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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 79| Part 12| December 2023| Pages 1132-1136
https://doi.org/10.1107/S2056989023009623

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

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Sema Öztürk Yıldırım,a,b Mehmet Akkurt,c Gökalp Çetin,d Rahime Şimşek,e Ray J. Butcherf and Ajaya Bhattaraig*

aDepartment of Physics, Faculty of Science, Eskisehir Technical University, Yunus Emre Campus 26470 Eskisehir, Türkiye, bDepartment of Physics, Faculty of Science, Erciyes University, 38039 Kayseri, Türkiye, cDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Türkiye, dDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, 24100 Erzincan, Türkiye, eDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhiye-Ankara, Türkiye, fDepartment of Chemistry, Howard University, Washington DC 20059, USA, and gDepartment of Chemistry, M.M.A.M.C (Tribhuvan University), Biratnagar, Nepal
*Correspondence e-mail: ajaya.bhattarai@mmamc.tu.edu.np

Edited by S. P. Kelley, University of Missouri-Columbia, USA (Received 2 October 2023; accepted 3 November 2023; online 10 November 2023)

In the title compound, C24H29F2NO4, which crystallizes in the ortho­rhom­bic Pca21 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⋯π 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.

CCDC reference: 2305562

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1. 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, anti-inflammatory, and anti­cancer activities (Ranjbar et al., 2019[Ranjbar, S., Edraki, N., Firuzi, O., Khoshneviszadeh, M. & Miri, R. (2019). Mol. Divers. 23, 471-508.]). Recent studies have shown that these compounds are effective in cancer-related inflammatory pathways such as TGF-β (Längle et al., 2019[Längle, D., Werner, T. R., Wesseler, F., Reckzeh, E., Schaumann, N., Drowley, L., Polla, M., Plowright, A. T., Hirt, M. N., Eschenhagen, T. & Schade, D. (2019). ChemMedChem, 14, 810-822.]). 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[Abo Al-Hamd, M. G., Tawfik, H. O., Abdullah, O., Yamaguchi, K., Sugiura, M., Mehany, A. B. M., El-Hamamsy, M. H. & El-Moselhy, T. F. (2023). J. Enzyme Inhib. Med. Chem. 38, 2241674. https://doi. org/10.1080/14756366.2023.2241674.]; Shahraki et al., 2020[Shahraki, O., Khoshneviszadeh, M., Dehghani, M., Mohabbati, M., Tavakkoli, M., Saso, L., Edraki, N. & Firuzi, O. (2020). Molecules, 25, 1839. https://doi. org/10.3390/molecules25081839.]).

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[Batista, V. F., Pinto, D. C. G. A. & Silva, A. M. S. (2016). ACS Sustainable Chem. Eng. 4, 4064-4078.]). 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.

[Scheme 1]

In this study, isobutyl 4-(4-di­fluoro­meth­oxy­phen­yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carb­oxyl­ate was synthesized and its mol­ecular structure was confirmed by IR, 1H NMR, 13C NMR, HRMS and X-ray crystallography. The inter­molecular inter­actions observed in the crystal packing were investigated by Hirshfeld surface analysis.

2. Structural commentary

The 1,4-di­hydro­pyridine ring (N1/C1/C6–C9) of the title compound (Fig. 1[link]), which crystallizes in the ortho­rhom­bic Pca21 space group with Z = 4, adopts a distorted boat conformation [puckering parameters (Cremer & Pople, 1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]) are QT = 0.2779 (16) Å, θ = 73.7 (3)° and φ = 179.1 (3)°], while the cyclo­hexene ring (C1–C6) has a distorted half-chair conformation [puckering parameters are QT = 0.4464 (18) Å, θ = 48.9 (2)° and φ = 126.3 (3)°]. The 4-(4-di­fluoro­meth­oxy­phenyl) ring (C18–C23) makes a dihedral angle of 88.73 (6)° with the mean plane of the quinoline ring system [N1/C1–C9; maximum deviation = 0.415 (2) Å for C3]. The geometrical parameters of the title compound are in agreement with those reported for similar compounds in the Database survey section.

