Base-Promoted Synthesis of Phenazines and their Cytotoxic Activity on U87MG Cells

Phenazines are well-known motifs that are widely found in biological molecules and natural products. These heterocyclic compounds are also fundamental building blocks in industrial materials, including sensors, photocatalysts, dyes, and others. However, the existing methods for the synthesis of such privileged heterocyclic compounds have drawbacks, including harsh reaction conditions, tedious procedures, and the use of expensive ligands and transition metals. Therefore, there is a demand for straightforward and efficient methods for the synthesis of phenazines.

Using NaN(SiMe3)2 as a base, the reaction was conducted at 100 °C with commercially available nitroarenes and arylamines as substrates, yielding the corresponding phenazines. The anti-proliferative effects of compounds 3aa-3dg were measured using the Cell Counting Kit-8 (CCK-8) assay.

Fourteen phenazines were synthesized in moderate to good yields via the protocol presented in this study. Among the phenazines evaluated for biological activity against U87MG cells, 3ca and 3ha exhibited cytotoxic activity.

A novel method for the synthesis of phenazines was presented in this study. Compared to the existing method for the synthesis of phenazines, the method described here is operationally simple, transition metal-free, and straightforward. The detailed mechanism study is currently underway. This study is an important part of our long-standing interest in base-promoted synthesis of heterocyclic compounds from simple starting materials.

Herein, an oxidant- and transition-metal-free method was introduced for the synthesis of phenazines from commercially available nitroarenes and arylamines. This protocol is straightforward, efficient, and environmental-friendly.