Crystal structure and Hirshfeld surface analysis of (22RS,23SR,25RS,26SR)-23,25,5-trimethyl-21-(2,2,2-tri­fluoro­acet­yl)-5-aza-2(2,6)-piperidina-1,3(2,5)-di­furana­cyclo­hexa­phan-24-one

Yıldırım, S. Ö.; Akkurt, M.; Ershova, A.A.; Grigoriev, M.S.; Rocha, B.G.M.; Bhattarai, A.

doi:10.1107/S2056989023001986

research communications

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 79| Part 4| April 2023| Pages 292-296

https://doi.org/10.1107/S2056989023001986

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Crystal structure and Hirshfeld surface analysis of (2²RS,2³SR,2⁵RS,2⁶SR)-2³,2⁵,5-trimethyl-2¹-(2,2,2-trifluoroacetyl)-5-aza-2(2,6)-piperidina-1,3(2,5)-difuranacyclohexaphan-2⁴-one

Sema Öztürk Yıldırım,^a,^b Mehmet Akkurt,^b Anastasia A. Ershova,^c Mikhail S. Grigoriev,^d Bruno G.M. Rocha ^e and Ajaya Bhattarai ^f ^*

^aDepartment of Physics, Faculty of Science, Eskisehir Technical University, Yunus Emre Campus 26470 Eskisehir, Türkiye, ^bDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Türkiye, ^cPeoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow, 117198, Russian Federation, ^dFrumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences (IPCE RAS), 31 Bldg 4, Leninsky prosp., Moscow, 119071, Russian Federation, ^eCentro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal, and ^fDepartment of Chemistry, M.M.A.M.C (Tribhuvan University), Biratnagar, Nepal
^*Correspondence e-mail: ajaya.bhattarai@mmamc.tu.edu.np

Edited by B. Therrien, University of Neuchâtel, Switzerland (Received 1 February 2023; accepted 2 March 2023; online 10 March 2023)

The title compound, C₂₀H₂₁F₃N₂O₄, features a main twelve-membered difuryl ring with which the furan rings make dihedral angles of 76.14 (5) and 33.81 (5)°. The dihedral angle between the furan rings is 42.55 (7)°. The six-membered nitrogen heterocycle has a twist-boat conformation. In the crystal, pairs of molecules are connected by intermolecular C—H⋯O interactions, generating an R²₂(14) ring motif. These pairs of molecules form zigzag chains along the a-axis direction by means of C—H⋯F interactions. Furthermore, C—H⋯π and C–F⋯π interactions link the molecules into chains along the b-axis direction, forming sheets parallel to the (001) plane. These sheets are also connected by van der Waals interactions.

Keywords: crystal structure; twelve-membered heterocycles; furan; alkylation; piperidon; Hirshfeld surface analysis; Mannich reaction.

CCDC reference: 2245808

1. Chemical context

Twelve-membered aza- and oxa-macrocycles possess a wide range of useful biological activities and exhibit a tendency to bind metal cations with their macrocyclic cavities (Simonov et al., 1993 ). For example, well-known naturally occurring macrocycles such as enniatins demonstrate a high cytotoxic activity (Levy et al., 1995 ; Ivanova et al., 2006 ) and azatri(tetra)pyrrolic macrocycles can be used as ion-pair receptors (Yadigarov et al., 2009 ). Chiral macrocycles with multiple non-covalent bonding sites show chiral recognition to different anions (Ema et al., 2014 ; Khalilov et al., 2021 ; Maharramov et al., 2010 ). S,N-Containing macrobicyclic azacryptands (Khabibullina et al., 2018 ; Naghiyev et al., 2020 ; Safavora et al., 2019 ) including dipyrrolylmethane subunits in their structures exhibit a high affinity to anions, especially the fluoride ion (Guchhait, et al., 2011 ; Shikhaliyev et al., 2018 , 2019 ) and can be used as chemical delivery systems.

On the other hand, the Mannich reaction is an extensively used method for the construction of various types of polycyclic systems (Rivera et al., 2015 ; Ma et al., 2021 ; Mahmoudi et al., 2016 ), including those containing pyrroles (Jana et al., 2019). In order to create a short pathway to macrocycles possessing two different donating atoms in a twelve-membered ring, we used an acid-catalysed Mannich type reaction between 2,6-difuryl-substituted piperidone and N-substituted 1,5,3-dioxazepane (Fig. 1). The main goal of this study was to obtain the first representative of a twelve-membered difuryl containing rings and to establish its stereochemistry and non-covalent bond donor or acceptor ability (Gurbanov et al., 2020a ,b ; Mahmudov et al., 2021 , 2022 ). The rings formed in this transformation can serve as precursors for studying the IMDAV (intramolecular Diels–Alder reaction of vinylarenes; Krishna, et al., 2022 ) and IMDAF (intramolecular Diels–Alder reaction of furans; Kvyatkovskaya et al., 2021a ,b ; Borisova, et al., 2018 ) reactions.

