The title molecule adopts a conformation with the two phenyl substituents disposed on opposite sides of the mean plane of the isoquinoline unit. In the crystal, corrugated layers of molecules are formed by N—H⋯O, C—H⋯N and C—H⋯S hydrogen bonds together with C—H⋯π(ring) interactions. These layers are connected by C—H⋯O contacts.
Keywords: crystal structure, tetrahydroisoquinoline, hydrogen bond, C—H⋯π(ring) interaction, amide
Abstract
The title molecule, C29H29N3O4S, adopts a conformation with the two phenyl substituents disposed on opposite sides of the mean plane of the isoquinoline unit. In the crystal, corrugated layers of molecules are formed by N—H⋯O, C—H⋯N and C—H⋯S hydrogen bonds together with C—H⋯π(ring) interactions. These layers are connected by C—H⋯O contacts. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (45.2%), C⋯H/H⋯C (20.2%), O⋯H/H⋯O (15.8%) and N⋯H/H⋯N (11.0%) interactions.
Chemical context
Many tetrahydroisoquinolines have medicinal importance as potent selective and orally active aldosterone synthase (CYP11B2) inhibitors (Martin et al., 2016 ▸). There are many natural and modified natural products that contain annulated pyridine rings such as the fatty acid bending protein inhibitor, (−)-oxerine, (−)-actinidine, indicaine, and other compounds that are derived from flavouring agents, namely (s)-(−)-perillaldehyde and (1R)-myrtenal (Uredi et al., 2019 ▸). In C—H activation reactions, the pyridine ring acts as the directing group (Zhang et al., 2014 ▸).
Tienopyridine derivatives show diverse pharmacological activities including antibacterial activity against a drug-resistant S. epidermidis clinical strain (Leal et al., 2008 ▸) and cytotoxic activity against human hepatocellular liver carcinoma (HepG2) (Hassan et al., 2013 ▸) and are used as antiplatelet drugs for the treatment of acute coronary syndromes (Peters et al., 2003 ▸).
Structural commentary
The title molecule adopts a conformation in which the C24–C29 phenyl group is on the same side of the mean plane of tetrahydroisoquinoline core as the O2–H2A hydroxy group, while the 4-methoxyphenyl group is situated on the opposite side (Fig. 1 ▸). There is an intramolecular O2—H2A⋯O1 hydrogen bond, which controls the orientation of the acetyl group. Puckering analysis (Cremer & Pople, 1975 ▸) shows that the conformation of the C1–C5/C9 ring is close to half-chair with the C2 atom as the flap. The mean planes of the C10–C15 and C24–C29 rings are inclined to that of the pyridine N1/C5–C9 ring by 77.17 (3) and 67.93 (5)°, respectively. All bond lengths and angles appear normal for the given formulation.
Figure 1.
The title molecule with the atom-labelling scheme and 50% probability ellipsoids. The intramolecular hydrogen bond is depicted by a dashed line.
Supramolecular features
In the crystal, N3—H3A⋯O2 hydrogen bonds and C25—H25⋯Cg1 interactions form chains of molecules extending along the a-axis direction, which are linked into corrugated layers parallel to (010) by C18—H18A⋯N2 and C2—H2⋯S1 hydrogen bonds (Table 1 ▸ and Fig. 2 ▸). The layers are connected by inversion-related C21—H21C⋯O1 contacts into the three-dimensional structure (Table 1 ▸ and Fig. 3 ▸).
Table 1. Hydrogen-bond geometry (Å, °).
Cg1 is the centroid of the N1/C–C9 ring.
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| O2—H2A⋯O1 | 0.87 | 2.13 | 2.8343 (14) | 138 |
| N3—H3A⋯O2i | 0.91 | 2.03 | 2.9335 (14) | 174 |
| C2—H2⋯S1ii | 1.00 | 2.86 | 3.8269 (12) | 163 |
| C18—H18A⋯N2ii | 0.98 | 2.52 | 3.493 (2) | 170 |
| C21—H21C⋯O1iii | 0.98 | 2.39 | 3.3593 (16) | 169 |
| C25—H25⋯Cg1i | 0.95 | 2.79 | 3.6141 (18) | 146 |
Symmetry codes: (i) x-1, y, z; (ii) x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}; (iii) -x+2, -y+1, -z+1.
Figure 2.
View of a portion of one layer seen along the b-axis direction. N—H⋯O, C—H⋯N and C—H⋯S hydrogen bonds are depicted, respectively, by dark-blue, light-blue and yellow dashed lines. C—H⋯π(ring) interactions are depicted by green dashed lines.
Figure 3.
View of portions of two layers showing their connection by C—H⋯O hydrogen bonds (black dashed lines). Other intermolecular interactions are depicted as in Fig. 2 ▸.
Hirshfeld surface analysis
Hirshfeld surface calculations (Spackman & Jayatilaka, 2009 ▸) were performed in order to further characterize the supramolecular association in the title compound. The Hirshfeld surface plotted over d norm in the range −0.5236 to +1.6751 a.u. and two-dimensional fingerprint plots (McKinnon et al., 2007 ▸) prepared using CrystalExplorer 17.5 (Turner et al., 2017 ▸) are shown in Figs. 4 ▸ and 5 ▸, respectively. The red spots on the Hirshfeld surface represent strong intermolecular interactions (Table 2 ▸), whereas the blue colour represents a lack of interactions. The fingerprint plots (Fig. 5 ▸) reveal that H⋯H (45.2%), C⋯H/H⋯C (20.2%), O⋯H/H⋯O (15.8%) and N⋯H/H⋯N (11.0%) interactions make the greatest contributions to the surface contacts. The lowest contributions are from S⋯H/H⋯S (6.2%), O⋯C/C⋯O (1.2%), N⋯C/C⋯N (0.3%) and C⋯C (0.1%) contacts.
