Powder diffraction reveals the crystal structure of the metastable polymorph of benzamide

The challenge
To obtain a crystal structure of metastable benzamide, unsolved for over 170 years.

Background
Understanding the influences of structural, thermodynamic and kinetic factors that control crystallisation processes is important for fields such as pharmaceuticals, health care, optoelectronics and speciality chemicals. A metastable transient Form II of benzamide has been known since 1832, but the crystal structure proved intractable until very recently.

Results
The crystal structure was solved from high-resolution powder diffraction data from ID31. Numerous powder diffraction patterns were collected to monitor Form II in the sample, which also contained Form I. The structure showed that the polymorphism arises from the disorder of one of the independent benzamide molecules in the unit cell and highlights the delicate balance between kinetics and thermodynamics in the appearance of polymorphs.

How did the synchrotron help?
Rapidly collected high-resolution powder diffraction patterns were the key to solving this structure, together with the in situ kinetic and temperature control of the sample. The very high angular resolution of the ID31 diffractometer allowed high-quality data to be collected with good separation of the powder peaks, which led to the final detailed crystal structure.

Figure 1. Crystal structure of Form II of benzamide showing the noncentric molecular dimer determined from the ID31 powder data.

Reference:
N. Blagden, R. Davey, G. Dent, M. Song, W.I.F. David, C.R. Pulham, and K. Shankland, Woehler and Liebig Revisited: A Small Molecule Reveals Its Secrets - The Crystal Structure of the Unstable Polymorph of Benzamide Solved after 173 Years, Crystal Growth & Design 5, 2218-2224 (2005).

Top image: Sketch of the crystal packings of the two forms of benzamide.