(544ab) Automated Microfluidic Platform for High-Throughput Screening of Rhodium-Catalyzed Hydroformylation

Abstract: Hydroformylation of alkenes has become one of the largest-scale applications of homogeneous catalysis where ligands play a significant role in tailoring the selectivity and yield of the aldehyde products. Conventionally, the lab-scale studies of hydroformylation reactions in the presence of toxic and flammable gases (i.e., carbon monoxide and hydrogen) are carried out by batch reactors with a volume size of 10-100 mL. Batch reactors suffer from inherent limitations including inefficient mass and heat transfer rates, lack of in-situ information, slow sampling rates, large amount of waste, and slow process start-up. In addition, large volumes of toxic and flammable gases raise major safety concerns. Recently, flow chemistry has emerged as an efficient technique for continuous synthesis of fine chemicals.^[1] Microreactor systems provide high surface to volume ratios, enhanced heat and mass transfer rates, and enhanced accessible parameter space. In addition, the small internal volume of the microreactor along with the reduced reagent volumes enhance significantly the process safety for continuous 24/7 operations in research labs. In this work, we designed, developed, and tested an automated high-throughput screening platform for rapid performance evaluation of traditional phosphine-based ligands in homogeneous hydroformylation of 1-octene. A single-droplet tube-in-tube microfluidic reactor is designed to address heat and mass transfer limitations associated with gas-liquid two-phase reactions. In addition, the autonomous operation of the developed flow chemistry platform enables precise control of the reaction parameters (e.g., reaction time, temperature, syngas pressure/composition, and chemical structure of the ligand) for each experiment and ensures the high reproducibility between runs. As a case study, we utilized the developed flow chemistry platform for screening and optimization of a library of phosphine-based ligands towards high catalytic activity, chemoselectivity to aldehydes, and regioselectivity to linear or branched product.

Reference

[1] Jensen, K.F., 2017. Flow chemistry—microreaction technology comes of age. AIChE Journal, 63(3), pp.858-869.