Methyl 2-{[(6S*,7R*,8S*)-7-acetyl-8-(4-chloro­phen­yl)-4-cyano-6-hy­droxy-1,6-dimethyl-5,6,7,8-tetra­hydro­isoquinolin-3-yl]sulfan­yl}acetate

Mague, J.T.; Al-Taifi, E.A.; Mohamed, S.K.; Akkurt, M.; Bakhite, E.A.

doi:10.1107/S2414314617008689

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 6| June 2017| x170868

https://doi.org/10.1107/S2414314617008689

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Methyl 2-{[(6S,7R,8S*)-7-acetyl-8-(4-chlorophenyl)-4-cyano-6-hydroxy-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetate

Joel T. Mague,^a Elham A. Al-Taifi,^b ^* Shaaban K. Mohamed,^c,^d Mehmet Akkurt ^e and Etify A. Bakhite ^f

^aDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, ^bChemistry Department, Faculty of Science, Sana'a University, Sana'a, Yemen, ^cChemistry and Environmental Division, Manchester Metropolitan University, Manchester M1 5GD, England, ^dChemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt, ^eDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, and ^fChemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt
^*Correspondence e-mail: s.mohamed@mmu.ac.uk

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 23 May 2017; accepted 11 June 2017; online 20 June 2017)

In the title compound, C₂₃H₂₃ClN₂O₄S, the 4-chlorophenyl ring is inclined to the pyridine ring of the isoquinoline group by 71.86 (13)°. In the crystal, molecules are linked by pairs of O—H⋯O hydrogen bonds, forming inversion dimers, which stack along the b-axis direction. The methyl acetate group attached to the S atom is disordered over two sites in a 50:50 ratio, which appears to prevent close intermolecular contacts between the methyl groups.

Keywords: crystal structure; isoquinoline; tetrahydroisoquinolines; hydrogen bonding.

CCDC reference: 1555400

Structure description

Many analogues of tetrahydroisoquinolines have been found to possess anti-tumor activity (Lane et al., 2006 ; Aubry et al., 2007 ). They also have the potential to treat Alzheimer's disease (Hu et al., 2008 ) and are widely studied cytotoxic agents. Berberrubine, a protoberberine alkaloid, exhibits anti-tumor activity in animal models (Kim et al., 1998 ). It has also been reported that noscapine, a plant alkaloid, binds to tubulin and induces apoptosis selectively in tumor cells to display anti-cancer activity in ovarian and T-cell lymphoma cancers (Aneja et al., 2006 ). These examples demonstrate the utility of the tetrahydroisoquinoline core and why these types of compounds are of great interest. In this context, we report herein on the synthesis and crystal structure of the title compound.

The molecular structure of the title compound is illustrated in Fig. 1. The cyclohexene ring (C1–C6) of the tetrahydroisoquinoline moiety, has a slightly distorted half-chair conformation [puckering parameters Q = 0.524 (3) Å, θ = 127.1 (3)° and φ = 319.0 (4)°]. The dihedral angle between the plane of the chloro-substituted phenyl ring (C13–C18) and the pyridine ring (N1/C1/C6–C9) of the tetrahydroisoquinoline moiety is 71.86 (13)°. The methyl acetate group attached to atom S1 is disordered over two sites in a 50:50 ratio, which appears to prevent close intermolecular contacts between the methyl groups.

Figure 1
The molecular structure of the title compound, with the atom labelling and 50% probability ellipsoids. Only the major portion of the disorder is shown.

In the crystal, molecules are linked by pairs of O—H⋯O hydrogen bonds, forming inversion dimers, which stack along the b-axis direction (Table 1 and Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2O⋯O1ⁱ	0.92 (4)	2.00 (4)	2.918 (3)	174 (3)
Symmetry code: (i) $[-x+{\script{3\over 2}}, -y+{\script{3\over 2}}, -z+1]$ .

