Mechanochemical Synthesis and NMR Crystallography of Multicomponent Crystals: New Perspectives from Chlorine and Alkali Metal Solid-State NMR Spectroscopy

We describe optimized mechanochemical syntheses of two classes of multicomponent crystals (MCCs) of the forms MCl:xCA (CA = cyanuric acid; x = 1, 2) and MCl:xBA·nH2O (BA = barbituric acid; x = 1, 2; n = 0, 2), which can be prepared in quantitative yields in as little as 1 to 5 min. Of the 12 MCCs discussed herein, seven novel MCl:xBA·nH2O MCCs were discovered, and for five of these, crystal structures are reported. All MCCs were characterized using powder X-ray diffraction and multinuclear solid-state NMR (SSNMR) spectroscopy, including 35Cl, 13C, and quadrupolar alkali metal (7Li, 23Na, 39K, 87Rb, and 133Cs) nuclides. SSNMR of the quadrupolar nuclides is useful for the identification of products, residual educts, and impurity phases within the mechanochemical reaction mixtures. In addition, 35Cl SSNMR spectra reveal broad central transition (+1/2 ↔ −1/2) powder patterns corresponding to the chloride ions, providing a unique spectral fingerprint for each MCC as defined by distinct chemical shift and electric field gradient (EFG) tensors, whereas alkali metal SSNMR spectra aid in determining the number of crystallographically and magnetically distinct sites. Dispersion-corrected plane-wave DFT calculations were used to obtain geometry-optimized structures from structural models based on known crystal structures, from which 35Cl EFG tensors were calculated and found to be in reasonable agreement with experiment. Examination of the 35Cl EFG tensor orientations, as well as their dependence on molecular symmetry, crystallographic symmetry, and H···Cl– hydrogen bonding, all point toward the great potential for their use in quadrupolar NMR-guided crystallographic studies and concomitant crystal structure prediction methods, which may be applied for the characterization of a wide range of MCCs and other organic solids, including those of pharmaceutical importance.