In the crystal, pairs of molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming inversion dimers with graph-set notation 
(8) and 
(11), which are connected by C—H⋯O hydrogen-bonding interactions into ribbons parallel to (100). The ribbons are further connected into a three-dimensional network by C—H⋯π interactions and π–π stacking interactions between benzene and the thiophene rings.
Keywords: crystal structure, dimer, 1H-pyrazole ring, thiophene ring, disorder, hydrogen-bonding patterns
Abstract
In the title compound, C16H13Cl2N3O3S2, the thiophene ring is disordered in a 0.762 (3):0.238 (3) ratio by an approximate 180° rotation of the ring around the S—C bond linking the ring to the sulfonyl unit. The dichlorobenzene group is also disordered over two sets of sites with the same occupancy ratio. The molecular conformation is stabilized by intramolecular C—H⋯Cl and C—H⋯N hydrogen bonds, forming rings with graph-set notation S(5). In the crystal, pairs of molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming inversion dimers with graph-set notation R 2 2(8) and R 1 2(11), which are connected by C—H⋯O hydrogen-bonding interactions into ribbons parallel to (100). The ribbons are further connected into a three-dimensional network by C—H⋯π interactions and π–π stacking interactions between benzene and thiophene rings, with centroid-to-centroid distances of 3.865 (2), 3.867 (7) and 3.853 (2) Å. Hirshfeld surface analysis has been used to confirm and quantify the supramolecular interactions.
Chemical context
The pyrazole core structure has been widely used as a common heterocyclic scaffold in medicinal chemistry to produce novel drug candidates with a great variety of pharmacological activities including anti-inflammatory, antiplatelet, anticancer, antimycobacterial, antidepressant and anticonvulsant properties (Küçükgüzel & Şenkardeş, 2015 ▸; Çalışkan et al., 2013 ▸; Ding et al., 2009 ▸; Baraldi et al., 2004 ▸; Palaska et al., 2008 ▸). Among them, pyrazole-carboxamide derivatives have been shown to exhibit antimycobacterial, antifungal and antiviral activities (Sun & Zhou, 2015 ▸; Yan et al., 2018 ▸; Comber et al., 1992 ▸). In the course of our ongoing research into bioactive pyrazole derivatives (Banoğlu et al., 2005 ▸; Şüküroğlu et al., 2005 ▸; Ergün et al., 2010 ▸; Çalışkan et al., 2011 ▸; Levent et al., 2013 ▸; Cankara Pirol et al., 2014 ▸), we have relied on the aforementioned biological properties of pyrazole-carboxamides and designed novel pyrazole-3-carboxamide derivatives for their potential antimicrobial activity. In this work, we report the crystallographic characterization and Hirshfeld surface analysis of one of these compounds bearing the 2,4-dichlorobenzyl substituent at one of the pyrazole nitrogen atoms.
Structural commentary
In the molecule of the title compound (Fig. 1 ▸), the dihedral angles between the planes of the pyrazole ring A (N2/N3/C6–C8), the major and minor components B (S1/C1–C4) and B′ (S1A/C1/C2/C3A/C4) of the disordered thiophene ring, and the disordered benzene ring C (C11–C16) and C′ (C11A–C16A) are A/B = 67.62 (16)°, A/B′ = 68.1 (5)°, B/B′ = 3.3 (5)°, A/C = 70.09 (16)°, B/C = 83.06 (19)° and B′/C = 80.2 (5)°, A/C′ = 78.4 (4)°, B/C′ = 77.3 (4)° and B′/C′ = 74.2 (6)°. The molecular conformation is stabilized by intramolecular C—H⋯Cl and C—H⋯N hydrogen bonds (Table 1 ▸), forming rings with graph-set notation S(5).
Figure 1.
The molecular structure of the title compound with displacement ellipsoids for non-H atoms drawn at the 30% probability level. The minor components of the disordered thiophene and dichlorobenzene groups have been omitted.
Table 1. Hydrogen-bond geometry (Å, °).
Cg1 is the centroid of the major component (S1/C1–C4) of the disordered thiophene ring.
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| N1—H1N⋯O2i | 0.84 (3) | 2.27 (3) | 3.029 (3) | 150 (3) |
| C7—H7⋯O3ii | 0.93 | 2.59 | 3.437 (3) | 152 |
| C10—H10B⋯O1iii | 0.97 | 2.52 | 3.141 (3) | 122 |
| C12—H12⋯N3 | 0.93 | 2.61 | 3.224 (3) | 124 |
| C12—H12⋯O2i | 0.93 | 2.51 | 3.348 (3) | 150 |
| C15—H15⋯Cg1iv | 0.93 | 2.97 | 3.893 (3) | 174 |
| C15A—H15A⋯Cg1iv | 0.93 | 2.95 | 3.836 (8) | 159 |
Symmetry codes: (i) 
; (ii) 
; (iii) 
; (iv) 
.
