Tetrahydro-3-benzazepines with a hydroxy group in the 1-position and a methyl group in the 2-position were designed as conformationally restricted ifenprodil analogues. The enantiomerically pure 3-benzazepine (S,R)-4 representing a constitutional isomer of ifenprodil shows high affinity towards the ifenprodil binding site (Ki = 26 nM) and high antagonistic activity at the NMDA receptor (IC50 = 9.0 nM). The crystal structure analysis of the intermediate sulfonamide (S,R)-2 was performed in order to assign unequivocally the relative configuration of the methyl and hydroxy groups.
Keywords: crystal structure, NMDA receptor antagonists, GluN2B antagonists, ifenprodil analogs, tetrahydro-3-benzazepines, relative configuration, conformational restriction, hydrogen bonding
Abstract
In the title compound, C25H27NO4S, which crystallized as a racemate, the relative configuration of the adjacent OH and CH3 groups on the azepine ring is trans. The seven-membered azepin ring has a chair-like conformation. The planar aromatic rings of the benzyl and tosylate moiety are inclined to the planar 3-benzazepine ring by 78.39 (15) and 77.03 (14)°, respectively, and to each another by 13.82 (15)°. In the crystal, molecules are linked via O—H⋯O and C—H⋯O hydrogen bonds, forming double-stranded chains along the a-axis direction. The chains are linked via C—H⋯π interactions, forming a three-dimensional architecture.
Chemical context
Inhibition of overactive N-methyl-d-aspartate (NMDA) receptors represents a promising strategy for the treatment of acute (e.g. stroke, epilepsy, traumatic brain injury) and chronic neuronal disorders (e.g. neuropathic pain, depression, Alzheimer’s and Parkinson’s disease) (Bräuner-Osborne et al., 2000 ▸; Kew & Kemp, 2005 ▸; Paoletti et al., 2013 ▸; Wu & Zhou, 2009 ▸). The NMDA receptor consists of four proteins (heterotetramer), which form a cation channel allowing the penetration of Ca2+ and Na+ ions into the neuron (Furukawa et al., 2005 ▸). In particular, NMDA receptors containing the GluN2B subunit are an attractive target for the development of innovative drugs, since the expression of the GluN2B subunit is limited to only a few regions of the central nervous system, including cortex, striatum and hippocampus (Borza & Domány, 2006 ▸; Layton et al., 2006 ▸; Mony et al., 2009 ▸). Moreover, the GluN2B subunit can be addressed selectively by ligands interacting with the so-called ifenprodil binding site, which is formed at the interface between GluN2B and GluN1 subunits (Karakas et al., 2011 ▸; Paoletti et al., 2013 ▸).
The 2-piperidino-1-phenylpropan-1-ol derivative ifenprodil (Paoletti et al., 2013 ▸; Williams, 2001 ▸) (Fig. 1 ▸) represents the first ligand interacting with this binding site at the NMDA receptor. As a result of its poor selectivity and low bioavailability, ifenprodil has not been developed as a drug for clinical use. In order to improve the selectivity and metabolic stability, the flexible β-aminoalcohol substructure of ifenprodil has been incorporated into a rigid tetrahydro-3-benzazepine ring (Tewes et al., 2010a ▸,b ▸; Schepmann et al., 2010 ▸; Falck et al., 2014 ▸).
Figure 1.
Synthesis of GluN2B antagonists including the lead compound ifenprodil and the target compound (S,R)-4. Reagents and reaction conditions: (a) NaBH4, CH3OH, (S,R)-2 50%, (R,R)-3 23%.
Elucidation of the relative configuration
For the synthesis of 3-benzazepine analogs of ifenprodil, we developed a chiral pool synthesis starting with (R)-alanine. In a five step synthesis (Fig. 1 ▸), the central intermediate ketone (R)-1 was prepared from (R)-alanine (Tewes et al., 2015 ▸).
