In the crystal, the molecules are linked by N—H⋯N and C—H⋯N hydrogen bonds, forming double layers parallel to the (001) plane. The layers are connected by van der Waals interactions, generating a three-dimensional supramolecular structure.
Keywords: crystal structure, hydrogen bonds, C—H⋯π interactions, π–π stacking interactions, Hirshfeld surface analysis
Abstract
The title compound, C11H8N4OS, crystallizes with two independent molecules in the asymmetric unit. In the crystal, the N—H⋯N and C—H⋯N hydrogen bonds connect the molecules, generating double layers parallel to the (001) plane. The layers are joined by C—H⋯π interactions to form a three-dimensional supramolecular structure.
Chemical context
Compounds with the five-membered isoxazole, isothiazole and 1,3,4-thiadiazole heterocycles possess high potential for biological activity and are privileged scaffolds for the development of pharmaceutical agents (Das & Chanda, 2021 ▸; Kletskov et al., 2020 ▸; Khalilullah et al., 2014 ▸; Yadigarov et al., 2009 ▸; Safavora et al., 2019 ▸; Zubkov et al., 2014 ▸). In particular, isoxazoles are able to enhance the action of ‘first-line’ antitumor substances, which makes it possible to reduce their therapeutic doses and thus reduce toxic side effects (Khalilov et al., 2021 ▸; Kulchitsky et al., 2012 ▸; Naghiyev et al., 2020 ▸). The combination of the pharmacophore fragments of isoxazole and thiadiazole in one molecule increases the variability of its binding to the key sites of enzymes regulating the biological action. The presence of an amino group additionally increases the biopotential of the molecule, and the introduction of an aromatic fragment makes it possible to implement binding with a biotarget by π-stacking (Shixaliyev et al., 2014 ▸, 2018 ▸; Mahmudov et al., 2011 ▸, 2013 ▸; Gurbanov et al., 2017 ▸, 2018a
▸,b
▸). To assess the biological potential of a molecule in silico and the molecular docking procedure, which is widely used for the development of new pharmaceuticals, information about the structures of promising molecules is needed. All this initiated our research on the synthesis of 5-(5-phenylisoxazol-3-yl)-1,3,4-thiadiazol-2-amine (1) and the further determination of the accurate structure of its molecule. The synthesis and structure of the compound has not published before. There are many approaches for building a thiadiazole heterocycle based on the use of carboxylic acids (Bhinge et al., 2015 ▸; Nayak et al., 2014 ▸), carbonyl chlorides (Sun et al., 2001 ▸; Kudelko et al., 2020 ▸), aldehydes (Shivakumara et al., 2019 ▸; Wang et al., 2019 ▸), etc. We chose here a method based on the transformation of carbonitriles (as shown in the scheme) as the shortest and most convenient way to achieve this purpose (Sakthivel et al., 2016 ▸; et al.; Abdelhamid et al., 2011 ▸). Its efficacy has recently been demonstrated by one of us (Petkevich et al., 2021 ▸). The synthetic procedure involves the interaction of 5-phenylisoxazole-3-carbonitrile with thiosemicarbazide. The starting 5-phenylisoxazole-3-carbonitrile was obtained according to the previously described method (Kulchitsky et al., 2012 ▸; Bumagin et al., 2018 ▸).
Structural commentary
The title compound 1 crystallizes in the orthorhombic space group Pca21, with two independent molecules (I with S1 and II with S2) in the asymmetric unit (Fig. 1 ▸). The oxazole (O1/N2/C3/C4/C5 and O12/N13/C14/C15/C16) and thiadiazole (S1/N3/N4/C1/C2 and S2/N14/N15/C12/C13) rings are essentially planar and inclined to one another by 18.8 (3) and 14.6 (3)° in molecules I and II, respectively. The phenyl rings (C6–C11 and C17–C22) make dihedral angles of 24.6 (3) and 26.8 (3)° with the oxazole rings in molecules I and II, respectively. Fig. 2 ▸ shows the overlay of molecules I and II in the asymmetric unit, with an r.m.s. deviation of 0.087 Å. The C—N bond distances to the amino N atom of 1.330 (6) and 1.328 (6) Å, respectively, in molecules I and II indicate strong conjugation of the amino groups with the thiadiazole π-systems.
Figure 1.
View of the two independent molecules, I and II, in the asymmetric unit of the title compound, with displacement ellipsoids for the non-hydrogen atoms drawn at the 30% probability level.
Figure 2.
Overlay image of two independent molecules in the asymmetric unit of the title compound.
Supramolecular features
In the crystal, molecules are linked by N—H⋯N and C—H⋯N hydrogen bonds (Table 1 ▸, Figs. 3 ▸ and 4 ▸), forming double layers of cross-linked molecules parallel to the (001) plane. The molecules within a layer are further linked by π–π stacking interactions between the thiadiazole rings [Cg1⋯Cg4(x, y, z) = 3.636 (3) Å, slippage = 1.283 Å, where Cg1 and Cg4 are the centroids of the rings S1/N3/N4/C1/C2 and S2/N14/N15/C12/C13, respectively]. The layers are linked by van der Waals interactions (Table 2 ▸), forming a three-dimensional supramolecular structure (Fig. 5 ▸).
Table 1. Hydrogen-bond geometry (Å, °).
