The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?

Molecular oxygen is arguably the greenest reagent available to the organic chemist. Most commonly, a diluted form of oxygen gas, consisting of less than 10 % O₂ in N₂ ("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when handling molecular oxygen. Concentrations of O₂ in N₂ below 10 % are generally required to prevent the risk of combustions in the presence of flammable organic solvents ("limiting oxygen concentration"). Nonetheless, the use of pure oxygen is more efficient than using O₂ diluted with N₂ and can often provide enhanced reaction rates, resulting in significant improvements in product quality and process efficiency. This Concept takes into account recent studies to make the argument that, for liquid-phase aerobic oxidations, pure oxygen can indeed be handled safely on large scale by employing continuous-flow reactors, while also providing highly convincing synthetic and manufacturing benefits.