A Theoretical and Experimental Study on the Mechanism for the Reductive Amination of 5-Hydroxymethylfurfural over a Ru ₁ /NbOPO ₄ Single-Atom Catalyst

5-Hydroxymethylfurfural (HMF) induces a complex reaction framework in the reductive amination reactions because its functional groups such as furan ring, hydroxymethyl, and aldehyde groups are competitive when interacting with catalytic active sites. This work combines density functional theory calculations with experimental validation to comprehensively investigate the reaction mechanisms for the reductive amination of HMF to 5-hydroxymethyl-2-furfurylamine (HMFA) over a Ru1/NbOPO4 single-atom catalyst in the methanol solvent, using H2 as the H-source and NH3 as the N-source. Molecular dynamics simulations demonstrate that NH3 preferentially is adsorbed on the Ru1/NbOPO4 catalyst over H2, guiding the reaction toward preferential amination rather than hydrogenation. Methanol acts as a bridge of H-shift, facilitating the heterolysis of H2, and then improving the hydrogenation efficiency. The reaction of HMF-to-HMFA is predominant, in which the optimal pathway involves the first amination of the CH2OH group in HMF to form 5-(aminomethyl)furan-2-carboxaldehyde (AMFC), followed by the hydrogenation of the –CHO group in AMFC to HMFA, and the rate-determining step is concerned with the formation of the –CH2–NH2 bond. Experimentally, AMFC is verified to be the key intermediate. This work provides a mechanistic framework for the selective reductive-amination of biomass-derived hydroxymethyl and carbonyl compounds on a single-atom catalyst.