Putting Safety Numbers On Aerobic Oxidation Reactions

Aerobic oxidations have much appeal in organic synthesis for their efficiency, yet they are often avoided in the production of pharmaceuticals because mixtures of O₂ and solvents can create a flammable atmosphere. Instead of taking a gamble, process chemists and engineers tend to avoid oxidations altogether and use reagents bought at the required or higher oxidation state. To address this issue, a research team led by Paul M. Osterberg of chemical process safety firm Fauske & Associates, in Burr Ridge, Ill., and Shannon S. Stahl of the University of Wisconsin, Madison, has filled a knowledge gap by experimentally determining safe operating conditions for using O₂ with nine common organic solvents (Org. Process Res. Dev. 2014, DOI: 10.1021/op500328f). The research was performed as part of a “precompetitive” consortium involving Eli Lilly & Co., Pfizer, and Merck & Co., formed to promote the development and application of aerobic oxidations for manufacturing. Using an explosion-compatible reactor, the researchers measured the minimum partial pressure of O₂ that will support a combustible mixture with each solvent at the elevated temperatures and pressures used in production-scale reactions—values that provide benchmarks for safe application of aerobic oxidations.