Figure 1
The synthetic route.

2. Structural commentary

As shown in Fig. 2, the title compound has a main twelve-membered difuryl-containing ring (O18 /C2/C1/N17/C13/C12/O19/C9/C8/N7/C6/C5) to which the furan rings (O18/C2–C5 and O19/C9–C12) subtend dihedral angles of 76.14 (5) and 33.81 (5)°, respectively. The dihedral angle subtended by the furan ring is 42.55 (7)°. The six-membered nitrogen heterocycle (N17/C1/C13–C16) adopts a twist-boat conformation with puckering parameters (Cremer & Pople, 1975 ) Q_T = 0.6999 (12) Å, θ = 90.12 (10)° and φ = 228.08 (10)°.

Figure 2
Molecular structure of the title compound. Displacement ellipsoids are drawn at the 30% probability level.

3. Supramolecular features and Hirshfeld surface analysis

In the crystal, pairs of molecules are connected by intermolecular C—H⋯O interactions, forming an R₂²(14) ring motif (Bernstein et al., 1995 ). These pairs of molecules form zigzag chains along the a-axis direction by C—H⋯F interactions (Table 1, Fig. 3). Furthermore, C—H⋯π and C—F⋯π interactions [C18—F1⋯Cg1ⁱ, C18⋯Cg1ⁱ = 3.9574 (14) Å, F1⋯Cg1ⁱ = 3.5265 (9) Å, C18—F1⋯Cg1ⁱ = 98.83 (6)° and C18—F3⋯Cg1ⁱ, C18⋯Cg1ⁱ = 3.9574 (14) Å, F1⋯Cg1ⁱ = 3.5496 (11) Å, C18—F1⋯Cg1ⁱ = 97.90 (7)° where Cg1 is the centroid of the O18/C2–C5 ring; symmetry code: (i) $[{1\over 2}]$ + x, y, $[{3\over 2}]$ − z] link the molecules into chains along the b-axis direction, forming sheets parallel to the (001) plane (Table 1, Fig. 4). These sheets are also connected by van der Waals interactions.

Table 1
Hydrogen-bond geometry (Å, °)

Cg2 is the centroid of the O19/C9–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O15ⁱ	0.95	2.51	3.3809 (15)	152
C20—H20B⋯F3ⁱⁱ	0.98	2.54	3.4700 (16)	160
C21—H21B⋯Cg2ⁱⁱⁱ	0.98	2.88	3.7561 (13)	150
Symmetry codes: (i) ; (ii) ; (iii) $[-x+{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ .

Figure 3
View down the b-axis showing the C—H⋯O and C—H⋯F hydrogen bonds (dashed lines).

Figure 4
A general view in the unit cell of the C—H⋯π and C—F⋯π interactions (dashed lines). Symmetry codes: (iii) −x + $[{1\over 2}]$ , y − $[{1\over 2}]$ , z; (iv) $[{1\over 2}]$ + x, y, $[{3\over 2}]$ − z.

Crystal Explorer17.5 (Turner et al., 2017 ) was used to perform a Hirshfeld surface analysis and to create the corresponding two-dimensional fingerprint plots, with the three-dimensional d_norm surfaces plotted at a standard resolution of −0.1525 (red) to 1.7277 (blue) a.u (Fig. 5). The bright-red patches near atoms O15 and H20B on the Hirshfeld surface represent weak C—H⋯O and C—H⋯F interactions (Tables 1 and 2).

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

N7⋯H4	2.71	$[{1\over 2}]$ + x, y, $[{3\over 2}]$ − z
F2⋯H19C	2.65	1 − x, − $[{1\over 2}]$ + y, $[{3\over 2}]$ − z
H20B⋯F3	2.54	1 − x, 1 − y, 1 − z
H21A⋯H19A	2.46	$[{1\over 2}]$ − x, 1 − y, − $[{1\over 2}]$ + z
H20A⋯H16	2.48	-x, 1 − y, 1 − z
H20C⋯H21B	2.50	$[{1\over 2}]$ − x, $[{1\over 2}]$ + y, z
H20A⋯H11	2.53	− $[{1\over 2}]$ + x, $[{3\over 2}]$ − y, 1 − z

Figure 5
(a) Front and (b) back views of the three-dimensional Hirshfeld surfaces of the title molecule.

