Crystal structure, Hirshfeld surface analysis and inter-action energy and DFT studies of 2-chloro-ethyl 2-oxo-1-(prop-2-yn-1-yl)-1,2-di-hydro-quinoline-4-carboxyl-ate.

The title compound, C15H12ClNO3, consists of a 1,2-di-hydro-quinoline-4-carb-oxyl-ate unit with 2-chloro-ethyl and propynyl substituents, where the quinoline moiety is almost planar and the propynyl substituent is nearly perpendicular to its mean plane. In the crystal, the mol-ecules form zigzag stacks along the a-axis direction through slightly offset π-stacking inter-actions between inversion-related quinoline moieties which are tied together by inter-molecular C-HPrpn-yl⋯OCarbx and C-HChlethy⋯OCarbx (Prpnyl = propynyl, Carbx = carboxyl-ate and Chlethy = chloro-eth-yl) hydrogen bonds. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (29.9%), H⋯O/O⋯H (21.4%), H⋯C/C⋯ H (19.4%), H⋯Cl/Cl⋯H (16.3%) and C⋯C (8.6%) inter-actions. Hydrogen bonding and van der Waals inter-actions are the dominant inter-actions in the crystal packing. Computational chemistry indicates that in the crystal, the C-HPrpn-yl⋯OCarbx and C-HChlethy⋯OCarbx hydrogen bond energies are 67.1 and 61.7 kJ mol-1, respectively. Density functional theory (DFT) optimized structures at the B3LYP/ 6-311 G(d,p) level are compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was elucidated to determine the energy gap. © Hayani et al. 2019.

Chemical context

The quinoline ring system is an important structural unit in naturally occurring quinoline alkaloids, therapeutics and synthetic analogues with inter­esting biological activities. Quinolone derivatives possess a variety of pharmacological properties such as anti-bacterial (Hu et al., 2017a ▸; Zhang et al., 2018 ▸), anti-tubercular (Fan et al., 2018a ▸; Xu et al., 2017 ▸), anti-malarial (Fan et al., 2018b ▸; Hu et al., 2017b ▸), anti-HIV (Sekgota et al., 2017 ▸; Luo et al., 2010 ▸), anti-HCV (Mandroni et al., 2014 ▸; Cheng et al., 2016 ▸) and anti-cancer (Pommier et al., 2010 ▸; Shahin et al., 2018 ▸; Bisacchi & Hale, 2016 ▸) activities. Recently, substituted quinolines have also been reported to act as antagonists for endothelin (Cheng et al., 1996 ▸), 5HT3 (Anzini et al., 1995 ▸), NK-3 (Giardina et al., 1997 ▸) and leukotriene D4 (Gauthier et al., 1990 ▸) receptors. They are also used as inhibitors of gastric (H+/K+)-ATPase (Ife et al., 1992 ▸), di­hydro­orotate de­hydrogenase (Chen et al., 1990 ▸) and 5-lipoxygenase (Musser et al., 1987 ▸). As a continuation of our research on the development of N-substituted quinoline derivatives and the assessments of their potential pharmacological activities (Filali Baba et al., 2016 ▸, 2017 ▸, 2019 ▸; Bouzian et al., 2018 ▸, 2019a ▸), we have studied the condensation reaction of propargyl bromide with 2-chloro­ethyl 2-oxo-1,2-di­hydro­quinoline-4-carboxyl­ate under phase-transfer catalysis conditions using tetra-n-butyl­ammonium bromide (TBAB) as catalyst and potassium carbonate as base. We report herein on the synthesis and the mol­ecular and crystal structures of the title compound along with the Hirshfeld surface analysis and the inter­molecular inter­action energies and the density functional theory (DFT) computational calculation carried out at the B3LYP/6–311 G(d,p) level.

Structural commentary

The title mol­ecule consists of a 1,2-di­hydro­quinoline-4-carboxyl­ate unit with 2-chloro­ethyl and propynyl substituents (Fig. 1 ▸). The constituent rings, A (C1–C6) and B (N1/C1/C6–C9), of the di­hydro­quinoline unit are oriented at a dihedral angle of 2.69 (17)°. The mean plane through the di­hydro­quinoline unit is almost planar with a maximum deviation of 0.040 (3) Å for atom N1, and the propynyl substituent is nearly perpendicular to that plane, the C6—N1—C10—C11 torsion angle being −79.6 (4)°. The carboxyl group is twisted out of coplanarity with the di­hydro­quinoline unit by a dihedral angle of 47.13 (23)°; this is also indicated by the C1—C9—C13—O2 torsion angle of −44.2 (6)°.