The reduction of the ketone (R)-1 with NaBH4 led to the diastereomeric alcohols (S,R)-2 and (R,R)-3, which were further transformed into potent GluN2B antagonists by reductive removal of the tosyl group, alkylation with 1-chloro-4-phenylbutane and finally, hydrogenolytic cleavage of the benzyl ether. For example, the phenol (S,R)-4 displays very high affinity towards the ifenprodil binding site of the NMDA receptor (K
i = 26 nM) and, moreover, (S,R)-4 is able to reduce the glutamate- and glycine-induced cytotoxicity with an IC50 value of 9.0 nM (Tewes et al., 2015 ▸).
The diastereomeric alcohols (S,R)-2 and (R,R)-3 were separated by flash column chromatography and isolated in 50% and 23% yield, respectively. However, as a result of flexibility of the seven-membered tetrahydro-3-benzazepine ring, it was not possible to assign the relative configuration of the methyl and hydroxy moiety. Therefore, the main diastereomer (1S,2R)-2 was crystallized and we report herein on its crystal structure.
Structural commentary
The molecular structure of the title compound (1S,2R)-2 is illustrated in Fig. 2 ▸. Since the starting material was not enantiomerically pure, the compound crystallized as a racemate. However, the relative trans-configuration of the OH and CH3 groups in the 1- and 2-positions on the azepine ring is clearly shown, leading to a trans-configuration for compound (S*,R*)-2. The CH3 and the OH groups adopt an axial orientation in the seven-membered azepine ring which has a chair conformation. The phenyl group of the benzyl moiety (C16–C21) and the phenyl group of the tosylate moiety (C25–C30) are inclined to the benzene ring of the 3-benzazepine ring (C6–C11) by 78.39 (15) and 77.03 (14)°, respectively, and to each another by 13.82 (15)°. In the azepine ring, the bonds between the N atom, N3, and its adjacent C atoms, C2 and C4 [1.483 (3) and 1.480 (3) Å, respectively] are naturally shorter than the corresponding C—C bonds [1.509 (4)–1.519 (4) Å]. The exocyclic N3—S22 bond is considerably longer at 1.622 (2) Å. The bond angles within the azepine ring are close to the tetrahedral angle [106.2 (2)–116.3 (2) °]. Fig. 2 ▸ also shows the tetrahedral geometry around the S atom, S22, of the sulfon-amide.
Figure 2.
The molecular structure of the title compound (1S,2R)-2 with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
Supramolecular features
In the crystal, molecules are linked via O—H⋯O and C—H⋯O hydrogen bonds, forming double-stranded chains along the a-axis direction (Table 1 ▸ and Fig. 3 ▸). The chains are linked via C—H⋯π interactions (Table 1 ▸), forming a three-dimensional architecture.
Table 1. Hydrogen-bond geometry (Å, °).
Cg1, Cg2 and Cg3 are the centroids of rings C6–C11, C16–C21 and C25–C30, respectively.
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| O12—H12⋯O23i | 0.83 | 2.22 | 3.034 (3) | 169 |
| C2—H2⋯O24ii | 0.99 | 2.52 | 3.265 (3) | 132 |
| C18—H18⋯Cg3iii | 0.94 | 2.89 | 3.738 (4) | 150 |
| C20—H20⋯Cg1iv | 0.94 | 2.83 | 3.631 (3) | 144 |
| C29—H29⋯Cg2v | 0.94 | 2.76 | 3.545 (3) | 142 |
Symmetry codes: (i) 
; (ii) 
; (iii) 
; (iv) 
; (v) 
.
Figure 3.
A view along the a axis of the crystal packing of the title compound (1S,2R)-2. The hydrogen bonds are shown as dashed lines (see Table 1 ▸); for clarity, H atoms not involved in these interactions are omitted.
Synthesis and crystallization
(1 S ,2 R )-7-Benzyloxy-2-methyl-3-(4-tosyl)-2,3,4,5-tetrahydro-1 H -3-benzazepin-1-ol [( S,R )-2] and (1 R ,2 R )-7-benzyloxy-2-methyl-3-(4-tosyl)-2,3,4,5-tetrahydro-1 H -3-benzazepin-1-ol [( R,R )-3]
Details of the synthesis of the title compound are illustrated in Fig. 1 ▸.
