In Situ Solid-State NMR Studies of Crystallization Processes

Abstract

While solid-state NMR spectroscopy is a versatile technique for studying structural and dynamic properties of solids, adaptation of this technique for in situ monitoring of chemical processes is often associated with technical challenges. In this regard, it is only very recently that an in situ solid-state NMR strategy for monitoring the evolution of crystallization processes has been developed. The early results from the application of this strategy suggest that it is a powerful approach both for identifying the sequence of polymorphic forms (or other solid forms) present as a function of time during crystallization from solution and for discovering new polymorphs. Furthermore, the latest development of this in situ technique (called “CLASSIC NMR”) allows the simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time during crystallization, yielding complementary information on the evolution of both the solid and liquid phases. This article describes the foundations of these techniques and presents several examples of applications that highlight the potential of in situ solid-state NMR to deepen our understanding of crystallization processes.