Continuous flow synthesis of pendimethalin in a microreactor for thermal risk reduction

In this study, pendimethalin synthesis was carried out in a microreactor to reduce its thermal risk. First, the nitration reaction was conducted in a semi-batch mode in the micro calorimeter. It was found the process was highly exothermic with a high adiabatic temperature rise (>133 °C). Then the reaction was transformed to a continuous flow mode in a microreactor. Effects of molar ratio, residence time and reaction temperature on the thermal behavior of the nitration process as well as the yield of pendimethalin were investigated and analyzed. Response surface methodology was used to optimize the reaction condition. The results showed that under the optimum condition in the microreactor, the yield reached 54.32%. The space-time yield in the microreactor was 1.38 g⋅L⁻¹∙s⁻¹, which was two orders of magnitude higher than that in the batch reactor. Further, a risk assessment using a recently developed method (m-ITHI) was carried out to compare the thermal hazards of the nitration process in the microreactor and the batch reactor. The index for the continuous flow mode was 3.77, corresponding to a risk level of Class I, which was safer than the batch mode with a risk level of Class II. Overall, this paper showcased an inherently safer design with the microreactor and provided a theoretical basis for the one-step synthesis of pendimethalin.