Protected diazonium salts: A continuous-flow preparation of triazenes including the anticancer compounds dacarbazine and mitozolomide

Herein, we report a continuous-flow process for the preparation of triazenes, whereby diazonium salts are generated and converted into their masked or protected triazene derivatives. Key to realizing the process, which is applicable to a wide range of substrates, is the identification of solvent and reagent parameters that avoid fouling and clogging in the tubing used in these studies. The process has also been applied to prepare the antineoplastic agents mitozolomide and dacarbazine. We also report isolation and differential scanning calorimetry (DSC) analysis of an anthranilic acidderived triazene whose related diazonium salt is a contact explosive. The data highlights improved stability but also suggests that an exothermic process does occur with an onset temperature of 118 °C. Finally, an 18-hour continuous operation of the reaction procedure using high-performance liquid chromatography (HPLC) pumps is reported.