Figure 2
A view along the b axis of the crystal packing of the title compound, with the intermolecular O—H⋯O hydrogen bonds shown as dotted lines (see Table 1

Synthesis and crystallization

A mixture of 7-acetyl-8-(4-chlorophenyl)-1,6-dimethyl-6-hydroxy-3-thioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile (3.87 g, 10 mmol), methyl chloroacetate (1.09 g, 10 mmol) and sodium acetate trihydrate (1.66 g,12 mmol) in ethanol (30 ml) was heated under reflux for one h. The precipitate that formed after cooling was collected and recrystallized from ethanol to give the title compound in the form of colourless needles (yield 83%, m.p. 422 K). IR: 3455 (OH), 2225(CN), 1740 (CO, ester), 1690 (CO, ketone) cm⁻¹.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The methyl acetate group attached to S1 is disordered over two sets of sites with equal occupancy although it appears that the methyl carbon atoms may be more highly disordered. Attempts to model additional disorder were unsuccessful so the two-component model was retained.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₃H₂₃ClN₂O₄S
M_r	458.94
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	150
a, b, c (Å)	27.4679 (6), 9.5818 (2), 20.2584 (5)
β (°)	117.398 (1)
V (Å³)	4733.78 (19)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	2.51
Crystal size (mm)	0.33 × 0.16 × 0.09

Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Bruker, 2016 )
T_min, T_max	0.65, 0.80
No. of measured, independent and observed [I > 2σ(I)] reflections	38901, 4440, 4119
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.610

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.058, 0.166, 1.03
No. of reflections	4440
No. of parameters	308
No. of restraints	21
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	1.36, −0.63
Computer programs: APEX3 and SAINT (Bruker, 2016), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ), DIAMOND (Brandenburg & Putz, 2012 ) and SHELXTL Sheldrick, 2008 ).

Structural data

CCDC reference: 1555400

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314617008689/su4155sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617008689/su4155Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314617008689/su4155Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2016); cell refinement: SAINT (Bruker, 2016); data reduction: SAINT (Bruker, 2016); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL Sheldrick, 2008).

Methyl 2-{[(6S*,7R*,8S*)-7-acetyl-8-(4-chlorophenyl)-4-cyano-6-hydroxy-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}acetate top

Crystal data top

C₂₃H₂₃ClN₂O₄S	F(000) = 1920
M_r = 458.94	D_x = 1.288 Mg m⁻³
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54178 Å
a = 27.4679 (6) Å	Cell parameters from 9777 reflections
b = 9.5818 (2) Å	θ = 3.3–69.9°
c = 20.2584 (5) Å	µ = 2.51 mm⁻¹
β = 117.398 (1)°	T = 150 K
V = 4733.78 (19) Å³	Needles, colourless
Z = 8	0.33 × 0.16 × 0.09 mm

Data collection top

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	4440 independent reflections
Radiation source: INCOATEC IµS micro-focus source	4119 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.035
Detector resolution: 10.4167 pixels mm^-1	θ_max = 70.0°, θ_min = 4.6°
ω scans	h = −32→31
Absorption correction: multi-scan (SADABS; Bruker, 2016)	k = −11→11
T_min = 0.65, T_max = 0.80	l = −24→24
38901 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.058	w = 1/[σ²(F_o²) + (0.0975P)² + 12.6727P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.166	(Δ/σ)_max = 0.001
S = 1.03	Δρ_max = 1.36 e Å⁻³
4440 reflections	Δρ_min = −0.63 e Å⁻³
308 parameters	Extinction correction: (SHELXL2014; Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
21 restraints	Extinction coefficient: 0.00050 (8)

