Medium and reaction engineering for the establishment of a chemo-enzymatic dynamic kinetic resolution of rac-benzoin in batch and continuous mode

• Water activity plays an important role for the dynamic kinetic resolution of rac-benzoin in chemo-enzymatic cascade. Catalytic performances of both the enzyme (Lipase TL) and the chemo-catalyst (Zr-TUD-1) were higher in dry solvents.
• Specific activity and half-life time of Lipase TL for kinetic resolution of rac-benzoin was higher in cyclopentyl methyl ether (CPME) in comparison to toluene, 2-methyltetrahydrofuran (2-MeTHF) and 1,3-dioxolane.
• Racemization activity of Zr-TUD-1 was the best in CPME and in toluene compared to 2-MeTHF and 1,3-dioxolane.
• Specific activity of Lipase TL in deep eutectic solvents was significantly lower than in toluene, 2-MeTHF, CPME, and 1,3-dioxolane, but product solubility in these alternative media hold promises for efficient downstream processing.
• Continuous dynamic kinetic resolution for synthesis of enantiopure (S)-benzoin ester was successfully established in stirred tank under optimized conditions (dry CPME).

The effect of the reaction parameters water activity and reaction solvent was investigated for the dynamic kinetic resolution (DKR) of rac-benzoin with immobilized Lipase TL as biocatalyst for transesterification and the heterogeneous chemo-catalyst Zr-TUD-1 (Si/Zr = 25) for in situ racemization. Overall dry reaction conditions led to the best results for both catalysts. The immobilized lipase in a more environmentally benign solvent like cyclopentyl methyl ether (CPME) exhibited a 1.6-fold higher activity and an up to 1.5-fold higher half-life time than in the standard solvents such as toluene and 2-methyltetrahydrofuran (2-MeTHF). Among a variety of deep eutectic solvents (DESs) choline chloride:isosorbide (ChCl:Iso) was found to be suitable for the reaction system. The activity was lower than in the aforementioned solvents, but the very low solubility of the product (S)-benzoin butyrate in ChCl:Iso compared to the investigated organic solvents possesses great potential with respect to downstream processing. Optimized reaction parameters (dry CPME) were applied for DKR in batch and continuous mode yielding comparable or slightly better results than in toluene or 2-MeTHF.

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