Addendum: Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations

Temozolomide (TMZ) was FDA approved for treatment of glioblastoma (GBM) in 1995 and is a life-extending (and sometimes life-saving1) drug GBM other cancers.2 TMZ has been administered to thousands patients shipped around the world over three decades; typically ingest grams during standard regimen.3 We recently reported use as reagent synthesis methyl esters cyclopropanes with many benefits (including safety convenience) compared diazomethane.4 Our paper utilized under aqueous conditions at temperatures up 60 °C, well decomposition point solid material.5 A recent manuscript from Sperry co-workers6 showed that more forcing potential be hazardous. After defining 170–180 °C range via differential scanning calorimetry, authors performed impact testing by dropping 10 kg weight on TMZ. Although no flame produced, smoke observed this testing. series detailed experiments are manuscript, including heating 75 two days, friction sensitivity test, burning 100 gram sample fire kerosene-soaked sawdust; explosions occurred any these tests. However, ignition confinement did lead production excess pressure. laboratory not experienced incidents our extensive reports explosive episodes absent literature, despite nearly four decades chemical biological research, distinguishing it diazomethane. co-workers have further defined safely working TMZ, caution warranted when especially elevated pressures or mentioned above.