The reduction of 2-bromomethyl-3-methyl- and 2,3-bis-bromomethyl-1,4-naphthoquinones, potential bioreductive alkylating agents. Electrochemical and computational studies

• Published in: Journal of electroanalytical chemistry (Lausanne, Switzerland) Vol. 560; no. 1; pp. 79 - 86
• Main Authors: de Abreu, Fabiane C, Lopes, Adriana C.O, do Monte, Silmar A, Soares, Nivaldo A, Goulart, Marı́lia O.F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2003; Elsevier Science
• Subjects: 2,3-Bis-methylbromo-1,4-naphthoquinone; 2-Methylbromo-3-methyl-1,4-naphthoquinone; Chemistry; Cyclic voltammetry; Electrochemistry; Exact sciences and technology; General and physical chemistry; Kinetics and mechanism of reactions; Leaving group effect; Redox potential; Reductive elimination; Cyclic voltammetry; 2,3-Bis-methylbromo-1,4-naphthoquinone; Redox potential; 2-Methylbromo-3-methyl-1,4-naphthoquinone; Reductive elimination; Leaving group effect; Electron transfer; Naphthoquinone derivatives; Experimental study; Chemical reduction; Organic solvent; N,N-Dimethylformamide; Reaction mechanism; Chronoamperometry; Electrochemical reaction; Aprotic solvent
• ISSN: 1572-6657; 1873-2569
• DOI: 10.1016/j.jelechem.2003.07.021

In the present work, 2,3-dimethyl-1,4-naphthoquinones, substituted at one or both side chains with bromine were prepared and submitted to electrochemical studies (cyclic voltammetry and electrolysis), in aprotic medium (DMF + 0.1 mol l −1 TBAP), using different electrodes (Hg, GC and Au), to observe the role of bromide, as a good leaving group, in their electroreductions. The cyclic voltammograms are complex. Combined results from CV, chronoamperometry and analysis of the products of electrolysis, mainly dimers and the parent unsubstituted quinone, allowed the qualitative definition of the electrodic mechanism for the reduction of the brominated quinones. A reversible electronic transfer to the quinonoid group followed by the cleavage of C–Br, in an EC type mechanism, more specifically a reductive elimination, is suggested. The quinonoid radical is generated and suffers dimerization to electroactive dimers or a second electron uptake, furnishing the anion that can be protonated to yield 2,3-dimethyl-1,4-naphthoquinone, also electroactive. The additional waves are probably related to the reduction of quinomethide-derived products, upon comparison with a synthetic dimer. Computational studies corroborate the electrochemical observations. Despite the lack of unequivocal proof of quinonemethide generation, its intermediacy is highly probable and this has been proved to be essential for the biological activity of these compounds.