Direct synthesis of N-formamides by integrating reductive amination of ketones and aldehydes with CO₂ fixation in a metal-organic framework

Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO₂ in the presence of H2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π···π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO₂ utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals.
Formamides are important platform chemicals for the production of pharmaceuticals, fragrances, agrochemicals, dyes and industrial solvents.^[1-4] State-of-the-art synthesis of formamides relies on the utilisation of an excess amount of the formylating agents (e.g., chloral, sodium formate, formaldehyde, acetic formic anhydride and formic acid) that react with organic amines to drive the formation of C–N bonds, yielding substantial amounts of waste and thus extremely poor atom-economy (Fig. 1a).^[2,5-7] In the context of development of sustainable chemistry, the utilisation of carbon dioxide (CO₂)^[8-10] and lignocellulosic biomass and their derivatives^[11-13] for the manufacture of feedstock chemicals has attracted much interest. Although methanol derived from CO₂ has been applied for the preparation of formamides,^[1,14,15] the formylation of amines via the direct use of CO₂ is a more promising but challenging target (Fig. 1b).^[16-19] This can be achieved by reducing CO₂ by H₂ over noble metals, followed by condensation with the amine compound to form the new C-N bonded formamides. In parallel, a wide range of ketones and aldehydes can be readily obtained from biomass,^[20] but their conversion to organic amines via reductive amination is also a highly challenging process.^[21-24]
Here, we report the first example of direct synthesis of N-formamides from carbonyl compounds, including various ketones and aldehydes derived from lignin (Figure S1), by reaction with CO₂, NH₃ and H₂ over a metal-organic framework (MOF) supporting a ruthenium catalyst, Ru/MFM-300(C_r) (Fig. 1c). This one-pot approach effectively integrates two challenging reactions, reductive amination of carbonyl compounds and CO₂ fixation, by developing a multifunctional porous reactor. MFM-300(Cr) acts as a support to achieve fine dispersion of Ru nanoparticles (0.54±0.29 nm), it acts as gas reservoir for CO₂ and NH3, and more importantly, provides a unique platform to activate carbonyl substrates via confinement effects induced by the formation of specific host-guest interactions within the pore. This has been analysed by in situ synchrotron X-ray powder diffraction (SXPD) and Fourier-transform infrared spectroscopy (FTIR), while nuclear magnetic resonance (NMR) spectroscopic analysis and control experiments suggest formate species as the intermediate derived from the reduction of CO₂. This one-pot system affords excellent catalytic performance as well as stability for the synthesis of a wide range of N-formamides, which can be isolated readily from the reaction.