Electrochemical synthesis of polyhydroxylated aromatic derivatives substituted with mono- and dipyrimidinyl thioethers in aqueous medium

Polyhydroxylated aromatic pyrimidinyl thioethers are important compounds due to their potential anti-HIV integrase activity. The present work describes an electrochemical synthetic strategy and environmentally benign approach for the synthesis of these compounds, superior to conventional chemical reactions. Thus, the electrochemical oxidation of 4-substituted catechols and caffeic acid, in the presence of 2-mercaptopyrimidine derivatives 2, generates monopyrimidinylthio-substituted polyhydroxylated aromatics 3a-f in moderate yields. In the case of catechol itself and 3-substituted catechols, both mono(3g-1) and dipyrimidinylthio-substituted derivatives (4g-1) were produced. Apparently, the anodic oxidation of catechol derivatives leads to nucleophilic addition products of types 3 and 4, which are different from the traditional nucleophilic substitution reaction of aryl halides and thiols. The electrochemically induced reaction mechanism is also discussed. (C) 2008 Elsevier B.V. All rights reserved.