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

3. 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[link]; Figs. 2[link] and 3[link]). These chains pack with C—H⋯π inter­actions between them, forming layers parallel to the (010) plane (Fig. 4[link]). The cohesion of the crystal structure is ensured by van der Waals inter­actions between these layers.

Table 1
Hydrogen-bond geometry (Å, °)

Cg3 is the centroid the benzene ring of the 4-(4-di­fluoro­meth­oxy­phenyl group of the title compound.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1N⋯O1i 0.87 (2) 1.98 (2) 2.8426 (17) 173 (2)
C19—H19A⋯O2i 0.95 2.43 3.100 (2) 127
C3—H3A⋯Cg3ii 0.99 2.84 3.7345 (18) 151
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+1, z]; (ii) [-x+1, -y+1, z+{\script{1\over 2}}].
[Figure 2]
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⋯π 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 4
View of the mol­ecular packing along the c-axis. Hydrogen bonds are shown as dashed lines.

The Hirshfeld surfaces and their corresponding two-dimensional fingerprint plots were calculated using the software package Crystal Explorer 17.5 (Spackman et al., 2021[Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006-1011.]). The dnorm surfaces are mapped over a fixed color scale from −0.5961 (red) to 1.9017 (blue) a.u. Red spots on the surface correspond to O⋯H/H⋯O inter­actions (Tables 1[link] and 2[link]; Fig. 5[link]a,b).

Table 2
Summary of short inter­atomic contacts (Å) in the title compound

H15A⋯H10B 2.37 1 − x, 1 − y, −[{1\over 2}] + z
F2⋯H11B 2.83 [{1\over 2}] − x, y, − [{1\over 2}] + z
O1⋯H1N 1.98 [{1\over 2}] + x, 1 − y, z
H10A⋯H22A 2.47 [{3\over 2}] − x, y, [{1\over 2}] + z
H17B⋯H22A 2.58 x, −1 + y, z
H12A⋯H17C 2.54 −[{1\over 2}] + x, −y, z
[Figure 5]
Figure 5
(a) Front and (b) back views of the three-dimensional Hirshfeld surface for the title compound.

In Fig. 6[link], fingerprint plots of the most important non-covalent inter­actions for the title compound are shown. 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. O⋯C/C⋯O (1.1%), F⋯C/C⋯F (1.0%), C⋯C (0.7%), F⋯O/O⋯F (0.6%), O⋯N/N⋯O (0.5%) and N⋯H/H⋯N (0.2%) contacts, which contribute less than 1.1%, are not shown in Fig.7.

[Figure 6]
Figure 6
The 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 di and de values are the closest inter­nal and external distances (in Å) from given points on the Hirshfeld surface.

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.42, update of September 2021; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) for similar structures with the 1,4,5,6,7,8-hexa­hydro­quinoline group showed that the nine most closely related to the title compound are LIMYUF (Pehlivanlar et al., 2023[Pehlivanlar, E., Yıldırım, S. Ö., Şimşek, R., Akkurt, M., Butcher, R. J. & Bhattarai, A. (2023). Acta Cryst. E79, 664-668.]), WEZJUK (Yıldırım et al., 2023[Yıldırım, S. Ö., Akkurt, M., Çetin, G., Şimşek, R., Butcher, R. J. & Bhattarai, A. (2023). Acta Cryst. E79, 187-191.]), ECUCUE (Yıldırım et al., 2022[Yıldırım, S. Ö., Akkurt, M., Çetin, G., Şimşek, R., Butcher, R. J. & Bhattarai, A. (2022). Acta Cryst. E78, 798-803.]), LOQCAX (Steiger et al., 2014[Steiger, S. A., Monacelli, A. J., Li, C., Hunting, J. L. & Natale, N. R. (2014). Acta Cryst. C70, 790-795.]), NEQMON (Öztürk Yildirim, et al., 2013[Öztürk Yildirim, S., Butcher, R. J., Gündüz, M. G., El-Khouly, A., Şimşek, R. & Şafak, C. (2013). Acta Cryst. E69, o40-o41.]), PECPUK (Gündüz et al., 2012[Gündüz, M. G., Butcher, R. J., Öztürk Yildirim, S., El-Khouly, A., Şafak, C. & Şimşek, R. (2012). Acta Cryst. E68, o3404-o3405.]), IMEJOA (Linden et al., 2011[Linden, A., Şafak, C., Şimşek, R. & Gündüz, M. G. (2011). Acta Cryst. C67, o80-o84.]), PUGCIE (Mookiah et al., 2009[Mookiah, P., Rajesh, K., Narasimhamurthy, T., Vijayakumar, V. & Srinivasan, N. (2009). Acta Cryst. E65, o2664.]), UCOLOO (Linden et al., 2006[Linden, A., Gündüz, M. G., Şimşek, R. & Şafak, C. (2006). Acta Cryst. C62, o227-o230.]) and DAYJET (Linden et al., 2005[Linden, A., Şimşek, R., Gündüz, M. & Şafak, C. (2005). Acta Cryst. C61, o731-o734.]). In all of these compounds, mol­ecules are linked by N—H⋯O hydrogen bonds. Furthermore, C—H⋯F hydrogen bonds in LIMYUF, C—H⋯O hydrogen bonds in WEZJUK, ECUCUE, NEQMON, IMEJOA and PUGCIE and C—H⋯π inter­actions in LIMYUF, WEZJUK and ECUCUE were also observed.

