Box-Behnken experimental design for optimizing process parameters in carbonate-promoted direct thiophene carboxylation reaction with carbon dioxide

A feasible synthesis route is developed for achieving the direct carboxylation of thiophene and CO2 in a relatively mild solvent-free carboxylate-assisted carbonate (semi) molten state. The effects of reaction factors on the carboxylate yield are investigated in the preliminary screening experiments, and the phase behavior analysis of the reaction medium is detected through the thermal characterization analysis of in-situ high temperature X-ray diffraction measurement (in-situ XRD). The application of response surface methodology (RSM) based on the Box-Behnken design (BBD) is conducted to investigate the effect of the reaction parameters, such as reaction temperature, carbonate proportion, CO2 pressure and thiophene amount, on the product yield. The regressed second-order polynomial model equation well correlates all the independent variables. The analysis of variance (ANOVA) results reveal that the quadratic effect of reaction temperature is the most effective parameter in this carboxylation reaction owing to it’s the highest contribution to the sum of square (30.18%). The optimum reaction conditions for maximum product yield are the reaction temperature of 287 °C, carbonate proportion of 32.20%, CO2 pressure of 1.0MPa and thiophene amount of 9.35 mmol. Operating under these selected experimental conditions, a high product yield (50.98%) can be achieved.