The fingerprint plots (Fig. 6) show that H⋯H (44.9%), F⋯H/H⋯F (23.0%), O⋯H/H⋯O (16.7%) and C⋯H/H⋯C (8.5%) interactions contribute the most to surface contacts. The crystal packing is additionally influenced by F⋯C/C⋯F (3.0%), N⋯H/H⋯N (1.4%), F⋯O/O⋯F (0.9%), C⋯O/O⋯C (0.9%), O⋯O (0.5%) and C⋯C (0.1%) interactions. The Hirshfeld surface study confirms the significance of H-atom interactions in the packing formation. The large number of H⋯H, F⋯H/H⋯F, O⋯H/H⋯O and C⋯H/H⋯C interactions indicate that van der Waals interactions and hydrogen bonding are important in the crystal packing (Hathwar et al., 2015 ).

Figure 6
Two-dimensional fingerprint plots for title molecules 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 Å) from given points on the Hirshfeld surface.

4. Database survey

1,8,12,19,24,26-Hexaazapentacyclo[17.3.1.13,6.18,12.114,17]hexacosa-3,5,14,16-tetraene ethyl acetate solvate dihydrate (CSD refcode NOYCOW; Jana et al., 2019 ) is the most similar compound to the title found in a search of the Cambridge Structural Database (CSD, Version 5.42, update of September 2021; Groom et al., 2016 ). It crystallizes in the monoclinic space group I2/a (15) with Z = 8. The two pyrrolic NH atoms are oriented in the same direction. It exhibits a different conformation from the title compound: the furan rings in the title compound are almost normal to the mean plane of the main twelve-membered difuryl-containing ring and their oxygen atoms are oriented to the opposite sides whereas in NOYCOW, they are also almost normal, but are on the same side.

5. Synthesis and crystallization

A mixture of N-trifluoro-acylated piperodone (2.6 mmol), 3-methyl-1,5,3-dioxazepane (2.7 mmol) and Me₃SiCl (1.1 mL, 8.6 mmol) in dry dichloromethane (CH₂Cl₂) (5 mL) was left for 5 days under an argon atmosphere without stirring. The reaction mixture was then poured into water (30 mL) and basified with solid K₂CO₃ until the pH was 9–10. The organic products were extracted with CH₂Cl₂ (2 × 20 mL) and dried over anhydrous Na₂SO₄. After evaporation of the solvent, the crude residue was purified by column chromatography on silica gel (ethyl acetate/hexane, from 1:20 to 1:4) and then the resulting solid fractions were recrystallized from a chloroform/hexane mixture to give the macrocycle as a white solid. Single crystals were obtained by slow crystallization from a hexane/chloroform mixture.

Yield 20% (0.21 g), m.p. 420–422 K. ¹H NMR (700 MHz, CDCl₃) δ (J, Hz): 6.24 (br.s, 2H), 6.19 (br.s, 1H), 6.02 (d, J = 2.9 Hz, 1H), 5.28 (s, 1H), 5.11 (d, J = 9.5 Hz, 1H), 3.86 (d, J = 15.5 Hz, 1H), 3.76 (d, J = 15.3 Hz, 1H), 3.71 (s, 2H), 3.55–3.49 (m, 1H), 3.20 (q, J = 7.2 Hz, 1H), 2.35 (s, 3H), 1.36 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.4 Hz, 3H); ¹³C{¹H} NMR (176 MHz, CDCl₃) δ 208.8, 156.5 (q, J = 36.5 Hz), 154.7, 152.3, 149.9, 148.6, 116.3 (q, J = 289.0 Hz), 111.4, 109.9, 109.8, 109.6, 57.2, 56.9, 53.3, 49.6, 44.7, 42.8, 42.0, 15.7, 12.9; HRMS (ESI) m/z: [M + H]⁺ 411.; Analysis calculated for C₂₀H₂₁F₃N₂O₄ %: C 58.53, H 5.16, N 6.83. Found: C 58.54, H 5.17, N 6.83.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. Carbon-bound H atoms were placed in calculated positions [C—H = 0.95–1.00 Å; U_iso(H) = 1.2 or 1.5U_eq(C)] and were included in the refinement in the riding-model approximation. Owing to poor agreement between observed and calculated intensities, twenty three outliers (0 0 6, 4 0 12, 5 1 6, 3 6 3, 4 8 5, 4 5 5, 12 11 0, 0 6 3, 4 7 5, 1 0 8, 1 1 2, 0 4 9, 6 5 2, 4 8 0, 3 6 7, 7 1 1, 4 1 9, 5 0 6, 0 0 2, 2 1 7, 4 2 8, 4 4 5, 2 5 5) were omitted during the final refinement cycle.

