Revision of the Crystal Structure of the First Molecular Polymorph in History

Despite being the earliest reported case of polymorphism in a molecular crystal, the unstable form II of benzamide has thus far evaded thorough structural characterization because collection of experimental data at atomic resolution has proven extremely challenging. Using a highly validated computational crystal structure prediction (CSP) method based on dispersion-corrected density functional theory, we correctly predict the stable form I with the lowest energy among all sampled structures and its polytypic form III with slightly higher energy. From Rietveld refinement of selected CSP models against synchrotron X-ray powder diffraction data of the historical polymorph, we are able to identify a subtle weakness in the available experimental data and arrive at a revised structure of form II. The revised crystal structure is the first benzamide structure to form catemers rather than dimers and possesses the rare space-group symmetry <i>Fdd</i>2 with two molecules in the asymmetric unit, which is necessary to support the new hydrogen bonding network. This rare space group is only found in the CSP by a complete structural search in all 230 space groups with one or two molecules in the asymmetric unit