title: The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?
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 % O2in N2("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when handling molecular oxygen. Concentrations of O2in N2below 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 O2diluted with N2and 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.
authors.affiliation: Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, A-8010, Graz, Austria.|Research Center Pharmaceutical Engineering (RCPE), Inffeldgasse 13, 8010, Graz, Austria.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hone
authors.affiliation: Chemical Manufacturing Technologies, Lonza AG, CH-3930, Visp, Switzerland.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: Roberge
authors.affiliation: Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, A-8010, Graz, Austria.|Research Center Pharmaceutical Engineering (RCPE), Inffeldgasse 13, 8010, Graz, Austria.
authors.forename: C Oliver
authors.identifier: http://orcid.org/0000-0003-2983-6007
authors.initials: CO
authors.lastname: Kappe
mesh_terms: D010100:Oxygen / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012449:Safety; D012997:Solvents / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D010100:Oxygen
keywords: continuous flow; oxidation; pharmaceuticals; photochemistry; singlet oxygen