Table 3
Experimental details

Crystal data
Chemical formula	C₂₀H₂₁F₃N₂O₄
M_r	410.39
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	100
a, b, c (Å)	11.1351 (1), 17.0545 (2), 19.9131 (3)
V (Å³)	3781.57 (8)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	1.03
Crystal size (mm)	0.25 × 0.20 × 0.20

Data collection
Diffractometer	XtaLAB Synergy, Dualflex, HyPix
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2021 $[Rigaku OD (2021). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.761, 0.801
No. of measured, independent and observed [I > 2σ(I)] reflections	24690, 4040, 3752
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.637

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.102, 1.03
No. of reflections	4040
No. of parameters	265
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.21
Computer programs: CrysAlis PRO (Rigaku OD, 2021 $[Rigaku OD (2021). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL2018 (Sheldrick, 2015b ), ORTEP-3 for Windows (Farrugia, 2012 ) and PLATON (Spek, 2020 ).

Supporting information

CCDC reference: 2245808

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989023001986/tx2063sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989023001986/tx2063Isup2.hkl

checkCIF report

Computing details top

Data collection: CrysAlis PRO 1.171.41.117a (Rigaku OD, 2021); cell refinement: CrysAlis PRO 1.171.41.117a (Rigaku OD, 2021); data reduction: CrysAlis PRO 1.171.41.117a (Rigaku OD, 2021); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2020).

/ (2²RS,2³SR,2⁵RS,2⁶SR)-\ 2³,2⁵,5-trimethyl-2¹-(2,2,2-\ trifluoroacetyl)-5-aza-2(2,6)-piperidina-1,3(2,5)-difuranacyclohexaphan-\ 2⁴-one top

Crystal data top

C₂₀H₂₁F₃N₂O₄	D_x = 1.442 Mg m⁻³
M_r = 410.39	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbca	Cell parameters from 15774 reflections
a = 11.1351 (1) Å	θ = 2.2–78.7°
b = 17.0545 (2) Å	µ = 1.03 mm⁻¹
c = 19.9131 (3) Å	T = 100 K
V = 3781.57 (8) Å³	Prism, colourless
Z = 8	0.25 × 0.20 × 0.20 mm
F(000) = 1712

Data collection top

XtaLAB Synergy, Dualflex, HyPix diffractometer	3752 reflections with I > 2σ(I)
Radiation source: micro-focus sealed X-ray tube	R_int = 0.031
φ and ω scans	θ_max = 79.3°, θ_min = 5.2°
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2021)	h = −12→14
T_min = 0.761, T_max = 0.801	k = −20→21
24690 measured reflections	l = −25→25
4040 independent reflections

Refinement top

Refinement on F²	Primary atom site location: difference Fourier map
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.102	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0586P)² + 1.2514P] where P = (F_o² + 2F_c²)/3
4040 reflections	(Δ/σ)_max = 0.001
265 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Special details top

Experimental. CrysAlisPro 1.171.41.117a (Rigaku OD, 2021) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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