Cg4 and Cg6 are the centroids of the S2/N14/N15/C12/C13 and C17–C22 rings, respectively
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| N1—H1A⋯N14i | 0.88 | 2.10 | 2.974 (6) | 172 |
| N1—H1B⋯N4ii | 0.88 | 2.20 | 3.071 (5) | 169 |
| N12—H12A⋯N3iii | 0.88 | 2.06 | 2.933 (6) | 174 |
| N12—H12B⋯N15iv | 0.88 | 2.24 | 3.108 (5) | 170 |
| C4—H4⋯N2iv | 0.95 | 2.56 | 3.363 (6) | 142 |
| C15—H15⋯N13ii | 0.95 | 2.46 | 3.323 (6) | 151 |
| C8—H8⋯Cg6v | 0.95 | 2.98 | 3.774 (6) | 142 |
| C22—H22⋯Cg4i | 0.95 | 2.95 | 3.648 (6) | 132 |
Symmetry codes: (i)
; (ii)
; (iii)
; (iv)
; (v)
.
Figure 3.
A view of the intermolecular N—H⋯N and C—H⋯N interactions in the crystal structure of the title compound projected along the a axis.
Figure 4.
A view of the intermolecular N—H⋯N and C—H⋯N interactions in the crystal structure of the title compound projected along the b axis.
Table 2. Summary of short interatomic contacts (Å) in the title compound.
| Contact | Distance | Symmetry operation |
|---|---|---|
| S1⋯H12B | 3.10 |
+ x, 1 − y, z
|
| N2⋯H4 | 2.56 |
+ x, 1 − y, z
|
| N3⋯H12A | 2.06 | x, −1 + y, z |
| H1B⋯S2 | 3.09 |
+ x, −y, z
|
| H1B⋯N4 | 2.20 |
+ x, −y, z
|
| C2⋯N14 | 3.437 (7) | x, y, z |
| C4⋯H10 | 3.05 | x, −1 + y, z |
| C7⋯H20 | 2.91 | 1 − x, −y,
+ z
|
| H10⋯H19 | 2.49 | 1 − x, 1 − y,
+ z
|
| H8⋯C18 | 2.87 |
− x, 1 + y,
+ z
|
| H9⋯H21 | 2.59 |
− x, 2 + y,
+ z
|
| N13⋯H15 | 2.46 | −
+ x, −y, z
|
| H12B⋯N15 | 2.24 | −
+ x, 1 − y, z
|
| C13⋯H22 | 2.91 | x, 1 + y, z |
| C19⋯H22 | 2.94 |
+ x, −1 − y, z
|
Figure 5.
A view of the layer structure formed by intermolecular N—H⋯N, C—H⋯N, C—H⋯π and π–π interactions in the crystal structure of the title compound projected along the b axis.
Hirshfeld surface analysis
Crystal Explorer 17 (Turner et al., 2017 ▸) was used to construct Hirshfeld surfaces for both independent molecules in the asymmetric unit of the title compound. The d norm mappings for molecule I were performed in the range of −0.5418 to 1.2328 a.u., and for molecule II in the range of −0.5446 to 1.1988 a.u. On the d norm surfaces, bold red circles show the locations of N—H⋯N interactions. Smaller red spots are caused by C—H⋯N interactions (Fig. 6 ▸ a,b for molecule I and Fig. 6 ▸ c,d for molecule II).
Figure 6.
Front (a) and back (b) views of the three-dimensional Hirshfeld surface for molecule I. Front (c) and back (d) views of the three-dimensional Hirshfeld surface for molecule II. Some intermolecular N—H⋯N and C—H⋯N interactions are shown as dashed lines.
Fingerprint plots (Fig. 7 ▸) reveal that while H⋯H (26.6% for molecule I and 25.3% for molecule II) interactions make the largest contributions to the surface contacts (Table 2 ▸), N⋯H/H⋯N (24.1% for I and 24.1% for II) and C⋯H/H⋯C (19.3% for I and 21.0% for II) contacts are also significant. The contributions of other, less noteworthy contacts are listed in Table 3 ▸. The environments of molecules I and II are quite similar, as indicated in Table 3 ▸.
Figure 7.
The two-dimensional fingerprint plots for molecules I and II of the title compound showing (a) all interactions, and delineated into (b) H⋯H, (c) N⋯H/H⋯N and (d) C⋯H/H⋯C interactions. The d i and d e values are the closest internal and external distances (in Å) from given points on the Hirshfeld surface.
Table 3. Percentage contributions of interatomic contacts to the Hirshfeld surface for the title compound.
| Contact | molecule I | molecule II |
|---|---|---|
| H⋯H | 26.6 | 25.3 |
| N⋯H/H⋯N | 24.1 | 24.1 |
| C⋯H/H⋯C | 19.3 | 21.0 |
| S⋯C/C⋯S | 6.7 | 5.5 |
| O⋯H/H⋯O | 6.0 | 5.5 |
| S⋯H/H⋯S | 5.9 | 6.9 |
| N⋯C/C⋯N | 4.5 | 5.3 |
| O⋯C/C⋯O | 2.5 | 2.6 |
| C⋯C | 1.3 | 0.9 |
| O⋯N/N⋯O | 1.1 | 1.0 |
| N⋯N | 1.0 | 0.9 |
| S⋯N/N⋯S | 0.9 | 0.8 |
| S⋯O/O⋯S | 0.1 | 0.1 |
Database survey
The only hit related to the title compound found in a search of the Cambridge Structural Database (CSD, Version 5.42; May 2021; Groom et al., 2016 ▸) was 1-{[3-(thiophen-2-yl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}-1H-indole-2,3-dione (NAQQOO: Rayni et al., 2017 ▸). In the structure of NAQQOO, the indole ring system is almost planar as expected. The dihedral angle between this plane and that of the thiophene ring is 2.01 (2)°. The mean plane of the isoxazole ring is inclined by 19.78 (14) and 20.83 (12)° to the thiophene and indoline mean planes, respectively. In the crystal, the combination of C—H⋯O hydrogen bonds forms stepped layers two molecules thick, or slabs, which are oriented parallel to (
03). These layers are associated through offset π-stacking interactions, involving inversion-related indole rings in adjacent layers [interplanar distance of 3.479 (1) Å], forming a supramolecular three-dimensional structure.