5. 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-n-hexane (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[link]). The resulting precipitates were purified again by crystallization with methanol (Yıldırım et al., 2023[Yıldırım, S. Ö., Akkurt, M., Çetin, G., Şimşek, R., Butcher, R. J. & Bhattarai, A. (2023). Acta Cryst. E79, 187-191.]).

[Figure 7]
Figure 7
Synthetic scheme.

Isobutyl 4-(4-di­fluoro­meth­oxy­phen­yl)-2,6,6-tri­methyl-5-oxo-1,4,5,6,7,8-hexa­hydro­quinoline-3-carbox­y­l­ate

Light-yellow solid, m.p: 489–491 K, yield: 85%. IR (cm−1) 3291 (N—H), 1674 (C=O, ester), 1597 (C=O, ketone). 1H NMR (400 MHz, DMSO-d6): δ 0.69 [3H, d, J = 9 Hz, –CH(CH3)a], 0.77 [3H, d, J = 9 Hz, –CH(CH3)b], 0.81 (3H, s, 6-CH3), 0.97 (3H, s, 6-CH3), 1.52–1.65 (2H, m, quinoline H7), 1.72–1.81 (H, m, –CH–), 2.26 (3H, s, 2-CH3), 2.46–2.50 (2H, m, quinoline H8), 3.63–3.72 (2H, m, –CH2)–, 4.94 (H, s, quinoline H4), 6.96 (2H, dd, J = 9.2, 6.8 Hz, Ar-H3,5), 7.16 (2H, dd, J = 9.2, 6.8 Hz, Ar-H4,6), 7.26 (H, s, OCHF2), 9.02 (H, s, NH). 13C NMR (100 MHz, DMSO-d6): 18.6 (2-CH3), 22.3 [–CH(CH3)a], 22.9 [–CH(CH3)b], 23.4 (C-8), 24.2 (6-CH3), 24.8 (6-CH3), 33.5 (C-7), 34.1 (C-4), 35 (–CH–), 39.5 (C-6), 68.2 (–CH2–), 103.8 (C-3), 108.4 (C-4a), 114.2, 116.7, 125.4, 128.2, 135.5, 157.4 (phenyl carbons), 147.1(C-2), 150.6 (C-8a), 166.9 (–COO–), 168.3 (OCHF2) 199.6 (C-5). HRMS (ESI/Q-TOF) m/z: [M + H]+ calculated for C23H25F4NO3: 420.1942; found: 420.2150.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. The N-bound H atom was located in a difference-Fourier map and refined freely [N1—H1N = 0.87 (2) Å]. All C-bound H atoms were positioned geometrically [C—H = 0.95–1.00 Å] and refined using a riding model with Uiso(H) = 1.2 or 1.5Ueq(C).