As described for the synthesis of (R,S)-2 and (S,S)-3 (Tewes et al. (2015 ▸), the ketone (R)-1 (5.20 g, 12.0 mmol) was reduced with NaBH4 (909 mg, 23.9 mmol) in CH3OH (125 ml).
(S,R)-2 (R f = 0.29): Colourless solid, m.p. 417 K, yield 2.60 g (50%). Purity (HPLC): 98.1%, t R = 22.6 min. [α]D = +1.20 (c = 0.91, CH3OH, 2.1% ee). Spectroscopic data are given in Tewes et al. (2015 ▸).
(R,R)-3 (R f = 0.44): Colourless solid, m.p. 425 K, yield 1.20 g (23%). Purity (HPLC): 95.6%, t R = 22.2 min. [α]D = +1.89 (c = 0.98, CH3OH, 8.5% ee). Spectroscopic data are given in Tewes et al. (2015 ▸).
Crystals of the title compound, suitable for X-ray diffraction analysis, were obtained by recrystallization from EtOAc.
Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The OH and C-bound H atoms were included in calculated positions and treated as riding atoms: O—H = 0.83 Å, C—H = 0.94–0.99 Å with U iso(H) = 1.5U eq(O or C-methyl) and 1.2U eq(C) for other H atoms.
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C25H27NO4S |
| M r | 437.54 |
| Crystal system, space group | Orthorhombic, P b c a |
| Temperature (K) | 223 |
| a, b, c (Å) | 7.5071 (2), 23.6113 (8), 24.5180 (8) |
| V (Å3) | 4345.9 (2) |
| Z | 8 |
| Radiation type | Cu Kα |
| μ (mm−1) | 1.59 |
| Crystal size (mm) | 0.25 × 0.15 × 0.08 |
| Data collection | |
| Diffractometer | Nonius KappaCCD APEXII |
| Absorption correction | Multi-scan (DENZO; Otwinowski et al., 2003 ▸) |
| T min, T max | 0.692, 0.884 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 40664, 3874, 3543 |
| R int | 0.064 |
| (sin θ/λ)max (Å−1) | 0.600 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.058, 0.151, 1.10 |
| No. of reflections | 3874 |
| No. of parameters | 283 |
| H-atom treatment | H-atom parameters constrained |
| Δρmax, Δρmin (e Å−3) | 0.64, −0.27 |
Supplementary Material
Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989016005855/su5286sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016005855/su5286Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016005855/su5286Isup3.cml
CCDC reference: 1472947
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
Financial support by the Deutsche Forschungsgemeinschaft is gratefully acknowledged.
supplementary crystallographic information
Crystal data
| C25H27NO4S | F(000) = 1856 |
| Mr = 437.54 | Dx = 1.337 Mg m−3 |
| Orthorhombic, Pbca | Cu Kα radiation, λ = 1.54178 Å |
| Hall symbol: -P 2ac 2ab | Cell parameters from 5365 reflections |
