Synthesis, characterization, crystal structure and Hirshfeld surface analysis of isobutyl 4-[4-(difluoromethoxy)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

In the crystal, the molecules are linked by N—H⋯O and C—H⋯O interactions, forming supramolecular chains parallel to the a axis. These chains pack with C—H⋯π interactions between them, forming layers parallel to the (010) plane.

In the title compound, C 24 H 29 F 2 NO 4 , which crystallizes in the orthorhombic Pca2 1 space group with Z = 4, the 1,4-dihydropyridine ring adopts a distorted boat conformation, while the cyclohexene ring is in a distorted half-chair conformation.In the crystal, the molecules are linked by N-H� � �O and C-H� � �O interactions, forming supramolecular chains parallel to the a axis.These chains pack with C-H� � �� interactions between them, forming layers parallel to the (010) plane.The cohesion of the crystal structure is ensured by van der Waals interactions between these layers.Hirshfeld surface analysis shows the major contributions to the crystal packing are from H� � �H (56.9%),F� � �H/H� � �F (15.7%),O� � �H/H� � �O (13.7%) and C� � �H/H� � �C (9.5%) contacts.

Chemical context
Hexahydroquinoline (HHQ) ring systems occupy a prominent place in medicinal chemistry, attracting the attention of researchers for their versatile structural attributes and pharmacological potential.These ring systems, characterized by a unique combination of pyridine and cyclohexane rings, have shown remarkable bioactivity across a spectrum of therapeutic areas.Their capacity to interact with specific biological targets has led to the development of HHQ-based compounds with diverse medicinal properties, including antimicrobial, antiinflammatory, and anticancer activities (Ranjbar et al., 2019).Recent studies have shown that these compounds are effective in cancer-related inflammatory pathways such as TGF-� (La ¨ngle et al., 2019).Additionally, they have been demonstrated to have inhibitory effects on receptors involved in cancer development, such as EGFR, or to reverse multi-drug resistance (Abo Al-Hamd et al., 2023;Shahraki et al., 2020).
The choice to synthesize HHQs is also fueled by the accessibility of various synthetic routes and the opportunity to fine-tune their chemical structure to optimize drug-like properties.Multi-component reactions and cyclization strategies provide versatile platforms for their synthesis, allowing for systematic modifications to explore structure-activity relationships (SAR; Batista et al., 2016).As a result, the strategic pursuit of hexahydroquinoline synthesis continues to be a compelling avenue in medicinal chemistry, promising innovative solutions to pressing medical challenges and drug discovery endeavors.

Supramolecular features and Hirshfeld surface analysis
In the crystal, the molecules are linked by N-H� � �O and C-H� � �O interactions, forming supramolecular chains parallel to the a-axis direction (see Table 1; Figs. 2 and 3).These chains pack with C-H� � �� interactions between them,   forming layers parallel to the (010) plane (Fig. 4).The cohesion of the crystal structure is ensured by van der Waals interactions between these layers.
The Hirshfeld surfaces and their corresponding twodimensional fingerprint plots were calculated using the software package Crystal Explorer 17.5 (Spackman et al., 2021).The d norm surfaces are mapped over a fixed color scale from À 0.5961 (red) to 1.9017 (blue) a.u.Red spots on the surface correspond to O� � �H/H� � �O interactions (Tables 1 and 2; Fig. 5a,b).

Synthesis and crystallization
The synthesis of the compound was carried out by refluxing 1 mmol of 4-(4-difluoromethoxy)benzaldehyde, isobutyl acetoacetate, 4,4-methyl-1,3-cyclohexandione and 5 mmol of ammonium acetate in methanol.The reaction process was monitored by thin-layer chromatography [ethyl acetate-nhexane (1:1)], and after the reaction was complete, the mixture was allowed to stand at room temperature for a while and then poured into an ice-water mixture (Fig. 7).The resulting precipitates were purified again by crystallization with methanol (Yıldırım et al., 2023).

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Figure 1
Figure 1View of the title molecule.Displacement ellipsoids are drawn at the 30% probability level.

Figure 2 A
Figure 2 A view of the molecular packing of the title compound along the a-axis with the N-H� � �O, C-H� � �O hydrogen bonds and C-H� � �� interactions shown as dashed lines.

Figure 3
Figure 3 View of the molecular packing along the b-axis.Hydrogen bonds are shown as dashed lines.

Figure 4
Figure 4View of the molecular packing along the c-axis.Hydrogen bonds are shown as dashed lines.

Figure 5 (
Figure 5 (a) Front and (b) back views of the three-dimensional Hirshfeld surface for the title compound.

Figure 6
Figure 6The two-dimensional fingerprint plots for the title compound showing (a) all interactions, and delineated into (b) H� � �H, (c) F� � �H/H� � �F, (d) O� � �H/H� � �O and (e) C� � �H/H� � �C interactions.The d i and d e values are the closest internal and external distances (in A ˚) from given points on the Hirshfeld surface.

Table 3
Experimental details.