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

	x	y	z	U_iso*/U_eq	Occ. (<1)
Cl1	0.78857 (3)	0.87497 (8)	0.93943 (3)	0.0365 (2)
S1	0.42650 (2)	0.67486 (7)	0.50425 (4)	0.0337 (2)
O1	0.76188 (7)	0.7626 (2)	0.57782 (10)	0.0337 (4)
O2	0.64464 (7)	0.74788 (19)	0.45364 (9)	0.0286 (4)
H2O	0.6734 (14)	0.738 (4)	0.4426 (19)	0.043*
N1	0.53338 (9)	0.6216 (2)	0.58959 (12)	0.0293 (5)
N2	0.43952 (11)	0.9130 (3)	0.37729 (15)	0.0510 (7)
C1	0.56952 (10)	0.8101 (3)	0.51663 (13)	0.0262 (5)
C2	0.58663 (10)	0.9072 (3)	0.47298 (14)	0.0284 (5)
H2A	0.5837	1.0045	0.4872	0.034*
H2B	0.5610	0.8964	0.4194	0.034*
C3	0.64480 (10)	0.8820 (3)	0.48486 (13)	0.0255 (5)
C4	0.68291 (10)	0.8814 (3)	0.56997 (13)	0.0247 (5)
H4	0.6772 (12)	0.972 (3)	0.5899 (16)	0.030*
C5	0.66910 (9)	0.7603 (3)	0.60879 (13)	0.0240 (5)
H5	0.6839 (12)	0.679 (3)	0.5982 (16)	0.029*
C6	0.60761 (9)	0.7383 (3)	0.57919 (13)	0.0248 (5)
C7	0.58742 (10)	0.6400 (3)	0.61211 (13)	0.0270 (5)
C8	0.49729 (10)	0.6960 (3)	0.53286 (14)	0.0283 (5)
C9	0.51353 (10)	0.7880 (3)	0.49294 (13)	0.0283 (5)
C10	0.66028 (11)	0.9948 (3)	0.44489 (15)	0.0342 (6)
H10A	0.6615	1.0856	0.4679	0.051*
H10B	0.6329	0.9975	0.3924	0.051*
H10C	0.6964	0.9739	0.4487	0.051*
C11	0.74318 (10)	0.8721 (3)	0.58661 (13)	0.0269 (5)
C12	0.77729 (12)	1.0014 (3)	0.61275 (17)	0.0421 (7)
H12A	0.7592	1.0775	0.5776	0.063*
H12B	0.8134	0.9840	0.6159	0.063*
H12C	0.7816	1.0274	0.6619	0.063*
C13	0.69897 (9)	0.7885 (2)	0.69231 (13)	0.0232 (5)
C14	0.75137 (10)	0.7349 (3)	0.73590 (13)	0.0256 (5)
H14	0.7680	0.6784	0.7134	0.031*
C15	0.77968 (10)	0.7624 (3)	0.81162 (14)	0.0272 (5)
H15	0.8155	0.7259	0.8408	0.033*
C16	0.75476 (10)	0.8441 (3)	0.84376 (13)	0.0257 (5)
C17	0.70294 (10)	0.8996 (3)	0.80178 (14)	0.0279 (5)
H17	0.6864	0.9558	0.8246	0.033*
C18	0.67548 (10)	0.8723 (3)	0.72617 (14)	0.0268 (5)
H18	0.6401	0.9112	0.6970	0.032*
C19	0.47278 (11)	0.8577 (3)	0.42859 (15)	0.0336 (6)
C20	0.62335 (10)	0.5444 (3)	0.67411 (15)	0.0329 (6)
H20A	0.6575	0.5270	0.6712	0.049*
H20B	0.6042	0.4559	0.6697	0.049*
H20C	0.6318	0.5880	0.7220	0.049*
C21A	0.4275 (2)	0.5666 (5)	0.5770 (3)	0.0353 (10)	0.5
H21A	0.3959	0.5019	0.5557	0.042*	0.5
H21B	0.4614	0.5096	0.5978	0.042*	0.5
C22A	0.4252 (2)	0.6476 (7)	0.6387 (4)	0.0440 (10)	0.5
O3A	0.3854 (3)	0.6537 (9)	0.6501 (4)	0.0937 (17)	0.5
O4A	0.46776 (19)	0.7276 (5)	0.6735 (3)	0.0579 (9)	0.5
C23A	0.4722 (4)	0.8397 (11)	0.7324 (4)	0.092 (2)	0.5
H23A	0.5075	0.8828	0.7492	0.138*	0.5
H23B	0.4440	0.9076	0.7072	0.138*	0.5
H23C	0.4689	0.8036	0.7744	0.138*	0.5
C21B	0.4273 (2)	0.5115 (5)	0.5455 (3)	0.0353 (10)	0.5
H21C	0.3921	0.4638	0.5144	0.042*	0.5
H21D	0.4568	0.4540	0.5441	0.042*	0.5
C22B	0.4357 (2)	0.5140 (6)	0.6237 (3)	0.0440 (10)	0.5
O3B	0.4116 (3)	0.5907 (9)	0.6469 (4)	0.0937 (17)	0.5
O4B	0.46763 (19)	0.4116 (5)	0.6610 (2)	0.0579 (9)	0.5
C23B	0.4711 (4)	0.3458 (12)	0.7333 (4)	0.092 (2)	0.5
H23D	0.5000	0.2696	0.7500	0.138*
H23E	0.4870	0.4173	0.7704	0.138*	0.5
H23F	0.4378	0.3130	0.7325	0.138*	0.5

