Reactivity of certain piperidin-4-ols towards oxidation with cerium(IV)

Abstract

Kinetics of the oxidation of six pairs of epimeric piperidin-4-ols by cerium(IV) in the presence of sulphuric acid in an aqueous acetic acid medium at 60°C have been investigated. The corresponding α-deuteriated piperidin-4-ols have been prepared and their oxidation rates measured. The oxidation is first-order in both oxidant and substrate at constant acid concentration. Mechanisms involving free-radical intermediates are proposed. The observed kinetic isotope effect in the case of t-2, t-6-diphenyl-c-3-isopropyl-N-methyl-piperdin-r-4-ol (4)(k_H/k_D= 6.26) suggests that the C–H (or C–D) bond of the carbinol carbon is involved in the rate-determining step. An alternative mechanism involving the participation of the O–H bond in the rate-limiting step is proposed to account for the absence of a kinetic isotope effect (k_H/k_D= 1.00) in the oxidation of t-2, t-6-diphenyl-c-3, c-5,N-trimethylpiperidin-r-4-ol (5) and c-2,c-6-diphenyl-t-3,t-5,N-trimethylpiperidin-r-4-ol (14). It is probable that both mechanisms operate simultaneously in the oxidation of those piperidin-4-ols which show a kinetic isotope effect of ca. 2.00. The conformational effects on the rates of oxidation are discussed.