A Kinetic Study on the Cu(0)-Catalyzed Ullmann-Type Nucleophilic Aromatic Substitution C-O Coupling of Potassium Phenolate and 4-Chloropyridine

A parametric study of the factors that influence C-O bond formation reactions has been carried out to elucidate the mechanism by which copper mediates the Ullmann-type nucleophilic aromatic substitution (SNAr) of 4-chloropyridine with potassium phenolate. Process conditions such as temperature, reactant concentrations, catalyst concentration, and amounts of solubilizing additive were varied to obtain the kinetic data. Both reactant and product concentration were found to have a significant effect on the reaction rate. An increased concentration of 18-crown-6 ether, used as an alkali metal solubilizing agent for potassium phenolate, proved to be effective only for low conversions, whereas an inhibited phenolate complexation at high product concentrations was observed. An apparent activation energy of 55 kJ.mol(-1) was observed for a Cu-0 catalyst in the liquid-phase coupling reaction in a temperature range of 100-150 degrees C. It was demonstrated that a Langmuir-Hinshelwood kinetic model is mechanistically most likely to be obeyed for this type of surface reaction. A maximum adsorption enthalpy on Cu was found for the product, 4-phenoxypyridine, followed by the reactants phenolate and 4-chloropyridine, respectively.