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0251 (3)	0.0529 (4)	0.0243 (3)	0.0036 (3)	0.0053 (3)	−0.0047 (3)
S1	0.0179 (3)	0.0439 (4)	0.0366 (4)	−0.0015 (2)	0.0102 (3)	0.0027 (3)
O1	0.0256 (9)	0.0424 (11)	0.0390 (10)	0.0002 (8)	0.0199 (8)	−0.0068 (8)
O2	0.0245 (9)	0.0355 (10)	0.0291 (9)	−0.0028 (7)	0.0152 (8)	−0.0067 (7)
N1	0.0214 (10)	0.0389 (12)	0.0276 (11)	−0.0021 (9)	0.0115 (9)	0.0007 (9)
N2	0.0360 (14)	0.0655 (18)	0.0425 (14)	0.0171 (13)	0.0103 (12)	0.0142 (13)
C1	0.0220 (12)	0.0352 (13)	0.0227 (11)	0.0026 (10)	0.0114 (10)	0.0004 (10)
C2	0.0240 (12)	0.0364 (13)	0.0259 (12)	0.0058 (10)	0.0124 (10)	0.0057 (10)
C3	0.0229 (12)	0.0315 (13)	0.0246 (12)	0.0004 (9)	0.0130 (10)	−0.0004 (9)
C4	0.0230 (12)	0.0301 (13)	0.0252 (12)	0.0011 (9)	0.0147 (10)	−0.0016 (9)
C5	0.0189 (11)	0.0302 (12)	0.0239 (12)	0.0027 (9)	0.0106 (10)	0.0002 (9)
C6	0.0202 (12)	0.0336 (13)	0.0216 (11)	0.0017 (9)	0.0105 (9)	−0.0006 (9)
C7	0.0209 (12)	0.0350 (13)	0.0241 (12)	−0.0007 (10)	0.0095 (10)	0.0000 (10)
C8	0.0203 (12)	0.0374 (14)	0.0272 (12)	−0.0003 (10)	0.0111 (10)	−0.0025 (10)
C9	0.0206 (12)	0.0398 (14)	0.0236 (12)	0.0046 (10)	0.0093 (10)	0.0008 (10)
C10	0.0330 (14)	0.0432 (15)	0.0293 (13)	−0.0016 (11)	0.0169 (11)	0.0046 (11)
C11	0.0231 (12)	0.0371 (14)	0.0228 (11)	−0.0024 (10)	0.0126 (10)	−0.0034 (10)
C12	0.0289 (14)	0.0488 (17)	0.0467 (16)	−0.0111 (12)	0.0157 (13)	−0.0122 (13)
C13	0.0184 (11)	0.0273 (11)	0.0239 (11)	0.0002 (9)	0.0096 (9)	0.0022 (9)
C14	0.0206 (11)	0.0302 (12)	0.0283 (13)	0.0040 (9)	0.0132 (10)	0.0012 (10)
C15	0.0170 (11)	0.0320 (12)	0.0298 (12)	0.0033 (9)	0.0085 (10)	0.0044 (10)
C16	0.0209 (12)	0.0302 (12)	0.0237 (12)	−0.0025 (9)	0.0085 (9)	0.0006 (9)
C17	0.0245 (12)	0.0343 (13)	0.0275 (12)	0.0043 (10)	0.0144 (10)	−0.0005 (10)
C18	0.0182 (11)	0.0359 (13)	0.0261 (12)	0.0062 (10)	0.0101 (10)	0.0034 (10)
C19	0.0233 (13)	0.0449 (15)	0.0328 (14)	0.0064 (11)	0.0130 (11)	0.0036 (12)
C20	0.0259 (13)	0.0378 (14)	0.0318 (13)	−0.0012 (11)	0.0105 (11)	0.0073 (11)
C21A	0.0260 (17)	0.030 (3)	0.043 (3)	−0.0075 (18)	0.010 (2)	−0.0018 (17)
C22A	0.034 (2)	0.057 (3)	0.046 (2)	−0.015 (2)	0.0227 (19)	−0.012 (2)
O3A	0.085 (4)	0.113 (5)	0.112 (4)	−0.025 (3)	0.070 (3)	−0.044 (3)
O4A	0.0497 (19)	0.073 (2)	0.0431 (17)	−0.0192 (18)	0.0142 (15)	−0.0105 (17)
C23A	0.074 (3)	0.166 (6)	0.028 (2)	0.021 (4)	0.017 (2)	0.008 (3)
C21B	0.0260 (17)	0.030 (3)	0.043 (3)	−0.0075 (18)	0.010 (2)	−0.0018 (17)
C22B	0.034 (2)	0.057 (3)	0.046 (2)	−0.015 (2)	0.0227 (19)	−0.012 (2)
O3B	0.085 (4)	0.113 (5)	0.112 (4)	−0.025 (3)	0.070 (3)	−0.044 (3)
O4B	0.0497 (19)	0.073 (2)	0.0431 (17)	−0.0192 (18)	0.0142 (15)	−0.0105 (17)
C23B	0.074 (3)	0.166 (6)	0.028 (2)	0.021 (4)	0.017 (2)	0.008 (3)

