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 13C NMR spectra are simplified considerably over those obtained at low field as the effect of the 14N nuclear quadrupoles on the 13C 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, R3̄c 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.