MOF808(Zr) as a Heterogenous Catalyst for the Synthesis of Amides via Acid–Amine Coupling

Abstract Amidebonds are fundamental structural motifs in pharmaceuticals, polymers, andbiomolecules, yet their synthesis often relies on stoichiometric couplingagents, generating substantial waste. Heterogeneous catalysis offers asustainable alternative, but existing systems face challenges such as watersensitivity and limited substrate scope. Herein, we report a Zr‐basedmetal‐organic framework (MOF808) as an efficient and recyclable catalyst fordirect amide formation from carboxylic acids and amines. MOF808 features Zr6O4(OH)4(BTC)2(HCOO)6, providing Lewis acidic sites that facilitate condensation with high atomeconomy (only H2O as byproduct). Under optimized conditions (90 °C, 12h), the catalyst achieves 83.4% yield in model reactions, outperformingconventional oxides (e.g., ZrO2). Remarkably, MOF808 retains 50.6%activity after five cycles, with XRD and BET analyses confirming structuralintegrity. Mechanistic studies reveal that Zr‐O sites activate carboxyl groupsvia coordination, while the porous framework mitigates water‐induceddeactivation. Compared to coupling reagents (e.g., EDC/HATU), this systemeliminates stoichiometric waste and operates without molecular sieves. The workdemonstrates how tailored MOF architectures can bridge the gap betweenhomogeneous and heterogeneous catalysis, offering a green strategy for amidesynthesis with industrial potential.