Continuous Ligand-Free Catalysis Using a Hybrid Polymer Network Support

Although the pharmaceuticaland fine chemical industries primarilyutilize batch homogeneous reactions to carry out chemical transformations,emerging platforms seek to improve existing shortcomings by designingeffective 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 intensifiedcontinuous flow synthesis of complex organic compounds via heterogeneousSuzuki-Miyaura cross-coupling and nitroarene hydrogenationreactions. The hydrophilicity of the hybrid polymer network facilitatesthe reagent mass transfer throughout the bulk of the catalyst particles.Through rapid automated exploration of the continuous and discreteparameters, as well as substrate scope screening, we identified optimalhybrid network-supported Pd catalyst composition and process parametersfor Suzuki-Miyaura cross-coupling reactions of aryl bromideswith steady-state yields up to 92% with a nominal residence time of20 min. The developed heterogeneous catalytic system exhibits highactivity and mechanical stability with no detectable Pd leaching atreaction temperatures up to 95 & DEG;C. Additionally, the versatilityof the hybrid network-supported Pd catalyst is demonstrated by successfullyperforming continuous nitroarene hydrogenation with short residencetimes (<5 min) at room temperature. Room temperature hydrogenationyields of >99% were achieved in under 2 min nominal residence timeswith no leaching and catalyst deactivation for more than 20 h continuoustime on stream. This catalytic system shows its industrial utilitywith significantly improved reaction yields of challenging substratesand its utility of environmentally-friendly solvent mixtures, highreusability, scalable and cost-effective synthesis, and multi-reactionsuccesses.

Automated summary

This study presents a versatile network-supported palladium catalyst for continuous synthesis of complex organic compounds. By using a hybrid polymer, the catalytic system achieves optimized performance in the Suzuki-Miyaura cross-coupling and nitroarene hydrogenation reactions. The system shows high activity, mechanical stability, and reusability, with improved reaction yields and environmentally-friendly solvent usage, making it suitable for industrial applications.