Figure 4.
A view of the three-dimensional Hirshfeld surface of the title molecule plotted over d norm in the range −0.5236 to +1.6751 a.u.
Figure 5.
A view of the two-dimensional fingerprint plots for the title compound, showing (a) all interactions, and those delineated into (b) H⋯H, (c) C⋯H/H⋯C, (d) O⋯H/H⋯O and (e) N⋯H/H⋯N interactions. The d i and d e values are the closest internal and external distances (in Å) from given points on the Hirshfeld surface.
Table 2. Summary of short intermolecular contacts (Å) in the title structure.
| Contact | Distance | Symmetry operation |
|---|---|---|
| N2⋯H18A | 2.52 | −{1\over 2} + x, {1\over 2} − y, − {1\over 2} + z |
| H21C⋯O1 | 2.39 | 2 − x, 1 − y, 1 − z |
| O2⋯H3A | 2.03 | 1 + x, y, z |
| O3⋯H27 | 2.70 | 1 + x, y, 1 + z |
| N2⋯H16B | 2.69 | {3\over 2} − x, − {1\over 2} + y, {3\over 2} − z |
| N2⋯H12 | 2.61 | {1\over 2} + x, {1\over 2} − y, −{1\over 2} + z |
| H26⋯H18C | 2.49 | 1 − x, 1 − y, 1 − z |
| H27⋯H16B | 2.47 | −x, 1 − y, 1 − z |
Database survey
Nine comparable tetrahydroisoquinoline derivatives are: NAQRIJ (Mague et al., 2017 ▸), KUGLIK (Langenohl et al., 2020 ▸), DUSVIZ (Selvaraj et al., 2020 ▸), AKIVUO (Al-Taifi et al., 2021 ▸), ULUTAZ (Naghiyev et al., 2021 ▸), CARCOQ (Lehmann et al., 2017 ▸), POPYEB (Ben Ali & Retailleau, 2019 ▸), ENOCIU (Naicker et al., 2011 ▸) and NIWPAL (Bouasla et al., 2008 ▸).
In the crystal of NAQRIJ, dimers are formed through complementary sets of inversion-related O—H⋯O and C—H⋯O hydrogen bonds, which are further connected into zigzag chains by pairwise C—H⋯N interactions that also form inversion dimers. In KUGLIK, the heterocyclic amines are alternately connected by hydrogen bonds thus forming syndiotactic polymeric chains. The hydrogen-bonding network of water molecules forms planes parallel to (100). In the crystal of DUSVIZ, molecules are linked via C—H⋯O hydrogen bonds. For the major disorder component, they form C(11) chains that propagate parallel to the a axis. In AKIVUO, a layer structure with the layers parallel to (10
) is generated by O—H⋯O and C—H⋯O hydrogen bonds. In ULUTAZ, the molecules are linked via N—H⋯O and C—H⋯N hydrogen bonds into a three-dimensional network. Furthermore, the crystal packing is dominated by C—H⋯π contacts involving the phenyl H atoms. In CARCOQ, molecules are linked by an O—H⋯O hydrogen bond, forming chains propagating along the a-axis direction. The chains are linked by C—H⋯F hydrogen bonds, forming layers lying parallel to (001). In POPYEB, molecules are packed in a herringbone manner parallel to (103) and (10
) via weak C—H⋯O and C—H⋯π(ring) interactions. In ENOCIU, various C—H⋯π and C—H⋯O bonds link the molecules together. In NIWPAL, the molecules are linked by N—H⋯O intermolecular hydrogen bonds involving the sulfonamide function to form an infinite two-dimensional network parallel to (001).
Synthesis and crystallization
A mixture of 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-methoxyphenyl)-5,6,7,8-tetrahydroisoquinoline-3(2H)-thione (10 mmol), N-(phenyl)-2-chloroacetamide (10 mmol) and sodium acetate trihydrate (1.77 g, 13 mmol) in ethanol (100 ml) was heated under reflux for 1 h. The reaction mixture was allowed to stand at room temperature overnight. The precipitate that formed was collected and recrystallized from ethanol giving colourless crystals of the title compound, m.p.: 508–510 K, yield 84%. Its IR spectrum showed characteristic absorption bands at 3474 cm−1 (OH); 3311 cm−1 (NH); 3023 cm−1 (C-H aromatic); 2910, 2956 cm−1 (C—H aliphatic); 1800, 1900 cm−1 (overtones of phenyl group); 2220 cm−1 (C≡N) and 1694 cm−1 (C=O). Its 1H NMR (500 MHz, DMSO-d6) spectrum exhibited the following signals: δ 10.21 (s, 1H, NH), 7.48–7.49 (d, 2H, J = 5 Hz, Ar-H); 7.22–7.25 (t, 2H, Ar-H); 6.97–7.00 (t, 1H, Ar-H); 6.89–6.91 (d, J = 10 Hz, 2H, Ar-H); 6.75–6.77 (d, J =10 Hz, 2H, Ar-H); 4.84 (s, 1H, OH); 4.41–4.43 (d, J = 10 Hz, 1H, CH at C-8); 4.04–4.11 (dd, 2H, SCH2); 3.66 (s, 3H, OCH3); 3.20–3.24 (d, J = 20 Hz, 1H, CH of cyclohexene ring); 2.83–2.85 (d, J = 10 Hz, 1H, CH at C-7); 2.81–2.84 (d, J = 15 Hz, 1H, CH of cyclohexene ring); 2.08 (s, 3H, COCH3); 1.86 (s, 3H, CH3 attached to pyridine ring) and 1.21 (s, 3H, CH3 at C-6).