	x	y	z	U_iso*/U_eq
F1	0.46254 (7)	0.40849 (4)	0.69241 (4)	0.03490 (19)
F2	0.47797 (8)	0.35558 (4)	0.59393 (4)	0.0394 (2)
F3	0.62779 (7)	0.41697 (5)	0.63772 (5)	0.0411 (2)
C1	0.25270 (10)	0.46229 (6)	0.61741 (6)	0.0228 (2)
H1	0.2891	0.4136	0.6366	0.027*
C2	0.18508 (10)	0.50270 (6)	0.67299 (6)	0.0234 (2)
C3	0.06815 (11)	0.52036 (7)	0.68327 (6)	0.0269 (2)
H3	0.0021	0.5056	0.6559	0.032*
C4	0.06377 (11)	0.56583 (7)	0.74372 (6)	0.0287 (3)
H4	−0.0059	0.5875	0.7641	0.034*
C5	0.17741 (11)	0.57194 (7)	0.76607 (6)	0.0264 (2)
C6	0.23342 (11)	0.61600 (7)	0.82269 (6)	0.0291 (3)
H6A	0.1701	0.6439	0.8481	0.035*
H6B	0.2730	0.5786	0.8536	0.035*
N7	0.32220 (10)	0.67275 (6)	0.79832 (5)	0.0295 (2)
C8	0.27337 (13)	0.73574 (7)	0.75550 (7)	0.0337 (3)
H8A	0.2940	0.7876	0.7747	0.040*
H8B	0.1848	0.7315	0.7532	0.040*
C9	0.32582 (12)	0.72806 (7)	0.68700 (6)	0.0299 (3)
C10	0.42408 (12)	0.75661 (7)	0.65530 (7)	0.0318 (3)
H10	0.4722	0.7997	0.6692	0.038*
C11	0.44143 (11)	0.70908 (7)	0.59651 (6)	0.0286 (3)
H11	0.5035	0.7143	0.5641	0.034*
C12	0.35196 (10)	0.65556 (7)	0.59651 (6)	0.0246 (2)
C13	0.32223 (10)	0.58544 (6)	0.55457 (6)	0.0230 (2)
H13	0.3733	0.5873	0.5133	0.028*
C14	0.18934 (10)	0.58564 (6)	0.53217 (6)	0.0247 (2)
H14	0.1393	0.5980	0.5725	0.030*
C15	0.15409 (10)	0.50470 (7)	0.50819 (6)	0.0243 (2)
O15	0.11156 (8)	0.49283 (5)	0.45311 (4)	0.0309 (2)
C16	0.17334 (10)	0.43780 (7)	0.55769 (6)	0.0250 (2)
H16	0.0930	0.4225	0.5759	0.030*
N17	0.35219 (9)	0.51181 (5)	0.59182 (5)	0.0220 (2)
C17	0.47033 (10)	0.49467 (7)	0.59476 (6)	0.0244 (2)
O17	0.54942 (7)	0.53360 (5)	0.56885 (4)	0.0294 (2)
O18	0.25418 (7)	0.53151 (5)	0.72431 (4)	0.02384 (18)
C18	0.50906 (11)	0.41827 (7)	0.63123 (7)	0.0303 (3)
O19	0.27850 (8)	0.66728 (5)	0.65050 (4)	0.02727 (19)
C19	0.39990 (13)	0.70224 (8)	0.85115 (7)	0.0353 (3)
H19A	0.4331	0.6581	0.8766	0.053*
H19B	0.3534	0.7360	0.8813	0.053*
H19C	0.4656	0.7325	0.8312	0.053*
C20	0.16602 (12)	0.64922 (7)	0.48000 (7)	0.0320 (3)
H20A	0.0798	0.6519	0.4704	0.048*
H20B	0.2098	0.6368	0.4387	0.048*
H20C	0.1934	0.6999	0.4974	0.048*
C21	0.22552 (12)	0.36654 (7)	0.52092 (6)	0.0311 (3)
H21A	0.1701	0.3501	0.4854	0.047*
H21B	0.2367	0.3234	0.5528	0.047*
H21C	0.3031	0.3806	0.5011	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0367 (4)	0.0339 (4)	0.0340 (4)	0.0041 (3)	−0.0030 (3)	0.0081 (3)
F2	0.0474 (5)	0.0240 (4)	0.0468 (5)	0.0084 (3)	−0.0041 (4)	−0.0032 (3)
F3	0.0281 (4)	0.0407 (4)	0.0544 (5)	0.0110 (3)	−0.0028 (3)	0.0045 (4)
C1	0.0233 (5)	0.0194 (5)	0.0258 (5)	−0.0018 (4)	0.0010 (4)	0.0013 (4)
C2	0.0253 (5)	0.0218 (5)	0.0231 (5)	−0.0035 (4)	−0.0007 (4)	0.0007 (4)
C3	0.0231 (5)	0.0307 (6)	0.0270 (6)	−0.0025 (4)	−0.0004 (4)	0.0010 (5)
C4	0.0246 (6)	0.0337 (6)	0.0279 (6)	0.0002 (5)	0.0034 (4)	−0.0007 (5)
C5	0.0270 (6)	0.0270 (6)	0.0253 (6)	−0.0001 (4)	0.0031 (4)	−0.0018 (4)
C6	0.0297 (6)	0.0311 (6)	0.0266 (6)	−0.0015 (5)	0.0011 (5)	−0.0028 (5)
N7	0.0329 (5)	0.0269 (5)	0.0288 (5)	−0.0024 (4)	−0.0017 (4)	−0.0021 (4)
C8	0.0418 (7)	0.0249 (6)	0.0345 (7)	0.0014 (5)	−0.0018 (5)	−0.0041 (5)
C9	0.0377 (7)	0.0207 (5)	0.0313 (6)	−0.0007 (5)	−0.0051 (5)	−0.0011 (4)
C10	0.0389 (7)	0.0211 (5)	0.0353 (7)	−0.0056 (5)	−0.0071 (5)	0.0025 (5)
C11	0.0300 (6)	0.0228 (5)	0.0330 (6)	−0.0038 (4)	−0.0018 (5)	0.0053 (5)
C12	0.0266 (5)	0.0205 (5)	0.0268 (5)	0.0005 (4)	−0.0016 (4)	0.0033 (4)
C13	0.0233 (5)	0.0200 (5)	0.0256 (5)	−0.0008 (4)	0.0005 (4)	0.0030 (4)
C14	0.0245 (5)	0.0228 (5)	0.0268 (6)	0.0003 (4)	−0.0011 (4)	0.0016 (4)
C15	0.0198 (5)	0.0262 (5)	0.0269 (6)	−0.0006 (4)	0.0016 (4)	−0.0010 (4)
O15	0.0305 (4)	0.0344 (5)	0.0278 (4)	−0.0005 (4)	−0.0040 (4)	−0.0028 (3)
C16	0.0263 (5)	0.0222 (5)	0.0265 (6)	−0.0048 (4)	0.0011 (4)	−0.0007 (4)
N17	0.0222 (5)	0.0185 (4)	0.0255 (5)	0.0001 (3)	0.0014 (4)	0.0017 (3)
C17	0.0236 (5)	0.0239 (5)	0.0258 (6)	0.0011 (4)	0.0004 (4)	−0.0019 (4)
O17	0.0234 (4)	0.0325 (4)	0.0322 (5)	−0.0013 (3)	0.0020 (3)	0.0012 (3)
O18	0.0223 (4)	0.0246 (4)	0.0246 (4)	−0.0010 (3)	0.0001 (3)	−0.0021 (3)
C18	0.0290 (6)	0.0270 (6)	0.0349 (6)	0.0049 (5)	−0.0005 (5)	0.0008 (5)
O19	0.0299 (4)	0.0235 (4)	0.0284 (4)	−0.0026 (3)	0.0005 (3)	−0.0017 (3)
C19	0.0393 (7)	0.0340 (6)	0.0326 (7)	−0.0059 (5)	−0.0025 (5)	−0.0057 (5)
C20	0.0332 (6)	0.0273 (6)	0.0355 (6)	0.0005 (5)	−0.0059 (5)	0.0059 (5)
C21	0.0407 (7)	0.0219 (5)	0.0307 (6)	−0.0039 (5)	0.0015 (5)	−0.0030 (5)