Synthesis and crystallization
5-(5-Phenylisoxazol-3-yl)-1,3,4-thiadiazol-2-amine:
Thiosemicarbazide (1.0 g, 11 mmol) was added at r.t to a solution of 5-phenylisoxazole-3-carbonitrile (1.70 g, 10 mmol) in CF3CO2H (10 mL), and the resulting mixture was heated under reflux for 6 h. After cooling, the mixture was poured into water (150 mL) and basified with 25% aqueous ammonia to pH ∼8. The precipitate was filtered off, washed with warm H2O (3 × 30 mL) and dried under reduced pressure over P2O5. The obtained solid product was recrystallized from MeOH giving light-yellow cubic crystals, yield 2.37 g (97%), m.p. = 501–503 K. IR (KBr), ν (cm−1): 3413, 3278, 3147, 3125, 2927, 1615, 1592, 1575, 1508, 1450, 1436, 1417, 1323, 1220, 1140, 1068, 947, 931, 817, 763, 686, 661, 629, 575. 1H NMR (DMSO-d 6, 500 MHz, 301 K): δ = 7.51–7.58 (m, 4H, 3HAr + 1H-isox), 7.80 (br.s, 2H, NH2), 7.92–7.98 (m, 2HAr). 13C NMR (DMSO-d 6, 125 MHz, 301 K): δ = 98.53 (CH-isox), 126.45 (2CHAr), 129.89 (2CHAr), 131.47 (1CHAr), 126.90, 145.57, 157.67, 170.46, 170.76 (5C). Mass-spectrum, m/z (I rel, %): 267 [M+Na]+ (5), 245 [M+H]+ (100). Elemental analysis calculated for C11H8N4OS (%): C 54.09, H 3.30, N 22.94, S 13.12; found (%): C 54.21, H 3.11, N 22.99, S 13.18.
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4 ▸. All H atoms were positioned geometrically (N—H = 0.88 Å, C—H = 0.95 Å) and refined using a riding model with U iso(H) = 1.2U eq(N, C).
Table 4. Experimental details.
| Crystal data | |
| Chemical formula | C11H8N4OS |
| M r | 244.27 |
| Crystal system, space group | Orthorhombic, P c a21 |
| Temperature (K) | 100 |
| a, b, c (Å) | 11.142 (2), 7.2555 (15), 27.333 (6) |
| V (Å3) | 2209.6 (8) |
| Z | 8 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.28 |
| Crystal size (mm) | 0.24 × 0.18 × 0.02 |
| Data collection | |
| Diffractometer | Bruker D8 QUEST PHOTON-III CCD |
| Absorption correction | Multi-scan (SADABS; Krause et al., 2015 ▸) |
| T min, T max | 0.924, 0.985 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 37296, 6442, 4347 |
| R int | 0.110 |
| (sin θ/λ)max (Å−1) | 0.703 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.053, 0.125, 1.03 |
| No. of reflections | 6442 |
| No. of parameters | 307 |
| No. of restraints | 1 |
| H-atom treatment | H-atom parameters constrained |
| Δρmax, Δρmin (e Å−3) | 0.32, −0.34 |
| Absolute structure | Flack x determined using 1699 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸) |
| Absolute structure parameter | 0.44 (7) |
Supplementary Material
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989022003450/yk2168sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989022003450/yk2168Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989022003450/yk2168Isup3.cml
CCDC reference: 2162503
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
The authors’ contributions are as follows: Conceptualization, EVN, MA and SM; synthesis, EVN, EKP, SKP and EAA; X-ray analysis, STÇ, VNK and MA; writing (review and editing of the manuscript), EVN, STÇ, MA and SM; funding acquisition, EVN, SKP, EAA and SM; supervision, MA, SKP and SM.
supplementary crystallographic information
Crystal data
| C11H8N4OS | Dx = 1.469 Mg m−3 |
| Mr = 244.27 | Mo Kα radiation, λ = 0.71073 Å |
| Orthorhombic, Pca21 | Cell parameters from 5781 reflections |
| a = 11.142 (2) Å | θ = 2.8–28.1° |
| b = 7.2555 (15) Å | µ = 0.28 mm−1 |
| c = 27.333 (6) Å | T = 100 K |
| V = 2209.6 (8) Å3 | Plate, yellow |
