Copper-Catalyzed Aerobic Photooxidative Coupling of Alcohols and Phenylacetylene to Ketones Using a Visible LED-Based Photo-Microreactor

Transition metal-based aerobic photooxidation of alcohols to ketones has a great industrial significance, but such an important transformation was previously performed in batch photoreactors, which suffer from meager transport characteristics, poor reaction rates, prolonged residence time, and low green credentials. In this report, we developed for the first time an efficient photo-microreactor module for Cu-based aerobic photooxidative coupling of hydroquinone and 4-chlorophenylacetylene, leading to the formation of 4-hydroxy-4′-chlorobenzophenone under visible light irradiation. The detailed parametric investigation was performed to optimize product yield and space-time yield to 74% and 19.55 g L^–1h^–1within a residence time of 42.5 and 21.2 min, respectively. The apparent rate constants evaluated at various initial concentrations using the photo-microreactor were higher than those obtained using batch photoreactors in previous investigations. Moreover, various E-factors for this photooxidative transformation showed a significant improvement in the green credentials for this photooxidative process using the photo-microreactor. We examined the scope of this photooxidative reaction using various starting materials and proposed a reaction mechanism for this reaction based on the identification of radical intermediates involved in this photoreaction. Transition state energy profiles of reaction mechanism steps were evaluated using DFT simulations to examine the potential energy barrier involved in each reaction mechanism step. Finally, we applied this product for the synthesis of fenofibrate, which is an FDA-approved drug against hypertriglyceridemia. In a nutshell, the photo-microreactor showed a phenomenal process intensification and scaling-up potential for this photooxidative transformation.