Table 3
Experimental details

Crystal data
Chemical formula C24H29F2NO4
Mr 433.48
Crystal system, space group Orthorhombic, Pca21
Temperature (K) 100
a, b, c (Å) 11.9879 (7), 12.1807 (7), 15.4518 (9)
V (Å3) 2256.3 (2)
Z 4
Radiation type Mo Kα
μ (mm−1) 0.10
Crystal size (mm) 0.27 × 0.24 × 0.16
 
Data collection
Diffractometer Bruker Quest D8 with Photon 2 detector
Absorption correction Multi-scan (SADABS; Krause et al., 2015[Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3-10.])
Tmin, Tmax 0.718, 0.744
No. of measured, independent and observed [I > 2σ(I)] reflections 103269, 9491, 7264
Rint 0.080
(sin θ/λ)max (Å−1) 0.826
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.045, 0.107, 1.03
No. of reflections 9491
No. of parameters 289
No. of restraints 1
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.32, −0.29
Absolute structure Flack x determined using 2721 quotients [(I+)−(I−)]/[(I+)+(I−)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter 0.0 (2)
Computer programs: APEX2 and SAINT (Bruker, 2018[Bruker (2018). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and PLATON (Spek, 2020[Spek, A. L. (2020). Acta Cryst. E76, 1-11.]).

Supporting information

CCDC reference: 2305562

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989023009623/ev2001sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989023009623/ev2001Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989023009623/ev2001Isup3.cml

