Kinetic and mechanistic investigation on the oxidation of Hantzsch 1,4-dihydropyridines with the tropylium cation: a model for NADH oxidation

The reaction kinetics of the reactions of Hantzsch esters (HEH) and Hantzsch 4-aryl-1,4-dihydropyridines (4-aryl-HEH) with the tropylium cation as a formal hydride acceptor were investigated. The observed kinetic isotope effect (KIE, kH/kD), using HEH and 4,4-d2-HEH as substrates, was 4.16, suggesting that the C–H bond cleavage was involved in the rate-limiting step. Correlation analysis on the reactions of para-substituted Hantzsch 4-aryl-1,4-dihydropyridines generated a linear Hammett plot (r=0.9946), with ρ equal to −1.16, which is also consistent with the one-step hydride removal (from 4-C) mechanism. Comparisons of the kinetics and of the reaction thermodynamics between the reactions of HEH and 4-phenyl-HEH both disfavor the one-electron-transfer-initiated multistep mechanism.