Generation and Reactions of Heteroaromatic Lithium Compounds by Using In-Line Mixer in a Continuous Flow Microreactor System at Mild Conditions

A lithium–halogen exchange reaction procedure was applied to introduce electrophilic substituents to the heteroaromatics, which exhibited potential in the syntheses of pharmaceutical intermediates. In this contribution, generation and reactions of heteroaromatic lithium compounds were successfully accomplished at 10 °C in a continuous flow microreactor equipped with an in-line mixer. Extensive reaction results revealed that such a synthetic method was widely applicable for different kinds of heteroaromatics with various substituents. All results highlighted that the lithium–halogen exchange reaction for large-scale syntheses might be realized by microreactor systems.