Disentangling Modulator and Fluoride Chemistry in Rare-Earth Metal–Organic Framework Formation via Multinuclear NMR Spectroscopy: A Mechanism-Guided Synthetic Redesign

Abstract Metal–organic framework (MOF) chemistry continues to expand, highlighting the need for molecular insight into framework formation. Solution-phase NMR provides a powerful, accessible, and economical means to probe these mechanisms. We examine the formation of rare-earth (RE) UiO-66, focusing on Yttrium(III)-UiO-66. RE-UiO-66 contains a hexa-metallic node in which the metals are bridged by μ3-fluorido, μ3-hydroxido, and/or μ3-oxido ligands, with benzenedicarboxylate linkers connecting nodes. The fluorido ligand derives from the α-fluorinated modulators required for this synthesis, yet its formation and incorporation pathways are unclear. Using in situ multinuclear NMR spectroscopy, we demonstrate that MOF formation proceeds via zero-order kinetics. Modulator is consumed approximately an order of magnitude faster than linker. The fluoride ligand is formed via nucleophilic aromatic substitution between modulator and in situ-generated dimethylamine. Mass balance suggests that the modulator plays a dual role, coordinating to the metal cation and generating fluoride. However, when solvent hydrolysis precedes MOF formation, the modulator acts primarily as a fluoride source; in situ-formed acetic acid acts as the modulator. Thus, the dual modulator role can be decoupled; benzoic acid functions as the modulator and tetramethylammonium fluoride serves as the fluoride source. Under these modified conditions, linker consumption is slow. When solvent hydrolysis precedes MOF formation, the reaction accelerates. This highlights the complex influence of acidity, competitive binding of fluoride, modulator, and linker on kinetically labile rare-earth metals. The tetramethylammonium fluoride procedure provides a versatile pathway to RE-UiO-66 derivatives (RE = Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu) and two Y-UiO-67 derivatives.