Kinetics and mechanism of oxidation of some substituted 4-piperidones by pyridinium fluorochromate (PFC)

Abstract

The kinetics of oxidation of several 3-alkyl and 3,5-dimethyl substituted 2,6-diphenylpiperidin-4- ones (1-6) by pyridinium fluorochromate (PFC) in the presence of perchloric acid in aqueous acetic acid medium have been investigated. Direct second order kinetics is observed, first order each in [oxidant] and [substrate]. A primary isotope effect, k_C-H/k_C-D = 4.2, suggests that the α_C-H bond is cleaved in the rate determining step. An interesting order of reactivity has been found to be: 3-ethyl > 3-methyl > 3- isopropyl > 3-H > 3,5-dimethyl. An explanation has been presented to justify the above rate differences. Further, the effect of electron-withdrawing NO₂ group or electron-donating OCH₃ group present at the <i>para </i>position of the phenyl ring of these piperidones (7,8) on the rate of oxidation suggests participation of the phenyl group. 3-Hydroxy-substituted piperidin-4-ones and substituted pyrrolidine-3-carboxylic acids are the major products of oxidation. Activation energies and related thermodynamic parameters have been determined and compared. Aprobable mechanism consistent with experimental observations has been proposed.