Experimental Limiting Oxygen Concentrations for Nine Organic Solvents at Temperatures and Pressures Relevant to Aerobic Oxidations in the Pharmaceutical Industry

ABSTRACT: Applications of aerobic oxidation methods in pharmaceutical manufacturing are limited in part because mixtures of oxygen gas and organic solvents often create the potential for a flammable atmosphere. To address this issue, limiting oxygen concentration (LOC) values, which define the minimum partial pressure of oxygen that supports a combustible mixture, have been measured for nine commonly used organic solvents at elevated temperatures and pressures. The solvents include acetic acid, N-methylpyrrolidone, dimethyl sulfoxide, tert-amyl alcohol, ethyl acetate, 2-methyltetrahydrofuran, methanol, acetonitrile, and toluene. The data obtained from these studies help define safe operating conditions for the use of oxygen with organic solvents. Oxidation is common in organic synthesis, yet it is often avoided in the large-scale production of pharmaceuticals because many of the reagents and methods for oxidations have difficulties or limitations on a large scale.1 Toxic metals, halogenated solvents