The Use of Molecular Oxygen for Liquid Phase Aerobic Oxidations in Continuous Flow

Molecular oxygen (O₂) is the ultimate "green" oxidant for organic synthesis. There has been recent intensive research within the synthetic community to develop new selective liquid phase aerobic oxidation methodologies as a response to the necessity to reduce the environmental impact of chemical synthesis and manufacture. Green and sustainable chemical processes rely not only on effective chemistry but also on the implementation of reactor technologies that enhance reaction performance and overall safety. Continuous flow reactors have facilitated safer and more efficient utilization of O₂, whilst enabling protocols to be scalable. In this article, we discuss recent advancements in the utilization of continuous processing for aerobic oxidations. The translation of aerobic oxidation from batch protocols to continuous flow processes, including process intensification (high T/p), is examined. The use of "synthetic air", typically consisting of less than 10% O₂ in N₂, is compared to pure O₂ (100% O₂) as an oxidant source in terms of process efficiency and safety. Examples of homogeneous catalysis and heterogeneous (packed bed) catalysis are provided. The application of flow photoreactors for the in situ formation of singlet oxygen (¹O₂) for use in organic reactions, as well as the implementation of membrane technologies, green solvents and recent reactor solutions for handling O₂ are covered.