Continuous Ligand-Free Catalysis Using a Hybrid Polymer Network Support

Although the pharmaceutical and fine chemical industries primarily utilize batch homogeneous reactions to carry out chemical transformations, emerging platforms seek to improve existing shortcomings by designing effective heterogeneous catalysis systems in continuous flow reactors. In this work, we present a versatile network-supported palladium (Pd) catalyst using a hybrid polymer of poly(methylvinylether-alt-maleic anhydride) and branched polyethyleneimine for intensified continuous flow synthesis of complex organic compounds via heterogeneous Suzuki-Miyaura cross-coupling and nitroarene hydrogenation reactions. The hydrophilicity of the hybrid polymer network facilitates the reagent mass transfer throughout the bulk of the catalyst particles. Through rapid automated exploration of the continuous and discrete parameters, as well as substrate scope screening, we identified optimal hybrid network-supported Pd catalyst composition and process parameters for Suzuki-Miyaura cross-coupling reactions of aryl bromides with steady-state yields up to 92% with a nominal residence time of 20 min. The developed heterogeneous catalytic system exhibits high activity and mechanical stability with no detectable Pd leaching at reaction temperatures up to 95 °C. Additionally, the versatility of the hybrid network-supported Pd catalyst is demonstrated by successfully performing continuous nitroarene hydrogenation with short residence times (<5 min) at room temperature. Room temperature hydrogenation yields of >99% were achieved in under 2 min nominal residence times with no leaching and catalyst deactivation for more than 20 h continuous time on stream. This catalytic system shows its industrial utility with significantly improved reaction yields of challenging substrates and its utility of environmentally-friendly solvent mixtures, high reusability, scalable and cost-effective synthesis, and multi-reaction successes.