| a = 7.5071 (2) Å | θ = 0.9–68.3° |
| b = 23.6113 (8) Å | µ = 1.59 mm−1 |
| c = 24.5180 (8) Å | T = 223 K |
| V = 4345.9 (2) Å3 | Plate, colourless |
| Z = 8 | 0.25 × 0.15 × 0.08 mm |
Data collection
| Nonius KappaCCD APEXII diffractometer | 3874 independent reflections |
| Radiation source: fine-focus sealed tube | 3543 reflections with I > 2σ(I) |
| Graphite monochromator | Rint = 0.064 |
| ω and φ scans | θmax = 67.7°, θmin = 4.2° |
| Absorption correction: multi-scan (DENZO; Otwinowski et al., 2003) | h = 0→9 |
| Tmin = 0.692, Tmax = 0.884 | k = 0→27 |
| 40664 measured reflections | l = 0→29 |
Refinement
| Refinement on F2 | Primary atom site location: structure-invariant direct methods |
| Least-squares matrix: full | Secondary atom site location: difference Fourier map |
| R[F2 > 2σ(F2)] = 0.058 | Hydrogen site location: inferred from neighbouring sites |
| wR(F2) = 0.151 | H-atom parameters constrained |
| S = 1.10 | w = 1/[σ2(Fo2) + (0.0619P)2 + 5.5349P] where P = (Fo2 + 2Fc2)/3 |
| 3874 reflections | (Δ/σ)max = 0.001 |
| 283 parameters | Δρmax = 0.64 e Å−3 |
| 0 restraints | Δρmin = −0.27 e Å−3 |
Special details
| Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
| 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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| C1 | −0.2632 (4) | 0.25588 (13) | 0.33843 (12) | 0.0433 (7) | |
| H1 | −0.3327 | 0.2614 | 0.3045 | 0.052* | |
| C2 | −0.0688 (4) | 0.26290 (13) | 0.32342 (11) | 0.0444 (7) | |
| H2 | −0.0462 | 0.2383 | 0.2914 | 0.053* | |
| N3 | 0.0518 (3) | 0.24359 (10) | 0.36757 (9) | 0.0382 (5) | |
| C4 | 0.0510 (4) | 0.27343 (13) | 0.42068 (11) | 0.0448 (7) | |
| H4A | 0.0656 | 0.3141 | 0.4142 | 0.054* | |
| H4B | 0.1530 | 0.2605 | 0.4423 | 0.054* | |
| C5 | −0.1175 (4) | 0.26389 (14) | 0.45294 (11) | 0.0480 (7) | |
| H5A | −0.0934 | 0.2721 | 0.4914 | 0.058* | |
| H5B | −0.1504 | 0.2238 | 0.4502 | 0.058* | |
| C6 | −0.2745 (4) | 0.29959 (12) | 0.43450 (11) | 0.0408 (6) | |
| C7 | −0.3588 (4) | 0.33478 (12) | 0.47111 (11) | 0.0403 (6) | |
| H7 | −0.3162 | 0.3369 | 0.5071 | 0.048* | |
| C8 | −0.5061 (4) | 0.36736 (11) | 0.45600 (10) | 0.0360 (6) | |
| C9 | −0.5624 (4) | 0.36714 (11) | 0.40220 (11) | 0.0384 (6) | |
| H9 | −0.6574 | 0.3902 | 0.3909 | 0.046* | |
| C10 | −0.4758 (4) | 0.33218 (12) | 0.36548 (11) | 0.0415 (7) | |
| H10 | −0.5136 | 0.3322 | 0.3289 | 0.050* | |
| C11 | −0.3365 (4) | 0.29737 (12) | 0.38014 (11) | 0.0411 (6) | |
