The Synthesis of 2-Chloro-3-methyl-1,4-naphthoquinone and Its Reaction with Amines
Vitamin K and its derivatives are biologically active compounds. They are known to be effective as blood clotters, antibacterials and antifungals, and are also believed to be potential anticancers. Here we started studying the synthesis of 2-chloro-3-methyl-1,4-naphthoquinone, a vitamin K3 derivative, by chlorinating 2-methyl-1,4-naphthoquinone. First, we applied chlorine gas to introduce chlorine atom, but the yield was poor. We then tried the synthesis of 2-chloro-3-methyl-1,4-naphthoquinone by using 2-methyl-2,3-dihydro-1,4-naphthoquinone oxide as the starting compound. We reacted the oxide with concentrated HCl and found that 2-chloro-3-methyl-1,4-naphthoquinone was formed in a reasonable yield. Once 2-chloro-3-methyl-1,4-naphthoquinone was at hand, its reaction with amines was studied. First, 2-chloro-3-methyl-1,4-naphthoquinone was reacted with isopropylamine. Two products were identified in the reaction mixture. Judging from the analysis of the NMR spectra after being purified on column chromatography, one product was found to be 2-chloro-3-isopropylamino-1, 4-naphthoquinone whereas the other was 2-isopropylamino-3-methyl-1,4-naphthoquinone. Similar demethylation product is also isolated in the reaction of 2-bromo-3-methyl-1,4-napthoquinone with an alkylamine such as isopropylamine.
Helgert, Theodore, "The Synthesis of 2-Chloro-3-methyl-1,4-naphthoquinone and Its Reaction with Amines" (2004). URC Student Scholarship.
Support provided by:NSF-Research Experience for Undergraduates in Chemistry Grant Fellowship