Tritium-Labeled Compounds X. Isotope Effects in the Oxidation of Aldoses-1-t With Bromine.

Abstract

Tritium isotope effects have been used in bromine oxidation studies of aldoses to evaluate two reaction paths previously postulated by Isbell and Pigman, namely, direct oxidation and oxidation after anomerization. Because the former path involves a primary isotope effect (k*/k = 0.14, approximately) and the latter a secondary isotope effect (k*/k = 0.80, approximately) it was found possible to evaluate the relative importance of the two reaction paths from the overall isotope effects, which ranged from 0.20 to 0.59.Under the conditions reported, the direct oxidation for the axial anomers ranges from 38 percent for α-d-galactose to 94 percent for α-d-lyxose. Differences in the proportion of the anomer oxidized by each of the two paths are explained by variations in the free energy required for reaching the respective transition states. Aldoses of high conformational stability having an axial C1-hydroxyl group resist the change in conformation necessary for direct oxidation and react in large measure through a change in configuration (anomerization). Aldoses of lower conformational stability having an axial C1-hydroxyl group react largely through a change in conformation, because this path does not have a high energy barrier.The equatorial anomers of d-glucose-1-t and maltose-1-t showed isotope effects of 0.32 and 0.23, respectively in comparison with a value of 0.14 previously found for the oxidation of aldoses-1-t with iodine in alkaline solution. The isotope effect in the oxidation of d-glucose-1-t with d-glucose oxidase at 30 °C was found to be 0.15. These strong isotope effects are in accord with the rupture of the C1 to H bond in the rate-determining step.The following reactions gave the values for k*/k cited in parentheses: d-glucose-1-t +NaCN (0.83); d-glucose-1-C14 + NaCN (1.00); d-glucose-1-t+NaBH4 (0.73); d-mannose-1-t + phenylhydrazine (0.83); and d-mannose-1-C14 + phenylhydrazine (0.95). The values of k*/k are typical of aldose reactions involving rate-determining isomerization of the pyranose structure.The isotope effects were measured by a double-label method and by a newly developed method based on the radioassay of water evolved in the reaction.