Kinetics and thermodynamics of paracetamol synthesis via hydrothermal amidation of hydroquinone by ammonium acetate employing Cu-V-W/Kaolinite catalyst

This study explored hydrothermal amidation of hydroquinone with ammonium acetate using a solid heterogeneous catalyst as a sustainable route for paracetamol synthesis. The study was carried out in four systematic stages. First, screening of various phyllosilicates as catalyst supports identified kaolinite as the most suitable support material based on its physicochemical properties and catalytic performance. Second, the evaluation of copper (Cu), vanadium (V), and tungsten (W) as active metals supported on kaolinite using a simplex centroid mixture design elucidated their individual and interactive effects on active site distribution, reactant conversion, and product yield. Third, mechanistic investigation demonstrated that the synergistic presence of Brønsted and Lewis acidic and basic sites played a crucial role in facilitating key reaction steps while simultaneously suppressing the formation of undesired byproducts. Lastly, multi-response optimization to determine the optimal metal composition resulted in Cu:V:W ratios of 17 , 36 , and 47 , respectively, for a reusable catalyst system characterized by a turnover number (TON) of 42.36 and a turnover frequency (TOF) of 7.0595 h¹, achieving an acetaminophen yield of approximately 96 . Thermodynamic and kinetic analyses at 200-300 °C and 16 h based on the Langmuir-Hinshelwood model revealed exothermic reactants adsorption, endothermic products desorption, endothermic surface-mediated reactions (deprotonation, amination, acetylation), and exothermic intermolecular coupling, indicating that maximal paracetamol yield favored higher temperatures. This study presents a green chemistry breakthrough for sustainable paracetamol production. © 2025 Elsevier Ltd