checkCIF report


Computing details top

Isobutyl 4-[4-(difluoromethoxy)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate top
Crystal data top
C24H29F2NO4Dx = 1.276 Mg m−3
Mr = 433.48Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pca21Cell parameters from 9859 reflections
a = 11.9879 (7) Åθ = 2.4–32.7°
b = 12.1807 (7) ŵ = 0.10 mm−1
c = 15.4518 (9) ÅT = 100 K
V = 2256.3 (2) Å3Chunk, light yellow
Z = 40.27 × 0.24 × 0.16 mm
F(000) = 920
Data collection top
Bruker Quest D8 with Photon 2 detector
diffractometer		7264 reflections with I > 2σ(I)
φ and ω scansRint = 0.080
Absorption correction: multi-scan
(SADABS; Krause et al., 2015)		θmax = 36.0°, θmin = 2.4°
Tmin = 0.718, Tmax = 0.744h = −18→19
103269 measured reflectionsk = −20→19
9491 independent reflectionsl = −25→21
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.045 w = 1/[σ2(Fo2) + (0.0508P)2 + 0.3823P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.107(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.32 e Å−3
9491 reflectionsΔρmin = −0.29 e Å−3
289 parametersAbsolute structure: Flack x determined using 2721 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraintAbsolute structure parameter: 0.0 (2)
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.49509 (14)0.92511 (11)0.20621 (10)0.0455 (4)
F20.36176 (12)0.80630 (13)0.21602 (10)0.0467 (4)
O10.65307 (10)0.66738 (10)0.65205 (8)0.0198 (2)
O20.72200 (10)0.33422 (10)0.48402 (9)0.0239 (3)
O30.60039 (10)0.19451 (9)0.48360 (8)0.0184 (2)
O40.53670 (11)0.76006 (11)0.24983 (8)0.0236 (3)
N10.36644 (10)0.41080 (11)0.60065 (9)0.0143 (2)
H1N0.299 (2)0.3886 (19)0.6122 (14)0.019 (5)*
C10.40589 (12)0.50413 (12)0.63969 (10)0.0128 (3)
C20.32686 (12)0.56285 (13)0.69932 (10)0.0149 (3)
H2A0.2798730.5085800.7300760.018*
H2B0.2771890.6111930.6651430.018*
C30.39163 (14)0.63141 (13)0.76504 (11)0.0171 (3)
H3A0.4290180.5816360.8065580.021*
H3B0.3385940.6776250.7979730.021*
C40.47947 (13)0.70546 (13)0.72264 (11)0.0165 (3)
C50.55598 (12)0.63711 (12)0.66451 (10)0.0142 (3)
C60.51077 (12)0.54097 (12)0.62178 (10)0.0134 (3)
C70.57801 (12)0.48870 (12)0.54998 (10)0.0129 (2)
H7A0.6582500.4882190.5676790.015*
C80.54078 (12)0.37018 (12)0.53589 (10)0.0135 (3)
C90.43551 (13)0.33826 (12)0.55678 (10)0.0142 (3)
C100.54927 (15)0.76147 (18)0.79303 (13)0.0285 (4)
H10A0.5841920.7054970.8296570.043*
H10B0.5009700.8082150.8285350.043*
H10C0.6072860.8065230.7659130.043*
C110.42455 (16)0.79274 (14)0.66419 (14)0.0246 (4)
H11A0.4821590.8413760.6406330.037*
H11B0.3713610.8359390.6982450.037*
H11C0.3852400.7563480.6165500.037*
C120.37972 (13)0.22972 (13)0.53973 (11)0.0186 (3)
H12A0.4007120.2033150.4820720.028*
H12B0.2985800.2388620.5425950.028*
H12C0.4035220.1762940.5834040.028*
C130.62870 (13)0.30006 (12)0.49936 (10)0.0150 (3)
C140.68925 (15)0.12977 (14)0.44523 (12)0.0208 (3)
H14A0.7518160.1223840.4866420.025*
H14B0.7174780.1665620.3924590.025*
