Thermal Switching of Brønsted Acid Sites in Defective UiO-66 Governs the Activity of Fructose Dehydration to 5-Hydroxymethylfurfural

The efficient dehydration of fructose to 5-hydroxymethylfurfural (HMF) is a crucial step in biomass valorization, requiring solid acids with precisely balanced Brønsted acidity. Defect engineering in Zr-based metal–organic frameworks (MOFs), such as UiO-66, is well known to enhance Lewis acidity; however, its impact on tailoring Brønsted acid sites remains insufficiently understood. Here, we demonstrate that defective UiO-66 possesses a dual-origin Brønsted acid system, comprising intrinsic μ3–OH groups and water molecules coordinated to defect-generated Lewis acidic Zr centers (Zr–H2O). The concentration of these Brønsted acid sites can be finely regulated by thermal activation treatment. A volcano-shaped dependence of catalytic activity on activation temperature is observed, with an optimum at 200 °C. At moderate activation temperatures below 200 °C, the removal of physisorbed water exposes both μ3–OH and Zr–H2O sites, maximizing Brønsted acid density and HMF yield. Activation beyond 200 °C reduces both types of Brønsted acid sites, resulting in diminished catalytic performance. This study reveals the cooperative effect of defect engineering and thermal activation in tuning the Brønsted acidity of MOFs, providing a rational strategy for designing highly selective catalysts for the sustainable production of platform chemicals.