In-situ solid-state NMR spectroscopy reveals competing crystallization pathways for a system that forms structurally diverse multicomponent crystalline phases

The development of NMR strategies for in-situ monitoring of crystallization processes has opened the opportunity to establish new mechanistic insights, including to understand the structural evolution of the solid phase produced in crystallization systems as a function of time. In this paper, we report the results of an in-situ solid-state ¹³C NMR study of crystallization from a solution containing 1,10-dihydroxydecane and urea in methanol, leading to the identification of two structurally diverse multicomponent crystalline phases that are formed at different stages of the crystallization process. The initially produced phase is a urea inclusion compound, in which 1,10-dihydroxydecane guest molecules are included within the well-known urea host tunnel structure. Subsequently, a second crystalline phase is formed, which is identified as a stoichiometric hydrogen-bonded co-crystal 1,10-dihydroxydecane-(urea)₂. The in-situ solid-state ¹³C NMR results suggest that the urea inclusion compound is not an intermediate phase on the crystallization pathway to form the co-crystal, as the urea inclusion compound remains after the formation of the co-crystal phase. However, after the appearance of the co-crystal phase, the subsequent crystallization process is dominated by rapid growth of the co-crystal rather than growth of the urea inclusion compound. The results demonstrate the capability of in-situ solid-state NMR strategies to monitor the structural evolution of multicomponent solid phases during crystallization from solution.