Figure 1

The mol­ecular structure of the title compound with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Supra­molecular features

In the crystal, the mol­ecules form zigzag stacks along the a-axis direction through slightly offset π-stacking inter­actions between inversion-related quinoline moieties (Fig. 2 ▸). The stacks are tied together by a network of inter­molecular C—HPrpn­yl⋯OCarbx and C—HChlethy⋯OCarbx (Prpnyl = propynyl, Carbx = carboxyl­ate and Chlethy = chloro­eth­yl) hydrogen bonds, enclosing (16) and (8) ring motifs (Table 1 ▸ and Fig. 3 ▸). The π–π contacts between the constituent rings, A (C1–C6) and B (N1/C1/C6–C9), of the di­hydro­quinoline unit, Cg2⋯Cg1i, Cg2⋯Cg1ii and Cg1⋯Cg1i [centroid–centroid distance = 3.728 (2), 3.571 (2) and 3.761 (2) Å, respectively, where Cg1 and Cg2 are the centroids of the rings, A and B; symmetry codes: (i) 1 − x, 1 − y, 1 − z and (ii) −x, 1 − y, 1 − z], may further stabilize the structure.

Figure 2

A partial packing diagram viewed along the c-axis direction with the π-stacking inter­actions shown as dashed lines.

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C10—H10A⋯O2viii	0.99	2.49	3.458 (5)	167
C10—H10B⋯O1iv	0.99	2.39	3.250 (4)	145
C15—H15A⋯O1iii	0.99	2.46	3.406 (6)	159
C15—H15B⋯O2xi	0.99	2.40	3.219 (6)	140

Symmetry codes: (iii) ; (iv) ; (viii) ; (xi) .

Figure 3

A partial packing diagram viewed along the a-axis direction with the C—HPrpn­yl⋯OCarbx and C—HChlethy⋯OCarbx (Prpnyl = propynyl, Carbx = carboxyl­ate and Chlethy = chloro­eth­yl) hydrogen bonds and π-stacking inter­actions shown, respectively, as black and orange dashed lines.

Hirshfeld surface analysis

In order to visualize the inter­molecular inter­actions in the crystal of the title compound, a Hirshfeld surface (HS) analysis (Hirshfeld, 1977 ▸; Spackman & Jayatilaka, 2009 ▸) was carried out by using CrystalExplorer17.5 (Turner et al., 2017 ▸). In the HS plotted over d norm (Fig. 4 ▸), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colours indicate distances shorter (in close contact) or longer (distinct contact) than the van der Waals radii, respectively (Venkatesan et al., 2016 ▸). The bright-red spots appearing near atoms O1, O2 and hydrogen atoms H10A, H10B, H15A and H15B indicate their roles as the respective donors and/or acceptors; they also appear as blue and red regions corresponding to positive and negative potentials on the HS mapped over electrostatic potential (Spackman et al., 2008 ▸; Jayatilaka et al., 2005 ▸) as shown in Fig. 5 ▸. The blue regions indicate the positive electrostatic potential (hydrogen-bond donors), while the red regions indicate the negative electrostatic potential (hydrogen-bond acceptors). The shape-index of the HS is a tool to visualize π–π stacking by the presence of adjacent red and blue triangles; if there are no adjacent red and/or blue triangles, then there are no π–π inter­actions. Fig. 6 ▸ clearly suggest that there are π–π inter­actions in (I).

Figure 4

View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm in the range −0.2177 to 1.3626 a.u.

Figure 5

View of the three-dimensional Hirshfeld surface of the title compound plotted over electrostatic potential energy in the range −0.0500 to 0.0500 a.u. using the STO-3 G basis set at the Hartree–Fock level of theory. Hydrogen-bond donors and acceptors are shown as blue and red regions around the atoms, corresponding to positive and negative potentials, respectively.

Figure 6

Hirshfeld surface of the title compound plotted over shape-index.

