Electrosynthesis of Clozapine Drug Derivative via an EC Electrochemical Mechanism

The fact that oxidation, as one of the main routes of phase I metabolism of drugs, follows by conjugation reactions, and also formation of nitrenium ion as one of the clozapine oxidation products, directed us to investigate the oxidation of clozapine (CLZ) in the presence of nucleophile. The oxidation of clozapine (CLZ) has been studied on a glassy carbon electrode in the absence and presence of ۲-thiobarbituric acid (TBA) as nucleophile in aqueous medium by means of cyclic voltammetry and on the graphite rods in controlled-potential coulometry. Cyclic voltammetry studies were realized for CLZ in the pHs ۱.۰ to ۸.۰. Results indicate that the electrochemical behavior of CLZ depends on the pH. Based on the obtained electrochemical results, an ECE mechanism was proposed to explain the electrochemical oxidation of CLZ. The results revealed that oxidized CLZ participates in Michael type addition reaction with TBA and via an EC mechanism converts to the corresponding new dibenzodiazepin derivatives. The product has been characterized by IR, ۱H NMR, ۱۳C NMR and MS.

Keywords:

Clozapine (CLZ) , Electrosynthesis , Dibenzodiazepin , Cyclic Voltammetry , ۲-Thiobarbituric acid (TBA)