Mechanochemical Co-crystallisation Mediated by a Eutectic

It is very likely that understanding of the role of eutectic formation in co-crystal synthesis will become increasingly important in the context of pharmaceutical 

The ability to construct pharmaceutical co-crystals on a large scale is important for the industrial application of mechanosynthesis. This aspect of mechanochemical co-crystallisation was recently addressed by Medina et al. who described a scalable solvent-free process for pharmaceutical co-crystallisation by using twin screw extrusion.  

The stepwise mechanism of co-crystal formation has been interpreted in terms of kinetic and thermodynamic co-crystallisation products, wherein the finite assemblies are the kinetic product whose formation is driven by the formation of stronger N I halogen bonds. The formation of the thermodynamic product is subsequently followed by the formation of enthalpically less favourable S I halogen bonds. 

This stepwise mechanism is most likely the consequence of the hierarchy of strong and weak halogen bonds in the reaction mixture. The stepwise mechanism is likely to be a general characteristic of co-crystal formation by grinding reactant molecules that have significantly different halogen- or 

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