The overall two-dimensional fingerprint plot, Fig. 7 ▸ a, and those delineated into H ⋯ H, H⋯O/O⋯H, H⋯C/C⋯H, H⋯Cl/Cl⋯H, C⋯C, C⋯N/N ⋯ C and O⋯Cl/Cl⋯O contacts (McKinnon et al., 2007 ▸) are illustrated in Fig. 7 ▸ b–h, respectively, together with their relative contributions to the Hirshfeld surface. The most important inter­action is H⋯H (Table 2 ▸), contributing 29.9% to the overall crystal packing, which is reflected in Fig. 7 ▸ b as widely scattered points of high density due to the large hydrogen content of the mol­ecule with the tip at d e = d i = 1.22 Å. The pair of characteristic wings in the fingerprint plot delineated into H⋯O/O⋯H contacts (21.4% contribution, Fig. 7 ▸ c) are viewed as a pair of spikes with the tips at d e + d i = 2.28 Å. In the absence of C—H⋯π inter­actions, the pairs of characteristic wings in Fig. 7 ▸ d arise from H⋯C/C⋯H contacts (19.4%) and are viewed as pairs of spikes with the tips at d e + d i = 2.65 Å and 2.70 Å for the thin and thick spikes, respectively. The scattered points in the pair of wings in the fingerprint plot delineated into H⋯Cl/Cl⋯H (16.3% contribution, Fig. 7 ▸ e) have a symmetrical distribution with the edges at d e + d i = 2.60 Å. The C⋯C contacts, Fig. 7 ▸ f, have an arrow-shaped distribution of points with the tip at d e = d i = 1.72 Å. Finally, the characteristic tip and wings in the fingerprint plots delineated into C⋯N/N⋯C and O⋯Cl/Cl⋯O contacts (1.6% and 1.1% contributions, respectively, Fig. 7 ▸ g and 7h) have the tips at d e = d i = 1.73 and 3.70 Å, respectively.

Figure 7

The full two-dimensional fingerprint plots for the title compound, showing (a) all inter­actions, and delineated into (b) H⋯H, (c) H⋯O/O⋯H, (d) H⋯C/C⋯H, (e) H⋯Cl/Cl⋯H, (f) C⋯C, (g) C⋯N/N⋯C and (h) O⋯Cl/Cl⋯O inter­actions. The di and de values are the closest inter­nal and external distances (in Å) from given points on the Hirshfeld surface contacts.

Table 2

Selected interatomic distances (Å)

Cl1⋯O3	3.110 (3)	C1⋯C6viii	3.534 (5)
Cl1⋯C12i	3.629 (5)	C2⋯C6ii	3.489 (5)
Cl1⋯H12i	2.75	C2⋯C10viii	3.388 (5)
Cl1⋯H5ii	3.03	C4⋯C7viii	3.597 (5)
Cl1⋯H8iii	2.96	C4⋯C9ii	3.452 (5)
O1⋯C10iv	3.250 (5)	C5⋯C11	3.241 (5)
O1⋯C12v	3.409 (6)	C5⋯C9viii	3.575 (5)
O1⋯C15vi	3.406 (5)	C6⋯C6viii	3.485 (4)
O2⋯C2	3.045 (5)	C2⋯H10A viii	2.88
O2⋯C15vii	3.219 (6)	C5⋯H10A	2.61
O3⋯Cl1	3.110 (3)	C10⋯H5	2.50
O1⋯H10B	2.30	C11⋯H3ix	2.85
O1⋯H10B iv	2.39	C11⋯H5	2.72
O1⋯H15A vi	2.46	C12⋯H14A x	2.95
O2⋯H14B	2.46	C12⋯H2ii	2.80
O2⋯H2	2.49	C12⋯H3ix	2.93
O2⋯H14A	2.80	C13⋯H2	2.65
O2⋯H15B vii	2.40	H5⋯H10A	2.10
O2⋯H10A viii	2.49	H8⋯H15A vi	2.55
O3⋯H8	2.50

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) ; (viii) ; (ix) ; (x) .

The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the H⋯H, H⋯O/O⋯H, H⋯C/C⋯H and H ⋯ Cl/Cl⋯H inter­actions in Fig. 8 ▸ a–d, respectively.

Figure 8

The Hirshfeld surface representations with the function d norm plotted onto the surface for (a) H⋯H, (b) H⋯O/O⋯H, (c) H⋯C/C⋯H and (d) H⋯Cl/Cl⋯H inter­actions.

