Solvent-drop grinding

Solvent-drop grinding was next applied as an eco-friendly modification to a previously described preparation of a crystalline organic inclusion compound. Initial work had demonstrated solution-mediated supramolecular organisation and solid-state topochemically controlled reactivity in a system involving l,2-bis(4-pyridyl)ethylene (bpe) 32 and 1,2,4,5-benzenetetracar-boxylic acid (bta) 33 [57]. A single crystal of a 2 1 bpe bta 32 33 cocrystal was... 

The utility of the solvent-drop grinding approach was recently extended by Trask et al. with a cocrystal system containing the model pharmaceutical... 

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. 

To understand why solution experiments sometimes fail to produce cocrystal products, and why solvent-drop grinding experiments can work when performed on the same system, the 1 1 cocrystal formed by nicotinamide and frans-cinnamic acid (frans-(2E)-3-phenylacrylic acid) has been studied [56]. In this work ternary isothermal phase diagrams of the cocrystal system was used to understand the crystallization phenomena, and to deduce methodologies and for the experimental design of cocrystal preparation. Cocrystals are most likely to form from solutions in which the two reactants have similar degrees of solubility, and the success of solvent-drop grinding was explained in that crystallization took place in the region of low solvent mole fractions where the cocrystal would be more stable relative to the separated reactants. 

A.V. Trask, W.D.S. Motherwell, W. Jones, Solvent-drop grinding green polymorph control of cocrystallization, Chem. Commun. (2004) 890-891. 

Characterization of the cocrystals obtained using [58] solution crystallization, high-throughput cocrystallization, dry grinding, and solvent-drop grinding... 

Solvent-drop grinding is a novel, efiScient and green procedure for polymorphic control [15,16]. It involves grinding a known polymorph of a compound with a very small amount of solvent added in order to effect a polymorphic transformation. Variation of the solvent may lead to different polymorphic outcomes. For example, polymorphic Form I of anthranilic acid (Figure 1, 2), ground in the presence of heptane, transforms to Form II, which in turn converts to Form III whai ground in tiie presence of chloroform [15]. 

Polymorph control by solvent-drop grinding during co-crystallization of caffeine with glutaric acid. 

Functionalization of cavitand structure by solvent-drop grinding. 

As shown by the results described above, the use of dry reactants is not the most productive method when dealing with molecular crystals. Often better results are obtained by adding a tiny amount of a given solvent to the mixture kneading, also called solvent drop grinding or liquid-assisted grinding). " " As a matter of fact, the use of a small quantity of solvent can accelerate or... 

Figure 12.8 Co-crystal formation in a solvent with asymmetric solubility of both components. Crystallizations starting from equimolar mixtures of A and B (dashed line) lead to solid A at low concentration and to mixtures of A and AB at higher concentration. A pure co-crystal solid phase is only obtained when excess B is added to the system or the content of solvent is essentially decreased to zero (solvent-drop grinding).

Currently there are four distinct experimental techniques for the mechanochemical synthesis of coordination polymers and MOFs neat grinding, LAG or kneading (also known under other names, such as solvent-drop grinding or solvent-assisted grinding), ILAG, and neat grinding followed by annealing. ... 

Trask AV, Shan N, Motherwell WDS, Jones W, Feng S, Tan RBH, Carpenter KJ (2005) Selective polymorph transformation via solvent-drop grinding. Chem Common 880... 

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