| O12 | −0.2846 (3) | 0.19835 (9) | 0.35386 (10) | 0.0508 (6) | |
| H12 | −0.3873 | 0.1933 | 0.3655 | 0.076* | |
| C13 | −0.0263 (5) | 0.32466 (13) | 0.30574 (13) | 0.0515 (8) | |
| H13A | −0.0412 | 0.3498 | 0.3367 | 0.077* | |
| H13B | −0.1067 | 0.3359 | 0.2767 | 0.077* | |
| H13C | 0.0956 | 0.3268 | 0.2928 | 0.077* | |
| O14 | −0.5837 (3) | 0.39821 (8) | 0.49686 (7) | 0.0425 (5) | |
| C15 | −0.7379 (4) | 0.43106 (13) | 0.48158 (12) | 0.0459 (7) | |
| H15A | −0.8273 | 0.4065 | 0.4646 | 0.055* | |
| H15B | −0.7039 | 0.4603 | 0.4551 | 0.055* | |
| C16 | −0.8140 (4) | 0.45824 (12) | 0.53175 (11) | 0.0393 (6) | |
| C17 | −0.9211 (4) | 0.42782 (14) | 0.56697 (13) | 0.0520 (8) | |
| H17 | −0.9428 | 0.3892 | 0.5605 | 0.062* | |
| C18 | −0.9964 (5) | 0.45419 (17) | 0.61180 (14) | 0.0611 (9) | |
| H18 | −1.0692 | 0.4334 | 0.6357 | 0.073* | |
| C19 | −0.9651 (5) | 0.51087 (16) | 0.62151 (13) | 0.0582 (9) | |
| H19 | −1.0168 | 0.5287 | 0.6519 | 0.070* | |
| C20 | −0.8587 (4) | 0.54114 (13) | 0.58683 (12) | 0.0499 (8) | |
| H20 | −0.8368 | 0.5797 | 0.5936 | 0.060* | |
| C21 | −0.7835 (4) | 0.51513 (12) | 0.54197 (12) | 0.0424 (7) | |
| H21 | −0.7110 | 0.5362 | 0.5182 | 0.051* | |
| S22 | 0.22307 (9) | 0.20715 (3) | 0.34775 (3) | 0.0364 (2) | |
| O23 | 0.3341 (2) | 0.19811 (9) | 0.39487 (8) | 0.0422 (5) | |
| O24 | 0.3039 (3) | 0.23240 (9) | 0.30048 (8) | 0.0447 (5) | |
| C26 | 0.1770 (4) | 0.12036 (12) | 0.27553 (12) | 0.0431 (7) | |
| H26 | 0.2349 | 0.1434 | 0.2498 | 0.052* | |
| C27 | 0.1279 (4) | 0.06527 (13) | 0.26233 (12) | 0.0483 (7) | |
| H27 | 0.1544 | 0.0511 | 0.2274 | 0.058* | |
| C28 | 0.0412 (4) | 0.03100 (13) | 0.29945 (12) | 0.0476 (7) | |
| C31 | −0.0091 (6) | −0.02894 (14) | 0.28515 (16) | 0.0657 (10) | |
| H31A | −0.0590 | −0.0299 | 0.2487 | 0.099* | |
| H31B | −0.0968 | −0.0427 | 0.3110 | 0.099* | |
| H31C | 0.0960 | −0.0528 | 0.2866 | 0.099* | |
| C29 | 0.0012 (4) | 0.05326 (14) | 0.35077 (12) | 0.0512 (8) | |
| H29 | −0.0591 | 0.0306 | 0.3763 | 0.061* | |
| C30 | 0.0483 (4) | 0.10756 (14) | 0.36461 (12) | 0.0467 (7) | |
| H30 | 0.0193 | 0.1222 | 0.3992 | 0.056* | |
| C25 | 0.1392 (3) | 0.14065 (12) | 0.32714 (11) | 0.0373 (6) |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| C1 | 0.0446 (16) | 0.0458 (16) | 0.0396 (14) | 0.0026 (13) | −0.0051 (13) | −0.0044 (12) |
| C2 | 0.0442 (16) | 0.0598 (18) | 0.0294 (13) | 0.0093 (14) | −0.0050 (12) | −0.0057 (12) |
| N3 | 0.0338 (11) | 0.0522 (14) | 0.0287 (11) | 0.0052 (10) | −0.0015 (9) | −0.0057 (10) |
