Development of a New Synthetic Process for Triflumezopyrim and Continuous Flow Attempts

Triflumezopyrim (TFM) is a novel class of mesoionic insecticides. Herein, a novel synthetic process for TFM was developed via imidization, reductive amination, and cyclization. Based on toluene as a universal solvent and simplifying postprocessing operations, TFM could be obtained in approx. 26 h with about 40% overall isolated yield, while the E-factor was decreased to 158, which improved the reaction efficiency and eco-friendliness. Subsequently, the synthetic route was attempted in continuous flow, and TFM was prepared in about 32 min with about 30% total isolated yield. Furthermore, by connecting to our previous research, TFM could also be obtained in less than 35 min total reaction time with about 30% yield based on continuous flow total synthesis, which shortened the total reaction residence time by about 48-fold compared to the batch mode and manifested a significant advantage of reaction efficiency in continuous flow.