We have identified an example of a mechanochemically milled organic reaction where liquid-assisted grinding controls the selectivity, such a phenomenon has not been reported/observed before.

Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields.

No abstract

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.