The Hirshfeld surface analysis confirms the importance of H-atom contacts in establishing the packing. The large number of H⋯H, H⋯O/O⋯H, H ⋯ C/C⋯H and H⋯Cl/Cl⋯H inter­actions suggest that van der Waals inter­actions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015 ▸).

Inter­action energy calculations

The inter­molecular inter­action energies were calculated using the CE–B3LYP/6–31G(d,p) energy model available in CrystalExplorer17.5 (Turner et al., 2017 ▸), where by default a cluster of mol­ecules are generated by applying crystallographic symmetry operations with respect to a selected central mol­ecule within a radius of 3.8 Å (Turner et al., 2014 ▸). The total inter­molecular energy (E tot) is the sum of electrostatic (E ele), polarization (E pol), dispersion (E dis) and exchange-repulsion (E rep) energies (Turner et al., 2015 ▸) with scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017 ▸). Hydrogen-bonding inter­action energies (in kJ mol−1) were calculated to be −25.2 (E ele), −2.1 (E pol), −85.4 (E dis), 57.5 (E rep) and −67.1 (E tot) for the C—HPrpn­yl⋯OCarbx hydrogen bond and −26.5 (E ele), −4.7 (E pol), −73.2 (E dis), 54.3 (E rep) and −61.7 (E tot) for the C—HChlethy⋯OCarbx hydrogen bond.

DFT calculations

The optimized structure of the title compound in the gas phase was generated theoretically via density functional theory (DFT) using the standard B3LYP functional and 6–311 G(d,p) basis-set calculations (Becke, 1993 ▸) as implemented in GAUSSIAN 09 (Frisch et al., 2009 ▸). The theoretical and experimental results were in good agreement (Table 3 ▸). The highest-occupied mol­ecular orbital (HOMO), acting as an electron donor, and the lowest-unoccupied mol­ecular orbital (LUMO), acting as an electron acceptor, are very important parameters for quantum chemistry. When the energy gap is small, the mol­ecule is highly polarizable and has high chemical reactivity. The DFT calculations provide some important information on the reactivity and site selectivity of the mol­ecular framework. E HOMO and E LUMO clarify the inevitable charge-exchange collaboration inside the studied material, and are recorded in Table 4 ▸ along with the electronegativity (χ), hardness (η), potential (μ), electrophilicity (ω) and softness (σ). The significance of η and σ is to evaluate both the reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 9 ▸. The HOMO and LUMO are localized in the plane extending from the whole 2-chloro­ethyl 2-oxo-1-(prop-2-yn-1-yl)-1,2-di­hydro­quinoline-4-carboxyl­ate ring. The energy band gap [ΔE = E LUMO − E HOMO] of the mol­ecule is 3.6984 eV, and the frontier mol­ecular orbital energies, E HOMO and E LUMO are −6.3024 and −2.6040 eV, respectively.

Table 3

Comparison of selected (X-ray and DFT) geometric data (Å, °)

Bonds/angles	X-ray	B3LYP/6–311G(d,p)
Cl1—C15	1.838 (6)	1.88121
O1—C7	1.235 (5)	1.25852
O2—C13	1.213 (5)	1.24099
O3—C13	1.322 (5)	1.38771
O3—C14	1.459 (5)	1.47976
N1—C7	1.381 (5)	1.40545
N1—C6	1.405 (4)	1.41686
N1—C10	1.469 (4)	1.49984
C13—O3—C14	115.2 (4)	116.83182
C7—N1—C6	123.1 (3)	121.89630
C7—N1—C10	116.9 (3)	117.96161
C6—N1—C10	120.0 (3)	117.10486
N1—C6—C1	119.5 (3)	120.53011
O1—C7—N1	121.4 (3)	122.42582
O1—C7—C8	122.5 (3)	121.61064
N1—C7—C8	116.1 (3)	115.96268

Table 4

Calculated energies

Mol­ecular Energy
Total Energy, TE	−35893.2971
EHOMO (eV)	−6.3024
ELUMO (eV)	−2.6040
Gap ΔE (eV)	3.6984
Dipole moment, μ (Debye)	3.8441
Ionization potential, I (eV)	6.3024
Electron affinity, A	2.6040
Electro negativity, χ	4.4532
Hardness, η	1.8492
Electrophilicity index, ω	5.3620
Softness, σ	0.5408
Fraction of electron transferred, ΔN	0.6886

Figure 9

The energy band gap of the title compound.

