Kinetic modeling of drug substance synthesis considering slug flow characteristics in a liquid-liquid reaction

This work presents a kinetic model of drug substance synthesis considering slug flow characteristics in Stevens oxidation. The developed model is also applied to determine the feasible range of the process parameters. Flow experiments were conducted to obtain kinetic data, varying the inner diameter, temperature, and residence time. A kinetic model was developed for the change in concentrations of the starting material, products, and catalysis. In the kinetic model, slug flow was considered by including a volumetric mass transfer coefficient during this flow. In the initial experiments, early-stage kinetic data were insufficient, conducting additional experiments at shorter residence times. Furthermore, the initial model could not reproduce the residual of the starting material, introducing the oxidant consumption that inhibits the starting material consumption and improving the initial model. The improved model could reproduce experimental results and demonstrated that, as the inner diameter increases, the efficiency of mass transfer in slug flow decreases with slowing down the reaction. Moreover, the improved model was considered applicable to different scales. The developed model was used to simulate the yields of the desired product, and the dimer, and the process mass intensity, thereby determining the feasible range. As a result, it was shown that when methanol and oxidant concentration was either too high or too low, operating conditions fell outside the feasible range. This kinetic model with flow characteristics will be useful for the process design of drug substance synthesis using liquid-liquid reactions.