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3 ▸. All C-bound H atoms were placed in geometrically idealized positions (C—H = 0.95–1.00 Å) while those attached to O and N atoms were positioned from a difference map, refined for a few cycles to ensure that reasonable displacement parameters could be achieved, and then their coordinates were adjusted to give O—H = 0.87 and N—H = 0.91 Å. All H atoms were refined using a riding model with isotropic displacement parameters 1.2–1.5 times those of the parent atoms.
Table 3. Experimental details.
| Crystal data | |
| Chemical formula | C29H29N3O4S |
| M r | 515.61 |
| Crystal system, space group | Monoclinic, P21/n |
| Temperature (K) | 150 |
| a, b, c (Å) | 8.4506 (16), 23.112 (5), 13.601 (3) |
| β (°) | 99.021 (3) |
| V (Å3) | 2623.5 (9) |
| Z | 4 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.16 |
| Crystal size (mm) | 0.39 × 0.25 × 0.14 |
| Data collection | |
| Diffractometer | Bruker SMART APEX CCD |
| Absorption correction | Multi-scan (SADABS; Krause et al., 2015 ▸) |
| T min, T max | 0.89, 0.98 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 50421, 7039, 5632 |
| R int | 0.034 |
| (sin θ/λ)max (Å−1) | 0.684 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.043, 0.126, 1.10 |
| No. of reflections | 7039 |
| No. of parameters | 338 |
| H-atom treatment | H-atom parameters constrained |
| Δρmax, Δρmin (e Å−3) | 0.49, −0.20 |
Supplementary Material
Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989021005430/yk2151sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989021005430/yk2151Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989021005430/yk2151Isup3.cml
CCDC reference: 2085564
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
Author contributions are as follows. Conceptualization, SKM and EAB; methodology, JTM, EAB and MA; investigation, EMS, RH and EAB; writing (original draft), JTM, MA and SKM; writing (review and editing of the manuscript), SKM, EAB and NF; visualization, SKM, EAB, MA and JTM; funding acquisition, SAHA; resources, SKM, EAB, JTM and RH; supervision, EAB and SKM.
supplementary crystallographic information
Crystal data
| C29H29N3O4S | F(000) = 1088 |
| Mr = 515.61 | Dx = 1.305 Mg m−3 |
| Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
| a = 8.4506 (16) Å | Cell parameters from 9458 reflections |
| b = 23.112 (5) Å | θ = 2.3–29.1° |
| c = 13.601 (3) Å | µ = 0.16 mm−1 |
| β = 99.021 (3)° | T = 150 K |
| V = 2623.5 (9) Å3 | Block, colourless |
| Z = 4 | 0.39 × 0.25 × 0.14 mm |
Data collection
| Bruker SMART APEX CCD diffractometer | 7039 independent reflections |
| Radiation source: fine-focus sealed tube | 5632 reflections with I > 2σ(I) |
| Graphite monochromator | Rint = 0.034 |
| Detector resolution: 8.3333 pixels mm-1 | θmax = 29.1°, θmin = 1.8° |
| φ and ω scans | h = −11→11 |
| Absorption correction: multi-scan (SADABS; Krause et al., 2015) | k = −31→31 |
| Tmin = 0.89, Tmax = 0.98 | l = −18→18 |
| 50421 measured reflections |
Refinement
| Refinement on F2 | Primary atom site location: dual |
| Least-squares matrix: full | Secondary atom site location: difference Fourier map |