Database survey

A non-alkyl­ated analogue, namely quinoline and its derivatives, has been reported (Filali Baba et al., 2016 ▸, 2017 ▸), as well as three similar structures, see: Bouzian et al., 2018 ▸, 2019a ▸,b ▸; Filali Baba et al., 2019 ▸.

Synthesis and crystallization

To a solution of 2-chloro­ethyl 2-oxo-1,2-di­hydro­quinoline-4-carboxyl­ate (0.50 g, 2.00 mmol) in DMF (10.00 ml) were added propargyl bromide (0.20 ml, 2.38 mmol), K2CO3 (0.82 g, 6.00 mmol) and TBAB (0.06 g, 0.20 mmol). The reaction mixture was stirred at room temperature for 6 h. After removal of the salts by filtration, the solvent was evaporated under reduced pressure and the resulting residue was dissolved in di­chloro­methane. The organic phase was dried with Na2SO4, and then concentrated under reduced pressure. The pure compound was obtained by column chromatography using hexa­ne/ethyl acetate (3/1) as eluent. The isolated solid was recrystallized from hexa­ne/ethyl acetate (3:1) to afford colourless crystals (yield: 84%, m.p. 394.15 K).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5 ▸. Hydrogen atoms were positioned geometrically (C—H = 0.95 and 0.99 Å, for CH and CH2 H atoms, respectively) and constrained to ride on their parent atoms, with U iso(H) = 1.2U eq(C). The largest peak and hole in the final difference map are +0.73 e Å−3 (1.00 Å away from Cl1) and −0.35 e Å−3 (0.64 Å away from C14), and are associated with the 2-chloro­ethyl­carb­oxy group and may indicate a slight degree of disorder here but it was not considered serious enough to model.

Table 5

Experimental details

Crystal data
Chemical formula	C15H12ClNO3
M r	289.71
Crystal system, space group	Monoclinic, P21/n
Temperature (K)	150
a, b, c (Å)	7.1809 (2), 21.4466 (5), 8.9173 (2)
β (°)	92.784 (2)
V (Å3)	1371.70 (6)
Z	4
Radiation type	Cu Kα
μ (mm−1)	2.53
Crystal size (mm)	0.19 × 0.14 × 0.01
Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.64, 0.97
No. of measured, independent and observed [I > 2σ(I)] reflections	10119, 2555, 2170
R int	0.047
(sin θ/λ)max (Å−1)	0.610
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.078, 0.178, 1.13
No. of reflections	2555
No. of parameters	181
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.73, −0.35

Computer programs: APEX3 and SAINT (Bruker, 2016 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2018 (Sheldrick, 2015b ▸), DIAMOND (Brandenburg & Putz, 2012 ▸) and SHELXTL (Sheldrick, 2008 ▸).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989019012283/lh5918sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989019012283/lh5918Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989019012283/lh5918Isup3.cdx

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989019012283/lh5918Isup4.cml

CCDC reference: 1951439

Additional supporting information: crystallographic information; 3D view; checkCIF report

C15H12ClNO3	F(000) = 600
Mr = 289.71	Dx = 1.403 Mg m−3
Monoclinic, P21/n	Cu Kα radiation, λ = 1.54178 Å
a = 7.1809 (2) Å	Cell parameters from 6719 reflections
b = 21.4466 (5) Å	θ = 4.1–69.9°
c = 8.9173 (2) Å	µ = 2.53 mm−1
β = 92.784 (2)°	T = 150 K
V = 1371.70 (6) Å3	Plate, colourless
Z = 4	0.19 × 0.14 × 0.01 mm

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	2555 independent reflections
Radiation source: INCOATEC IµS micro–focus source	2170 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.047
Detector resolution: 10.4167 pixels mm-1	θmax = 70.1°, θmin = 4.1°
ω scans	h = −8→8
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −26→25
Tmin = 0.64, Tmax = 0.97	l = −10→10
10119 measured reflections

