The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?. Issue 1 (16th November 2016)

• Record Type: Journal Article
• Authors: Hone, Christopher A.; Roberge, Dominique M.; Kappe, C. Oliver
• Is Part Of: ChemSusChem. Volume 10:Issue 1(2017)
• Page Start: 32
• Page End: 41
• Publication Date: 2016-11-16
• Subjects: continuous flow -- oxidation -- pharmaceuticals -- photochemistry -- singlet oxygen; Green chemistry -- Periodicals; Sustainable engineering -- Periodicals; Chemistry -- Periodicals; Chemical engineering -- Periodicals; 660
• DOI: 10.1002/cssc.201601321
• Languages: English
• ISSNs: 1864-5631

Abstract

Abstract: 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. Abstract : Pharma seeks oxidant : Molecular oxygen is one of the greenest reagents available, but the unique challenges of gas–liquid aerobic oxidation reactions, particularly in terms of safety, make conventional batch reactors unsuitable to handle such processes above 10 % O2 in N2 . Continuous‐flow reactors enable these challenges to be overcome and give access to otherwise unsafe oxygen concentration levels, even at manufacturing scales, while also providing synthetic benefits.