Crystal structure and Hirshfeld surface analysis of 3-cyano-4-hydroxy-2-(4-methylphenyl)-6-oxo-N-phenyl-4-(thiophen-2-yl)cyclohexane-1-carboxamide 0.04-hydrate

In the crystal structure, molecules are linked by N—H⋯O, C—H⋯O and C—H⋯N hydrogen bonds, forming molecular layers parallel to the bc plane, which interact by the van der Waals forces between them.


Figure 2
A view down the a axis of the intermolecular N-HÁ Á ÁO, C-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds of the title compound.

Figure 3
A view down the b axis of the intermolecular N-HÁ Á ÁO, C-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds of the title compound.
In the crystal of HALROB, the amide carbonyl groups are oriented in different directions with respect to the cyclohexanone ring. These orientations of the carboxamide groups facilitate the formation of an intramolecular O-HÁ Á ÁO hydrogen bond. The molecules are packed such that chains are formed along the b-axis direction. These chains are held together by N-HÁ Á ÁO hydrogen bonds.
In the crystal IFUDOD, there are no classical hydrogen bonds. Intermolecular C-HÁ Á ÁO contacts and weak C-HÁ Á Á interactions lead to the formation of a three-dimensional network.
In the crystal of IWEVOV, the molecules pack such that both carbonyl O atoms, participate in hydrogen-bond formation with symmetry-related amide nitrogen atoms, present in the carbamoyl substituents, forming N-HÁ Á ÁO hydrogen bonds in a helical arrangement. In the crystal, the phenyl rings are positioned so as to favour edge-to-edge aromatic stacking. When the crystal packing is viewed normal to the ac plane, it reveals a 'wire-mesh' type hydrogen-bond network.
In the crystal of IWEVUB, unlike in IWEVOV where both carbonyl O atoms participate in hydrogen bonding, only one of the carbonyl oxygen atoms participates in intermolecular N-HÁ Á ÁO hydrogen bonding while the other carbonyl oxygen participates in a weak C-HÁ Á ÁO interaction. In addition, one of the amide nitrogen atoms participates in N-HÁ Á ÁO hydrogen bonding with the hydroxyl oxygen atom, linking the molecules in a helical arrangement, which is similar to that in the structure of IWEVOV. As observed in the structure of IWEVOV, the packing of the molecules viewed normal to the ab plane resembles a 'wiremesh' arrangement of the molecules.
In OZUKAX, molecules are linked by intermolecular N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, forming sheets parallel to the ac plane. C-HÁ Á Á interactions are also observed. Intermolecular O-HÁ Á ÁO hydrogen bonds consolidate the molecular conformation.
In PEWJUZ, molecules are linked by intermolecular N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, forming sheets parallel to the bc plane. C-HÁ Á Á interactions are also observed.
Intermolecular interactions can be weaker or more robust based on the presence or absence of different functional groups and the molecular environment, depending on the crystal system, which all affect the molecular conformation.

Synthesis and crystallization
To a dissolved mixture of 2-(thiophene-2-carbonyl)-3-(p-tolyl)acrylonitrile (1.32 g; 5.2 mmol) and acetoacetanilide (0.92 g; 5.2 mmol) in methanol (35 mL), 2-3 drops of methyl piperazine were added and the mixture was stirred at room temperature for 5-7 min. The reaction mixture was kept in a closed flask for 24-48 h. Then, 25 mL of methanol was removed from the reaction mixture and it was left overnight. The precipitated needle-like crystals were separated by filtration and recrystallized from ethanol (yield 72%; m.p. 483-484 K).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The H atoms of the OH and NH groups were located from the difference-Fourier synthesis and refined freely. All C-bound H atoms were positioned geometrically and refined using a riding model, with C-H = 0.95-1.00 Å , and with U iso (H) = 1.2 or 1.5U eq (C).
Data with a resolution higher than 0.8 Å have a mean I/(I) of less than 4, and significant errors in the equivalent intensities (high R merge ). The dataset was therefore truncated at 0.8 Å . Furthermore, there is a small cavity in the crystal, which is only partially occupied by a water molecule (only about 4%) and the protons could not be located. It is also highly probable that, in the presence of a fully occupied water molecule, the proton of the OH group would have a different orientation.