Vanishing Polymorphism of (2E)-2-Cyano-3-[4-(Diethylamino)phenyl]prop-2-enethioamide:  X-ray Structural Study and Polymorph Prediction

Synthesis and crystallization of a polar organic compound (2E)-2-cyano-3-[4-(diethylamino)phenyl]prop-2-enethioamide (CDPE) gave two new crystalline polymorphs (1 and 2) and an acetonitrile solvate (pseudopolymorph, 3) of this compound. The third crystalline polymorph of CDPE (4) was described in the literature earlier. It was found that in crystalline polymorphs 1, 2, and 4 molecules adopt three different conformations. Experimental observations show that polymorph 1 is a predominant form of the CDPE compound, while all other crystalline forms we were unable to reproduce under different conditions. Quantum ab initio calculations of relative conformational energies of molecules found in these polymorphs revealed that the conformer in polymorph 1 has significantly lower energy than conformers in polymorphs 2 and 4. This fact explains the predominant formation of polymorph 1 under different experimental conditions. The polarity of CDPE molecules and distinctions in their molecular and crystal structures make CDPE polymorphs 1, 2, and 4 a perfect model for testing of the methodology of crystal structure prediction with the Polymorph Predictor module from the Cerius² program package. It was shown that if the starting molecular model corresponds to X-ray data and considered to be rigid it is possible to predict all three polymorphs. In contrast, usage of a flexible molecular model does not give positive results. Reasons for such differences are discussed.