Abstract

Amino-p-quinones constitute an important class of compounds, known for their pharmaceutical properties as well as redox-active properties that make them promising candidates for energy storage and electronic applications. The direct coupling of C(sp²)–H and N–H bonds for C–N bond formation in these compounds presents a compelling strategy for their synthesis. Conventional methods, however, typically involve hazardous organic solvents in bulk amounts, contributing significantly to environmental pollution. In fact, approximately 80% of the waste produced by the pharmaceutical and fine-chemical industries comes from solvent use.
In this context, mechanochemical methods offer a promising alternative. By using mechanical energy to drive reactions in the solid state, they can drastically reduce solvent use, simplify workup, and sometimes allow direct use of crude products in subsequent steps. This thesis highlights our recent progress in developing mechanochemical coupling of 1,4-naphthoquinone with different amines to yield 2-amino-1,4-naphthoquinone products, using either catalytic methods or catalyst-free approaches with blue LED light, which simplify the workup process and allow direct use of the crude product for further synthetic steps.
Using the oxidative amination of 1,4-naphthoquinone and morpholine as a model system, four complementary strategies were evaluated, including iron catalysis, copper catalysis, blue-light-driven resonant acoustic mixing, and a copper(II) acetate / acetic acid protocol under mildly acidic conditions. Across primary and secondary aliphatic, cyclic, and aromatic amines, the latter protocol emerged as the most general and operationally simple platform for the oxidative mechanochemical amino-p-quinone synthesis.