Packing and Conformational Polymorphism in 1,2-Bis(aminocarbonyl(1-tert-butyl-1H-pyrazol-(3)5-yl))ethanes: Illuminating Examples of Highly Flexible Molecules

Abstract

Insights into the occurrence of packing and conformational polymorphs and anhydrous/hydrate forms of 1,2-bis­(aminocarbonyl­(1-tert-butyl-1H-pyrazol-[3]­5-yl))­ethanes with the substituents R = Me (a), F-4-Ph (b), Cl-4-Ph (c), and Br-4-Ph (d) in positions 5 (1) and 3 (2) of the pyrazole rings are presented. In this series, two molecular forms were observed, linear and folded. Compound 1a revealed an illuminating and rare example of a highly flexible molecule with packing polymorphism. The molecular stacking and absence of NH···OC interactions promoted polymorph growth. Structure 2a showed chains driven by NH···OC bonds in the anhydrous form and closed dimers by water binding the molecules (NHamide···OHwt···COamide) in the hydrate form. Two different forms were observed for conformational polymorph 2d (linear and folded). The folded form was about −10 kcal mol–1 more stable than the linear form, showing significant crystalline packing differences. This occurrence is attributed to the rotation of the amide groups through the NH···OC bonds. The linear shape showed a higher stabilization energy for NH···OC bonds and a cluster −6 kcal mol–1 more stable than polymorph 2dI. Compounds 1b–d and 2b-c also had their crystal growth proposed and features highlighted.

Effect of hydrogen bonds and π⋯π interactions on the crystallization of phenyl-perfluorophenyl amides: understanding the self-organization of a cocrystal

“…Based on the analysis of normalized NC and NG data, we have proposed the crystallization mechanisms of a series of organic compounds to understand the crystal formation process. [30][31][32][33][34][40][41][42][43][44] The construction of a crystallization mechanism proposal involves hierarchizing supramolecular cluster dimers, mainly considering the interaction energies. The most energetic dimers are supposed to interact first, building small blocks that, through a selection process based on greater stability and greater possibility of cooperativity with other blocks, will persist and form the first aggregates that give the protocrystal.…”

Polymorphism in Pyridine-2,6-dicarboxamides: The Role of Molecular Conformation in Hydrate Formation

“…A recent study of our research group showed that molecules with carboxamide groups (OC–NH−) can form hydrates . With this capacity of forming hydrogen bonds, we assumed carboxamide groups could be used as molecular substituents capable of retaining water molecules and forming hydrates.…”

“…For the first, the final stabilization energy of the crystal may not define the formation of one polymorph at the expense of the formation of another polymorph. This is because many compounds form polymorphs with large energy differences. − However, when considering polymorph competition, we could imagine the formation of only the most stable because the process in equilibrium must move in this direction. This energy can be important in the case of metastable polymorphs that, in an internal structural rearrangement process, can decay into more stable crystalline phases .…”

“…Given this context, our investigations have shown that the hydrogen bonds between water and organic molecules can be classified into two main categories related to their role in crystallization: bridge hydrates , and prison hydrates. , In the first case, water plays an essential role in the genesis of the crystal, participating as a bridge between the molecules. In these cases, the organic molecules have difficulty interacting directly due to noncomplementary topology and/or the presence of groups with significant steric effects.…”

“…However, these researchers still emphasized that hydrate formation is challenging to predict and that hydrates can indeed be described as a nemesis to crystal engineering. 18 Given this context, our investigations have shown that the hydrogen bonds between water and organic molecules can be classified into two main categories related to their role in crystallization: bridge hydrates 13,19 and prison hydrates. 20,21 In the first case, water plays an essential role in the genesis of the crystal, participating as a bridge between the molecules.…”