Reactive crystallization: a review

Reactive crystallization is not new, but there has been recent growth in its use as a means of improving performance and sustainability of industrial processes. This review examines phenomena and processes in which reaction and crystallization are coupled in the production of a desired chemical species. Coverage includes fundamental phenomena, such as solubility, supersaturation, crystal nucleation and growth, and chemical kinetics. Systems examined are divided into two groups, those best described as undergoing ionic reactions (including neutralizations), which have near instantaneous rates and result in the formation of ionic bonds, and those undergoing covalent reactions in which the key step occurs at measurable rates and results in the formation of covalent bonds. Discussion of the latter category also includes the impact of catalysis. Examples of a variety of reactions and applications are enumerated, and special attention is given to the utility of reactive crystallization in chiral resolution. Integration of reactive crystallization into process design, including both batch and continuous operations, and the development and efficacy of modeling, monitoring and control are reviewed. Finally, a perspective addressing needs to advance the usefulness and applications of reactive crystallization is included.