A Tribute to Ullmann’s Work: Expanding Copper Coil Reactor Applications toward the Hydroxylation of Aryl Bromides

Abstract

Copper coil flow reactors represent an economic, abundant, and durable platform for conducting copper-catalyzed reactions. These have been used in the past for Ullmann-type reactions starting from aryl iodides. However, no procedures have been described for the activation of less reactive aryl bromides. In this work, we successfully developed a method for the hydroxylation of aryl bromides promoted by a copper coil reactor. Notably, the presence of both a diamine ligand and DMF is key for the reaction to proceed. An inorganic base such as Na₂CO₃ also improved the reaction yield by minimizing the formation of side products. The setup has been applied to a range of disubstituted aryl bromides in moderate to good yields and was tested under 24 h of continuous operation, showing stable yields, thus proving the robustness of the catalysis. Finally, the lifetime of a copper reactor operating under the described conditions has been calculated for the first time, proving that this technology is safe to operate at an industrial scale.