Efficient continuous synthesis of 2-hydroxycarbazole and 4-hydroxycarbazole in a millimeter scale photoreactor

Abstract

2-Hydroxycarbazole and 4-hydroxycarbazole are important chemicals with extensive applications in optoelectronic materials and pharmaceutical field. State of the art yield of 2-hydroxycarbazole is ∼30% and the reaction time is typically in hours or days. Herein, we developed a green route for the continuous and high-throughput synthesis of 2-hydroxycarbazole and 4-hydroxycarbazole via photochemical intramolecular cyclization of 3‑hydroxy-2′‑chloro-diphenylamine using a self-designed millimeter scale photoreactor, which was designed based on sizing-up and numbering-up strategies for a decent liquid holdup (6.8 mL) and fabricated via femtosecond laser engraving technique. The photochemical synthesis was carried out continuously under the illumination of 365 nm UV-LED with dimethyl sulfoxide as solvent and potassium t-butoxide as catalyst. It was found that under optimized conditions a 2-hydroxycarbazole yield of 31.6% and a 4-hydroxycarbazole yield of 11.1% were obtained with a residence time of 1 min. Compared to semi-batch operations, the reaction time was shortened by 1–2 orders of magnitude. As a result, a throughput of 11.3 g/day 2-hydroxycarbazole and 4.0 g/day 4-hydroxycarbazole can be achieved from the photoreactor. It was proposed that the short reaction time and high product yield are resulted from higher photon transfer rates and more uniform photon distribution provided by the millimeter scale photoreactor, which enhances the reaction rates and mitigates overreaction.