AbstractThe oxidation of 4‐methylcatechol by dioxygen and the subsequent reactions of the two nucleophiles OH−and MeO−with the oxidation products were studied by electron spin resonance (ESR) spectroscopy. These reactions are models for those of skin proteins with substituted 1,2‐dihydroxybenzenes (catechols) which produce the severe allergic contact dermatitis associated with plants such as poison ivy, poison oakd and the Japanese lac tree. The rates of formation of the primary and secondary semiquinone radical anions show a large kinetic deuterium isotope effect (ca10) at 20°C, which is ascribed to a slow deprotonation of the hydrogen bridged 4‐methylcatechol monoanion. There is a marked difference in regioselectivity for OH−and MeO−substitution of the 4‐methylcatechol monoanione; OH−reacts exclusively at the 3‐position whereas MeO−attacks at the 5‐position. This dissimilarity between two normally similar nucleophiles is also ascribed to the occurrence of hydrogen bridging between the substituting OH−at the 3‐position and the adjacent quinone oxygen at the 2‐position. The expected attack at the more electropositive 5‐position occurs with MeO−because no such hydrogen bonding can occur. Disubstitution occurs for OH−but not for MeO−, probably reflecting the