Acid- and Base-Catalyzed D-Glucosylurea Anomerization

Abstract

The D-glucosylureas have been found to undergo both acid- and base-catalyzed anomerization. Water was not an effective catalyst for the transformation but the addition of either an acid or base resulted in the formation of an equilibrium mixture. Kinetic investigations of the acid-catalyzed reaction indicated that the key intermediate step was die formation of an iminium ion. A deuterium isotope effect of k_H/k_D = 0.77 − 0.80 for the acid-catalyzed reactions of either N-β-D-glucopyranosylurea (1) or N.,N′-bis(β-D-glucopyranosyl)urea (3) in both DMF and water excludes an anomerization pathway similar to aldose mutarotation. The lack of significant glucose formation in dilute aqueous acid prior to complete equilibration indicated that the D-glucosyl carbonium ion intermediate was not an important factor. The carbonium ion may, however, contribute to carbohydrate disappearance at high acidity levels. The rate of base-catalyzed anomerization of 3 depended on pH. The transformation resulted in >95% anomer recovery without D-glucose formation, and a mechanism involving the formation of an imine is proposed. Neutralization of an acid- or base-catalyzed mixture provided a stable solution which did not undergo any additional transformations.