Operation Strategy Development for Grignard Reaction in a Continuous Stirred Tank Reactor

This paper presents a case study in establishing the operation space of a Grignard reaction in a continuous stirred tank reactor (CSTR). The operation space is the multivariate space with the boundary defined by the proven acceptable range of every CSTR process parameter such as flow rates and temperature. The mapping of the operation space was conducted by a thorough understanding of reaction kinetics, magnesium (Mg) sequestration efficiency, equipment characterization, and the impact of process disturbances has on steady state. A fit-for-use reaction kinetics model was developed to parametrize the kinetics and mass transfer rates of the batch Grignard reaction across different scales from 250 mL to 500 gallons. The reaction kinetics model was applied to design the Mg recharge frequency accounting operational variability to ensure a state of control can be maintained. Furthermore, reactor temperature was determined to be suitable to detect process failures to ensure process safety and product quality at manufacturing scale. Computational fluid dynamics (CFD) models were also applied to aid equipment design to maximize Mg sequestration in the CSTR. Based on the optimal equipment design, the unit operation was scaled-down to test the sequestration efficiency. The resulting process understanding enabled the team to define the final operation strategy to ensure a safe and robust commercial process.