Thiol Additions to 1,4-Napthoquinone Epoxide Derivatives in the Presence of a Base

Abstract

Derivatives of 1,4-napthoquinone are known to possess numerous biological activities, including potential anti-cancer properties. Their reactivity toward a nucleophile is responsible for many of these biological activities. Here, we studied the reaction of 2,3-dihydro-1,4-napthoquinone epoxide derivatives with alkylthiols, a process that requires the presence of a base. When 2-methyl-2,3-dihydro-1,4-naphthoquinone epoxide was reacted, two different classes of products were identified. The base strength controls the formation of the two different products. The first was the ?one-to-one? product, where one molecule of thiol reacts with each molecule of 1,4-napthoquinone derivative. The ?one-to-one? product was exclusively formed when the base used was mild, such as N-methylimidazole. In order to yield the ?two-to-one? product, two thiols for every 1,4-napthoquionone derivative, we found that the reaction required a stronger base, for example, triethylamine. The ?two-to-one? product was formed via the Michael addition process with the ?one-to-one? product as an intermediate. To shed light on the reaction mechanism for the formation of these two products the reaction 2,3-dimethyl-2,3-dihydro-1,4-naphthoquinone epoxide was studied. Also, we observed the reactions with both compound and several different thiols. The mechanism of the formation of these products is presented.