| R[F2 > 2σ(F2)] = 0.043 | Hydrogen site location: mixed |
| wR(F2) = 0.126 | H-atom parameters constrained |
| S = 1.10 | w = 1/[σ2(Fo2) + (0.0798P)2 + 0.1546P] where P = (Fo2 + 2Fc2)/3 |
| 7039 reflections | (Δ/σ)max = 0.001 |
| 338 parameters | Δρmax = 0.49 e Å−3 |
| 0 restraints | Δρmin = −0.20 e Å−3 |
Special details
| Experimental. The diffraction data were obtained from 3 sets of 400 frames, each of width 0.5° in ω, collected at φ = 0.00, 90.00 and 180.00° and 2 sets of 800 frames, each of width 0.45° in φ, collected at ω = –30.00 and 210.00°. The scan time was 20 sec/frame. |
| 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 - 1.00 Å) while that attached to oxygen was placed in a location derived from a difference map and its coordinates adjusted to give O—H = 0.87 %A. All were included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| S1 | 0.49743 (4) | 0.21951 (2) | 0.34201 (2) | 0.02816 (10) | |
| O1 | 1.20833 (12) | 0.46549 (4) | 0.59462 (8) | 0.0424 (3) | |
| O2 | 1.15692 (10) | 0.36411 (4) | 0.47667 (6) | 0.02629 (19) | |
| H2A | 1.193331 | 0.399275 | 0.484612 | 0.039* | |
| O3 | 0.60807 (11) | 0.50037 (4) | 0.89281 (7) | 0.0355 (2) | |
| O4 | 0.22412 (14) | 0.25356 (5) | 0.17522 (7) | 0.0472 (3) | |
| N1 | 0.55129 (11) | 0.32668 (4) | 0.41455 (7) | 0.0221 (2) | |
| N2 | 0.89889 (15) | 0.16351 (5) | 0.41504 (9) | 0.0376 (3) | |
| N3 | 0.11079 (13) | 0.31512 (5) | 0.27523 (7) | 0.0283 (2) | |
| H3A | 0.123005 | 0.327808 | 0.339295 | 0.034* | |
| C1 | 0.89205 (13) | 0.40578 (4) | 0.57616 (8) | 0.0193 (2) | |
| H1 | 0.912963 | 0.436858 | 0.528669 | 0.023* | |
| C2 | 1.05704 (13) | 0.38474 (5) | 0.63229 (8) | 0.0205 (2) | |
| H2 | 1.037934 | 0.365533 | 0.695266 | 0.025* | |
| C3 | 1.14103 (13) | 0.34073 (5) | 0.57288 (8) | 0.0216 (2) | |
| C4 | 1.03246 (13) | 0.28858 (5) | 0.55317 (9) | 0.0225 (2) | |
| H4A | 1.079572 | 0.261207 | 0.509824 | 0.027* | |
| H4B | 1.026798 | 0.268725 | 0.617023 | 0.027* | |
| C5 | 0.86588 (13) | 0.30393 (5) | 0.50451 (8) | 0.0193 (2) | |
| C6 | 0.77354 (13) | 0.26220 (5) | 0.44664 (8) | 0.0204 (2) | |
| C7 | 0.61510 (13) | 0.27491 (5) | 0.40627 (8) | 0.0208 (2) | |
| C8 | 0.64077 (13) | 0.36804 (5) | 0.46651 (8) | 0.0207 (2) | |
| C9 | 0.79759 (13) | 0.35800 (4) | 0.51612 (8) | 0.0187 (2) | |
| C10 | 0.80553 (13) | 0.43324 (5) | 0.65445 (8) | 0.0204 (2) | |
| C11 | 0.71854 (14) | 0.39936 (5) | 0.71205 (9) | 0.0225 (2) | |
| H11 | 0.704102 | 0.359333 | 0.697472 | 0.027* | |
| C12 | 0.65289 (14) | 0.42303 (5) | 0.79006 (9) | 0.0251 (2) | |
| H12 | 0.592213 | 0.399454 | 0.827603 | 0.030* | |
| C13 | 0.67580 (14) | 0.48133 (5) | 0.81346 (9) | 0.0263 (2) | |
| C14 | 0.76132 (15) | 0.51598 (5) | 0.75698 (9) | 0.0284 (3) | |
| H14 | 0.776837 | 0.555878 | 0.772287 | 0.034* | |
| C15 | 0.82427 (14) | 0.49165 (5) | 0.67751 (9) | 0.0249 (2) | |
| H15 | 0.881237 | 0.515577 | 0.638293 | 0.030* | |
| C16 | 0.6676 (2) | 0.55312 (7) | 0.93842 (12) | 0.0465 (4) | |
| H16A | 0.784465 | 0.550913 | 0.955575 | 0.070* | |
| H16B | 0.620648 | 0.559492 | 0.999005 | 0.070* | |
| H16C | 0.638604 | 0.585256 | 0.892094 | 0.070* | |
| C17 | 1.16474 (14) | 0.43673 (5) | 0.66046 (10) | 0.0286 (3) | |