| C4 | 0.0424 (16) | 0.0570 (18) | 0.0349 (14) | 0.0026 (14) | −0.0042 (12) | −0.0040 (13) |
| C5 | 0.0465 (17) | 0.065 (2) | 0.0320 (14) | 0.0151 (15) | 0.0018 (13) | 0.0027 (13) |
| C6 | 0.0420 (15) | 0.0484 (16) | 0.0322 (14) | 0.0081 (13) | −0.0002 (12) | −0.0002 (12) |
| C7 | 0.0445 (16) | 0.0467 (15) | 0.0295 (13) | 0.0076 (13) | −0.0026 (12) | 0.0003 (11) |
| C8 | 0.0392 (14) | 0.0344 (13) | 0.0345 (13) | 0.0005 (12) | 0.0011 (11) | −0.0008 (10) |
| C9 | 0.0397 (15) | 0.0369 (14) | 0.0387 (14) | 0.0057 (12) | −0.0057 (12) | 0.0002 (11) |
| C10 | 0.0465 (16) | 0.0453 (16) | 0.0328 (13) | 0.0080 (13) | −0.0084 (12) | −0.0028 (11) |
| C11 | 0.0399 (15) | 0.0465 (16) | 0.0368 (14) | 0.0039 (13) | −0.0019 (12) | −0.0005 (12) |
| O12 | 0.0405 (12) | 0.0410 (11) | 0.0709 (15) | −0.0013 (9) | −0.0018 (11) | −0.0050 (10) |
| C13 | 0.0531 (18) | 0.0531 (18) | 0.0483 (17) | 0.0045 (15) | 0.0078 (15) | 0.0148 (14) |
| O14 | 0.0424 (11) | 0.0503 (11) | 0.0346 (10) | 0.0144 (9) | −0.0010 (8) | −0.0037 (8) |
| C15 | 0.0469 (16) | 0.0475 (16) | 0.0432 (15) | 0.0129 (14) | −0.0060 (13) | −0.0047 (13) |
| C16 | 0.0356 (14) | 0.0421 (15) | 0.0401 (14) | 0.0084 (12) | −0.0039 (12) | −0.0004 (12) |
| C17 | 0.0545 (19) | 0.0481 (17) | 0.0533 (18) | −0.0031 (15) | −0.0016 (15) | 0.0022 (14) |
| C18 | 0.0516 (19) | 0.082 (3) | 0.0494 (19) | −0.0063 (18) | 0.0107 (15) | 0.0127 (17) |
| C19 | 0.0538 (19) | 0.078 (2) | 0.0425 (17) | 0.0188 (18) | 0.0036 (15) | −0.0082 (16) |
| C20 | 0.0566 (19) | 0.0456 (17) | 0.0473 (17) | 0.0131 (15) | −0.0035 (15) | −0.0065 (13) |
| C21 | 0.0411 (16) | 0.0430 (15) | 0.0432 (15) | 0.0047 (13) | 0.0000 (12) | 0.0006 (12) |
| S22 | 0.0295 (3) | 0.0466 (4) | 0.0330 (3) | 0.0008 (3) | 0.0022 (3) | −0.0022 (3) |
| O23 | 0.0300 (9) | 0.0565 (12) | 0.0401 (10) | 0.0032 (9) | −0.0036 (8) | −0.0038 (9) |
| O24 | 0.0428 (11) | 0.0533 (12) | 0.0379 (10) | −0.0057 (9) | 0.0086 (9) | −0.0006 (9) |
| C26 | 0.0448 (16) | 0.0470 (16) | 0.0374 (14) | −0.0002 (13) | 0.0059 (12) | 0.0012 (12) |
| C27 | 0.0576 (19) | 0.0493 (17) | 0.0380 (16) | 0.0012 (15) | 0.0049 (14) | −0.0051 (13) |
| C28 | 0.0494 (17) | 0.0473 (16) | 0.0461 (16) | −0.0006 (14) | −0.0014 (14) | −0.0003 (13) |
| C31 | 0.084 (3) | 0.0484 (19) | 0.065 (2) | −0.0099 (18) | 0.003 (2) | −0.0034 (16) |
| C29 | 0.0523 (19) | 0.0571 (19) | 0.0443 (17) | −0.0119 (16) | 0.0052 (14) | 0.0047 (14) |
| C30 | 0.0468 (17) | 0.0580 (18) | 0.0354 (14) | −0.0075 (14) | 0.0084 (13) | −0.0043 (13) |