| Z = 8 | 0.24 × 0.18 × 0.02 mm |
| F(000) = 1008 |
Data collection
| Bruker D8 QUEST PHOTON-III CCD diffractometer | 4347 reflections with I > 2σ(I) |
| φ and ω scans | Rint = 0.110 |
| Absorption correction: multi-scan (SADABS; Krause et al., 2015) | θmax = 30.0°, θmin = 2.8° |
| Tmin = 0.924, Tmax = 0.985 | h = −15→15 |
| 37296 measured reflections | k = −10→10 |
| 6442 independent reflections | l = −38→38 |
Refinement
| Refinement on F2 | Secondary atom site location: difference Fourier map |
| Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
| R[F2 > 2σ(F2)] = 0.053 | H-atom parameters constrained |
| wR(F2) = 0.125 | w = 1/[σ2(Fo2) + 1.1115P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.03 | (Δ/σ)max < 0.001 |
| 6442 reflections | Δρmax = 0.32 e Å−3 |
| 307 parameters | Δρmin = −0.34 e Å−3 |
| 1 restraint | Absolute structure: Flack x determined using 1699 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
| Primary atom site location: difference Fourier map | Absolute structure parameter: 0.44 (7) |
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| S1 | 0.55238 (9) | 0.15104 (17) | 0.56580 (4) | 0.0346 (3) | |
| O1 | 0.4133 (3) | 0.6622 (5) | 0.63143 (14) | 0.0407 (8) | |
| N1 | 0.5629 (3) | −0.1735 (6) | 0.51880 (17) | 0.0411 (11) | |
| H1A | 0.5313 | −0.2668 | 0.5028 | 0.049* | |
| H1B | 0.6408 | −0.1700 | 0.5241 | 0.049* | |
| N2 | 0.4659 (3) | 0.5198 (6) | 0.60417 (16) | 0.0404 (10) | |
| N3 | 0.3753 (3) | −0.0298 (6) | 0.52886 (16) | 0.0368 (10) | |
| N4 | 0.3268 (3) | 0.1278 (6) | 0.54882 (15) | 0.0363 (9) | |
| C1 | 0.4931 (4) | −0.0378 (7) | 0.53495 (18) | 0.0337 (11) | |
| C2 | 0.4066 (3) | 0.2358 (7) | 0.56877 (18) | 0.0324 (10) | |
| C3 | 0.3784 (4) | 0.4041 (7) | 0.59427 (18) | 0.0325 (10) | |
| C4 | 0.2667 (4) | 0.4653 (7) | 0.61365 (18) | 0.0339 (10) | |
| H4 | 0.1905 | 0.4077 | 0.6107 | 0.041* | |
| C5 | 0.2934 (4) | 0.6234 (7) | 0.63716 (19) | 0.0353 (11) | |
| C6 | 0.2228 (4) | 0.7554 (7) | 0.66463 (18) | 0.0381 (11) | |
| C7 | 0.1161 (4) | 0.6999 (7) | 0.68654 (19) | 0.0400 (11) | |
| H7 | 0.0917 | 0.5746 | 0.6847 | 0.048* | |
| C8 | 0.0454 (5) | 0.8268 (9) | 0.7110 (2) | 0.0547 (16) | |
| H8 | −0.0272 | 0.7883 | 0.7261 | 0.066* | |
| C9 | 0.0801 (6) | 1.0089 (10) | 0.7136 (2) | 0.0622 (17) | |
| H9 | 0.0305 | 1.0958 | 0.7299 | 0.075* | |
| C10 | 0.1865 (6) | 1.0655 (9) | 0.6926 (2) | 0.0586 (16) | |
| H10 | 0.2103 | 1.1910 | 0.6949 | 0.070* | |
| C11 | 0.2591 (5) | 0.9399 (7) | 0.66806 (19) | 0.0435 (12) | |
| H11 | 0.3325 | 0.9788 | 0.6538 | 0.052* | |
| S2 | 0.25267 (9) | 0.34769 (16) | 0.43188 (5) | 0.0345 (3) | |
| O12 | 0.3748 (3) | −0.1645 (5) | 0.36528 (14) | 0.0414 (8) | |
| N12 | 0.2466 (3) | 0.6713 (6) | 0.47918 (16) | 0.0401 (10) | |
| H12A | 0.2801 | 0.7631 | 0.4952 | 0.048* | |
| H12B | 0.1686 | 0.6711 | 0.4740 | 0.048* | |
| N13 | 0.3275 (3) | −0.0167 (6) | 0.39175 (17) | 0.0406 (10) | |
| N14 | 0.4322 (3) | 0.5220 (6) | 0.46910 (15) | 0.0354 (9) | |
| N15 | 0.4782 (3) | 0.3622 (5) | 0.44954 (15) | 0.0336 (9) | |
| C12 | 0.3137 (4) | 0.5330 (7) | 0.46289 (18) | 0.0325 (11) | |
| C13 | 0.3977 (3) | 0.2571 (7) | 0.42917 (19) | 0.0324 (10) | |
| C14 | 0.4201 (4) | 0.0858 (7) | 0.40348 (19) | 0.0339 (11) | |
| C15 | 0.5296 (4) | 0.0103 (7) | 0.38637 (18) | 0.0355 (11) | |
| H15 | 0.6085 | 0.0576 | 0.3907 | 0.043* | |
| C16 | 0.4959 (4) | −0.1445 (7) | 0.36254 (19) | 0.0348 (10) | |
| C17 | 0.5587 (4) | −0.2878 (7) | 0.33530 (18) | 0.0354 (11) | |