| C18 | 1.21626 (19) | 0.44933 (7) | 0.76823 (11) | 0.0431 (4) | |
| H18A | 1.267619 | 0.414967 | 0.801321 | 0.065* | |
| H18B | 1.122528 | 0.459723 | 0.798737 | 0.065* | |
| H18C | 1.292503 | 0.481576 | 0.775466 | 0.065* | |
| C19 | 1.30468 (14) | 0.32302 (6) | 0.62869 (9) | 0.0290 (3) | |
| H19A | 1.293501 | 0.310103 | 0.695891 | 0.044* | |
| H19B | 1.377685 | 0.356189 | 0.633079 | 0.044* | |
| H19C | 1.347991 | 0.291385 | 0.592961 | 0.044* | |
| C20 | 0.84162 (14) | 0.20690 (5) | 0.43026 (9) | 0.0247 (2) | |
| C21 | 0.56021 (15) | 0.42595 (5) | 0.46529 (10) | 0.0265 (2) | |
| H21A | 0.519924 | 0.431841 | 0.528302 | 0.040* | |
| H21B | 0.470632 | 0.427392 | 0.410039 | 0.040* | |
| H21C | 0.637465 | 0.456448 | 0.456723 | 0.040* | |
| C22 | 0.29909 (14) | 0.24507 (5) | 0.35184 (9) | 0.0257 (2) | |
| H22A | 0.234973 | 0.212181 | 0.370639 | 0.031* | |
| H22B | 0.307145 | 0.274003 | 0.406068 | 0.031* | |
| C23 | 0.21135 (15) | 0.27208 (5) | 0.25746 (9) | 0.0273 (3) | |
| C24 | −0.00831 (16) | 0.34254 (5) | 0.20589 (9) | 0.0285 (3) | |
| C25 | −0.13620 (19) | 0.36782 (6) | 0.24298 (11) | 0.0396 (3) | |
| H25 | −0.141122 | 0.365874 | 0.312204 | 0.047* | |
| C26 | −0.2556 (2) | 0.39563 (8) | 0.18009 (13) | 0.0514 (4) | |
| H26 | −0.343050 | 0.412373 | 0.206057 | 0.062* | |
| C27 | −0.2491 (2) | 0.39938 (7) | 0.07906 (12) | 0.0492 (4) | |
| H27 | −0.331596 | 0.418599 | 0.035625 | 0.059* | |
| C28 | −0.1216 (2) | 0.37489 (7) | 0.04246 (11) | 0.0437 (4) | |
| H28 | −0.115917 | 0.377920 | −0.026552 | 0.052* | |
| C29 | −0.00134 (18) | 0.34587 (6) | 0.10445 (10) | 0.0351 (3) | |
| H29 | 0.084748 | 0.328480 | 0.077982 | 0.042* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| S1 | 0.02272 (16) | 0.03016 (17) | 0.03103 (18) | 0.00082 (11) | 0.00246 (12) | −0.01154 (12) |
| O1 | 0.0374 (5) | 0.0381 (5) | 0.0533 (6) | −0.0143 (4) | 0.0119 (5) | 0.0018 (5) |
| O2 | 0.0251 (4) | 0.0342 (4) | 0.0211 (4) | −0.0026 (3) | 0.0085 (3) | 0.0007 (3) |
| O3 | 0.0362 (5) | 0.0424 (5) | 0.0303 (5) | −0.0006 (4) | 0.0130 (4) | −0.0128 (4) |
| O4 | 0.0612 (7) | 0.0552 (6) | 0.0236 (5) | 0.0261 (5) | 0.0014 (5) | −0.0100 (4) |
| N1 | 0.0203 (5) | 0.0248 (4) | 0.0216 (5) | 0.0017 (4) | 0.0043 (4) | −0.0006 (4) |
| N2 | 0.0387 (6) | 0.0308 (5) | 0.0423 (7) | 0.0087 (5) | 0.0035 (5) | −0.0053 (5) |
| N3 | 0.0318 (6) | 0.0322 (5) | 0.0209 (5) | 0.0055 (4) | 0.0039 (4) | −0.0030 (4) |
| C1 | 0.0191 (5) | 0.0201 (5) | 0.0194 (5) | −0.0001 (4) | 0.0051 (4) | 0.0011 (4) |
| C2 | 0.0203 (5) | 0.0231 (5) | 0.0186 (5) | −0.0001 (4) | 0.0044 (4) | 0.0003 (4) |
| C3 | 0.0193 (5) | 0.0275 (5) | 0.0186 (5) | 0.0013 (4) | 0.0048 (4) | 0.0005 (4) |
| C4 | 0.0193 (5) | 0.0238 (5) | 0.0244 (6) | 0.0038 (4) | 0.0034 (4) | −0.0004 (4) |
| C5 | 0.0186 (5) | 0.0222 (5) | 0.0181 (5) | 0.0013 (4) | 0.0061 (4) | 0.0019 (4) |
| C6 | 0.0209 (5) | 0.0215 (5) | 0.0196 (5) | 0.0024 (4) | 0.0054 (4) | −0.0002 (4) |
| C7 | 0.0199 (5) | 0.0244 (5) | 0.0188 (5) | −0.0002 (4) | 0.0052 (4) | −0.0015 (4) |
| C8 | 0.0202 (5) | 0.0222 (5) | 0.0206 (5) | 0.0016 (4) | 0.0058 (4) | 0.0015 (4) |
| C9 | 0.0183 (5) | 0.0206 (5) | 0.0180 (5) | 0.0006 (4) | 0.0054 (4) | 0.0014 (4) |
