Mechanistic Study of the Substitution Reactions of 1,4-Naphthoquinones
The reactions of 1,4-naphoquinones with nucleophiles and/or electron donors are often related to various biological activities. In the substitution reactions at 2-/3-positions of 1,4-naphoquinones, alkylamines as an electron donor substitute certain groups at these positions. The involvement of electron transfer was suggested. The key to the success in this substitution by alkylamines is the generation of an anion radical where a radical center is localized on the carbon next to a leaving substituent at the 2-/3-position of the 1,4-naphthoquinone. Only the methoxy group in 2-bromo-3-methoxy-1,4-napthoquinone, for example, is replaced with alkylamine, not the bromine atom. This is odd because the bromine atom is a better leaving group than a methoxy group. Considering the size difference between oxygen and bromine, a radical on the carbon atom next to methoxy group is more stable than next to bromine due to the captodative effect. A methoxy group is not unique in serving a leaving group via an electron-transfer-initiated substitution with an alkylamine. An alkylamino group can also be substituted by another alkylamine. In the reaction with ethylamine, for example, 2-bromo-3-methylamino-1,4-napthoquinone yields 2-bromo-3-ethylamino-1,4-napthoquinone. This is because the radical center is more favorably localized next to methoxy or alkylamino group in the anion radical of these 1,4-naphthoquionones, instead of next to the bromine atom. It recombines with the cation radical derived from an alkylamine, which leads to the substitution product.
Dittmer, Sarah, " Mechanistic Study of the Substitution Reactions of 1,4-Naphthoquinones" (2010). URC Student Scholarship.
Occidental Research Award to Prof. Otsuki