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.

合成与结晶极性有机化合物（2E）-2-氰基-3-[4-(二乙氨基)苯基]丙-2-烯硫酰胺（CDPE）产生了两种新的结晶多晶型（1和2）以及一种乙腈溶剂化物（伪多晶型，3）的该化合物。CDPE的第三种结晶多晶型（4）在文献中已有描述。研究发现，在结晶多晶型1、2和4中，分子采取了三种不同的构象。实验观察表明，多晶型1是CDPE化合物的优势形式，而我们在不同条件下均未能再现其他所有结晶形式。对这些多晶型中发现的分子相对构象能的量子初态计算揭示了，在多晶型1中的构象具有比多晶型2和4中的构象显著更低的能量。这一事实解释了在不同实验条件下多晶型1的优势形成。CDPE分子的极性和其分子与晶体结构之间的差异使得CDPE的多晶型1、2和4成为检验Cerius2程序包中的多晶型预测模块晶体结构预测方法的理想模型。研究表明，如果起始分子模型与X射线数据相符且被视为刚性，则可以预测所有三种多晶型。相反，使用柔性分子模型并不能给出积极的结果。这种差异的原因已进行讨论。