Importance of Thermal Stability Data to Avoid Dangerous Reagents: Temozolomide Case Study

First disclosed in the 1970s, Temozolomide (TMZ) was recently reported to be a nonexplosive surrogate for methyl diazonium. As part of a program to explore an esterification reaction of a hindered carboxylic acid, TMZ was considered as a possible reagent to perform this challenging transformation. After preliminary DSC screening resulted in an alarming difference from what was previously reported, the decision was made to further investigate TMZ from a thermal stability perspective. DSC, impact testing, accelerating rate calorimetry, U.N. Test Series 2, and U.N. Test Series 3 testing were performed on TMZ. The results showed that TMZ is tentatively considered a Class 1 explosive. Extreme caution should be used if TMZ is to be produced or used to perform esterification or cyclopropanation reactions.