Chemical and physical transformations by milling are attracting enormous interest for their ability to access new materials and clean reactivity, and are central to a number of core industries, from mineral processing to pharmaceutical manufacturing. While continuous mechanical stress during milling is thought to create an environment supporting nonconventional reactivity and exotic intermediates, such speculations have remained without proof. Here we use in situ, real-time powder X-ray diffraction monitoring to discover and capture a metastable, novel-topology intermediate of a mechanochemical transformation. Monitoring the mechanochemical synthesis of an archetypal metal-organic framework ZIF-8 by in situ powder X-ray diffraction reveals unexpected amorphization, and on further milling recrystallization into a non-porous material via a metastable intermediate based on a previously unreported topology, herein named katsenite (kat). The discovery of this phase and topology provides direct evidence that milling transformations can involve short-lived, structurally unusual phases not yet accessed by conventional chemistry.

Looking in: The penetrating power of high-energy X-rays provides a means to monitor in situ and in real time the course of ball-milling reactions of organic pharmaceutical solids by detecting crystalline phases and assessing the evolution of their particle sizes. Upon switching from neat grinding to liquid-assisted grinding, cocrystal formation is enabled or tremendously accelerated, while the reaction mechanism alters its course.

An experimental technique for in situ and real-time monitoring of mechanochemical reactions in a shaker ball mill was recently described, which utilises highly penetrating X-ray radiation available at the ID15B beamline of the European Synchrotron Radiation Facility. Herein, we describe the first attempts to perform such reaction monitoring in a quantitative fashion, by introducing an internal X-ray diffraction standard. The use of silicon as an internal standard resolved the issue with variations of the amount of the sample in the X-ray beam due to the non-uniform distribution of the sample in the reaction jar and allowed, via Rietveld analysis, the first quantitative estimate of the amorphous phase content in a mechanochemical reaction as it is being milled. We also highlight problems associated with the non-ideal mixing of the reaction mixture.

We describe the first in situ and real-time study of a mechanochemical reaction by variable-temperature synchrotron powder X-ray diffraction. Using the dry milling synthesis of a coordination polymer as a model system, we reveal a change in reaction mechanism if temperature is increased, and a strong dependence of the reaction rate on temperature, with a ca. 6-fold increase of the rate of reactant depletion for a 45 °C rise in temperature. These experiments provide also the first direct evidence how a formally dry milling reaction is facilitated by water released from a hydrated reactant.

Die Durchdringungskraft hochenergetischer Röntgenstrahlen macht es möglich, den Verlauf von Reaktionen fester organischer Pharmazeutika in einer Kugelmühle in situ und in Echtzeit zu verfolgen, indem kristalline Phasen detektiert und auf die Entwicklung ihrer Partikelgrößen hin ausgewertet werden. Wird beim Mahlen eine Flüssigkeit hinzugefügt, wird eine Cokristallbildung ermöglicht oder stark beschleunigt, während sich der Reaktionsverlauf ändert.