MECHANISTIC STUDIES OF SELECTIVE CATECHOL FORMATION FROM O-METHOXYPHENOLS USING A COPPER(II) ASCORBIC-ACID DIOXYGEN SYSTEM

Mechanistic details of selective conversion of o-methoxyphenols to the corresponding catechols using a Cu2+-ascorbic acid-O2 system, were studied. 2,5-Dimethoxyphenol was converted predominantly to the o-demethylated compound and partially to the m-demethylated one. Anisole with no phenolic hydroxy group was much less reactive. When guaiacol (1), [Me-H-2(3)]guaiacol and 2-[H-2(3)]methoxy-6-methoxyphenol were used as substrates, moderate intermolecular and intramolecular kinetic isotope effects were observed (1.4-1.9). [O-18]Catechol was derived from 1 in nine-fold excess over [O-16]catechol when the reaction was run in an O-18(2) atmosphere with natural water as a solvent, though no [O-18]catechol was formed when using natural O2 and (H2O)-O-18. It was determined that the Cu2+-ascorbic acid-O2 system operates in a monooxygenase mode because the oxygen atom of dioxygen (not water) was incorporated into the products, and this oxidative conversion proceeded mainly via ipso-substitution at the methoxy position, probably with hydroxyl radical coordinated to the cupric ion as the active oxygen species.