A rapid and scalable method for visible light induced bromination of uracil derivatives in a falling film looping photoreactor

Abstract

Visible light induced green synthesis of 5-bromouracil derivatives using N-bromosuccinimide (NBS) in acetonitrile under batch operation with a constant photon flux of 46 μmol s⁻¹ is reported. This methodology has shown excellent tolerance with various 6-substituted and N-substituted uracils and is also applicable for various pyrimidine and arene derivatives. The reaction proceeded through the formation of a bromine molecule via a radical pathway followed by an electrophilic substitution reaction, and this hybrid nature of the reaction pathway in the presence of light made the process faster. We successfully synthesized twenty-one derivatives and characterized them using various spectroscopic methods. Finally, the three different modules of the looping falling film reactor were used to show the successive scalability of the process with comparable photonic characteristics and reaction conditions. We achieved milligram to multigram scale reaction with almost equal efficiency and maximum productivity up to 1.2 kg per day.