Calorimetric study reveals hazardous chemical interactions of DMSO during chemical scale-up, indicating the need for runaway index evaluation to ensure process safety.
During the process development of the product 6 via the route presented in Scheme 1, we encountered several safety issues that had to be resolved before moving these stages to production. In each case, the safety issues are related to the interaction of the solvent used, DMSO (dimethylsulphoxide, 3 ), with one of the other chemicals. Also in this case (Bollyn, M. Org. Process Res. Dev. 2005, 9, 982−996) we applied the runaway index as a guide to decide whether a process could be run at production scale. The combination of reaction calorimetry in the RC1 (Mettler Toledo's R eaction C alorimeter 1; http://www.RXEForum.com ) and thermal analysis in the ARC ( A ccelerating R ate C alorimeter; http://www.thermalhazardtechnology.com ) was used in combination with the process parameters study to design process stages that were considered safe (enough) for production scale.
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Marcus Bollyn (2006) studied this question.
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