Benzamide, polymorphs

FIGURE 7.4 Top Predicted XRPD pattern from experimental SXRD structure of Form I of benzamide Middle Predicted XRPD pattern from predicted benzamide polymorph 01-126. Bottom Predicted XRPD pattern from predicted benzamide polymorph 01-127. 

FIGURE 7.5 Interaction tree diagram for different polymorphs of benzamide. Polymorph IDs are highlighted in bold, and polymorph FF-energy ranks in numerals on the right-hand side. 

Concomitant polymorphs concomitant polymorphs are polymorphic forms of a substance that crystallise out at the same time from the same crystallisation mixture. Here at the same time does not necessarily mean that the crystals form at exactly the same instant, just that they can be observed co-existing at some point during the crystallisation process. We have already come across concomitant polymorphs in the early example of benzamide where forms I and II are concomitant. Many more interesting and beautiful examples are covered in a recent review.62... 

As the energy-temperature phase diagram (Section 2.2.3) indicates, at any particular temperature only one polymorphic form is the thermodynamically stable one (except, of course at the temperature of a transition point). The stable form is also the least soluble form at a given temperature (Bym et al. 1999). All other phases are higher in energy and metastable with respect to the most stable phase. A metastable phase may be fleeting in nature (e.g. benzamide, Bernstein and Davis 1999) or may coexist indefinitely with its more stable counterpart in the absence of any perturbations... 

Thun, J., Seyfarth, L., Senker, J., Dinnebier, R. E., Breu, J., Polymorphism in benzamide solving a 175-year-old riddle. 

Polymorphism in organic molecules has been studied for more than 180 years/ since the first report of polymorphism of benzamide by Wohler and Liebig in 1832. ... 

Figure 7.1 Hydrogen bonding in the crystal structures of polymorphic benzamide...

To illustrate this, we here provide an example of how a compound may be computationally analyzed when it comes to polymorphism, structural aspects of the crystal structures, and also example of an interaction analysis. As the example we have chosen a simple molecule, benzamide (Fig. 7.1). 

A typical calculated polymorph landscape may look as in Figure 7.2 as generated for benzamide, with calculated interaction energies plotted versus the Kitaigorodsky packing index [20]. As a reminder to the reader, the most stable polymorph is the calculated crystal structure with the most negative interaction energy. However,... 

FIGURE 7.2 Predicted polymorph landscape for benzamide. The two conformers investigated are illustrated by diamonds and circles. 

FIGURE 7.3 Overlay of experimental polymorph I and DFT-D optimized crystal structure 01-126 of benzamide. Fifteen molecules are overlaid to calculate the RMSD. 

FIGURE 7.6 Trimer structural motif of polymorphs of benzamide. Hydrogen bonds indicated by dashed line. 

The first observation of polymorphism in organic materials is attributed to Friedrich Wohler and Justus von Liebig, when in 1832, they examined a boiling solution of benzam-ide on cooling the benzamide initially crystallized as silky needles, but on standing, these were slowly replaced by rhombic crystals. Present day analysis identifies three polymorphs for benzamide. The least stable one, formed by flash cooling is the orthorhombic form 11. This type is followed by the monoclinic form III (observed by Wohler/Liebig). The most... 

Organic componnds are susceptible to forming various intermolecular interactions and hence there is an increased chance of polymorphism. Benzamide is one of the earliest... 

Figure 5.2 Structure of three polymorphs (forms I, II, and III) of benzamide. (adapted from Ref [2])...

Mocilac P, Donnelly K, Gallagher JF (2012) Structural systematics and conformational analyses of a 3x3 isomer grid of fluoro-N-(pyridyl)benzamides physicochemical correlations, polymorphism and isomorphous relationships. Acta Cryst B68 189... 

J. Thun, M. Schoeffel and 1. Breu. Crystal structure prediction could have helped the experimentalists with polymorphism in benzamide. Mol. Simul. 34, 2008, 10-15. 

---