Photocatalyzed Synthesis of Benzothiazoles Under Continuous-Flow Process Optimization

Benzothiazoles are privileged sulfur-containing heterocycles found in pharmaceuticals, bioactive compounds, and functional materials. Conventional syntheses rely on oxidative cyclization under harsh conditions, long reaction times, and stoichiometric oxidants, highlighting the need for sustainable methodologies. Herein, we report a photocatalyzed continuous-flow approach for benzothiazole synthesis from 2-amino(disulfides) and alcohols under blue LED irradiation. Initial transfer of batch conditions to flow revealed the influence of light intensity and residence time. At a residence time of 60 min, conversions ranged from 53–58% under 50–100 W irradiation, increasing to 70% at 200 W, whereas 300 W caused substrate and product degradation. Reducing the residence time to 10 min provided the best balance between conversion and degradation control. Two sequential Design of Experiments studies ultimately identified light intensity as the key parameter and enabled up to 97% conversion (residence time of 10 minutes, 300 W irradiation, 30 mol% photocatalyst, and 8 equiv. of benzyl alcohol).