De novo construction of amine-functionalized metal-organic cages as heterogenous catalysts for microflow catalysis

Abstract

Microflow catalysis is a cutting-edge approach to advancing chemical synthesis and manufacturing, but the challenge lies in developing efficient and stable multiphase catalysts. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, enabling highly continuous flow catalysis. Two Fe₄L₄ tetrahedral cages bearing four uncoordinated amines were designed and synthesized. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane, introducing silane chains immobilized on the inner walls of the microfluidic reactor. The immobilized cages prove highly efficient for the reaction of anthranilamide with aldehydes, showing superior reactivity and recyclability relative to free cages. This superiority arises from the large cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and the potential for future automated synthesis processes.

Fig. 1. Schematic diagram.

a Self-assembly of the metal-organic cages and covalent silane modification of cages 1 and 2. b Heterogenization of Si-1 and Si-2 in microfluidic reactor.

Fig. 2. NMR and ESI-MS spectra of cages 1 and 2.

a, c Partial ¹H NMR and 2D DOSY spectra (500 MHz, CD₃CN, 298 K) of 1 and 2. b, d Experimental ESI-MS and calculated isotope patterns of 1 and 2 (Observed: Obs.; Simulated: Sim.).

Fig. 3. X-ray crystallographic structure of cage.

a, b The single-crystal X-ray structures of 1 from two different directions. c, d The energy-minimized conformations of 2 from two different directions. Gray: C; white: H; dodger blue: N; purple: Fe. The cavities are highlighted by yellow balls.

Fig. 4. NMR spectra and simulated structures of Si-1 and Si-2.

a, c ¹H NMR spectra of cages 1, 2, Si-1 and Si-2 (500 MHz, CD₃CN, 298 K). b, d The energy-minimized conformations of Si-1 and Si-2. Gray: C; white: H; dodger blue: N; red: O; tea green: Si; purple: Fe. The cavities are highlighted by yellow balls.

Fig. 5. Characterizations of the modified microreactor.

a Schematic of the CLSC model display. b Changes in microchannels after loading Si-2. c SEM images and EDS mappings of Si-1 and Si-2@PDMS. d F 1 s and N 1 s XPS spectra of Si-1 and Si-2@PDMS.

Fig. 6. Catalytic results. a Sequential condensation and cyclization of anthranilamide with aldehydes catalyzed by the cages.

a Reaction conditions: 2-aminobenzamides (1.0 mmol), aldehyde (1.0 mmol), cage: 0.1 mol %, CH₃CN (6.0 mL), rt, 20 h. b Isolated yield. b Effect of flow rate of reaction mixture on the catalytic performance of cage-loaded microreactor. c Kinetic results for cyclocondensation of benzaldehyde and anthranilamide both in batch and microreactor system with the cage loading of 0.5 mol%. d Recycling tests of cage 2 and Si-2@PDMS for cyclocondensation of benzaldehyde and anthranilamide. e Schematic of the amplified continuous flow experimental system.