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

Abstract

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 Fdd2 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.

Crystals of Benzamide, the First Polymorphous Molecular Compound, Are Helicoidal

“…Benzamide I platelike crystals show single-crystal-like selected area electron diffraction (SAED) patterns (projected along [1 11] zone axis) with sharp reflections free of diffuse scattering (Figure 8a), while benzamide II needles show strong diffuse scattering in planes perpendicular to the needle elongation direction (Figures 8b-d;F igure S6). Thel attice periodicity of % 5.2 along the crystal elongation direction is consistent with the orientation of hydrogen-bond tapes in all proposed crystal structures [12] (Figure S3). This direction is also confirmed by the analysis of preferred orientations in powder X-ray patterns collected from an assembly of needles on af lat substrate.B ased on our indexing of PXRD data in P2 1 /c, needles are elongated along [100]*.…”

“…[6,7] Despite reasonably good R-factors,the data was burdened with strong preferred orientations of crystallites,c ontributions from amorphous material (aqueous solution), and admixtures of form I.E leven years later, the structure was re-examined using the same experimental data and crystal structure prediction (CSP) methods. [12] It was concluded that the Pba2s tructure had an unreasonably high lattice energy. Instead, two other candidate structures, Fdd2and P2 1 /c,were suggested, which provided low lattice energies and good agreement with the experimental data.…”

“…[6,7] This study initiated research on benzamide crystals that resulted in the discovery of benzamide III [8][9][10] and IV [11] and ar erefinement of the benzamide II crystal structure with the help of crystal structure prediction methods. [12] Thea forementioned studies were focused on benzamide crystal structures.H owever, ag lance at the published benzamide II micrographs [6,7] shows clearly their helicoidal habits.C rystals with curvature contradict definitions of ideal crystals as polyhedra [13] with long-range translational symmetry.A ccording to F. Bernauer, [14] and our own observations, twisting affects at least 25 %o fmolecular crystals.H owever, the etiology of twisting has not been well understood. [15][16][17][18][19] In this manuscript we analyze the origin of twisting in benzamide II crystals by in situ crystal growth observations,c ryoscanning electron microscopy (cryo-SEM), cryo-transmission electron microscopy (cryo-TEM), electron diffraction (ED), and powder X-ray diffraction (PXRD).…”

CrystalCMP: an easy-to-use tool for fast comparison of molecular packing

“…According to the literature (Thun et al, 2009;Johansson & van de Streek, 2016), the small organic molecule benzamide crystallizes as three different polymorphs, Form I, Form II and Form III. After comparison of the packings of the benzamide entries in the Cambridge Structural Database (CSD, Version 5.37; Groom et al, 2016), one would expect a simple similarity matrix and a dendrogram with three different similarity groups.…”

Structures and energetic properties of 4-halobenzamides

“…Entries 1-4 are from this study and are X-ray structures, entry 5 is from Johansson & van de Streek (2016) and is an X-ray structure, and entry 6 is from Greenberg & Venanzi (1993) and are calculated values. Table 4 Resonance energies of amides 1a-1e calculated using the COSNAR method a .…”