Kinetic studies of oxidative dealkylation of alkylcobalamins by hexachloroplatinate(IV)

Abstract

The dealkylation of methylcobalamin (CH₃–B₁₂), methyl 3,5,6-trimethylbenzimidazolylcobamide, and ethylcobalamin (C₂H₅–B₁₂) by PtCl₆^2– in acidic solution have been examined. The demethylation of CH₃–B₁₂ by PtCl₆^2– in perchlorate solution proceeds very slowly. In chloride media, however, the reaction occurs readily, yielding H₂O–B₁₂⁺, PtCl₄^2–, and CH₃Cl. In bromide or pyridine media the methyl-transfer product is CH₃Br or N-methylated pyridine. Kinetic studies show that the reactions are first order in alkylcobalamin concentration, with the observed rates displaying a hyperbolic dependence upon [PtCl₆^2–]. This non-linear dependence is interpreted in terms of a pre-association of the reactants, followed by the dealkylation steps. The rates of dealkylation, after correction for the association constants, are not significantly affected by the ligands trans to the alkyl groups. This observation, together with the comparable rates of dealkylation of the base-off forms of CH₃–B₁₂ and C₂H₅–B₁₂, is taken as kinetic evidence against direct electrophilic attack at the α carbon, and favouring a one-electron transfer to form a R–B₁₂⁺,PtCl₆^3– radical pair. The latter collapses to the products observed. The mechanism for the cleavage of Co–C bonds in the oxidized alkylcorrinoid intermediates is discussed.