C150.64362 (16)0.01733 (14)0.42246 (14)0.0260 (4)
H15A0.5766420.0274340.3847170.031*
C160.6088 (3)−0.04712 (19)0.5015 (2)0.0529 (8)
H16A0.544199−0.0116570.5285030.079*
H16B0.670705−0.0494240.5429020.079*
H16C0.588934−0.1220880.4844140.079*
C170.7331 (2)−0.04286 (16)0.37018 (15)0.0330 (4)
H17A0.747606−0.0026830.3164030.050*
H17B0.706990−0.1170840.3564130.050*
H17C0.801872−0.0473570.4042320.050*
C180.56699 (12)0.55695 (12)0.46724 (10)0.0137 (3)
C190.46204 (13)0.59010 (14)0.43930 (11)0.0184 (3)
H19A0.3980460.5674890.4708780.022*
C200.44827 (14)0.65559 (15)0.36621 (12)0.0208 (3)
H20A0.3759300.6764160.3472310.025*
C210.54288 (14)0.68982 (13)0.32165 (11)0.0183 (3)
C220.64869 (13)0.65619 (13)0.34636 (11)0.0175 (3)
H22A0.7123750.6782210.3141550.021*
C230.66020 (13)0.58949 (13)0.41925 (11)0.0159 (3)
H23A0.7323700.5658620.4365030.019*
C240.45780 (18)0.84020 (16)0.25354 (14)0.0294 (4)
H24A0.4443260.8631920.3147770.035*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0608 (9)0.0302 (6)0.0454 (8)0.0086 (6)0.0104 (7)0.0181 (6)
F20.0317 (7)0.0612 (9)0.0474 (8)0.0089 (6)−0.0074 (6)0.0154 (7)
O10.0120 (5)0.0199 (5)0.0276 (6)−0.0016 (4)0.0042 (4)−0.0068 (5)
O20.0134 (5)0.0212 (5)0.0371 (7)−0.0005 (4)0.0070 (5)−0.0075 (5)
O30.0158 (5)0.0142 (5)0.0252 (6)0.0018 (4)0.0030 (4)−0.0036 (4)
O40.0262 (6)0.0255 (6)0.0191 (6)0.0043 (5)0.0044 (5)0.0068 (5)
N10.0093 (5)0.0162 (6)0.0173 (6)−0.0009 (4)0.0014 (5)−0.0004 (5)
C10.0110 (6)0.0149 (6)0.0124 (6)0.0015 (5)0.0006 (5)0.0011 (5)
C20.0116 (6)0.0179 (6)0.0153 (7)0.0009 (5)0.0033 (5)−0.0012 (5)
C30.0151 (7)0.0203 (7)0.0158 (7)−0.0002 (6)0.0034 (5)−0.0026 (6)
C40.0129 (6)0.0187 (7)0.0177 (7)−0.0003 (5)0.0031 (5)−0.0051 (5)
C50.0122 (7)0.0156 (6)0.0148 (6)0.0015 (5)0.0004 (5)−0.0007 (5)
C60.0113 (6)0.0143 (6)0.0145 (6)0.0004 (5)0.0005 (5)−0.0005 (5)
C70.0095 (6)0.0147 (6)0.0145 (6)0.0001 (5)0.0017 (5)−0.0013 (5)
C80.0110 (6)0.0141 (6)0.0154 (6)0.0006 (5)0.0009 (5)−0.0011 (5)
C90.0130 (6)0.0151 (6)0.0146 (7)0.0004 (5)−0.0001 (5)0.0012 (5)
C100.0201 (8)0.0368 (10)0.0285 (9)−0.0063 (7)0.0049 (7)−0.0175 (8)
C110.0202 (8)0.0184 (7)0.0353 (10)0.0029 (6)0.0080 (7)0.0023 (7)
C120.0159 (7)0.0172 (7)0.0229 (8)−0.0034 (5)0.0021 (6)−0.0016 (6)
C130.0141 (6)0.0153 (6)0.0156 (7)0.0010 (5)−0.0002 (5)−0.0020 (5)
C140.0185 (7)0.0177 (7)0.0261 (8)0.0051 (6)0.0032 (6)−0.0039 (6)
C150.0286 (9)0.0163 (7)0.0331 (10)0.0030 (6)0.0065 (7)−0.0029 (7)
C160.0751 (19)0.0233 (10)0.0603 (17)0.0074 (11)0.0366 (15)0.0097 (10)
C170.0388 (11)0.0202 (8)0.0401 (11)0.0047 (7)0.0097 (9)−0.0055 (8)
C180.0115 (6)0.0139 (6)0.0157 (7)−0.0003 (5)0.0021 (5)−0.0013 (5)
C190.0124 (6)0.0234 (7)0.0195 (7)0.0007 (6)0.0024 (5)0.0035 (6)
C200.0144 (7)0.0279 (8)0.0201 (8)0.0024 (6)0.0000 (6)0.0044 (7)
C210.0202 (7)0.0183 (7)0.0164 (7)0.0010 (6)0.0036 (6)0.0019 (6)
C220.0160 (7)0.0176 (7)0.0190 (7)−0.0020 (5)0.0049 (6)−0.0007 (6)
C230.0118 (6)0.0160 (6)0.0200 (7)−0.0013 (5)0.0023 (5)−0.0015 (5)