| C10 | 0.0194 (5) | 0.0209 (5) | 0.0210 (5) | 0.0015 (4) | 0.0034 (4) | −0.0004 (4) |
| C11 | 0.0222 (5) | 0.0216 (5) | 0.0238 (5) | 0.0002 (4) | 0.0046 (4) | 0.0005 (4) |
| C12 | 0.0224 (6) | 0.0291 (6) | 0.0247 (6) | −0.0012 (4) | 0.0065 (5) | 0.0006 (4) |
| C13 | 0.0222 (6) | 0.0334 (6) | 0.0237 (6) | 0.0037 (5) | 0.0045 (4) | −0.0058 (5) |
| C14 | 0.0297 (6) | 0.0234 (5) | 0.0319 (6) | 0.0006 (5) | 0.0049 (5) | −0.0058 (5) |
| C15 | 0.0250 (6) | 0.0219 (5) | 0.0287 (6) | −0.0007 (4) | 0.0074 (5) | 0.0010 (4) |
| C16 | 0.0458 (9) | 0.0524 (9) | 0.0426 (8) | −0.0003 (7) | 0.0107 (7) | −0.0253 (7) |
| C17 | 0.0217 (6) | 0.0272 (6) | 0.0359 (7) | 0.0009 (4) | 0.0016 (5) | −0.0037 (5) |
| C18 | 0.0401 (8) | 0.0420 (8) | 0.0420 (8) | 0.0037 (6) | −0.0101 (6) | −0.0156 (6) |
| C19 | 0.0202 (6) | 0.0375 (7) | 0.0285 (6) | 0.0038 (5) | 0.0011 (5) | −0.0028 (5) |
| C20 | 0.0243 (6) | 0.0260 (5) | 0.0236 (6) | 0.0017 (4) | 0.0030 (5) | −0.0023 (4) |
| C21 | 0.0230 (6) | 0.0220 (5) | 0.0335 (6) | 0.0044 (4) | 0.0017 (5) | 0.0026 (5) |
| C22 | 0.0217 (5) | 0.0305 (6) | 0.0248 (6) | −0.0004 (5) | 0.0035 (4) | −0.0037 (5) |
| C23 | 0.0275 (6) | 0.0301 (6) | 0.0236 (6) | 0.0000 (5) | 0.0026 (5) | −0.0054 (5) |
| C24 | 0.0332 (7) | 0.0260 (6) | 0.0261 (6) | 0.0022 (5) | 0.0037 (5) | −0.0003 (5) |
| C25 | 0.0448 (8) | 0.0434 (7) | 0.0323 (7) | 0.0137 (6) | 0.0118 (6) | 0.0066 (6) |
| C26 | 0.0488 (9) | 0.0588 (10) | 0.0482 (9) | 0.0255 (8) | 0.0126 (8) | 0.0086 (7) |
| C27 | 0.0509 (10) | 0.0524 (9) | 0.0413 (8) | 0.0168 (7) | −0.0023 (7) | 0.0072 (7) |
| C28 | 0.0532 (9) | 0.0480 (8) | 0.0277 (7) | 0.0080 (7) | −0.0006 (6) | 0.0016 (6) |
| C29 | 0.0394 (7) | 0.0394 (7) | 0.0264 (6) | 0.0052 (6) | 0.0052 (6) | −0.0020 (5) |
Geometric parameters (Å, º)
| S1—C7 | 1.7661 (12) | C11—H11 | 0.9500 |
| S1—C22 | 1.8018 (12) | C12—C13 | 1.3911 (17) |
| O1—C17 | 1.2176 (16) | C12—H12 | 0.9500 |
| O2—C3 | 1.4414 (13) | C13—C14 | 1.3884 (18) |
| O2—H2A | 0.8696 | C14—C15 | 1.3955 (16) |
| O3—C13 | 1.3711 (14) | C14—H14 | 0.9500 |
| O3—C16 | 1.4233 (17) | C15—H15 | 0.9500 |
| O4—C23 | 1.2182 (15) | C16—H16A | 0.9800 |
| N1—C7 | 1.3245 (14) | C16—H16B | 0.9800 |
| N1—C8 | 1.3482 (15) | C16—H16C | 0.9800 |
| N2—C20 | 1.1463 (15) | C17—C18 | 1.4908 (19) |
| N3—C23 | 1.3545 (16) | C18—H18A | 0.9800 |
| N3—C24 | 1.4164 (16) | C18—H18B | 0.9800 |
| N3—H3A | 0.9097 | C18—H18C | 0.9800 |
| C1—C10 | 1.5216 (15) | C19—H19A | 0.9800 |
| C1—C9 | 1.5229 (15) | C19—H19B | 0.9800 |
| C1—C2 | 1.5587 (15) | C19—H19C | 0.9800 |
| C1—H1 | 1.0000 | C21—H21A | 0.9800 |
| C2—C17 | 1.5198 (16) | C21—H21B | 0.9800 |
| C2—C3 | 1.5399 (15) | C21—H21C | 0.9800 |
| C2—H2 | 1.0000 | C22—C23 | 1.5128 (17) |
| C3—C4 | 1.5129 (16) | C22—H22A | 0.9900 |
| C3—C19 | 1.5255 (16) | C22—H22B | 0.9900 |
| C4—C5 | 1.5011 (15) | C24—C25 | 1.3911 (19) |
| C4—H4A | 0.9900 | C24—C29 | 1.3923 (18) |
| C4—H4B | 0.9900 | C25—C26 | 1.375 (2) |
| C5—C9 | 1.3958 (15) | C25—H25 | 0.9500 |
| C5—C6 | 1.4021 (16) | C26—C27 | 1.386 (2) |
| C6—C7 | 1.3964 (16) | C26—H26 | 0.9500 |
| C6—C20 | 1.4334 (15) | C27—C28 | 1.378 (2) |
| C8—C9 | 1.4088 (15) | C27—H27 | 0.9500 |
| C8—C21 | 1.5006 (15) | C28—C29 | 1.387 (2) |