Geometric parameters (Å, º) top

Cl1—C16	1.747 (2)	C12—H12B	0.9800
S1—C8	1.767 (3)	C12—H12C	0.9800
S1—C21B	1.770 (4)	C13—C18	1.392 (3)
S1—C21A	1.792 (4)	C13—C14	1.395 (3)
O1—C11	1.217 (3)	C14—C15	1.389 (4)
O2—C3	1.431 (3)	C14—H14	0.9500
O2—H2O	0.92 (4)	C15—C16	1.384 (4)
N1—C8	1.328 (3)	C15—H15	0.9500
N1—C7	1.349 (3)	C16—C17	1.385 (3)
N2—C19	1.150 (4)	C17—C18	1.386 (3)
C1—C6	1.398 (3)	C17—H17	0.9500
C1—C9	1.400 (3)	C18—H18	0.9500
C1—C2	1.500 (3)	C20—H20A	0.9800
C2—C3	1.521 (3)	C20—H20B	0.9800
C2—H2A	0.9900	C20—H20C	0.9800
C2—H2B	0.9900	C21A—C22A	1.496 (7)
C3—C10	1.524 (3)	C21A—H21A	0.9900
C3—C4	1.552 (3)	C21A—H21B	0.9900
C4—C11	1.533 (3)	C22A—O3A	1.219 (8)
C4—C5	1.544 (3)	C22A—O4A	1.300 (6)
C4—H4	1.00 (3)	O4A—C23A	1.569 (8)
C5—C6	1.525 (3)	C23A—H23A	0.9600
C5—C13	1.527 (3)	C23A—H23B	0.9600
C5—H5	0.95 (3)	C23A—H23C	0.9600
C6—C7	1.407 (3)	C21B—C22B	1.493 (7)
C7—C20	1.500 (3)	C21B—H21C	0.9900
C8—C9	1.401 (4)	C21B—H21D	0.9900
C9—C19	1.433 (4)	C22B—O3B	1.218 (8)
C10—H10A	0.9800	C22B—O4B	1.301 (6)
C10—H10B	0.9800	O4B—C23B	1.557 (7)
C10—H10C	0.9800	C23B—H23D	1.0152
C11—C12	1.496 (4)	C23B—H23E	0.9600
C12—H12A	0.9800	C23B—H23F	0.9601