Geometric parameters (Å, º) top

F1—C18	1.3344 (15)	C11—C12	1.3511 (16)
F2—C18	1.3470 (15)	C11—H11	0.9500
F3—C18	1.3286 (15)	C12—O19	1.3655 (14)
C1—N17	1.4833 (14)	C12—C13	1.4958 (15)
C1—C2	1.5056 (16)	C13—N17	1.4961 (13)
C1—C16	1.5393 (16)	C13—C14	1.5455 (16)
C1—H1	1.0000	C13—H13	1.0000
C2—C3	1.3521 (17)	C14—C15	1.5125 (16)
C2—O18	1.3702 (14)	C14—C20	1.5239 (16)
C3—C4	1.4328 (17)	C14—H14	1.0000
C3—H3	0.9500	C15—O15	1.2117 (15)
C4—C5	1.3454 (17)	C15—C16	1.5230 (16)
C4—H4	0.9500	C16—C21	1.5333 (16)
C5—O18	1.3776 (14)	C16—H16	1.0000
C5—C6	1.4916 (16)	N17—C17	1.3489 (15)
C6—N7	1.4661 (16)	C17—O17	1.2176 (15)
C6—H6A	0.9900	C17—C18	1.5527 (16)
C6—H6B	0.9900	C19—H19A	0.9800
N7—C19	1.4520 (16)	C19—H19B	0.9800
N7—C8	1.4755 (17)	C19—H19C	0.9800
C8—C9	1.4895 (19)	C20—H20A	0.9800
C8—H8A	0.9900	C20—H20B	0.9800
C8—H8B	0.9900	C20—H20C	0.9800
C9—C10	1.3537 (19)	C21—H21A	0.9800
C9—O19	1.3713 (14)	C21—H21B	0.9800
C10—C11	1.4370 (18)	C21—H21C	0.9800
C10—H10	0.9500

