The structure of two anhydrous polymorphs of caffeine from single-crystal diffraction and ultrahigh-field solid-state 13C NMR spectroscopy

In this work, we examine two anhydrous polymorphs of caffeine, as well as the monohydrate, by high-field (21 T) NMR spectroscopy, and since suitable single crystals of the anhydrous forms could be obtained, the crystal structures were also determined. At high field, the C-13 NMR spectra are simplified considerably over those obtained at low field as the effect of the N-14 nuclear quadrupoles on the C-13 resonances becomes minimal. The spectra of the two anhydrous polymorphs provide information about the number of distinct caffeine sites and indicate structural disorder. The NMR observations are consistent with single-crystal X-ray diffraction, which shows that the structures are indeed complicated by disorder. Furthermore, the space groups obtained previously from powder diffraction were, in fact, incorrect, R(3) over bar c rather than R3c for the low-temperature polymorph and C2/c rather than Cc for the high-temperature polymorph. As a result, the structures are different from those proposed on the basis of modeling calculations.