Refinement on F2	Primary atom site location: dual space
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.078	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.178	H-atom parameters constrained
S = 1.13	w = 1/[σ2(Fo2) + (0.0332P)2 + 4.0657P] where P = (Fo2 + 2Fc2)/3
2555 reflections	(Δ/σ)max < 0.001
181 parameters	Δρmax = 0.73 e Å−3
0 restraints	Δρmin = −0.35 e Å−3

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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å) and included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. The largest peaks and holes in the final difference map are < +/-1 e--/%A-3 and are associated with the 2-chloroethylcarboxy group and may indicate a slight degree of disorder here but it was not considered serious enough to model.

	x	y	z	Uiso*/Ueq
Cl1	0.7800 (2)	0.24965 (6)	0.45136 (18)	0.0683 (4)
O1	0.1693 (4)	0.43876 (13)	0.9233 (3)	0.0390 (7)
O2	0.1917 (5)	0.33835 (15)	0.3272 (4)	0.0569 (9)
O3	0.3893 (5)	0.30409 (14)	0.5116 (4)	0.0505 (8)
N1	0.1864 (4)	0.50421 (13)	0.7226 (3)	0.0269 (6)
C1	0.2615 (5)	0.46384 (17)	0.4782 (4)	0.0282 (8)
C2	0.2997 (5)	0.47567 (19)	0.3269 (4)	0.0345 (9)
H2	0.324683	0.441692	0.262595	0.041*
C3	0.3014 (5)	0.5349 (2)	0.2715 (4)	0.0372 (9)
H3	0.326460	0.541915	0.169253	0.045*
C4	0.2661 (5)	0.58513 (19)	0.3654 (4)	0.0363 (9)
H4	0.267501	0.626395	0.326807	0.044*
C5	0.2290 (5)	0.57527 (18)	0.5145 (4)	0.0312 (8)
H5	0.205814	0.609762	0.577824	0.037*
C6	0.2256 (5)	0.51487 (17)	0.5719 (4)	0.0266 (7)
C7	0.1967 (5)	0.44600 (17)	0.7888 (4)	0.0296 (8)
C8	0.2365 (5)	0.39456 (17)	0.6907 (4)	0.0326 (8)
H8	0.244434	0.353690	0.731581	0.039*
C9	0.2627 (5)	0.40246 (17)	0.5429 (4)	0.0308 (8)
C10	0.1343 (5)	0.55651 (17)	0.8183 (4)	0.0295 (8)
H10A	0.047696	0.584337	0.760268	0.035*
H10B	0.067963	0.540162	0.904796	0.035*
C11	0.2966 (6)	0.59261 (18)	0.8741 (4)	0.0346 (9)
C12	0.4275 (7)	0.6208 (2)	0.9178 (5)	0.0485 (11)
H12	0.533984	0.643689	0.953389	0.058*
C13	0.2778 (6)	0.34610 (18)	0.4461 (5)	0.0385 (9)
C14	0.4018 (8)	0.2450 (2)	0.4316 (6)	0.0595 (14)
H14A	0.286502	0.220384	0.441323	0.071*
H14B	0.419443	0.252540	0.323617	0.071*
C15	0.5603 (9)	0.2122 (2)	0.4990 (6)	0.0629 (14)
H15A	0.559154	0.168527	0.463120	0.076*
H15B	0.551442	0.211642	0.609416	0.076*

