Oxidation of aldoses with bromine

Abstract

Rates of oxidation of aldoses with bromine have been reappraised and interpreted in the light of present concepts of conformation and reaction mechanism. It is suggested that differences in the rates of oxidation of the a and 0 anomers are largely determined by differences in the free energy required by the reactants for passing from the ground state to the complex in the transition state. Structures for the aldoses in the ground states and in the transition states are postulated, and factors affecting the energy required for reaching the transition states from the ground states are discussed. The relative rates of oxidation are in accordance with the hypothesis that each of the aldoses in the ground state has the conformation predicted by Reeves, and, in the transition state, has a conformation in which the oxygen atom of the Cl-hydroxyl group lies in the plane formed by the ring oxygen atom, Cl, C2, and C5. Presumably, this conformation is stabilized by resonance involving the oxygen atom of the ring. For aldoses having high stability in one chair conformation, the rates of oxidation of the anomers differ widely; in each instance, the anomer in which the Cl-hydroxyl group is axial is oxidized more slowly than the anomer in which this group is equatorial. For aldoses having less stability in a chair conformation, the rates of oxidation of the anomers differ less widely, but, nevertheless, show a definite correlation with the angular position of the Cl-hydroxyl group relative to the plane of the ring. For aldoses for which the stability in both chair conformations is so low that they probably exist in a variety of conformations, the rates of oxidation of the anomers show little difference and no particular correlation with the angular position of the Cl-hydroxyl group. The presence or absence of an oxygen atom in the ring is used to account for the large differences between the rates of bromine oxidation of the aldoses and those of derivatives of cyclohexanol. Differences in conformation in the transition state, associated with the presence or absence of this oxygen atom, likewise account for the fact that the relative rates of oxidation of the axial and equatorial isomers in the two classes of compound are reversed. Because of uncertainty as to the anomeric configurations commonly assigned to some of the aldoses, the configurations of 22 aldoses were reappraised. Advantage was taken of the principle that the anomer preponderating in the equilibrium solution has trans hydroxyl groups at Cl and C2. Except for crystalline v-glycero-v-ido-heptose, the assignments of configuration based on this principle agree with the configurations generally accepted. Classificiation of crystalline D-glycero-v-ido-heptose as an a-D-pyranose necessitates correction of earlier records in which this sugar was considered to be a /3-D-pyranose. In accordance with the author's earlier formulation, oxidation of the axial anomer is believed to take place by two courses: (1) direct oxidation and (2) conversion to the equatorial anomer by the anomerization reaction and the subsequent oxidation of this anomer. The relative importance of the two courses is not considered in this paper. It is pointed out, however, that the actual difference in the rates for the direct oxidation of the two anomers must be at least as great as that observed for the overall rates of oxidation.