α-Bromination of Aldehydes by Continuous Flow Chemistry and Its Application to the Flow Synthesis of 2-Aminothiazoles

A continuous flow protocol for the α-bromination of aldehydes with bromine is reported, demonstrating significantly improved reaction efficiency and superior mono/dibromination selectivity compared to conventional batch methods. A wide range of aldehydes, including both aryl-substituted and simple aliphatic aldehydes, exhibited excellent reactivity and selectivity under optimized flow conditions. Utilizing this α-bromination flow strategy, a two-step flow synthesis of 2-aminothiazoles, a core structural motif present in many biologically active molecules, was successfully developed, starting from aldehydes. Furthermore, by integrating the α-bromination, 2-aminothiazole formation, and subsequent condensation, a three-step flow process was established for the synthesis of a 2-aminothiazole-containing Hep3B inhibitor. This study highlights the potential of continuous flow chemistry in both bromination reactions and the downstream multistep synthesis of complex bioactive molecules.