Accelerated Diffusion of a Copper(I)-Functionalized COF Packed Bed Reactor for Efficient Continuous Flow Catalysis

Abstract

Flow chemistry provides a neo-orientation for the research and development of chemical technology, in which heterogeneous continuous catalysis based on packed beds can realize rapid separation and recycling. However, options for heterogeneous catalysts are still limited. In this work, we gradually grow covalent organic frameworks (COFs, TpBpy) on the surface of a silica gel (SiO 2 )-supported substrate to obtain a stable copper(I)-chelated high-loading heterogeneous catalyst (SiO 2 @CuI-TpBpy). SiO 2 @CuI-TpBpy shows high catalytic activity in three-component Huisgen 1,3-dipolar cycloaddition, giving the corresponding triazoles with excellent yields and reposeful recyclability under batch conditions. The structures of the catalysts remain steady, and the copper contents are basically unchanged after five cycles. Then, the catalysts are successfully applied for threecomponent heterogeneous catalysis in a one-pot continuous flow to prepare rufinamide in 89% yield for 24 h stably and efficiently with mere traces of copper ions remaining. More importantly, the catalytic system reveals a minuscule effect of catalyst particle size on internal diffusion. This COF encapsulation strategy presents a new possibility for the design of industrial heterogeneous catalysts with high metal loading and low internal diffusion resistance.

Continuous Flow Synthesis of a Key Intermediate Common to Gefitinib and Larotinib

“…Chemical reactions carried out in conventional batch reactors can suffer from long reaction times, high safety risks, and low production efficiencies for certain transformations . In the past decade, the field of flow chemistry has received widespread attention as a means to overcome some of these limitations, with advantages such as high heat transfer area, efficient mixing, outstanding mass transfer rate, and improved safety . In addition, continuous flow synthesis technology can contribute to better impurity profiles through precise control of the residence time and efficient optimization of the postprocessing, with great potential for facilitating innovation and process development, and for quality improvement and cost reduction …”

Concise synthesis of pyrrolo[3,4-c]quinolines via a P(NMe2)3-catalyzed [4 + 2] annulation followed by a Zn/AcOH-mediated reduction–hydroamination–isomerization

“…Terminal alkynes can be transformed into various functional groups. 12 Therefore, the above encouraging results on the synthesis of tetrahydroquinolines 3 bearing a terminal alkyne group prompted us to obtain pyrrolo[3,4- c ]quinoline scaffolds, which are the core structural motifs of a broad range of natural products and biologically active molecules. The pyrrolo[3,4- c ]quinolines 4 were obtained smoothly through a designed zinc/acetic acid-mediated reduction–hydroamination–isomerization cascade reaction of tetrahydro-quinolines 3 (Scheme 4).…”