Electrochemical Behavior of 2-Halo-N-Phenylacetamides at a Carbon Cathode

Abstract

Haloacetamides and haloacetanilides have been utilized for the synthesis of many compounds such as, but not limited to, β-lactams,1 N,N-bis-(phenylcarbamoylmethyl) dimethylammonium,2 and oxazolidine-2,4-diones.3 Therefore, it is important to understand fully how these haloacetamides behave as well as the reaction pathways they undergo. Electrochemical studies of 2-chloro-N-phenylacetamide have been reported at carbon cathodes, and were successful in demonstrating the reductive cleavage of the carbon–halogen bond. A mechanism for the aforementioned reduction has been proposed.4 This project’s primary objective is to compare the electrochemical behavior of a series of 2-halo-N-phenylacetamides and to elucidate a more complete mechanistic picture for the reduction of this class of compounds. In the present investigation, we have conducted cyclic voltammetry and controlled-potential electrolysis studies of 2-iodo-N-phenylacetamide and 2-bromo-N-phenylacetamide at a carbon cathode to understand further the electrochemical behavior of 2-halo-N-phenylacetamides. Reduction of 2-bromo-N-phenylacetamide and 2-iodo-N-phenylacetamide in dimethylformamide (DMF) containing 0.05 M tetramethylammonium tetrafluoroborate (TMABF4) results in cyclic voltammetry peaks at –0.9 and –1.4 V (bromo) and –0.6 and –1.1 V (iodo) vs. a Cd(Hg) reference electrode. Analysis of the products resulting from controlled-potential electrolyses of both analytes by means of gas chromatography–mass spectrometry (GC–MS) indicates the presence of dehalogenated species as the primary products. Casadei, M. A.; Di Rienzo, B.; Inesi, A.; Moracci, F. M., Electrochemical studies on haloamides. Part 3. Haloacetamides and halo-acetohydroxamates. J. Chem. Soc., Perkin Trans. 1 1992, 375–378.Walker, M. J., Treating cough and tussive attacks. Google Patents: 2012.Casadei, M. A.; Cesa, S.; Inesi, A., Electrochemical studies on haloamides. Part XII. Electrosynthesis of oxazolidine-2,4-diones. Tetrahedron 1995, 51, 5891–5900.Pasciak, E. M.; Sengupta, A.; Mubarak, M. S.; Raghavachari, K.; Peters, D. G., Electrochemical reduction of 2-chloro-N-phenylacetamides at carbon and silver cathodes in dimethylformamide. Electrochim. Acta 2014, 127, 159–166.