Structural refinement of carbimazole by nmr crystallography

The characterization of the three-dimensional structure of solids is of major importance, especially in the pharmaceutical field. In the present work, NMR crystallography methods are applied with the aim to refine the crystal structure of carbimazole, an active pharmaceutical ingredient used for the treatment of hyperthyroidism and Grave's disease. Starting from previously reported X-ray diffraction data, two refined structures were obtained by geometry optimization methods. Experimental 1H and 13C isotropic chemical shift measured by the suitable 1H and 13C high-resolution solid state NMR techniques were compared with DFT-GIPAW calculated values, allowing the quality of the obtained structure to be experimentally checked. The refined structure was further validated through the analysis of 1H-1H and 1H-13C 2D NMR correlation experiments. The final structure differs from that previously obtained from X-ray diffraction data mostly for the position of hydrogen atoms.