(686c) Cyclodextrin Network Supported Catalysis in Flow

Synthesis of fine chemicals is traditionally performed in a series of batch reactions, that possess certain limitations at process scale, including lower transport rates, safety hazards related to large quantities of toxic/flammable chemicals, and purification steps that are both labor-intensive and costly.¹ Homogeneous catalysis, although very effective, has the disadvantage of requiring a post-reaction catalyst separation step, and traditional heterogeneous catalysis suffers from lower reactivity.¹ In response, we have developed a catalytic microreactor using a cyclodextrin network support loaded with highly active Pd nanoparticles for the continuous synthesis of organic compounds using Suzuki-Miyaura cross coupling and nitroarene reduction reactions.

In this work, we functionalized beta-cyclodextrin’s primary alcohol groups into azide groups, and, through an azide-alkyne cycloaddition click reaction with 1,4-diethynylbenzene, formed a crosslinked cyclodextrin network (i.e., the catalyst support). The unique chemical environments of the network support provide advantageous aspects for catalysis. ² The triazole forms complexes with Pd, beneficial for embedding and attaching the catalytic nanoparticles, while the cyclodextrin forms inclusion complexes with many organic compounds that are present in organic synthesis. The cyclodextrin catalyst is adapted to continuous flow reactions by packing it in a stainless-steel tube where organic reactants are continuously fed for conducting the Suzuki-Miyaura cross-coupling and nitroarene reduction reactions. Reaction kinetics were obtained via automated sampling using an in-line HPLC unit integrated with a sampling valve. The catalyst performed nitroarene reduction reactions at room temperature to a high yield (99%) at fast flow rates (5 min residence time), while Suzuki-Miyaura reactions of aryl bromides and iodides resulted in high yields (98%) at low temperatures (40°C) and residence times (10 min). In comparison with the batch and homogeneous Suzuki-Miyaura/nitroarene reduction reactions, the developed continuous flow chemistry strategy using the cyclodextrin-supported Pd catalyst enables a lower cost of catalyst recovery.