The aerobic oxidation of benzylamine by model compounds of topaquinone, the active site organic cofactor in copper-containing amine oxidases, was studied in order to elucidate the chemical function of the cofactor in substrate oxidation. In this study, topaquinone hydantoin (1(ox)) and a series of 2-hydroxy-5-alkyl-1,4-benzoquinones which differ in the bulk of their alkyl substituent (5, 6, 7, and 8) were employed as model compounds of the cofactor. The p-quinones (9, 10, 11, and 12) and the o-quinones (13 and 14) were prepared in order to compare them to the topaquinone analogs. Benzylamine was oxidized by the topaquinone analogs (1(ox), 5, 6, 7, and 8) to yield N-benzylidenebenzylamine (PhCH=NCH(2)Ph) as a sole product in acetonitrile at room temperature, The quinones bearing a bulky substituent (1(ox), 5, and 6) were found to be more efficient catalysts than those bearing a small primary alkyl group (7 and 8). In the latter case, the dimers (16 and 17) of the substrate Schiff base intermediates (15, R = methyl, ethyl) were isolated. The p-quinones (9, 10, 11, and 12) were catalytically inactive, The o-quinones (13 and 14) had detectable catalytic activity at room temperature, In anaerobic reactions of the o-quinones (13 and 14) with benzylamine, quantitative formation of the product (PhCH=NCH(2)Ph) was observed. For both o-quinones, products and intermediates which support a transamination mechanism were identified by H-1 NMR spectroscopy. The order of reactivity of quinones (5 > 14 > 13) reflects their redox potentials, such that regeneration of quinone may be rate-determining with o-quinones. These results demonstrate a substantial role of the 2-hydroxyl group of the topaquinone in preventing the formation of Michael adducts with substrate amine and in facilitating the reoxidation of aminoresorcinol intermediates.