Challenges of Mechanochemistry: Is In Situ Real‐Time Quantitative Phase Analysis Always Reliable? A Case Study of Organic Salt Formation

Mechanochemical methods offer unprecedented academic and industrial opportunities for solvent‐free synthesis of novel materials. The need to study mechanochemical mechanisms is growing, and has led to the development of real‐time in situ X‐ray powder diffraction techniques (RI‐XRPD). However, despite the power of RI‐XRPD methods, there remain immense challenges. In the present contribution, many of these challenges are highlighted, and their effect on the interpretation of RI‐XRPD data considered. A novel data processing technique is introduced for RI‐XRPD, through which the solvent‐free mechanochemical synthesis of an organic salt is followed as a case study. These are compared to ex situ studies, where notable differences are observed. The process is monitored over a range of milling frequencies, and a nonlinear correlation between milling parameters and reaction rate is observed. Kinetic analysis of RI‐XRPD allows, for the first time, observation of a mechanistic shift over the course of mechanical treatment, resulting from time evolving conditions within the mechanoreactor. In situ X‐ray powder diffraction is used to follow a mechanochemical synthesis using a new data processing strategy. Current techniques can monitor processes in the centre of the milling jar, but give little insight into transformations that occur at the ends of the milling jars, where mechanical impact is greatest. The two regions may not always yield the same result.