"CLASSIC NMR": an in-situ NMR strategy for mapping the time-evolution of crystallization processes by combined liquid-state and solid-state measurements.

Colan E Hughes,Kenneth D M Harris,P Andrew Williams

doi:10.1002/anie.201404266

Colan E Hughes, Kenneth D M Harris + Show 1 more

Open Access

https://doi.org/10.1002/anie.201404266

Copy DOI

Abstract

A new in-situ NMR strategy (termed CLASSIC NMR) for mapping the evolution of crystallization processes is reported, involving simultaneous measurement of both liquid-state and solid-state NMR spectra as a function of time. This combined strategy allows complementary information to be obtained on the evolution of both the solid and liquid phases during the crystallization process. In particular, as crystallization proceeds (monitored by solid-state NMR), the solution state becomes more dilute, leading to changes in solution-state speciation and the modes of molecular aggregation in solution, which are monitored by liquid-state NMR. The CLASSIC NMR experiment is applied here to yield new insights into the crystallization of m-aminobenzoic acid.

Highlights

A new in-situ NMR strategy for mapping the evolution of crystallization processes is reported, involving simultaneous measurement of both liquidstate and solid-state NMR spectra as a function of time
We recently developed a new in-situ solidstate NMR technique[3] which exploits the ability of NMR to selectively observe the solid phase in heterogeneous solid/ liquid systems, of the type that exist during crystallization from solution, under conditions in which the liquid phase is “invisible” to the measurement
The technique allows the first solid particles formed during crystallization to be identified, and allows the evolution of different solid phases present during the crystallization process to be monitored as a function of time

Summary

Introduction

A new in-situ NMR strategy (termed CLASSIC NMR) for mapping the evolution of crystallization processes is reported, involving simultaneous measurement of both liquidstate and solid-state NMR spectra as a function of time. The evolution of the crystallization process in terms of both the amount and the polymorphic identity of the solid phase present is established as a function of time from the solid-state NMR spectra.

Results

Conclusion