Solid-state grinding

Trask AV, Jones W (2005) Crystal Engineering of Organic Cocrystals by the Solid-State Grinding Approach. 254 41-70 Tuntulani T, see Suksai C (2005) 255 163-198... 

Crystal Engineering of Organic Cocrystals by the Solid-State Grinding Approach... 

Keywords Solid-state grinding Cocrystal formation Crystal engineering Pharmaceutical materials Polymorphism... 

An alternative to the solution-based approach exists in the approach of solid-state grinding. The act of solid-state grinding to induce chemical change. 

Quinhydrone charge-transfer complexes were the subject of study by Paul, Curtin and co-workers in the 1980s [15-18]. Unsymmetrically substituted quinhydrones, which are very labile in solution with respect to redox self-iso-merisation, form asymmetric charge-transfer complexes upon solid-state grinding. For example, 1,4-benzoquinone and 2-methylhydroquinone form the charge-transfer complex 3 upon solid-state grinding with a mortar and pestle. 

The product of solid-state grinding exhibits no evidence of complex 4, which would be expected to result following solution-mediated redox isomerisation of the starting components. Solid-state grinding preparation of quinhydrone complexes was later pursued by Guarrera et al. [19]. 

Fig. 1 Carboxylic acid heterodimer formed by solution and solid-state grinding cocrystallisation approaches[21]...

Lacking a meta constituent, it is clear that 19 alone cannot satisfy an analogous ring of continuous intermolecular interactions aroimd anthracene. Hence, no cocrystalhsation occurred by sohd-state grinding, and the incorporation of a benzene solvent molecule upon solution evaporation was necessary to permit cocrystalhsation (Fig. 4c). The authors thus attributed the lack of cocrystal formation by solid-state grinding to an inabihty of reactants to satisfy the desired intermolecular interactions, rather than the relative stabihty of reactants. 

One great attraction of preparing cocrystals by solid-state grinding is that, in certain cases, cocrystals unobtainable by other methods may be prepared. The number of reported instances of these cases is small, but may grow as the field of solid-state cocrystal preparation widens. From the standpoint of novel materials design, these cases are of great interest in that they may lead to understanding, prediction and exploitation of this phenomenon. 

An illustrative example was provided by the work of Kuroda and co-workers [50]. They reported that different methods of preparation resulted in distinct cocrystal products in their work with racemic bis-P-napthol (BN) 20 and ben-zoquinone (BQ) 21. Upon solid-state grinding with a mortar and pestle, a 1 1.5 BN BQ cocrystal resulted, termed form I. In contrast, from a solution of ether and hexane, a cocrystal containing 20 and 21 in a 1 1 BN BQ ratio resulted. 

Interestingly, in the same work [23] Etter and Adsmond reported two polymorphs of a 1 1 cocrystal containing 25 and malonic acid 27. Both crystallised from solution, but only one was obtainable from solid-state grinding. Contrary to the examples mentioned above, this instance suggests that solution crystallisation may at times offer more product diversity than grinding. 

The examples of this section summarise the recent application of the solvent-drop grinding approach to solid-state cocrystal preparation. The approach has been shown in certain instances to provide for either acceleration of CO crystallisation kinetics or selection of a particular polymorph via solid-state grinding. The approach is attractive, as it appears to incorporate some of the beneficial aspects of solvent participation while maintaining an essentially green, eco-friendly process. 

Structure Determination of New Materials Produced by Solid-State Grinding 160... 

Certain solid phases, on the other hand, cannot be obtained (even as microcrystalline powders) by crystallization experiments, but instead can be generated only by other types of preparation procedure. Some types of preparation processes commonly (or in some cases inherently) yield microcrystaUine products, including (1) preparation of materials directly from solid-state chemical reactions (see Sect. 6.6), (2) preparation of materials by solid-state desolvation processes (see Sect. 6.4), (3) preparation of materials by solid-state grinding (mechanochemical) processes (see Sect. 6.2), and (4) preparation of materials directly by rapid precipitation from solution (as opposed to crystallization) (see Sect. 6.7). Again, structure determination from powder XRD data may represent the only opportunity for determining the structural properties of new solid phases obtained by such processes. 

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