The preparation and reactivity of biologically important p-benzoquinol imines. In search of the 'ultimate' carcinogen of N-acetyl-2-aminofluoren

The formation of an N-acylated p-benzoquinol imine has been postulated for the metabolism of the carcinogen, N-acetyl-2-aminofluorene. However, the synthesis of N-acylated p-benzoquinol imines have not been reported, and the chemistry of these important metabolites relatively unknown. Therefore investigations were undertaken to prepare these intermediates utilizing electrochemical oxidation methodology. Interestingly, the anodic oxidation of 4-substituted alkyl and aryl N-acylated anilines in methanolic solution using a Pt anode and cathode and 2% LiClO$sb4$ as electrolyte formed the respective N-acylated p-benzoquinol methyl ether imines in 40%-80% yield. In addition the electrochemical oxidation was performed in aqueous acetonitrile forming N-acylated p-benzoquinol imines in 30%-45% yield.;In addition to their preparation, the chemistry of quinol imines were examined with aqueous media, alkyl and aryl amines and ethanethiol. Interestingly, under acidic, neutral and mildly basic conditions, hydrolysis of the imine functionality generated the respective 4-substituted cyclohexadienones in high yield (70%-80%). With the addition of primary alkyl and aryl amines, a new class of compounds, e.g., N-alkyl- and N-aryl-p-benzoquinol methyl ether imines, were obtained in 65%-80% yield. Finally, investigations with N-benzoyl-p-benzoquinone imine dimethyl ketal found ethanethiol adds to the carbon-nitrogen double bond to form a labile but isolable adduct. This product may then undergo a 1,2-migration of the ethylthio group upon standing or reaction with acid resulting in the formation of an ortho-substituted amide. Analogous reactions explain the production of 1- and 3-substituted glutathione conjugates during the metabolism of N-acetyl-2-aminofluorene in the rat.