Development of an Extremely Efficient Oxidative Chlorination Reaction: The Value of Routine Data Collection

• Published in: Organic process research & development Vol. 14; no. 1; pp. 278 - 288
• Main Authors: Barnwell, Neil, Cornwall, Philip, Horner, Daniel, Knott, Jason, Liddon, John
• Format: Journal Article
• Language: English
• Published: American Chemical Society 15.01.2010
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/op900241e

This contribution describes the development of an extremely efficient process for the oxidative chlorination of a benzyl, alkyl thioether to yield an alkylsulfonyl chloride. This process was subsequently run on >100 kg scale. The product alkylsulfonyl chloride was required as an intermediate, being used by several drug projects, to prepare sulfonamides. Routine data collection and reaction profiling has led to understanding, which has allowed an alternative reaction pathway to be exploited for the development of a two-step, oxidation−chlorination process. The scope of this new two-step process was briefly examined. The results of this study have allowed us to propose an empirical method for predicting the course of these oxidative chlorination reactions. During these studies we have developed a simple laboratory rig, constructed from inexpensive, readily available equipment, which allows the controlled accurate delivery of known volumes (100s of milliliters) of chlorine gas at a given rate. In our laboratories, this has made the use of gaseous chlorine a considerably less onerous task. This work is testimony to the fruit which may be borne from attempts to gain process understanding, even of an already high-yielding reaction.