| C10—C15 | 1.3894 (16) | C28—H28 | 0.9500 |
| C10—C11 | 1.3957 (15) | C29—H29 | 0.9500 |
| C11—C12 | 1.3847 (16) | ||
| C7—S1—C22 | 100.59 (6) | C15—C14—H14 | 120.3 |
| C3—O2—H2A | 108.6 | C10—C15—C14 | 121.50 (11) |
| C13—O3—C16 | 117.10 (11) | C10—C15—H15 | 119.3 |
| C7—N1—C8 | 118.87 (10) | C14—C15—H15 | 119.3 |
| C23—N3—C24 | 127.59 (10) | O3—C16—H16A | 109.5 |
| C23—N3—H3A | 115.3 | O3—C16—H16B | 109.5 |
| C24—N3—H3A | 117.1 | H16A—C16—H16B | 109.5 |
| C10—C1—C9 | 114.12 (9) | O3—C16—H16C | 109.5 |
| C10—C1—C2 | 106.17 (9) | H16A—C16—H16C | 109.5 |
| C9—C1—C2 | 112.94 (8) | H16B—C16—H16C | 109.5 |
| C10—C1—H1 | 107.8 | O1—C17—C18 | 122.75 (13) |
| C9—C1—H1 | 107.8 | O1—C17—C2 | 118.98 (12) |
| C2—C1—H1 | 107.8 | C18—C17—C2 | 118.24 (12) |
| C17—C2—C3 | 110.33 (9) | C17—C18—H18A | 109.5 |
| C17—C2—C1 | 109.33 (9) | C17—C18—H18B | 109.5 |
| C3—C2—C1 | 113.55 (9) | H18A—C18—H18B | 109.5 |
| C17—C2—H2 | 107.8 | C17—C18—H18C | 109.5 |
| C3—C2—H2 | 107.8 | H18A—C18—H18C | 109.5 |
| C1—C2—H2 | 107.8 | H18B—C18—H18C | 109.5 |
| O2—C3—C4 | 106.15 (9) | C3—C19—H19A | 109.5 |
| O2—C3—C19 | 110.25 (9) | C3—C19—H19B | 109.5 |
| C4—C3—C19 | 110.59 (10) | H19A—C19—H19B | 109.5 |
| O2—C3—C2 | 110.17 (9) | C3—C19—H19C | 109.5 |
| C4—C3—C2 | 107.61 (9) | H19A—C19—H19C | 109.5 |
| C19—C3—C2 | 111.88 (9) | H19B—C19—H19C | 109.5 |
| C5—C4—C3 | 112.99 (9) | N2—C20—C6 | 177.76 (14) |
| C5—C4—H4A | 109.0 | C8—C21—H21A | 109.5 |
| C3—C4—H4A | 109.0 | C8—C21—H21B | 109.5 |
| C5—C4—H4B | 109.0 | H21A—C21—H21B | 109.5 |
| C3—C4—H4B | 109.0 | C8—C21—H21C | 109.5 |
| H4A—C4—H4B | 107.8 | H21A—C21—H21C | 109.5 |
| C9—C5—C6 | 118.41 (10) | H21B—C21—H21C | 109.5 |
| C9—C5—C4 | 122.51 (10) | C23—C22—S1 | 114.22 (9) |
| C6—C5—C4 | 119.07 (9) | C23—C22—H22A | 108.7 |
| C7—C6—C5 | 119.41 (10) | S1—C22—H22A | 108.7 |
| C7—C6—C20 | 120.66 (10) | C23—C22—H22B | 108.7 |
| C5—C6—C20 | 119.93 (10) | S1—C22—H22B | 108.7 |
| N1—C7—C6 | 122.32 (10) | H22A—C22—H22B | 107.6 |
| N1—C7—S1 | 119.46 (9) | O4—C23—N3 | 124.77 (12) |
| C6—C7—S1 | 118.22 (8) | O4—C23—C22 | 122.14 (11) |
| N1—C8—C9 | 122.85 (10) | N3—C23—C22 | 112.92 (10) |
| N1—C8—C21 | 114.24 (10) | C25—C24—C29 | 119.47 (12) |
| C9—C8—C21 | 122.90 (10) | C25—C24—N3 | 117.25 (11) |
| C5—C9—C8 | 117.89 (10) | C29—C24—N3 | 123.27 (12) |
| C5—C9—C1 | 121.24 (10) | C26—C25—C24 | 120.45 (14) |
| C8—C9—C1 | 120.80 (9) | C26—C25—H25 | 119.8 |
| C15—C10—C11 | 118.02 (10) | C24—C25—H25 | 119.8 |
| C15—C10—C1 | 120.86 (10) | C25—C26—C27 | 120.43 (14) |
| C11—C10—C1 | 120.80 (10) | C25—C26—H26 | 119.8 |
| C12—C11—C10 | 121.20 (11) | C27—C26—H26 | 119.8 |
| C12—C11—H11 | 119.4 | C28—C27—C26 | 119.13 (14) |
| C10—C11—H11 | 119.4 | C28—C27—H27 | 120.4 |
| C11—C12—C13 | 119.99 (11) | C26—C27—H27 | 120.4 |
| C11—C12—H12 | 120.0 | C27—C28—C29 | 121.28 (14) |
| C13—C12—H12 | 120.0 | C27—C28—H28 | 119.4 |
| O3—C13—C14 | 124.61 (11) | C29—C28—H28 | 119.4 |
| O3—C13—C12 | 115.51 (11) | C28—C29—C24 | 119.22 (13) |
| C14—C13—C12 | 119.87 (11) | C28—C29—H29 | 120.4 |
| C13—C14—C15 | 119.40 (11) | C24—C29—H29 | 120.4 |
| C13—C14—H14 | 120.3 | ||
| C10—C1—C2—C17 | −73.07 (11) | C2—C1—C9—C5 | −7.81 (14) |
