Process Development of an Inherently Safer Oxidation:  Synthesis of 2-Chloro-6-methylbenzoic Acid in the R411 Manufacturing Process

Many oxidation reactions can be hazardous when run on large scale. The manufacturing process for the production of R411, a developmental compound indicated for the treatment of asthma, includes the oxidation of 2-chloro-6-methylbenzaldehyde to the corresponding carboxylic acid. The use of sodium chlorite in this transformation was efficient and economical, but there were safety concerns regarding the use of hydrogen peroxide to scavenge unwanted hypochlorite, which was generated as a byproduct of the reaction. During the development of the R411 manufacturing process, an inherently safer oxidation system was discovered using a stoichiometric quantity of dimethyl sulfoxide (DMSO) as scavenger. The new process provided equivalent yields and purities to the hydrogen peroxide procedure, thus maintaining the economic viability of the process. The developed process was demonstrated in fixed equipment on a 300 gal scale.