During the process safety analysis of a fluoride displacement reaction, a highly exothermic event was observed when the reaction mixture was heated, which appears to be due to the decomposition of DMSO catalyzed by the HF byproduct from the displacement reaction. Although the T D24 for the decomposition is 42 °C above the reaction temperature and the synthesis reaction is mild, the consequences of the decomposition reaction are severe and could exceed the emergency venting capability of the reactor in the case of uncontrolled heating or an external fire, even at pilot plant scale. The use of several bases, cosolvents, and alternative solvents was investigated. Administrative safeguards, including temperature control system limits and removal of flammable solvents from the area, were identified to establish a basis of safety for a scale up to pilot scale. However, these safeguards would be impractical in a manufacturing facility. Eventually, an N-methyl-2-pyrrolidone (NMP)/tert-butyl methyl ether (MTBE) solvent system was identified, which provided an acceptable process while eliminating the use of DMSO and the associated decomposition reaction. This work shows some of the potential hazards that need to be investigated when using DMSO in a process. While DMSO alone can decompose near its boiling point, the effect of impurities, including byproducts of reactions, can lower the onset and increase the rate of this decomposition. Also, although this process falls into a Stoessel criticality index of 2, which is on the lower risk side of the scale, this case provides a good example where a low probability event needs to be investigated due to the severity of the consequences.

The synthesis of N-acyl 3,4-disubstituted pyrroles can be accomplished directly from hydrazine and an aldehyde via a Piloty-Robinson pyrrole synthesis. The use of microwave radiation for the cyclization and pyrrole formation greatly reduces the time necessary for this process and facilitates moderate to good yields from hydrazine for the corresponding 3,4-disubstituted products (5-12). By simple hydrolysis, the free N-H pyrroles can be accessed after the Piloty-Robinson reaction and then used directly in the synthesis of octaethylporphyrin (H2OEP, 14) and octaethyltetraphenylporphyrin (H2OETPP, 15).

Thermal hazard analyses of two reactions, one with DMSO as the solvent and a reactant and one with DMSO as the solvent and a byproduct, identified low-probability but severe consequence process risks associated with violent decomposition of DMSO during heating control failure or external heating. Although DMSO cannot be totally eliminated from these reactions, using an alternative solvent to replace DMSO proved to be an effective measure in reducing the thermal hazards to allow safe scale-up.