| C25 | 0.0313 (13) | 0.0460 (15) | 0.0347 (13) | 0.0014 (12) | 0.0012 (11) | −0.0004 (12) |
Geometric parameters (Å, º)
| C1—O12 | 1.419 (4) | C15—C16 | 1.500 (4) |
| C1—C2 | 1.514 (4) | C16—C17 | 1.381 (4) |
| C1—C11 | 1.519 (4) | C16—C21 | 1.386 (4) |
| C2—N3 | 1.483 (3) | C17—C18 | 1.384 (5) |
| C2—C13 | 1.554 (4) | C18—C19 | 1.379 (5) |
| N3—C4 | 1.480 (3) | C19—C20 | 1.368 (5) |
| N3—S22 | 1.622 (2) | C20—C21 | 1.380 (4) |
| C4—C5 | 1.509 (4) | S22—O24 | 1.438 (2) |
| C5—C6 | 1.518 (4) | S22—O23 | 1.441 (2) |
| C6—C7 | 1.377 (4) | S22—C25 | 1.765 (3) |
| C6—C11 | 1.413 (4) | C26—C25 | 1.382 (4) |
| C7—C8 | 1.397 (4) | C26—C27 | 1.390 (4) |
| C8—O14 | 1.369 (3) | C27—C28 | 1.381 (4) |
| C8—C9 | 1.385 (4) | C28—C29 | 1.396 (4) |
| C9—C10 | 1.384 (4) | C28—C31 | 1.506 (4) |
| C10—C11 | 1.377 (4) | C29—C30 | 1.373 (4) |
| O14—C15 | 1.443 (3) | C30—C25 | 1.386 (4) |
| O12—C1—C2 | 106.2 (2) | C17—C16—C21 | 119.2 (3) |
| O12—C1—C11 | 113.4 (2) | C17—C16—C15 | 120.8 (3) |
| C2—C1—C11 | 116.3 (3) | C21—C16—C15 | 120.0 (3) |
| N3—C2—C1 | 112.2 (2) | C16—C17—C18 | 120.0 (3) |
| N3—C2—C13 | 111.5 (2) | C19—C18—C17 | 120.2 (3) |
| C1—C2—C13 | 111.6 (3) | C20—C19—C18 | 120.0 (3) |
| C4—N3—C2 | 119.5 (2) | C19—C20—C21 | 120.1 (3) |
| C4—N3—S22 | 121.29 (18) | C20—C21—C16 | 120.5 (3) |
| C2—N3—S22 | 115.37 (17) | O24—S22—O23 | 117.62 (12) |
| N3—C4—C5 | 113.2 (2) | O24—S22—N3 | 110.87 (12) |
| C4—C5—C6 | 114.3 (2) | O23—S22—N3 | 107.28 (11) |
| C7—C6—C11 | 119.1 (3) | O24—S22—C25 | 106.78 (12) |
| C7—C6—C5 | 119.9 (2) | O23—S22—C25 | 107.70 (12) |
| C11—C6—C5 | 121.1 (2) | N3—S22—C25 | 105.96 (13) |
| C6—C7—C8 | 121.5 (2) | C25—C26—C27 | 118.9 (3) |
| O14—C8—C9 | 124.7 (2) | C28—C27—C26 | 121.3 (3) |
| O14—C8—C7 | 115.8 (2) | C27—C28—C29 | 118.3 (3) |
| C9—C8—C7 | 119.5 (2) | C27—C28—C31 | 121.0 (3) |
| C10—C9—C8 | 118.6 (3) | C29—C28—C31 | 120.6 (3) |
| C11—C10—C9 | 122.9 (3) | C30—C29—C28 | 121.3 (3) |
| C10—C11—C6 | 118.3 (3) | C29—C30—C25 | 119.3 (3) |
| C10—C11—C1 | 119.0 (3) | C26—C25—C30 | 120.8 (3) |
| C6—C11—C1 | 122.6 (3) | C26—C25—S22 | 119.8 (2) |
| C8—O14—C15 | 116.0 (2) | C30—C25—S22 | 119.2 (2) |
| O14—C15—C16 | 108.8 (2) | ||
| O12—C1—C2—N3 | −53.8 (3) | O14—C15—C16—C17 | −80.1 (3) |
| C11—C1—C2—N3 | 73.3 (3) | O14—C15—C16—C21 | 102.7 (3) |
| O12—C1—C2—C13 | −179.8 (2) | C21—C16—C17—C18 | 0.0 (5) |
| C11—C1—C2—C13 | −52.6 (3) | C15—C16—C17—C18 | −177.2 (3) |
| C1—C2—N3—C4 | −64.1 (3) | C16—C17—C18—C19 | 0.0 (5) |