N17—C1—C2	111.43 (9)	N17—C13—H13	107.9
N17—C1—C16	108.54 (9)	C14—C13—H13	107.9
C2—C1—C16	113.89 (9)	C15—C14—C20	112.95 (10)
N17—C1—H1	107.6	C15—C14—C13	109.73 (9)
C2—C1—H1	107.6	C20—C14—C13	111.19 (10)
C16—C1—H1	107.6	C15—C14—H14	107.6
C3—C2—O18	110.37 (10)	C20—C14—H14	107.6
C3—C2—C1	134.01 (11)	C13—C14—H14	107.6
O18—C2—C1	115.57 (10)	O15—C15—C14	122.66 (11)
C2—C3—C4	106.29 (10)	O15—C15—C16	121.05 (10)
C2—C3—H3	126.9	C14—C15—C16	116.28 (10)
C4—C3—H3	126.9	C15—C16—C21	109.76 (10)
C5—C4—C3	106.73 (11)	C15—C16—C1	112.18 (9)
C5—C4—H4	126.6	C21—C16—C1	111.50 (10)
C3—C4—H4	126.6	C15—C16—H16	107.7
C4—C5—O18	110.19 (10)	C21—C16—H16	107.7
C4—C5—C6	133.02 (11)	C1—C16—H16	107.7
O18—C5—C6	116.68 (10)	C17—N17—C1	126.16 (9)
N7—C6—C5	111.36 (10)	C17—N17—C13	114.89 (9)
N7—C6—H6A	109.4	C1—N17—C13	118.79 (9)
C5—C6—H6A	109.4	O17—C17—N17	124.67 (11)
N7—C6—H6B	109.4	O17—C17—C18	117.06 (11)
C5—C6—H6B	109.4	N17—C17—C18	118.23 (10)
H6A—C6—H6B	108.0	C2—O18—C5	106.33 (9)
C19—N7—C6	113.00 (10)	F3—C18—F1	107.18 (11)
C19—N7—C8	112.71 (10)	F3—C18—F2	107.23 (10)
C6—N7—C8	115.05 (10)	F1—C18—F2	107.72 (10)
N7—C8—C9	108.70 (10)	F3—C18—C17	109.62 (10)
N7—C8—H8A	109.9	F1—C18—C17	115.10 (10)
C9—C8—H8A	109.9	F2—C18—C17	109.68 (10)
N7—C8—H8B	109.9	C12—O19—C9	107.32 (9)
C9—C8—H8B	109.9	N7—C19—H19A	109.5
H8A—C8—H8B	108.3	N7—C19—H19B	109.5
C10—C9—O19	109.59 (11)	H19A—C19—H19B	109.5
C10—C9—C8	135.42 (12)	N7—C19—H19C	109.5
O19—C9—C8	113.66 (11)	H19A—C19—H19C	109.5
C9—C10—C11	106.59 (11)	H19B—C19—H19C	109.5
C9—C10—H10	126.7	C14—C20—H20A	109.5
C11—C10—H10	126.7	C14—C20—H20B	109.5
C12—C11—C10	106.38 (11)	H20A—C20—H20B	109.5
C12—C11—H11	126.8	C14—C20—H20C	109.5
C10—C11—H11	126.8	H20A—C20—H20C	109.5
C11—C12—O19	110.05 (10)	H20B—C20—H20C	109.5
C11—C12—C13	134.69 (11)	C16—C21—H21A	109.5
O19—C12—C13	115.09 (10)	C16—C21—H21B	109.5
C12—C13—N17	110.17 (9)	H21A—C21—H21B	109.5
C12—C13—C14	111.80 (9)	C16—C21—H21C	109.5
N17—C13—C14	111.01 (9)	H21A—C21—H21C	109.5
C12—C13—H13	107.9	H21B—C21—H21C	109.5

