Safety Hazard of the Thermal Decomposition of Difluoromethyl and -Methoxy Arenes Catalyzed by Boron Derivatives

Abstract A thermal safety investigation was conducted following multiple laboratory incidents involving difluoromethoxy-substituted aryl boronic acids. Differential scanning calorimetry (DSC) revealed that compounds bearing both a difluoromethoxy (or difluoromethyl) group and a boronic acid or boronate ester exhibit pronounced low-temperature exothermic decomposition. This instability was observed both intramolecularly and through intermolecular interactions among otherwise thermally stable components. The severity of decomposition was enhanced by the steric proximity between the two functional groups and could be triggered by catalytic quantities of boron-containing species or contact with borosilicate glass. Structural modifications, notably the replacement of the boronic acid group, significantly improved thermal stability. These findings identify a previously underappreciated thermal hazard associated with this functional group combination and have important implications for compound design, storage, and process safety evaluation. Finally, an initial mechanistic investigation of the decomposition process as well as recommendations for compound handling are presented.