Nucleophilic Additions and Substitutions of 2,3-Epoxy-2,3-dihydro-1,4-naphthoquinone Derivatives

Derivatives of 1,4-napthoquinone are known to possess numerous biological activities, including potential anti-cancer properties, which is made possible by their propensity for reacting with nucleophiles. Here, we study the reactions of 2,3-epoxy-2-methyl-2,3-dihydro-1,4-nathoquinone with alkylthiols, alkylamines, and arylamines. Two different classes of products were identified, a single addition product, 2-alkylthio-3-methyl-1,4-naphthoquinone, and a double addition product, 2-alkylthio-3-alkylthioalkyl-1,4-naphthoquinone. When 2,3-epoxy-2-methyl-2,3-dihydro-1,4-nathoquinone reacted with alkylthiols in the presence of a base, the strength of the base determined which class of product was formed as the major product. With a weak base, like N-methylimidazole, only a single addition product was identified, while with a strong base, like triethylamine, the major product was the double addition product. In the formation of the double addition product a slightly acidic alpha-methyl proton from a single addition product is further replaced by the alkylthiol via Michael addition process. Currently, we are able to identify one major product in the reaction of 2,3-epoxy-2-methyl-2,3-dihydro-1,4-naphthoquinone with alkylamines, that is, a single addition product