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

Abstract

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.

Precompetitive Collaborations in the Pharmaceutical Industry: Process Safety Groups Work Together to Reduce Hazards, from R&D Laboratories to Manufacturing Facilities

“…Process safety scientists in the pharmaceutical industry are chemists and engineers who dedicate themselves to identify and minimize potential risks associated with thermally unstable materials, combustible dusts, and runaway reactions from R&D laboratories to manufacturing facilities. Numerous publications illustrate such work accomplished by process safety scientists. − For example, Tian et al evaluated thermal safety on a hydroamination reaction using DMSO as solvent, studied the potential autocatalytic decomposition with DMSO, and successfully launched the process for commercial production safely.…”

A Physical Organic Approach towards Statistical Modeling of Tetrazole and Azide Decomposition**

“…Tetrazoles and azides have also emerged as high energy materials (HEMs) that rival traditional nitro‐ and lead‐based explosives owing to their energetic properties, relatively mild syntheses, and reduced toxicity [6, 7, 12] . Nevertheless, the energetic nature of these N‐rich compounds can pose hazards during their preparation, storage, and handling; predicting their sensitivity properties and understanding decomposition mechanisms is thus integral to these applications [13–17] …”

“…[6,7,12] Nevertheless, the energetic nature of these N-rich compounds can pose hazards during their preparation, storage, and handling; predicting their sensitivity properties and understanding decomposition mechanisms is thus integral to these applications. [13][14][15][16][17] In this context, the in silico study of molecular decomposition has been a common practice in the field of high energy materials and in process hazard risk assessments. [13,14] While considerable computational work has been devoted to the prediction of HEMs performance properties (detonation velocity, detonation pressure, etc.…”

Dynamics of Ring-Cleavage Reactions in Temozolomide Induced by Low-Energy Electron Attachment

“…TMZ is an imidazotetrazine derivative of dacarbazin and the 3-methyl derivative of the prodrug mitozolomide. The drug has shown a wide range of antineoplastic activity [13][14][15][16] and cytotoxic activity in cell lines and on human tumors that were refractory to several clinically antitumor agents [14,15,[17][18][19].…”