| C13—C2—N3—C4 | 61.9 (3) | C17—C18—C19—C20 | −0.2 (5) |
| C1—C2—N3—S22 | 137.5 (2) | C18—C19—C20—C21 | 0.3 (5) |
| C13—C2—N3—S22 | −96.4 (3) | C19—C20—C21—C16 | −0.3 (5) |
| C2—N3—C4—C5 | 69.7 (3) | C17—C16—C21—C20 | 0.1 (4) |
| S22—N3—C4—C5 | −133.3 (2) | C15—C16—C21—C20 | 177.4 (3) |
| N3—C4—C5—C6 | −79.2 (3) | C4—N3—S22—O24 | −114.3 (2) |
| C4—C5—C6—C7 | −123.1 (3) | C2—N3—S22—O24 | 43.7 (2) |
| C4—C5—C6—C11 | 56.9 (4) | C4—N3—S22—O23 | 15.4 (3) |
| C11—C6—C7—C8 | 1.3 (4) | C2—N3—S22—O23 | 173.3 (2) |
| C5—C6—C7—C8 | −178.6 (3) | C4—N3—S22—C25 | 130.2 (2) |
| C6—C7—C8—O14 | 176.6 (3) | C2—N3—S22—C25 | −71.8 (2) |
| C6—C7—C8—C9 | −4.1 (4) | C25—C26—C27—C28 | 0.7 (5) |
| O14—C8—C9—C10 | −177.5 (3) | C26—C27—C28—C29 | 0.8 (5) |
| C7—C8—C9—C10 | 3.2 (4) | C26—C27—C28—C31 | −179.1 (3) |
| C8—C9—C10—C11 | 0.3 (5) | C27—C28—C29—C30 | −0.8 (5) |
| C9—C10—C11—C6 | −3.1 (5) | C31—C28—C29—C30 | 179.1 (3) |
| C9—C10—C11—C1 | 173.4 (3) | C28—C29—C30—C25 | −0.8 (5) |
| C7—C6—C11—C10 | 2.2 (4) | C27—C26—C25—C30 | −2.3 (4) |
| C5—C6—C11—C10 | −177.9 (3) | C27—C26—C25—S22 | 172.5 (2) |
| C7—C6—C11—C1 | −174.1 (3) | C29—C30—C25—C26 | 2.4 (5) |
| C5—C6—C11—C1 | 5.8 (5) | C29—C30—C25—S22 | −172.4 (2) |
| O12—C1—C11—C10 | −116.8 (3) | O24—S22—C25—C26 | 7.2 (3) |
| C2—C1—C11—C10 | 119.7 (3) | O23—S22—C25—C26 | −120.0 (2) |
| O12—C1—C11—C6 | 59.5 (4) | N3—S22—C25—C26 | 125.5 (2) |
| C2—C1—C11—C6 | −64.0 (4) | O24—S22—C25—C30 | −177.9 (2) |
| C9—C8—O14—C15 | 1.8 (4) | O23—S22—C25—C30 | 54.9 (3) |
| C7—C8—O14—C15 | −178.9 (2) | N3—S22—C25—C30 | −59.7 (3) |
| C8—O14—C15—C16 | 175.5 (2) |
Hydrogen-bond geometry (Å, º)
Cg1, Cg2 and Cg3 are the centroids of rings C6–C11, C16–C21 and C25–C30, respectively.
| D—H···A | D—H | H···A | D···A | D—H···A |
| O12—H12···O23i | 0.83 | 2.22 | 3.034 (3) | 169 |
| C2—H2···O24ii | 0.99 | 2.52 | 3.265 (3) | 132 |
| C18—H18···Cg3iii | 0.94 | 2.89 | 3.738 (4) | 150 |
| C20—H20···Cg1iv | 0.94 | 2.83 | 3.631 (3) | 144 |
| C29—H29···Cg2v | 0.94 | 2.76 | 3.545 (3) | 142 |
Symmetry codes: (i) x−1, y, z; (ii) x−1/2, y, −z+1/2; (iii) x−3/2, −y+1/2, −z+1; (iv) −x−1, −y+1, −z+1; (v) x+1/2, −y+1/2, −z+1.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989016005855/su5286sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016005855/su5286Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016005855/su5286Isup3.cml
CCDC reference: 1472947
Additional supporting information: crystallographic information; 3D view; checkCIF report