Oxidative Cleavage of Acetaminophen by Cetyltrimethylammonium Dichromate: A Mechanistic Study

Abstract

In this contribution, we report the oxidation of a potential analgesic and anti-inflammatory drug acetaminophen by lipopathic oxidant, cetyltrimethylammonium dichromate (CTADC), in a nonpolar medium and in the presence of surfactants. Acetaminophen is oxidized to p-benzoquinone and acetamide by CTADC in the presence of acetic acid. Michaelis–Menten-type kinetics are observed with respect to the substrate. The chemical nature of the intermediate, transition state, and reaction mechanism are proposed on the basis of (i) the observed rate constant dependencies on the [reactants], (ii) the high negative entropy of activation, and (iii) the effect of solvent polarity on rate constant values. The deuterium kinetic isotope effect and solvent kinetic isotope effect are also determined and provide further support for the proposed mechanism. The decrease in rate with the addition of different ionic and nonionic surfactants confirms the formation of a reverse micellar aggregate, which controls the reaction because of the charge on the interface and also because of the partition of the oxidant and the substrate in two different domains.