| C9—C1—C2—C17 | 161.14 (9) | C10—C1—C9—C8 | 53.90 (13) |
| C10—C1—C2—C3 | 163.24 (9) | C2—C1—C9—C8 | 175.28 (9) |
| C9—C1—C2—C3 | 37.45 (12) | C9—C1—C10—C15 | −145.75 (11) |
| C17—C2—C3—O2 | −68.34 (12) | C2—C1—C10—C15 | 89.18 (12) |
| C1—C2—C3—O2 | 54.80 (12) | C9—C1—C10—C11 | 40.85 (14) |
| C17—C2—C3—C4 | 176.35 (9) | C2—C1—C10—C11 | −84.22 (12) |
| C1—C2—C3—C4 | −60.51 (11) | C15—C10—C11—C12 | −0.12 (17) |
| C17—C2—C3—C19 | 54.68 (13) | C1—C10—C11—C12 | 173.46 (10) |
| C1—C2—C3—C19 | 177.82 (9) | C10—C11—C12—C13 | −1.27 (18) |
| O2—C3—C4—C5 | −64.32 (11) | C16—O3—C13—C14 | −19.52 (18) |
| C19—C3—C4—C5 | 176.09 (9) | C16—O3—C13—C12 | 161.09 (12) |
| C2—C3—C4—C5 | 53.62 (12) | C11—C12—C13—O3 | −179.06 (10) |
| C3—C4—C5—C9 | −26.75 (15) | C11—C12—C13—C14 | 1.52 (18) |
| C3—C4—C5—C6 | 154.50 (10) | O3—C13—C14—C15 | −179.75 (11) |
| C9—C5—C6—C7 | −2.77 (16) | C12—C13—C14—C15 | −0.39 (18) |
| C4—C5—C6—C7 | 176.02 (10) | C11—C10—C15—C14 | 1.28 (17) |
| C9—C5—C6—C20 | 177.84 (10) | C1—C10—C15—C14 | −172.30 (11) |
| C4—C5—C6—C20 | −3.36 (16) | C13—C14—C15—C10 | −1.03 (18) |
| C8—N1—C7—C6 | −2.18 (16) | C3—C2—C17—O1 | 59.92 (14) |
| C8—N1—C7—S1 | 177.89 (8) | C1—C2—C17—O1 | −65.65 (14) |
| C5—C6—C7—N1 | 4.95 (17) | C3—C2—C17—C18 | −118.40 (12) |
| C20—C6—C7—N1 | −175.67 (11) | C1—C2—C17—C18 | 116.04 (12) |
| C5—C6—C7—S1 | −175.12 (8) | C7—S1—C22—C23 | 103.44 (9) |
| C20—C6—C7—S1 | 4.25 (15) | C24—N3—C23—O4 | 7.0 (2) |
| C22—S1—C7—N1 | −22.84 (10) | C24—N3—C23—C22 | −168.25 (11) |
| C22—S1—C7—C6 | 157.23 (9) | S1—C22—C23—O4 | 36.74 (17) |
| C7—N1—C8—C9 | −2.71 (16) | S1—C22—C23—N3 | −147.86 (9) |
| C7—N1—C8—C21 | 176.15 (10) | C23—N3—C24—C25 | 155.07 (13) |
| C6—C5—C9—C8 | −1.73 (15) | C23—N3—C24—C29 | −25.9 (2) |
| C4—C5—C9—C8 | 179.52 (10) | C29—C24—C25—C26 | 0.4 (2) |
| C6—C5—C9—C1 | −178.72 (9) | N3—C24—C25—C26 | 179.45 (14) |
| C4—C5—C9—C1 | 2.53 (16) | C24—C25—C26—C27 | −0.7 (3) |
| N1—C8—C9—C5 | 4.65 (16) | C25—C26—C27—C28 | 0.0 (3) |
| C21—C8—C9—C5 | −174.11 (10) | C26—C27—C28—C29 | 1.0 (3) |
| N1—C8—C9—C1 | −178.34 (10) | C27—C28—C29—C24 | −1.3 (2) |
| C21—C8—C9—C1 | 2.90 (16) | C25—C24—C29—C28 | 0.6 (2) |
| C10—C1—C9—C5 | −129.19 (11) | N3—C24—C29—C28 | −178.39 (13) |
Hydrogen-bond geometry (Å, º)
Cg1 is the centroid of the N1/C–C9 ring.
| D—H···A | D—H | H···A | D···A | D—H···A |
| O2—H2A···O1 | 0.87 | 2.13 | 2.8343 (14) | 138 |
| N3—H3A···O2i | 0.91 | 2.03 | 2.9335 (14) | 174 |
| C2—H2···S1ii | 1.00 | 2.86 | 3.8269 (12) | 163 |
| C18—H18A···N2ii | 0.98 | 2.52 | 3.493 (2) | 170 |
| C21—H21C···O1iii | 0.98 | 2.39 | 3.3593 (16) | 169 |
| C25—H25···Cg1i | 0.95 | 2.79 | 3.6141 (18) | 146 |
Symmetry codes: (i) x−1, y, z; (ii) x+1/2, −y+1/2, z+1/2; (iii) −x+2, −y+1, −z+1.
Funding Statement
This work was funded by Tulane University grant .
References
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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/S2056989021005430/yk2151sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989021005430/yk2151Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989021005430/yk2151Isup3.cml
CCDC reference: 2085564
Additional supporting information: crystallographic information; 3D view; checkCIF report