In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction


We describe the only currently available protocol for in situ, real-time monitoring of mechanochemical reactions and intermediates by X-ray powder diffraction. Although mechanochemical reactions (inducing transformations by mechanical forces such as grinding and milling) are normally performed in commercially available milling assemblies, such equipment does not permit direct reaction monitoring. We now describe the design and in-house modification of milling equipment that allows the reaction jars of the operating mill to be placed in the path of a high-energy (90 keV) synchrotron X-ray beam while the reaction is taking place. Resulting data are analyzed using conventional software, such as TOPAS. Reaction intermediates and products are identified using the Cambridge Structural Database or Inorganic Crystal Structure Database. Reactions are analyzed by fitting the time-resolved diffractograms using structureless Pawley refinement for crystalline phases that are not fully structurally characterized (such as porous frameworks with disordered guests), or the Rietveld method for solids with fully determined crystal structures (metal oxides, coordination polymers).

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Figure 1: Milling equipment for in situ X-ray diffraction measurements.
Figure 2: Chemical reaction and experimental setup.
Figure 3: Experiment preparation.
Figure 4: Outside control of mill operation.
Figure 5: Data processing.
Figure 6: Data presentation and quantitative analysis.
Figure 7: Qualitative identification of products using Mercury.


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We acknowledge financial support from the Herchel Smith Fund; the British Council/The German Academic Exchange Service (DAAD) (grant no. 1377); the ESRF; NanoDTC, the University of Cambridge; the Ministry of Science, Education and Sports of the Republic of Croatia (grant no. 098-0982904-2953) and EPSRC (A.M.B.); as well as from a research fellowship (T.F.) and a doctoral fellowship (P.J.B.). McGill University, the Fonds Québécois de la Recherche sur la Nature et les Technologies (FRQNT) Centre for Green Chemistry and Catalysis, a FRQNT Nouveaux Chercheurs grant and a Canadian Natural Sciences and Engineering Research Council (NSERC) Discovery grant are acknowledged for support (T.F.). We thank A.K. Cheetham for comments, W. Jones for support in acquiring the instrumentation and J.K.M. Sanders for support. The assistance of A. Kovač and V. Dunjko with graphics preparation is acknowledged. N. Pitt is acknowledged for photography.

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The manuscript was composed and research was performed by I.H., S.A.J.K., P.J.B., A.M.B., F.A., V.H. and T.F. Detailed designs for mill modification were provided by R.C.N. Research was organized by T.F., I.H. and R.E.D. Manuscript preparation and submission were organized by T.F.

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Correspondence to Tomislav Friščić.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Manual

Technical drawings of the mill extension and milling jar. (PDF 566 kb)

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Halasz, I., Kimber, S., Beldon, P. et al. In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction. Nat Protoc 8, 1718–1729 (2013).

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