(71c) Combining Crystallization and Chemical Reactions in Separation and Purification Processes

Separation and purification processes are created to recover specific compounds from mixtures found in nature or those resulting from chemical transformations. The process selected often must address unique challenges presented by the product of interest. In some cases, integration of reaction and separation can be effective in meeting such challenges. Here, for example, we are concerned with two challenges: (1) overcoming limitations associated with solid-liquid equilibrium in recovering an enantiomerically pure compound (EPC) and (2) enhancing the yield of an intermediate in a complex reaction network. In both of these instances, we show how crystallization and tailored reaction conditions can be coupled to achieve enhanced purity and greater yield. Moreover, since such attributes are achieved using a single stage, the reactive separations offer operational advantages such as reducing the cost, time, and energy consumption of the process.

Separation of EPCs is challenging because such compounds have similar chemical and physical properties, with their structures differing only in their spatial orientation. Crystallization is one of the few techniques that has been successful in resolving a significant number of racemic systems, and here we exploit reactive crystallization to recover enantiomerically pure amino acids from racemic systems by overcoming thermodynamic limitations.

β-lactam antibiotics can be produced by means of an enzymatically catalyzed reaction, but the catalyst also hydrolyzes the antibiotics into undesired by-products. This challenge corresponds to a classic kinetically controlled system where the desired product is an intermediate of the overall reaction. We show how a reactive crystallization scheme that selectively removes the desired product from solution, before it is consumed by undesired reactions, can significantly enhance the yield of the product.