C240.0336 (10)0.0265 (9)0.0280 (10)0.0059 (7)0.0031 (8)0.0076 (7)
Geometric parameters (Å, º) top
F1—C241.343 (2)C10—H10B0.9800
F2—C241.354 (3)C10—H10C0.9800
O1—C51.2361 (19)C11—H11A0.9800
O2—C131.2166 (19)C11—H11B0.9800
O3—C131.3518 (18)C11—H11C0.9800
O3—C141.4520 (19)C12—H12A0.9800
O4—C241.360 (2)C12—H12B0.9800
O4—C211.403 (2)C12—H12C0.9800
N1—C11.371 (2)C14—C151.516 (2)
N1—C91.388 (2)C14—H14A0.9900
N1—H1N0.87 (2)C14—H14B0.9900
C1—C61.363 (2)C15—C161.511 (3)
C1—C21.503 (2)C15—C171.530 (3)
C2—C31.527 (2)C15—H15A1.0000
C2—H2A0.9900C16—H16A0.9800
C2—H2B0.9900C16—H16B0.9800
C3—C41.533 (2)C16—H16C0.9800
C3—H3A0.9900C17—H17A0.9800
C3—H3B0.9900C17—H17B0.9800
C4—C51.530 (2)C17—H17C0.9800
C4—C101.532 (2)C18—C191.390 (2)
C4—C111.543 (2)C18—C231.398 (2)
C5—C61.449 (2)C19—C201.392 (2)
C6—C71.512 (2)C19—H19A0.9500
C7—C81.527 (2)C20—C211.391 (2)
C7—C181.531 (2)C20—H20A0.9500
C7—H7A1.0000C21—C221.386 (2)
C8—C91.359 (2)C22—C231.396 (2)
C8—C131.469 (2)C22—H22A0.9500
C9—C121.505 (2)C23—H23A0.9500
C10—H10A0.9800C24—H24A1.0000
C13—O3—C14113.95 (12)C9—C12—H12B109.5
C24—O4—C21116.16 (14)H12A—C12—H12B109.5
C1—N1—C9122.48 (13)C9—C12—H12C109.5
C1—N1—H1N119.2 (15)H12A—C12—H12C109.5
C9—N1—H1N117.1 (15)H12B—C12—H12C109.5
C6—C1—N1120.11 (14)O2—C13—O3121.40 (14)
C6—C1—C2123.32 (14)O2—C13—C8122.38 (14)
N1—C1—C2116.55 (13)O3—C13—C8116.23 (13)
C1—C2—C3110.33 (12)O3—C14—C15108.70 (14)
C1—C2—H2A109.6O3—C14—H14A109.9
C3—C2—H2A109.6C15—C14—H14A109.9
C1—C2—H2B109.6O3—C14—H14B109.9
C3—C2—H2B109.6C15—C14—H14B109.9
H2A—C2—H2B108.1H14A—C14—H14B108.3
C2—C3—C4112.76 (13)C16—C15—C14112.43 (19)
C2—C3—H3A109.0C16—C15—C17111.82 (17)
C4—C3—H3A109.0C14—C15—C17107.61 (16)
C2—C3—H3B109.0C16—C15—H15A108.3
C4—C3—H3B109.0C14—C15—H15A108.3
H3A—C3—H3B107.8C17—C15—H15A108.3
C5—C4—C10109.37 (13)C15—C16—H16A109.5
C5—C4—C3110.02 (13)C15—C16—H16B109.5
C10—C4—C3109.49 (14)H16A—C16—H16B109.5
C5—C4—C11106.68 (13)C15—C16—H16C109.5
C10—C4—C11109.99 (15)H16A—C16—H16C109.5
C3—C4—C11111.25 (13)H16B—C16—H16C109.5
O1—C5—C6121.47 (14)C15—C17—H17A109.5
O1—C5—C4119.58 (14)C15—C17—H17B109.5
C6—C5—C4118.88 (13)H17A—C17—H17B109.5
C1—C6—C5121.21 (14)C15—C17—H17C109.5
C1—C6—C7120.13 (14)H17A—C17—H17C109.5
C5—C6—C7118.37 (13)H17B—C17—H17C109.5
C6—C7—C8110.30 (12)C19—C18—C23118.43 (15)
C6—C7—C18109.76 (12)C19—C18—C7119.69 (13)
C8—C7—C18111.67 (12)C23—C18—C7121.86 (13)
C6—C7—H7A108.3C18—C19—C20121.71 (15)
C8—C7—H7A108.3C18—C19—H19A119.1
C18—C7—H7A108.3C20—C19—H19A119.1
C9—C8—C13126.22 (14)C21—C20—C19118.47 (15)
C9—C8—C7120.53 (13)C21—C20—H20A120.8
C13—C8—C7113.25 (12)C19—C20—H20A120.8
C8—C9—N1119.20 (14)C22—C21—C20121.41 (15)
C8—C9—C12128.48 (14)C22—C21—O4116.50 (14)
N1—C9—C12112.32 (13)C20—C21—O4122.09 (15)
C4—C10—H10A109.5C21—C22—C23118.99 (15)
C4—C10—H10B109.5C21—C22—H22A120.5
H10A—C10—H10B109.5C23—C22—H22A120.5
C4—C10—H10C109.5C22—C23—C18120.93 (15)
H10A—C10—H10C109.5C22—C23—H23A119.5
H10B—C10—H10C109.5C18—C23—H23A119.5
