Davis Bradley A, Genzer Jan, Efimenko Kirill, Abolhasani Milad
Department of Chemical & Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695-7905, United States.
Biomanufacturing Training and Education Center, North Carolina State University, Raleigh, North Carolina 27606, United States.
JACS Au. 2023 Jul 14;3(8):2226-2236. doi: 10.1021/jacsau.3c00261. eCollection 2023 Aug 28.
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--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.
尽管制药和精细化工行业主要利用间歇均相反应来进行化学转化，但新兴平台试图通过在连续流动反应器中设计有效的多相催化系统来改善现有缺点。在这项工作中，我们展示了一种通用的网络负载钯（Pd）催化剂，该催化剂使用聚（甲基乙烯基醚-马来酸酐）和支化聚乙烯亚胺的杂化聚合物，通过多相铃木-宫浦交叉偶联和硝基芳烃氢化反应强化复杂有机化合物的连续流动合成。杂化聚合物网络的亲水性促进了试剂在整个催化剂颗粒主体中的传质。通过对连续和离散参数的快速自动探索以及底物范围筛选，我们确定了用于芳基溴化物铃木-宫浦交叉偶联反应的最佳杂化网络负载Pd催化剂组成和工艺参数，在20分钟的标称停留时间下稳态产率高达92%。所开发的多相催化系统表现出高活性和机械稳定性，在高达95°C的反应温度下没有可检测到的Pd浸出。此外，杂化网络负载Pd催化剂的通用性通过在室温下以短停留时间（<5分钟）成功进行连续硝基芳烃氢化得以证明。在2分钟的标称停留时间内实现了>99%的室温氢化产率，在连续运行超过20小时的时间内没有浸出和催化剂失活。该催化系统显示出其工业实用性，具有挑战性底物的反应产率显著提高，以及在环境友好型溶剂混合物、高可重复使用性、可扩展和成本效益高的合成以及多反应成功方面的实用性。
