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

Abstract

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 Cerius 2 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.

Ethyl (E)-3-anilino-2-cyano-3-mercaptoacrylate

“…The C≡N bond length (1.145 (2) Å), C?C (1.405 (2) Å) and C?O (1.2202 (18) Å) are in agreement with those observed before (Timofeeva et al, 2004;Azim et al, 1997). The S-H hydrogen bond length corresponds well to the the value 1.197 (9) Å from 247 observations yielded by the Cambridge Crystallographic Database (Allen, 2002).…”

“…For related literature, see: Allen (2002); Azim et al (1997); Gao et al (2006); Timofeeva et al (2004); Xue et al (2004); Etter et al (1990).…”

A non-linear optical chromophore: 2-[3-cyano-4-((E)-{5-[4-(diethylamino)styryl]thiophen-2-yl}vinyl)-5,5-dimethylfuran-2-(5H)-ylidene]propanedinitrile

“…These results suggest that, under different crystallization conditions, it could be possible to crystallize another isomer of (I), as has been achieved, for instance, for the NLO material (2E)-2-cyano-3-[4-(diethylamino)phenyl]prop-2-enethioamide (Timofeeva et al, 2004).…”

Analysis of Known Crystals to Design Polymorph Prediction Strategies

“…Timofeeva et al 22 and Nowell and Price 27 have found that RB simulations are superior to CA simulations. In this study, two factors have been postulated as being important: (1) E conformational error occurs during CA simulations because initial IM partial charges are used inappropriately with all new CA produced conformations, and (2) E unit cell optimization process during CA simulations is prone to the possibility of having E cohesive overwhelmed by E conformational .…”

“…The deviations using CA can be seen to be much larger than for RB strategy. Timofeeva et al 22 have suggested that the superiority of the RB over the CA strategy could be due to the inability of molecular mechanics to properly assess the conformational energy dependence with respect to torsion angles. There may be an alternative explanation for the poor performance of the CA strategy.…”