| C18 | 0.6693 (4) | −0.2494 (8) | 0.31302 (18) | 0.0403 (12) | |
| H18 | 0.7024 | −0.1289 | 0.3145 | 0.048* | |
| C19 | 0.7299 (5) | −0.3898 (8) | 0.2886 (2) | 0.0487 (14) | |
| H19 | 0.8046 | −0.3646 | 0.2733 | 0.058* | |
| C20 | 0.6826 (5) | −0.5652 (9) | 0.2866 (2) | 0.0519 (14) | |
| H20 | 0.7252 | −0.6607 | 0.2704 | 0.062* | |
| C21 | 0.5732 (5) | −0.6019 (8) | 0.3082 (2) | 0.0492 (14) | |
| H21 | 0.5400 | −0.7223 | 0.3063 | 0.059* | |
| C22 | 0.5121 (5) | −0.4653 (7) | 0.3324 (2) | 0.0422 (12) | |
| H22 | 0.4372 | −0.4923 | 0.3474 | 0.051* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| S1 | 0.0126 (4) | 0.0464 (6) | 0.0447 (7) | −0.0005 (4) | −0.0026 (4) | −0.0051 (6) |
| O1 | 0.0207 (14) | 0.047 (2) | 0.055 (2) | −0.0023 (14) | 0.0010 (14) | −0.0061 (18) |
| N1 | 0.0154 (16) | 0.047 (3) | 0.061 (3) | 0.0009 (17) | −0.0043 (17) | −0.011 (2) |
| N2 | 0.0187 (18) | 0.049 (3) | 0.053 (3) | −0.0012 (17) | 0.0002 (17) | −0.006 (2) |
| N3 | 0.0159 (17) | 0.047 (2) | 0.048 (3) | −0.0013 (16) | −0.0018 (16) | −0.002 (2) |
| N4 | 0.0162 (17) | 0.050 (3) | 0.043 (2) | 0.0009 (17) | −0.0030 (15) | 0.0001 (19) |
| C1 | 0.0166 (19) | 0.047 (3) | 0.037 (3) | −0.0025 (18) | 0.0005 (18) | 0.000 (2) |
| C2 | 0.0130 (16) | 0.048 (3) | 0.036 (3) | 0.0006 (17) | −0.0018 (18) | 0.003 (2) |
| C3 | 0.0170 (19) | 0.044 (3) | 0.036 (3) | −0.0025 (18) | −0.0032 (17) | 0.003 (2) |
| C4 | 0.0175 (19) | 0.045 (3) | 0.039 (3) | −0.0010 (19) | −0.0010 (18) | 0.001 (2) |
| C5 | 0.0191 (19) | 0.050 (3) | 0.037 (3) | −0.0005 (18) | −0.0018 (19) | 0.006 (2) |
| C6 | 0.031 (2) | 0.049 (3) | 0.034 (3) | 0.006 (2) | −0.0073 (19) | 0.000 (2) |
| C7 | 0.028 (2) | 0.059 (3) | 0.033 (3) | 0.008 (2) | −0.005 (2) | −0.001 (2) |
| C8 | 0.038 (3) | 0.086 (5) | 0.040 (3) | 0.012 (3) | 0.002 (2) | −0.004 (3) |
| C9 | 0.062 (4) | 0.071 (4) | 0.053 (4) | 0.020 (3) | 0.003 (3) | −0.021 (3) |
| C10 | 0.064 (4) | 0.056 (4) | 0.056 (4) | 0.005 (3) | −0.002 (3) | −0.012 (3) |
| C11 | 0.044 (3) | 0.048 (3) | 0.039 (3) | 0.003 (2) | −0.003 (2) | −0.003 (2) |
| S2 | 0.0129 (4) | 0.0473 (6) | 0.0433 (6) | −0.0003 (5) | −0.0025 (4) | −0.0049 (6) |
| O12 | 0.0193 (15) | 0.049 (2) | 0.056 (2) | −0.0022 (14) | −0.0014 (15) | −0.0103 (18) |
| N12 | 0.0158 (17) | 0.051 (3) | 0.053 (3) | 0.0013 (17) | −0.0033 (16) | −0.013 (2) |
| N13 | 0.0206 (19) | 0.048 (3) | 0.054 (3) | 0.0026 (18) | −0.0004 (18) | −0.007 (2) |
| N14 | 0.0158 (17) | 0.047 (2) | 0.044 (2) | −0.0001 (15) | −0.0025 (15) | −0.0051 (19) |
| N15 | 0.0155 (16) | 0.044 (2) | 0.041 (2) | −0.0003 (15) | −0.0010 (14) | −0.0016 (18) |
| C12 | 0.0150 (19) | 0.043 (3) | 0.039 (3) | −0.0015 (18) | −0.0035 (17) | 0.000 (2) |
| C13 | 0.0147 (16) | 0.044 (3) | 0.039 (3) | −0.0014 (17) | −0.0005 (18) | 0.005 (2) |
| C14 | 0.0138 (18) | 0.046 (3) | 0.041 (3) | 0.0009 (18) | −0.0021 (17) | 0.004 (2) |
| C15 | 0.0135 (18) | 0.051 (3) | 0.042 (3) | 0.0038 (19) | −0.0004 (18) | 0.002 (2) |
| C16 | 0.0163 (19) | 0.051 (3) | 0.037 (2) | 0.0032 (19) | −0.0007 (17) | 0.005 (2) |
| C17 | 0.025 (2) | 0.048 (3) | 0.033 (3) | 0.003 (2) | −0.0036 (19) | 0.004 (2) |
| C18 | 0.021 (2) | 0.056 (3) | 0.044 (3) | 0.005 (2) | −0.0004 (18) | 0.004 (2) |
| C19 | 0.033 (3) | 0.070 (4) | 0.042 (3) | 0.014 (2) | 0.008 (2) | 0.009 (3) |
| C20 | 0.051 (3) | 0.061 (4) | 0.044 (3) | 0.018 (3) | 0.003 (3) | −0.002 (3) |
| C21 | 0.052 (4) | 0.050 (3) | 0.045 (3) | 0.002 (3) | 0.003 (3) | 0.000 (3) |
| C22 | 0.035 (3) | 0.052 (3) | 0.039 (3) | 0.001 (2) | −0.001 (2) | 0.000 (2) |