	U11	U22	U33	U12	U13	U23
Cl1	0.0708 (9)	0.0393 (6)	0.0940 (11)	0.0187 (6)	−0.0052 (7)	−0.0096 (6)
O1	0.0464 (16)	0.0416 (15)	0.0301 (15)	0.0056 (13)	0.0132 (12)	0.0061 (12)
O2	0.074 (2)	0.0488 (19)	0.0469 (19)	0.0006 (17)	−0.0037 (17)	−0.0143 (15)
O3	0.057 (2)	0.0357 (16)	0.060 (2)	0.0087 (14)	0.0107 (16)	−0.0126 (14)
N1	0.0262 (15)	0.0270 (15)	0.0282 (16)	0.0024 (12)	0.0081 (12)	−0.0009 (12)
C1	0.0206 (16)	0.0332 (19)	0.0314 (19)	−0.0018 (14)	0.0064 (14)	−0.0014 (15)
C2	0.0276 (19)	0.047 (2)	0.030 (2)	−0.0039 (17)	0.0062 (15)	−0.0071 (17)
C3	0.033 (2)	0.051 (2)	0.028 (2)	−0.0076 (18)	0.0037 (16)	0.0055 (17)
C4	0.033 (2)	0.041 (2)	0.035 (2)	−0.0045 (17)	−0.0001 (16)	0.0091 (17)
C5	0.0264 (18)	0.0325 (19)	0.035 (2)	−0.0008 (15)	0.0035 (15)	0.0018 (16)
C6	0.0194 (16)	0.0335 (19)	0.0273 (18)	0.0005 (14)	0.0058 (13)	0.0004 (15)
C7	0.0252 (18)	0.0302 (19)	0.034 (2)	0.0011 (14)	0.0082 (15)	0.0029 (15)
C8	0.0317 (19)	0.0285 (19)	0.038 (2)	0.0020 (15)	0.0080 (16)	0.0044 (16)
C9	0.0249 (18)	0.0323 (19)	0.036 (2)	0.0006 (14)	0.0088 (15)	−0.0020 (16)
C10	0.0287 (18)	0.0307 (19)	0.0297 (19)	0.0034 (15)	0.0076 (15)	−0.0025 (15)
C11	0.043 (2)	0.034 (2)	0.028 (2)	0.0003 (17)	0.0101 (17)	−0.0039 (16)
C12	0.047 (3)	0.056 (3)	0.043 (3)	−0.009 (2)	0.006 (2)	−0.010 (2)
C13	0.038 (2)	0.030 (2)	0.049 (3)	0.0004 (17)	0.0092 (19)	−0.0001 (18)
C14	0.086 (4)	0.029 (2)	0.065 (3)	0.012 (2)	0.021 (3)	−0.005 (2)
C15	0.091 (4)	0.046 (3)	0.051 (3)	0.013 (3)	0.007 (3)	0.002 (2)

