Continuous flow Friedel–Crafts acetylation of phenols and electron-rich arenes and heteroarenes

Abstract

An expedient and efficient synthesis of acetyl phloroglucinol from phloroglucinol under continuous flow is reported. This compound is an important building block to access numerous flavonoids. The reported acetylation reaction of phloroglucinol is more efficient than under batch conditions (residence time of 1 min in flow vs 10–15 h in batch; ≥ 98% yield in flow vs 65–86% yield in batch), and proceeds without any formation of the diacetylated product. The desired product was produced with a throughput of ≥ 98 g/h using a simple set-up. The conditions that highlight the use of ethyl acetate, a biomass-derived solvent and acetic anhydride or acetyl chloride were tested in the Friedel–Crafts acetylation of other electron-rich phenols and heterocycles.