Mechanochemical Synthesis of 2‑Amino-1,4-naphthoquinones and Telescopic Synthesis of Lawsone.

Abstract

A mechanochemical solvent-free synthesis of 2-amino-1,4-naphthoquinones was developed by the reaction of aromatic/aliphatic amines with naphthoquinone, and better yields were obtained with aromatic amines. The combination of sodium acetate as a base and silica as solid auxiliary grinding was crucial in most cases. The simplest 2-amino-1,4-naphthoquinone was prepared via mechanochemistry and under microwave heating (high yield) by applying the known combination of sodium azide/acetic acid. In the mechanochemical reaction of binucleophile 2-amino-4-methylphenol, a selectivity dependence was observed with applied frequency, and chemotherapeutic 10-methyl-benzo-[a]-phenoxazine-5-one was isolated as a minor product at a high frequency, which was alternatively synthesized via microwave from Lawsone and from naphthoquinone, being an innovation to this class of bioactive compound. Mechanochemistry had the advantage of multigram preparation of 2-amino-1,4-naphthoquinone and 2-(phenyl)-amino-1,4-naphthoquinone, which were applied in the two-step synthesis of natural product Lawsone via acid hydrolysis. A more sustainable telescopic synthesis of Lawsone was accomplished and is the first straightforward total synthesis involving mechanochemistry.