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

Abstract

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.

Continuous-flow synthesis and application of polymer-supported BODIPY Photosensitisers for the generation of singlet oxygen; process optimised by in-line NMR spectroscopy

“…We elected to use lab air for our reactions as an operationally simple and cheap source of molecular oxygen. Using pure oxygen is known to greatly enhance the rate of liquid phase oxidations as oxygen, which is poorly soluble in most organic solvents, is no longer in competition with other gases from the atmosphere for dissolution [46]. This is demonstrated in Table 2 (entry 13) and Table 4 (entry 11), where using pure oxygen led to a 5% and 25% rate enhancement respectively, over the same conditions with lab air.…”

“…Additionally, pure oxygen removes variability associated with air caused by changes in weather or location. However, use of pure oxygen is not preferred for industrial settings due to the hazards associated with forming a potentially explosive mixture of volatile organics and O 2 in a reactor's headspace, and typically 'synthetic air' (<10% O 2 in N 2 ) is preferred [46].…”

Recent Advances on Copper-Catalyzed C–C Bond Formation via C–H Functionalization

“…These latter technologies are outside the scope of this review and have been described in detail elsewhere in the literature. [72][73][74][75][76][77][78][79] N H…”

Vanillin: The Case for Greener Production Driven by Sustainability Megatrend

“…In a recent account [39] on liquid phase aerobic oxidations in continuous flow, Kappe and Hone aptly called molecular oxygen "the ultimate" green oxidant. The team noted therein the limited uptake of O2 or air as primary oxidant in the fine chemical industry, most often due to the high solvent flammability.…”

“…"Water", wrote the scholars, "is the ideal solvent for aerobic oxidations carried out with air's oxygen, However, a significant limitation associated with using water within flow reactors is that the inherent carbon richness of organic substrates mean that most do not dissolve in water, causing slow reaction rates". [39] Ferulic acid solubility in water at room temperature is low (0.78 g L -1, affording a 4 mM solution), [40] but large enough to smoothly carry out the biotransformation used to manufacture natural vanillin. [11] In conclusion, the photocatalytic conversion of ferulic acid to vanillin and vanillic acid is both feasible and desirable, while the extraction of ferulic acid can similarly be made greener, more efficient, and cheaper.…”