C4—C11—H11A109.5F1—C24—F2106.55 (17)
C4—C11—H11B109.5F1—C24—O4107.35 (17)
H11A—C11—H11B109.5F2—C24—O4110.76 (17)
C4—C11—H11C109.5F1—C24—H24A110.7
H11A—C11—H11C109.5F2—C24—H24A110.7
H11B—C11—H11C109.5O4—C24—H24A110.7
C9—C12—H12A109.5
C9—N1—C1—C613.6 (2)C13—C8—C9—C12−7.0 (3)
C9—N1—C1—C2−168.22 (14)C7—C8—C9—C12173.21 (15)
C6—C1—C2—C3−25.9 (2)C1—N1—C9—C8−13.9 (2)
N1—C1—C2—C3155.98 (14)C1—N1—C9—C12165.30 (14)
C1—C2—C3—C450.56 (18)C14—O3—C13—O2−1.8 (2)
C2—C3—C4—C5−53.48 (18)C14—O3—C13—C8178.30 (14)
C2—C3—C4—C10−173.70 (14)C9—C8—C13—O2−178.39 (17)
C2—C3—C4—C1164.52 (17)C7—C8—C13—O21.4 (2)
C10—C4—C5—O1−31.4 (2)C9—C8—C13—O31.5 (2)
C3—C4—C5—O1−151.72 (15)C7—C8—C13—O3−178.68 (13)
C11—C4—C5—O187.49 (18)C13—O3—C14—C15−174.28 (15)
C10—C4—C5—C6151.64 (15)O3—C14—C15—C16−64.8 (2)
C3—C4—C5—C631.3 (2)O3—C14—C15—C17171.65 (16)
C11—C4—C5—C6−89.44 (17)C6—C7—C18—C19−48.25 (19)
N1—C1—C6—C5−177.73 (14)C8—C7—C18—C1974.40 (18)
C2—C1—C6—C54.2 (2)C6—C7—C18—C23130.33 (15)
N1—C1—C6—C78.5 (2)C8—C7—C18—C23−107.02 (16)
C2—C1—C6—C7−169.55 (14)C23—C18—C19—C20−1.0 (2)
O1—C5—C6—C1176.01 (15)C7—C18—C19—C20177.62 (15)
C4—C5—C6—C1−7.1 (2)C18—C19—C20—C21−1.3 (3)
O1—C5—C6—C7−10.1 (2)C19—C20—C21—C222.8 (3)
C4—C5—C6—C7166.76 (14)C19—C20—C21—O4−176.98 (16)
C1—C6—C7—C8−26.47 (19)C24—O4—C21—C22−142.79 (17)
C5—C6—C7—C8159.58 (13)C24—O4—C21—C2037.0 (2)
C1—C6—C7—C1896.98 (16)C20—C21—C22—C23−2.1 (3)
C5—C6—C7—C18−76.97 (17)O4—C21—C22—C23177.71 (14)
C6—C7—C8—C926.2 (2)C21—C22—C23—C18−0.2 (2)
C18—C7—C8—C9−96.17 (17)C19—C18—C23—C221.8 (2)
C6—C7—C8—C13−153.64 (13)C7—C18—C23—C22−176.84 (14)
C18—C7—C8—C1384.02 (15)C21—O4—C24—F1151.23 (16)
C13—C8—C9—N1172.06 (15)C21—O4—C24—F2−92.82 (19)
C7—C8—C9—N1−7.7 (2)
Hydrogen-bond geometry (Å, º) top
Cg3 is the centroid the benzene ring of the 4-(4-difluoromethoxyphenyl group of the title compound.
D—H···AD—HH···AD···AD—H···A
N1—H1N···O1i0.87 (2)1.98 (2)2.8426 (17)173 (2)
C12—H12A···O30.982.402.817 (2)105
C19—H19A···O2i0.952.433.100 (2)127
C3—H3A···Cg3ii0.992.843.7345 (18)151
Symmetry codes: (i) x−1/2, −y+1, z; (ii) −x+1, −y+1, z+1/2.
Summary of short interatomic contacts (Å) in the title compound top
H15A···H10B2.371 - x, 1 - y, -1/2 + z
F2···H11B2.831/2 - x, y, - 1/2 + z
O1···H1N1.981/2 + x, 1 - y, z
H10A···H22A2.473/2 - x, y, 1/2 + z
H17B···H22A2.58x, -1 + y, z
H12A···H17C2.54-1/2 + x, -y, z
 

Acknowledgements

Authors' contributions are as follows. Conceptualization, RS and SÖY; methodology, RS and GÇ; investigation, RS and SÖY; writing (original draft), GÇ and MA; writing (review and editing of the manuscript), RS and SÖY; crystal data production and validation, RJB and SÖY; visualization, MA; funding acquisition, RJB; resources, AB, RJB and RS.

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ISSN: 2056-9890
Volume 79| Part 12| December 2023| Pages 1132-1136
https://doi.org/10.1107/S2056989023009623
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