Geometric parameters (Å, º)
| S1—C1 | 1.739 (5) | S2—C12 | 1.729 (5) |
| S1—C2 | 1.739 (4) | S2—C13 | 1.746 (4) |
| O1—C5 | 1.374 (5) | O12—C16 | 1.359 (5) |
| O1—N2 | 1.402 (5) | O12—N13 | 1.398 (5) |
| N1—C1 | 1.330 (6) | N12—C12 | 1.328 (6) |
| N1—H1A | 0.8800 | N12—H12A | 0.8800 |
| N1—H1B | 0.8800 | N12—H12B | 0.8800 |
| N2—C3 | 1.315 (6) | N13—C14 | 1.312 (6) |
| N3—C1 | 1.324 (5) | N14—C12 | 1.334 (5) |
| N3—N4 | 1.377 (6) | N14—N15 | 1.376 (5) |
| N4—C2 | 1.304 (6) | N15—C13 | 1.302 (6) |
| C2—C3 | 1.441 (7) | C13—C14 | 1.449 (7) |
| C3—C4 | 1.424 (6) | C14—C15 | 1.417 (6) |
| C4—C5 | 1.348 (7) | C15—C16 | 1.352 (7) |
| C4—H4 | 0.9500 | C15—H15 | 0.9500 |
| C5—C6 | 1.449 (7) | C16—C17 | 1.458 (7) |
| C6—C7 | 1.391 (7) | C17—C22 | 1.391 (7) |
| C6—C11 | 1.402 (7) | C17—C18 | 1.402 (7) |
| C7—C8 | 1.384 (7) | C18—C19 | 1.393 (7) |
| C7—H7 | 0.9500 | C18—H18 | 0.9500 |
| C8—C9 | 1.378 (9) | C19—C20 | 1.379 (8) |
| C8—H8 | 0.9500 | C19—H19 | 0.9500 |
| C9—C10 | 1.379 (9) | C20—C21 | 1.380 (8) |
| C9—H9 | 0.9500 | C20—H20 | 0.9500 |
| C10—C11 | 1.391 (8) | C21—C22 | 1.373 (7) |
| C10—H10 | 0.9500 | C21—H21 | 0.9500 |
| C11—H11 | 0.9500 | C22—H22 | 0.9500 |
| C1—S1—C2 | 86.9 (2) | C12—S2—C13 | 87.1 (2) |
| C5—O1—N2 | 108.4 (3) | C16—O12—N13 | 108.7 (4) |
| C1—N1—H1A | 120.0 | C12—N12—H12A | 120.0 |
| C1—N1—H1B | 120.0 | C12—N12—H12B | 120.0 |
| H1A—N1—H1B | 120.0 | H12A—N12—H12B | 120.0 |
| C3—N2—O1 | 105.7 (4) | C14—N13—O12 | 105.3 (4) |
| C1—N3—N4 | 112.0 (4) | C12—N14—N15 | 111.7 (4) |
| C2—N4—N3 | 113.4 (4) | C13—N15—N14 | 113.8 (4) |
| N3—C1—N1 | 124.7 (4) | N12—C12—N14 | 124.0 (4) |
| N3—C1—S1 | 113.8 (4) | N12—C12—S2 | 122.1 (3) |
| N1—C1—S1 | 121.5 (3) | N14—C12—S2 | 113.9 (4) |
| N4—C2—C3 | 124.3 (4) | N15—C13—C14 | 126.2 (4) |
| N4—C2—S1 | 113.9 (4) | N15—C13—S2 | 113.5 (4) |
| C3—C2—S1 | 121.7 (3) | C14—C13—S2 | 120.2 (3) |
| N2—C3—C4 | 111.9 (4) | N13—C14—C15 | 112.2 (5) |
| N2—C3—C2 | 118.6 (4) | N13—C14—C13 | 117.9 (4) |
| C4—C3—C2 | 129.4 (4) | C15—C14—C13 | 129.8 (4) |
| C5—C4—C3 | 104.4 (4) | C16—C15—C14 | 103.9 (4) |
| C5—C4—H4 | 127.8 | C16—C15—H15 | 128.0 |
| C3—C4—H4 | 127.8 | C14—C15—H15 | 128.0 |
| C4—C5—O1 | 109.6 (4) | C15—C16—O12 | 109.8 (4) |
| C4—C5—C6 | 133.6 (4) | C15—C16—C17 | 134.9 (4) |
| O1—C5—C6 | 116.8 (4) | O12—C16—C17 | 115.4 (4) |
| C7—C6—C11 | 119.6 (5) | C22—C17—C18 | 119.2 (5) |
| C7—C6—C5 | 119.7 (5) | C22—C17—C16 | 120.6 (5) |
| C11—C6—C5 | 120.6 (5) | C18—C17—C16 | 120.1 (5) |
| C8—C7—C6 | 120.1 (5) | C19—C18—C17 | 119.2 (5) |
| C8—C7—H7 | 119.9 | C19—C18—H18 | 120.4 |
| C6—C7—H7 | 119.9 | C17—C18—H18 | 120.4 |
| C9—C8—C7 | 120.2 (6) | C20—C19—C18 | 120.6 (5) |
| C9—C8—H8 | 119.9 | C20—C19—H19 | 119.7 |
| C7—C8—H8 | 119.9 | C18—C19—H19 | 119.7 |
| C8—C9—C10 | 120.4 (6) | C19—C20—C21 | 119.9 (5) |
| C8—C9—H9 | 119.8 | C19—C20—H20 | 120.0 |
| C10—C9—H9 | 119.8 | C21—C20—H20 | 120.0 |
| C9—C10—C11 | 120.3 (6) | C22—C21—C20 | 120.4 (6) |
| C9—C10—H10 | 119.8 | C22—C21—H21 | 119.8 |
| C11—C10—H10 | 119.8 | C20—C21—H21 | 119.8 |
| C10—C11—C6 | 119.4 (5) | C21—C22—C17 | 120.7 (5) |
| C10—C11—H11 | 120.3 | C21—C22—H22 | 119.7 |
| C6—C11—H11 | 120.3 | C17—C22—H22 | 119.7 |
| C5—O1—N2—C3 | 0.5 (5) | C16—O12—N13—C14 | 0.4 (5) |
| C1—N3—N4—C2 | 0.8 (6) | C12—N14—N15—C13 | 0.3 (6) |
| N4—N3—C1—N1 | −179.2 (5) | N15—N14—C12—N12 | 178.6 (5) |
| N4—N3—C1—S1 | −0.2 (5) | N15—N14—C12—S2 | −0.7 (5) |
| C2—S1—C1—N3 | −0.2 (4) | C13—S2—C12—N12 | −178.6 (5) |