C8—S1—C21B	100.0 (2)	C18—C13—C14	118.5 (2)
C8—S1—C21A	101.43 (19)	C18—C13—C5	120.9 (2)
C3—O2—H2O	112 (2)	C14—C13—C5	120.5 (2)
C8—N1—C7	119.3 (2)	C15—C14—C13	121.3 (2)
C6—C1—C9	118.8 (2)	C15—C14—H14	119.4
C6—C1—C2	122.2 (2)	C13—C14—H14	119.4
C9—C1—C2	119.0 (2)	C16—C15—C14	118.7 (2)
C1—C2—C3	113.5 (2)	C16—C15—H15	120.7
C1—C2—H2A	108.9	C14—C15—H15	120.7
C3—C2—H2A	108.9	C15—C16—C17	121.3 (2)
C1—C2—H2B	108.9	C15—C16—Cl1	119.50 (19)
C3—C2—H2B	108.9	C17—C16—Cl1	119.19 (19)
H2A—C2—H2B	107.7	C16—C17—C18	119.3 (2)
O2—C3—C2	106.4 (2)	C16—C17—H17	120.4
O2—C3—C10	110.3 (2)	C18—C17—H17	120.4
C2—C3—C10	109.4 (2)	C17—C18—C13	120.9 (2)
O2—C3—C4	110.56 (19)	C17—C18—H18	119.6
C2—C3—C4	107.39 (19)	C13—C18—H18	119.6
C10—C3—C4	112.5 (2)	N2—C19—C9	179.0 (3)
C11—C4—C5	109.7 (2)	C7—C20—H20A	109.5
C11—C4—C3	110.66 (18)	C7—C20—H20B	109.5
C5—C4—C3	111.7 (2)	H20A—C20—H20B	109.5
C11—C4—H4	108.4 (17)	C7—C20—H20C	109.5
C5—C4—H4	109.1 (17)	H20A—C20—H20C	109.5
C3—C4—H4	107.1 (16)	H20B—C20—H20C	109.5
C6—C5—C13	113.17 (19)	C22A—C21A—S1	113.3 (4)
C6—C5—C4	113.0 (2)	C22A—C21A—H21A	108.9
C13—C5—C4	107.37 (19)	S1—C21A—H21A	108.9
C6—C5—H5	108.1 (18)	C22A—C21A—H21B	108.9
C13—C5—H5	109.2 (18)	S1—C21A—H21B	108.9
C4—C5—H5	105.6 (18)	H21A—C21A—H21B	107.7
C1—C6—C7	117.7 (2)	O3A—C22A—O4A	122.0 (5)
C1—C6—C5	121.3 (2)	O3A—C22A—C21A	124.7 (5)
C7—C6—C5	120.9 (2)	O4A—C22A—C21A	112.7 (4)
N1—C7—C6	122.6 (2)	C22A—O4A—C23A	123.6 (5)
N1—C7—C20	113.7 (2)	O4A—C23A—H23A	106.1
C6—C7—C20	123.7 (2)	O4A—C23A—H23B	107.3
N1—C8—C9	121.9 (2)	H23A—C23A—H23B	109.5
N1—C8—S1	119.52 (19)	O4A—C23A—H23C	114.9
C9—C8—S1	118.54 (19)	H23A—C23A—H23C	109.5
C1—C9—C8	119.2 (2)	H23B—C23A—H23C	109.5
C1—C9—C19	121.1 (2)	C22B—C21B—S1	116.7 (4)
C8—C9—C19	119.7 (2)	C22B—C21B—H21C	108.1
C3—C10—H10A	109.5	S1—C21B—H21C	108.1
C3—C10—H10B	109.5	C22B—C21B—H21D	108.1
H10A—C10—H10B	109.5	S1—C21B—H21D	108.1
C3—C10—H10C	109.5	H21C—C21B—H21D	107.3
H10A—C10—H10C	109.5	O3B—C22B—O4B	124.9 (6)
H10B—C10—H10C	109.5	O3B—C22B—C21B	125.0 (6)
O1—C11—C12	121.9 (2)	O4B—C22B—C21B	109.8 (4)
O1—C11—C4	120.3 (2)	C22B—O4B—C23B	125.8 (5)
C12—C11—C4	117.8 (2)	O4B—C23B—H23D	107.7
C11—C12—H12A	109.5	O4B—C23B—H23E	104.8
C11—C12—H12B	109.5	H23D—C23B—H23E	104.4
H12A—C12—H12B	109.5	O4B—C23B—H23F	118.1
C11—C12—H12C	109.5	H23D—C23B—H23F	111.4
H12A—C12—H12C	109.5	H23E—C23B—H23F	109.5
H12B—C12—H12C	109.5

