The Swern Oxidation: Development of a High-Temperature Semicontinuous Process

Abstract

The Swern oxidation has been widely exploited for the oxidation of alcohols to their respective carbonyl compounds. The cryogenic operating conditions (<−60 °C) employed for the Swern oxidation, however, limit its utility for scale-up operations. Process development efforts on the Swern oxidation have demonstrated that an in-line reactor system can be used for the successful formation of the alkoxysulfonium salt precursor of the carbonyl compound. Two reagent streams, consisting of the alcohol/dimethylsulfoxide/methylene chloride and the oxalyl chloride, are loaded at ambient temperature to an in-line reactor, allowing the temperature to rise to 40 °C. The alkoxysulfonium chloride intermediate is discharged directly into triethylamine to complete the reaction. Residence times of 0.1−1.4 s in the in-line reactor were demonstrated to produce successful results in 750-gal pilot-plant equipment.