| C2—S1—C1—N1 | 178.7 (5) | C13—S2—C12—N14 | 0.7 (4) |
| N3—N4—C2—C3 | −176.7 (5) | N14—N15—C13—C14 | 176.6 (5) |
| N3—N4—C2—S1 | −1.0 (6) | N14—N15—C13—S2 | 0.3 (6) |
| C1—S1—C2—N4 | 0.7 (4) | C12—S2—C13—N15 | −0.5 (4) |
| C1—S1—C2—C3 | 176.5 (4) | C12—S2—C13—C14 | −177.1 (4) |
| O1—N2—C3—C4 | 0.7 (6) | O12—N13—C14—C15 | −0.9 (6) |
| O1—N2—C3—C2 | −176.3 (4) | O12—N13—C14—C13 | 176.6 (4) |
| N4—C2—C3—N2 | −166.4 (5) | N15—C13—C14—N13 | 169.7 (5) |
| S1—C2—C3—N2 | 18.2 (7) | S2—C13—C14—N13 | −14.2 (7) |
| N4—C2—C3—C4 | 17.1 (9) | N15—C13—C14—C15 | −13.3 (9) |
| S1—C2—C3—C4 | −158.3 (4) | S2—C13—C14—C15 | 162.9 (4) |
| N2—C3—C4—C5 | −1.7 (6) | N13—C14—C15—C16 | 1.1 (6) |
| C2—C3—C4—C5 | 174.9 (5) | C13—C14—C15—C16 | −176.1 (5) |
| C3—C4—C5—O1 | 2.0 (6) | C14—C15—C16—O12 | −0.7 (6) |
| C3—C4—C5—C6 | −180.0 (5) | C14—C15—C16—C17 | 178.6 (6) |
| N2—O1—C5—C4 | −1.7 (6) | N13—O12—C16—C15 | 0.2 (6) |
| N2—O1—C5—C6 | 179.9 (4) | N13—O12—C16—C17 | −179.2 (4) |
| C4—C5—C6—C7 | 24.7 (9) | C15—C16—C17—C22 | 152.5 (6) |
| O1—C5—C6—C7 | −157.4 (4) | O12—C16—C17—C22 | −28.2 (7) |
| C4—C5—C6—C11 | −153.3 (6) | C15—C16—C17—C18 | −25.4 (9) |
| O1—C5—C6—C11 | 24.5 (7) | O12—C16—C17—C18 | 154.0 (5) |
| C11—C6—C7—C8 | 0.9 (8) | C22—C17—C18—C19 | −0.2 (7) |
| C5—C6—C7—C8 | −177.2 (5) | C16—C17—C18—C19 | 177.7 (5) |
| C6—C7—C8—C9 | 0.3 (8) | C17—C18—C19—C20 | −0.4 (8) |
| C7—C8—C9—C10 | −1.2 (10) | C18—C19—C20—C21 | 1.0 (9) |
| C8—C9—C10—C11 | 0.8 (10) | C19—C20—C21—C22 | −1.1 (9) |
| C9—C10—C11—C6 | 0.4 (9) | C20—C21—C22—C17 | 0.5 (9) |
| C7—C6—C11—C10 | −1.2 (8) | C18—C17—C22—C21 | 0.1 (8) |
| C5—C6—C11—C10 | 176.8 (5) | C16—C17—C22—C21 | −177.8 (5) |
Hydrogen-bond geometry (Å, º)
Cg4 and Cg6 are the centroids of the S2/N14/N15/C12/C13 and C17–C22 rings, respectively
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1A···N14i | 0.88 | 2.10 | 2.974 (6) | 172 |
| N1—H1B···N4ii | 0.88 | 2.20 | 3.071 (5) | 169 |
| N12—H12A···N3iii | 0.88 | 2.06 | 2.933 (6) | 174 |
| N12—H12B···N15iv | 0.88 | 2.24 | 3.108 (5) | 170 |
| C4—H4···N2iv | 0.95 | 2.56 | 3.363 (6) | 142 |
| C15—H15···N13ii | 0.95 | 2.46 | 3.323 (6) | 151 |
| C8—H8···Cg6v | 0.95 | 2.98 | 3.774 (6) | 142 |
| C22—H22···Cg4i | 0.95 | 2.95 | 3.648 (6) | 132 |
Symmetry codes: (i) x, y−1, z; (ii) x+1/2, −y, z; (iii) x, y+1, z; (iv) x−1/2, −y+1, z; (v) −x+1/2, y+1, z+1/2.
Funding Statement
This work was funded by Russian Foundation for Basic Research grant 19–53-04002, Bel_mol_a to E. V. Nikitina; Belarusian Republican Foundation for Fundamental Research grant X20PM-056 to E. V. Nikitina.
References
- Abdelhamid, A. A., Mohamed, S. K., Khalilov, A. N., Gurbanov, A. V. & Ng, S. W. (2011). Acta Cryst. E67, o744. [DOI] [PMC free article] [PubMed]
- Bhinge, S. D., Chature, V. & Sonawane, L. V. (2015). Pharm. Chem. J. 49, 367–372.
- Bruker (2013). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
- Bruker (2018). APEX3. Bruker AXS Inc., Madison, Wisconsin, USA.
- Bumagin, N. A., Kletskov, A. V., Petkevich, S. K., Kolesnik, I. A., Lyakhov, A. S., Ivashkevich, L. S., Baranovsky, A. V., Kurman, P. V. & Potkin, V. I. (2018). Tetrahedron, 74, 3578–3588.
- Das, S. & Chanda, K. (2021). RSC Adv. 11, 32680–32705. [DOI] [PMC free article] [PubMed]
- Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.
- Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. [DOI] [PMC free article] [PubMed]
- Gurbanov, A. V., Maharramov, A. M., Zubkov, F. I., Saifutdinov, A. M. & Guseinov, F. I. (2018a). Aust. J. Chem. 71, 190–194.
