Optimization of Continuous Enantiospecific Purification with Kinetic Modeling

Carloni, Griffin; Carney, Zachary; Dec, Robert

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Optimization of Continuous Enantiospecific Purification with Kinetic Modeling

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While rarely used in the industrial development of pharmaceuticals, continuous flow processing offers many benefits compared to traditional batch processes such as energy efficiency, minimized chemical waste, and lower operating costs. However, more research on continuous processing is needed for companies to consider switching from traditional batch processes. This study investigates the enantio-purification of (R,S)-1-phenylethanol in batch and flow configurations. The individual reactions comprising dynamic kinetic resolution (DKR) were studied, including kinetic resolution (KR) catalyzed by CALB Novazyme and acid-catalyzed H-Beta zeolite racemization (RAC). Reaction parameters of KR, RAC, and DKR were varied to determine optimal reaction conditions. KR and RAC reaction data was fit to Menten inhibition and pseudo-first order rate expressions. For kinetic resolution, vinyl acetate was determined to be an improved acyl donor in comparison to ethyl acetate, as observed from their fitted first order rate constants, k_VA^'=3.60E"-" 3 L/(g_cat "-" min) and k_EA^'=2.15E"-" 5 L/(g_cat "-" min) . The optimal temperature for the racemization of 1-phenylethanol was determined to be 45°C, resulting in a 68% selectivity and an effective enantiomeric excess of 10.5%. A series packed bed reactor system with temperature control was created to optimize DKR conversion through altering recycle ratio. An optimal recycle ratio of zero was experimentally determined. Future studies should investigate the effect of racemization catalyst on RAC selectivity, alternate PBR designs, and catalyst loadings.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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