Biologically active quinone derivatives synthesized from the basic 1,4-naphthoquinone structure have been known to benefit various aspects of medicine including anti-cancer and anti-bacterial pharmaceuticals. When exploring the reactivity of 2-bromo-3-methoxy-1,4-naphthoquinone with alkylamine and alkythiolate anions, we find that the reactivity of the 2- and 3- positions varies depending upon reaction condition, whether thermal or photochemical, and is greatly effected by the bulkiness of an existing or an incoming group. The chemoselectivity of this substitution reaction enables the selective introduction of substituents at desired locations, specifically at the 2- and 3- positions. In the reaction of 2-bromo-3-methoxy-1,4-naphthoquinone with an alkylamine, as preliminary studies suggested, the incoming alkylamino group exclusively replaces the 3-methoxy group, not the 2-bromo group. The 2-bromo group is progressively substituted with an alkylthiolate anion. This tandem substitution process allows us to synthesize 2-alkylamino-3-alkylthio-1,4-naphthoquinones in satisfactory yields. Detailed mechanisms of the reactions remain unclear. However, we believe the first substitution to involve an electron transfer and the second substitution to be a Michael Addition reaction. Further studies will reveal a more concrete mechanism scheme.