- Gurbanov, A. V., Mahmoudi, G., Guedes da Silva, M. F. C., Zubkov, F. I., Mahmudov, K. T. & Pombeiro, A. J. L. (2018b). Inorg. Chim. Acta, 471, 130–136.
- Gurbanov, A. V., Mahmudov, K. T., Sutradhar, M., Guedes da Silva, F. C., Mahmudov, T. A., Guseinov, F. I., Zubkov, F. I., Maharramov, A. M. & Pombeiro, A. J. L. (2017). J. Organomet. Chem. 834, 22–27.
- Khalilov, A. N., Tüzün, B., Taslimi, P., Tas, A., Tuncbilek, Z. & Cakmak, N. K. (2021). J. Mol. Liq. 344, 117761.
- Khalilullah, H., Khan, M. U., Mahmood, D., Akhtar, J. & Osman, G. (2014). Int. J. Pharm. Pharm. Sci. 6, 8–15.
- Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. [DOI] [PMC free article] [PubMed]
- Kletskov, A. V., Bumagin, N. A., Zubkov, F. I., Grudinin, D. G. & Potkin, V. I. (2020). Synthesis, 52, 159–188.
- Kudelko, A., Olesiejuk, M., Luczynski, M., Swiatkowski, M., Sieranski, T. & Kruszynski, R. (2020). Molecules, 25, 2822. [DOI] [PMC free article] [PubMed]
- Kulchitsky, V. A., Potkin, V. I., Zubenko, Y. S., Chernov, A. N., Talabaev, M. V., Demidchik, Y. E., Petkevich, S. K., Kazbanov, V. V., Gurinovich, T. A., Roeva, M. O., Grigoriev, D. G., Kletskov, A. V. & Kalunov, V. N. (2012). Med. Chem. 8, 22–32. [DOI] [PubMed]
- Mahmudov, K. T., Kopylovich, M. N., Haukka, M., Mahmudova, G. S., Esmaeila, E. F., Chyragov, F. M. & Pombeiro, A. J. L. (2013). J. Mol. Struct. 1048, 108–112.
- Mahmudov, K. T., Maharramov, A. M., Aliyeva, R. A., Aliyev, I. A., Askerov, R. K., Batmaz, R., Kopylovich, M. N. & Pombeiro, A. J. L. (2011). J. Photochem. Photobiol. Chem. 219, 159–165.
- Naghiyev, F. N., Cisterna, J., Khalilov, A. N., Maharramov, A. M., Askerov, R. K., Asadov, K. A., Mamedov, I. G., Salmanli, K. S., Cárdenas, A. & Brito, I. (2020). Molecules, 25, 2235–2248. [DOI] [PMC free article] [PubMed]
- Nayak, A. S. & Madhav, N. V. (2014). Acta Chim. Pharm. Indica, 4, 63–67.
- Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. [DOI] [PMC free article] [PubMed]
- Petkevich, S. K., Zhukovskaya, N. A., Dikusar, E. A., Akishina, E. A., Kurman, P. V., Nikitina, E. V., Zaytsev, V. P. & Potkin, V. I. (2021). Chem. Heterocycl. Compd, 57, 594–598.
- Rayni, I., El Bakri, Y., Sebhaoui, J., El Bourakadi, K., Essassi, E. M. & Mague, J. T. (2017). IUCrData, 2, x170315.
- Safavora, A. S., Brito, I., Cisterna, J., Cárdenas, A., Huseynov, E. Z., Khalilov, A. N., Naghiyev, F. N., Askerov, R. K. & Maharramov, A. M. Z. (2019). Z. Kristallogr. New Cryst. Struct. 234, 1183–1185.
- Sakthivel, P., Ilangovan, A. & Kaushik, M. P. (2016). Eur. J. Med. Chem. 122, 302–318. [DOI] [PubMed]
- Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.
- Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.
- Shikhaliyev, N. Q., Ahmadova, N. E., Gurbanov, A. V., Maharramov, A. M., Mammadova, G. Z., Nenajdenko, V. G., Zubkov, F. I., Mahmudov, K. T. & Pombeiro, A. J. L. (2018). Dyes Pigments, 150, 377–381.
- Shivakumara, N. & Krishna, P. M. (2019). Curr. Chem. Lett. 8, 157–168.
- Shixaliyev, N. Q., Gurbanov, A. V., Maharramov, A. M., Mahmudov, K. T., Kopylovich, M. N., Martins, L. M. D. R. S., Muzalevskiy, V. M., Nenajdenko, V. G. & Pombeiro, A. J. L. (2014). New J. Chem. 38, 4807–4815.
- Spek, A. L. (2020). Acta Cryst. E76, 1–11. [DOI] [PMC free article] [PubMed]
- Sun, X.-W., Hui, X.-P., Chu, C.-H. & Zhang, Z.-Y. (2001). Indian J. Chem. Sect. B, 40, 15–19.
- Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17. The University of Western Australia.
- Wang, J., Tang, X. & Yi, L. (2019). Pharmacology, 103, 273–281. [DOI] [PubMed]
- Yadigarov, R. R., Khalilov, A. N., Mamedov, I. G., Nagiev, F. N., Magerramov, A. M. & Allakhverdiev, M. A. (2009). Russ. J. Org. Chem. 45, 1856–1858.
- Zubkov, F. I., Nikitina, E. V., Galeev, T. R., Zaytsev, V. P., Khrustalev, V. N., Novikov, R. A., Orlova, D. N. & Varlamov, A. V. (2014). Tetrahedron, 70, 1659–1690.
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. DOI: 10.1107/S2056989022003450/yk2168sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989022003450/yk2168Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989022003450/yk2168Isup3.cml
CCDC reference: 2162503
Additional supporting information: crystallographic information; 3D view; checkCIF report