N17—C1—C2—C3	125.68 (14)	O15—C15—C16—C21	42.86 (15)
C16—C1—C2—C3	2.49 (18)	C14—C15—C16—C21	−137.91 (10)
N17—C1—C2—O18	−51.30 (13)	O15—C15—C16—C1	167.40 (11)
C16—C1—C2—O18	−174.48 (9)	C14—C15—C16—C1	−13.37 (14)
O18—C2—C3—C4	2.27 (13)	N17—C1—C16—C15	−40.88 (12)
C1—C2—C3—C4	−174.82 (12)	C2—C1—C16—C15	83.87 (12)
C2—C3—C4—C5	−0.54 (14)	N17—C1—C16—C21	82.69 (11)
C3—C4—C5—O18	−1.37 (14)	C2—C1—C16—C21	−152.56 (10)
C3—C4—C5—C6	174.71 (13)	C2—C1—N17—C17	116.85 (12)
C4—C5—C6—N7	−118.73 (15)	C16—C1—N17—C17	−116.96 (12)
O18—C5—C6—N7	57.15 (14)	C2—C1—N17—C13	−67.88 (12)
C5—C6—N7—C19	−165.25 (11)	C16—C1—N17—C13	58.31 (12)
C5—C6—N7—C8	63.35 (13)	C12—C13—N17—C17	−75.59 (12)
C19—N7—C8—C9	112.65 (12)	C14—C13—N17—C17	160.03 (10)
C6—N7—C8—C9	−115.81 (12)	C12—C13—N17—C1	108.62 (11)
N7—C8—C9—C10	−90.45 (17)	C14—C13—N17—C1	−15.77 (13)
N7—C8—C9—O19	74.55 (13)	C1—N17—C17—O17	174.16 (11)
O19—C9—C10—C11	−1.95 (14)	C13—N17—C17—O17	−1.27 (17)
C8—C9—C10—C11	163.48 (14)	C1—N17—C17—C18	−3.30 (17)
C9—C10—C11—C12	0.47 (14)	C13—N17—C17—C18	−178.73 (10)
C10—C11—C12—O19	1.19 (13)	C3—C2—O18—C5	−3.10 (12)
C10—C11—C12—C13	−173.65 (12)	C1—C2—O18—C5	174.59 (9)
C11—C12—C13—N17	103.88 (15)	C4—C5—O18—C2	2.73 (13)
O19—C12—C13—N17	−70.77 (12)	C6—C5—O18—C2	−174.06 (10)
C11—C12—C13—C14	−132.19 (14)	O17—C17—C18—F3	11.43 (15)
O19—C12—C13—C14	53.16 (13)	N17—C17—C18—F3	−170.92 (10)
C12—C13—C14—C15	−163.52 (9)	O17—C17—C18—F1	132.31 (12)
N17—C13—C14—C15	−40.06 (12)	N17—C17—C18—F1	−50.03 (15)
C12—C13—C14—C20	70.80 (12)	O17—C17—C18—F2	−106.05 (12)
N17—C13—C14—C20	−165.74 (10)	N17—C17—C18—F2	71.60 (14)
C20—C14—C15—O15	−0.18 (16)	C11—C12—O19—C9	−2.39 (13)
C13—C14—C15—O15	−124.85 (12)	C13—C12—O19—C9	173.57 (9)
C20—C14—C15—C16	−179.39 (10)	C10—C9—O19—C12	2.69 (13)
C13—C14—C15—C16	55.94 (13)	C8—C9—O19—C12	−166.19 (10)

Hydrogen-bond geometry (Å, º) top

Cg2 is the centroid of the O19/C9–C12 ring.

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···F1	1.00	2.23	2.9210 (14)	125
C1—H1···F2	1.00	2.47	3.1341 (14)	123
C3—H3···O15ⁱ	0.95	2.51	3.3809 (15)	152
C14—H14···O19	1.00	2.49	2.9114 (14)	105
C20—H20B···F3ⁱⁱ	0.98	2.54	3.4700 (16)	160
C21—H21B···Cg2ⁱⁱⁱ	0.98	2.88	3.7561 (13)	150

Symmetry codes: (i) −x, −y+1, −z+1; (ii) −x+1, −y+1, −z+1; (iii) −x+1/2, y−1/2, z.

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

N7···H4	2.71	1/2 + x, y, 3/2 - z
F2···H19C	2.65	1 - x, -1/2 + y, 3/2 - z
H20B···F3	2.54	1 - x, 1 - y, 1 - z
H21A···H19A	2.46	1/2 - x, 1 - y, -1/2 + z
H20A···H16	2.48	-x, 1 - y, 1 - z
H20C···H21B	2.50	1/2 - x, 1/2 + y, z
H20A···H11	2.53	-1/2 + x, 3/2 - y, 1 - z

Acknowledgements

The authors' contributions are as follows. Conceptualization, MA, AAE and AB; synthesis, AAE, MSG and BGMR; X-ray analysis, SÖY and MA; writing (review and editing of the manuscript) SÖY, MA and AB; funding acquisition, AAE and MSG; supervision, MA, AAE and AB.

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