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-2H3]guaiacol and 2-[2H3]methoxy-6-methoxyphenol were used as substrates, moderate intermolecular and intramolecular kinetic isotope effects were observed (1.4–1.9). [18O]Catechol was derived from 1 in nine-fold excess over [16O]catechol when the reaction was run in an 18O2 atmosphere with natural water as a solvent, though no [18O]catechol was formed when using natural O2 and H218O. 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.