Reaction of 2-Methyl-2,3-dihydro-1,4-naphthoquinone Oxide with Thiols

Abstract

The reactivity of 1,4-naphthoquinones toward various nucleophiles, such as thiols, leads to biological activities including anticancer and antibacterial properties. Here we studied the reaction of 2-methyl-2,3-dihydro-1,4-naphthoquinone oxide, a vitamin K3 derivative, with thiols. For example, the reaction of 2-methyl-2,3-dihydro-1,4-naphthoquinone oxide with alkylthiolate in methanol affords two addition products, 2-alkylthio-3-methyl-1,4-naphthoquinone (one-to-one addition product) and 2-alklythio-3-alkylthiomethyl-1,4-naphthoquinone (one-to-two addition product). We found that the one-to-two product was derived from a one-to-one product due to the acidic nature of its a-protons. The formation of these two products can be selectively controlled by choosing the stoichiometry of thiolate to quinone and also by the strength of the base used to generate an alkylthiolate from the corresponding alkylthiol. The bases examined here are triphenylamine, imidazole, N-methylmorpholine, hexamethylenetetramine, DABCO (1,4-diazabicyclo[2.2.2]octane), 1,2,2,6,6-pentamethylpiperidine, and triethylamine. When a base whose pKa is not enough to abstract an a-proton from a one-to-one product, the one-to-one product is exclusively formed.