C6—C1—C2—C3	20.3 (3)	C2—C1—C9—C8	179.1 (2)
C9—C1—C2—C3	−158.2 (2)	C6—C1—C9—C19	−179.2 (2)
C1—C2—C3—O2	66.7 (3)	C2—C1—C9—C19	−0.7 (4)
C1—C2—C3—C10	−174.1 (2)	N1—C8—C9—C1	−4.7 (4)
C1—C2—C3—C4	−51.7 (3)	S1—C8—C9—C1	177.55 (19)
O2—C3—C4—C11	70.3 (2)	N1—C8—C9—C19	175.1 (2)
C2—C3—C4—C11	−174.0 (2)	S1—C8—C9—C19	−2.6 (3)
C10—C3—C4—C11	−53.5 (3)	C5—C4—C11—O1	49.8 (3)
O2—C3—C4—C5	−52.3 (2)	C3—C4—C11—O1	−74.0 (3)
C2—C3—C4—C5	63.4 (3)	C5—C4—C11—C12	−130.9 (2)
C10—C3—C4—C5	−176.1 (2)	C3—C4—C11—C12	105.3 (3)
C11—C4—C5—C6	−164.64 (19)	C6—C5—C13—C18	−39.4 (3)
C3—C4—C5—C6	−41.5 (3)	C4—C5—C13—C18	86.0 (3)
C11—C4—C5—C13	69.9 (2)	C6—C5—C13—C14	142.9 (2)
C3—C4—C5—C13	−167.01 (19)	C4—C5—C13—C14	−91.7 (3)
C9—C1—C6—C7	4.3 (4)	C18—C13—C14—C15	0.7 (4)
C2—C1—C6—C7	−174.2 (2)	C5—C13—C14—C15	178.4 (2)
C9—C1—C6—C5	−178.6 (2)	C13—C14—C15—C16	0.4 (4)
C2—C1—C6—C5	3.0 (4)	C14—C15—C16—C17	−0.9 (4)
C13—C5—C6—C1	130.4 (2)	C14—C15—C16—Cl1	177.75 (19)
C4—C5—C6—C1	8.1 (3)	C15—C16—C17—C18	0.3 (4)
C13—C5—C6—C7	−52.5 (3)	Cl1—C16—C17—C18	−178.4 (2)
C4—C5—C6—C7	−174.8 (2)	C16—C17—C18—C13	0.9 (4)
C8—N1—C7—C6	1.8 (4)	C14—C13—C18—C17	−1.3 (4)
C8—N1—C7—C20	−177.2 (2)	C5—C13—C18—C17	−179.0 (2)
C1—C6—C7—N1	−5.7 (4)	C8—S1—C21A—C22A	93.2 (4)
C5—C6—C7—N1	177.1 (2)	S1—C21A—C22A—O3A	107.5 (9)
C1—C6—C7—C20	173.2 (2)	S1—C21A—C22A—O4A	−63.5 (7)
C5—C6—C7—C20	−4.0 (4)	O3A—C22A—O4A—C23A	−0.5 (12)
C7—N1—C8—C9	3.5 (4)	C21A—C22A—O4A—C23A	170.8 (6)
C7—N1—C8—S1	−178.79 (19)	C8—S1—C21B—C22B	87.6 (4)
C21B—S1—C8—N1	−18.7 (3)	S1—C21B—C22B—O3B	46.9 (8)
C21A—S1—C8—N1	8.5 (3)	S1—C21B—C22B—O4B	−140.4 (4)
C21B—S1—C8—C9	159.1 (3)	O3B—C22B—O4B—C23B	14.8 (11)
C21A—S1—C8—C9	−173.6 (3)	C21B—C22B—O4B—C23B	−157.9 (6)
C6—C1—C9—C8	0.6 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···O1ⁱ	0.92 (4)	2.00 (4)	2.918 (3)	174 (3)

Symmetry code: (i) −x+3/2, −y+3/2, −z+1.

Acknowledgements

The support of NSF–MRI Grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged.

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