Cl1—C15	1.838 (6)	C5—C6	1.393 (5)
O1—C7	1.235 (5)	C5—H5	0.9500
O2—C13	1.213 (5)	C7—C8	1.445 (5)
O3—C13	1.322 (5)	C8—C9	1.351 (5)
O3—C14	1.459 (5)	C8—H8	0.9500
N1—C7	1.381 (5)	C9—C13	1.492 (5)
N1—C6	1.405 (4)	C10—C11	1.465 (5)
N1—C10	1.469 (4)	C10—H10A	0.9900
C1—C6	1.409 (5)	C10—H10B	0.9900
C1—C2	1.412 (5)	C11—C12	1.169 (6)
C1—C9	1.437 (5)	C12—H12	0.9500
C2—C3	1.363 (6)	C14—C15	1.444 (8)
C2—H2	0.9500	C14—H14A	0.9900
C3—C4	1.396 (6)	C14—H14B	0.9900
C3—H3	0.9500	C15—H15A	0.9900
C4—C5	1.385 (5)	C15—H15B	0.9900
C4—H4	0.9500
Cl1···O3	3.110 (3)	C1···C6viii	3.534 (5)
Cl1···C12i	3.629 (5)	C2···C6ii	3.489 (5)
Cl1···H12i	2.75	C2···C10viii	3.388 (5)
Cl1···H5ii	3.03	C4···C7viii	3.597 (5)
Cl1···H8iii	2.96	C4···C9ii	3.452 (5)
O1···C10iv	3.250 (5)	C5···C11	3.241 (5)
O1···C12v	3.409 (6)	C5···C9viii	3.575 (5)
O1···C15vi	3.406 (5)	C6···C6viii	3.485 (4)
O2···C2	3.045 (5)	C2···H10Aviii	2.88
O2···C15vii	3.219 (6)	C5···H10A	2.61
O3···Cl1	3.110 (3)	C10···H5	2.50
O1···H10B	2.30	C11···H3ix	2.85
O1···H10Biv	2.39	C11···H5	2.72
O1···H15Avi	2.46	C12···H14Ax	2.95
O2···H14B	2.46	C12···H2ii	2.80
O2···H2	2.49	C12···H3ix	2.93
O2···H14A	2.80	C13···H2	2.65
O2···H15Bvii	2.40	H5···H10A	2.10
O2···H10Aviii	2.49	H8···H15Avi	2.55
O3···H8	2.50
C13—O3—C14	115.2 (4)	C7—C8—H8	118.8
C7—N1—C6	123.1 (3)	C8—C9—C1	120.5 (3)
C7—N1—C10	116.9 (3)	C8—C9—C13	118.7 (3)
C6—N1—C10	120.0 (3)	C1—C9—C13	120.6 (3)
C6—C1—C2	118.5 (3)	C11—C10—N1	112.3 (3)
C6—C1—C9	118.1 (3)	C11—C10—H10A	109.1
C2—C1—C9	123.4 (3)	N1—C10—H10A	109.1
C3—C2—C1	121.3 (4)	C11—C10—H10B	109.1
C3—C2—H2	119.4	N1—C10—H10B	109.1
C1—C2—H2	119.4	H10A—C10—H10B	107.9
C2—C3—C4	119.8 (4)	C12—C11—C10	179.1 (5)
C2—C3—H3	120.1	C11—C12—H12	180.0
C4—C3—H3	120.1	O2—C13—O3	124.4 (4)
C5—C4—C3	120.5 (4)	O2—C13—C9	124.6 (4)
C5—C4—H4	119.8	O3—C13—C9	110.8 (4)
C3—C4—H4	119.8	C15—C14—O3	106.6 (5)
C4—C5—C6	120.1 (4)	C15—C14—H14A	110.4
C4—C5—H5	119.9	O3—C14—H14A	110.4
C6—C5—H5	119.9	C15—C14—H14B	110.4
C5—C6—N1	120.7 (3)	O3—C14—H14B	110.4
C5—C6—C1	119.8 (3)	H14A—C14—H14B	108.6
N1—C6—C1	119.5 (3)	C14—C15—Cl1	111.0 (4)
O1—C7—N1	121.4 (3)	C14—C15—H15A	109.4
O1—C7—C8	122.5 (3)	Cl1—C15—H15A	109.4
N1—C7—C8	116.1 (3)	C14—C15—H15B	109.4
C9—C8—C7	122.4 (3)	Cl1—C15—H15B	109.4
C9—C8—H8	118.8	H15A—C15—H15B	108.0
C6—C1—C2—C3	−0.3 (5)	O1—C7—C8—C9	178.7 (4)
C9—C1—C2—C3	−178.4 (4)	N1—C7—C8—C9	0.1 (5)
C1—C2—C3—C4	0.4 (6)	C7—C8—C9—C1	3.3 (6)
C2—C3—C4—C5	−0.1 (6)	C7—C8—C9—C13	−171.9 (3)
C3—C4—C5—C6	−0.4 (6)	C6—C1—C9—C8	−2.3 (5)
C4—C5—C6—N1	−179.4 (3)	C2—C1—C9—C8	175.9 (4)
C4—C5—C6—C1	0.5 (5)	C6—C1—C9—C13	172.9 (3)
C7—N1—C6—C5	−174.3 (3)	C2—C1—C9—C13	−9.0 (5)
C10—N1—C6—C5	4.7 (5)	C7—N1—C10—C11	99.5 (4)
C7—N1—C6—C1	5.7 (5)	C6—N1—C10—C11	−79.6 (4)
C10—N1—C6—C1	−175.2 (3)	C14—O3—C13—O2	−0.9 (6)
C2—C1—C6—C5	−0.2 (5)	C14—O3—C13—C9	175.3 (4)
C9—C1—C6—C5	178.0 (3)	C8—C9—C13—O2	131.0 (5)
C2—C1—C6—N1	179.7 (3)	C1—C9—C13—O2	−44.2 (6)
C9—C1—C6—N1	−2.1 (5)	C8—C9—C13—O3	−45.2 (5)
C6—N1—C7—O1	176.8 (3)	C1—C9—C13—O3	139.6 (4)
C10—N1—C7—O1	−2.3 (5)	C13—O3—C14—C15	166.2 (4)
C6—N1—C7—C8	−4.7 (5)	O3—C14—C15—Cl1	−70.8 (5)
C10—N1—C7—C8	176.2 (3)

D—H···A	D—H	H···A	D···A	D—H···A
C10—H10A···O2viii	0.99	2.49	3.458 (5)	167
C10—H10B···O1iv	0.99	2.39	3.250 (4)	145
C15—H15A···O1iii	0.99	2.46	3.406 (6)	159
C15—H15B···O2xi	0.99	2.40	3.219 (6)	140