A very interesting PTC patent issued this month that describes the last step in the production of the herbicide sulfentrazone. We have been citing a model reaction for this N-mesylation in our 2-day Industrial PTC course for more than decade. Therefore, this new patent caught our attention.
The inventor (no assignee company!) reports that high yield is obtained when using water as the fluidizing agent for suspension of solids AND simultaneous addition of methanesulfonyl chloride and aqueous sodium carbonate to maintain the pH at 7.8, all in the presence of TBAB. As we have noted in dozens of PTC Tips of the Month since 2002, chemists often find it very surprising that we can work under PTC conditions with water-sensitive compounds in the presence of water. Surely, we all recognize the methanesulfonyl chloride is a water sensitive compound and indeed, PTC Organics measured the hydrolysis of MesCl in toluene to provide a guideline to process development chemists when to estimate a high probability of success for using PTC with water-sensitive compounds.
The inventor also reported that the addition of a small volume of toluene was crucial to achieve high conversion. When this small volume of toluene was not added, no conversion was observed, even when adding a second dose of 1.2 equiv MesCl. One may speculate that the toluene protects the methanesulfonyl chloride from hydrolysis, similar to what we see in many other PTC systems using water-sensitive compounds such as in a patent issued to our sister company using dilute aqueous waste streams at high pH in the presence of benzoyl chloride (US Patent 6,846,946 by Joyce, Bielski and Halpern)
If there was no simultaneous addition of MesCl and the aqueous sodium carbonate (i.e., the MesCl is added in one portion at the outset of the reaction), conversion of 41% is observed.
The inventor concludes that “using an inorganic base to dynamically control the reaction pH in the presence of a phase transfer catalyst suspended in a 1:1 aromatic solution” is required together with simultaneous addition of the MesCl.
There are likely other PTC fundamentals at work here that are responsible for the high performance in tightly controlled process conditions (that we don’t discuss without a PTC Process Consulting agreement with PTC Organics Inc.).
