Electrochemical oxidative CN bond cleavage in mefenamic acid and electrosynthesis of new coumarin derivatives

This research focuses on the electrochemical oxidation of mefenamic acid ( MFA ), the breaking of the C N bond and the subsequent reaction of the resulting fragment with coumarin and 4-hydroxycoumarin in a 70/30 buffer/ethanol mixture. The synthesis involves an initial electrochemical oxidation of mefenamic acid, followed by C N bond cleavage, and two subsequent nucleophilic substitution reactions with the coumarins via a mechanism called EC Cleavage Bond C Michael addition EC Michael addition . The identity of all products has been established through a combination of electrochemical and spectroscopic techniques: 1 HNMR, 13 CNMR, Mass spectrometry, and IR spectroscopy. Also, a theoretical study based on Density Functional Theory (DFT) at the B3LYP/6-311++ G (d, p) level was performed to identify the chemical reactivity of the studied compounds. Mulliken charges, frontier molecular orbitals (FMOs) and Fukui function analyses were applied to determine electrophilicity values and identify the most favorable sites for both initial and subsequent nucleophilic attacks. The local electrophilicity trends obtained from these analyses clearly support the proposed reaction mechanism. • Electrooxidation of mefnamic acid in the presence of coumarins was assessed. • Mefnamic acid chevage after the electrooxidation step. • New bis-coumarin derivatives synthesized under ECCEC electrochemical mechanism.