me/a-hydroxymethylation yield was very dependent on large excess formaldehyde used and insensitive to acid concentration and temperature. After extensive exploration of the reaction condition variables it was discovered that a decrease in water content of the solvent results in the increase of hydroxymethylation yields. Eventually conditions were devised to achieve close to 100% memethylene linkage formation. Both softwood and hardwood model compounds gave only mono-mepulling effect of the introduced hydroxymethyl group. 

L. M. J. Kroon-Batenburg and J. Kroon, Biopolymers, 29,1243 (1990). Solvent Effect on the Conformation of the Hydroxymethyl Group Established by Molecular Dynamics Simulations of Methyl-p-D-Glucoside in VChter. 

However, NMR titration of a mixture of the anomerie glueopyranosylimi-dazoles in a variety of solvents established eonelusively that the a-anomer was more basie than the p-anomer by around 0.3 pA units in D2O, but less in less polar solvents. This is exactly the opposite of what is predicted by any reverse anomerie effect, but is what would be predicted on the frontier orbital picture of the normal anomerie effect of Figure 2.12, since protonation would increase the electron demand of the anomerie substituent. The additional hydroxymethyl group of glucopyranosylimidazoles, ensures that they, unlike xylopyranosyl-imidazoles, remain in the conformation on protonation. On the electrostatic model, therefore, the protonated a-anomer is expected to be destabilised and the protonated p-anomer stabilised, which should make the p-anomer more basic. 

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