(126c) The Application of Flow NMR Toward the Development of a Kinetic Model for Continuous Grignard Formation

A kinetic model was developed to describe the formation of benzylmagnesium chloride from benzylchloride and magnesium metal. This work follows on previously reported kinetic studies by Eli Lilly and Co. (Changi, S.M., and S. Wong, Org. Process Res. Dev. 2016, 20, 525−539), although for a different substrate and the new studies include the kinetics of the Wurtz homocoupling impurity. Interestingly, the initial rate of homocoupling was found to be sensitive to the type of magnesium initiation employed. The significant species could be followed and quantified for each experiment using flow NMR when an internal standard was used. The impact of nuclei relaxation and absolute integral response, relative to flow rate through the NMR flow-loop, necessitated the use of correction factors for accurate quantitation of each species. The kinetic model was ultimately used to guide the operating conditions including feed strategies for a continuous stirred tank reactor (CSTR). The details of the flow NMR, the kinetic model development, sensitivities identified, and the process modeling results will be discussed.