Supramolecular features
In the crystal, pairs of molecules are linked by intermolecular N—H⋯O and C—H⋯O hydrogen bonds (Table 1 ▸; Figs. 2 ▸ and 3 ▸), forming inversion dimers with graph-set notation (8) and (11), which are connected by C—H⋯O hydrogen-bonding interactions into ribbons parallel to (100). The ribbons are further connected into a three-dimensional network by C—H⋯π interactions (Table 1 ▸) and π–π stacking interactions between the benzene and thiophene rings, with centroid-to-centroid distances of 3.865 (2) Å for Cg1⋯Cg1v, 3.867 (7) Å for Cg2⋯Cg2v and 3.853 (2) Å for Cg4⋯Cg4vi where Cg1, Cg2 and Cg4 are the centroids of the thiophene ring B, the thiophene ring B′ and the benzene ring C [symmetry codes: (v) 2 − x, 1 − y, 1 − z; (vi) 1 − x, 1 − y, −z].
Figure 2.
Crystal structure of the title compound viewed along the a axis. Dashed lines show hydrogen-bonding interactions. The minor components of the disordered groups have been omitted.
Figure 3.
Crystal structure of the title compound viewed along the b axis. Dashed lines show hydrogen-bonding interactions. The minor components of the disordered groups have been omitted.
Hirshfeld surface analysis
A Hirshfeld surface analysis (Hirshfeld, 1977 ▸; Spackman & Jayatilaka, 2009 ▸) of the title compound was carried out to investigate the location of atoms with potential to form hydrogen bonds and the quantitative ratio of these interactions. CrystalExplorer17.5 (Turner et al., 2017 ▸) was used to generate the Hirshfeld surface and two-dimensional fingerprint plots (Parkin et al., 2007 ▸; Rohl et al., 2008 ▸), using the atomic coordinates of the major disorder component of the disordered atoms (Figs. 4 ▸ and 5 ▸). The electrostatic potentials were calculated using TONTO (Spackman et al., 2009 ▸) integrated into CrystalExplorer, wherein the respective experimental structure was used as the input to TONTO. Further, the electrostatic potentials were mapped on Hirshfeld surfaces using the STO-3G basis set at the Hartree–Fock level of theory.
Figure 4.
The Hirshfeld surface of the title compound mapped over d norm.
Figure 5.
The two-dimensional fingerprint plots of the title compound, showing (a) all interactions, and delineated into (b) H⋯H, (c) C⋯H, (d) Cl⋯H, (e) Cl⋯Cl and (f) C⋯C interactions. The outline of the full fingerprint plots is shown in grey. d i is the closest internal distance from a given point on the Hirshfeld surface and d e is the closest external contact.
The intermolecular distance information on the surface can be condensed into a two-dimensional histogram of d e and d i, which is a unique identifier for molecules in a crystal structure, and is known as a fingerprint plot. Instead of plotting d e and d i on the Hirshfeld surface, contact distances are normalized in CrystalExplorer using the van der Waals radius of the appropriate internal (r i vdw) and external (r e vdw) atom of the surface:
d norm= (d i − r i vdw)/r i vdw + (d e − r e vdw)/re vdw.
The molecular Hirshfeld surfaces were obtained using a standard (high) surface resolution with the three-dimentional d norm surfaces mapped over a fixed colour scale of −1.9033 (red) to 1.1934 (blue). In the fingerprint plots (Rohl et al., 2008 ▸), shown in Fig. 5 ▸, the points indicated by b, c, d and e correspond to H⋯H, C⋯H, Cl⋯H, Cl⋯Cl and C⋯C interactions with relative contributions of 28.4, 7.0, 6.8, 6.5 and 5.7%, respectively. These types of interactions add up to 54.4% of the intermolecular contacts of the Hirshfeld surface area. The remaining contributions (8.3%) correspond to C⋯Cl (1.3%), N⋯C (1.3%) and other less important interactions (<1%). C⋯C contacts correspond to intermolecular π–π interactions. The occurrence of non-high interaction rates can be attributed to the fact that the small disordered portion of the molecule is not considered.
Database survey
All bond lengths and angles are within normal ranges and are similar to those reported for related molecules such as trans-rac-[1-oxo-2-phenethyl-3-(2-thienyl)-1,2,3,4-tetrahydroisoquinolin-4-yl]methyl 4-methylbenzenesulfonate (Akkurt et al., 2008 ▸), 2-benzenesulfonamidobenzoic acid (Asiri et al., 2009 ▸), propyl 2-(4-methylbenzenesulfonamido)benzoate (Mustafa, Khan et al., 2012 ▸), 2-{4-[acetyl(ethyl)amino]benzenesulfonamido}benzoic acid (Mustafa, Muhmood et al., 2012 ▸), 2-(5-bromopyridin-3-yl)-5-[3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5-ylsulfonyl)thiophen-2-yl]-1,3,4-oxadiazole (Fun et al., 2011a ▸) and 2-(biphenyl-4-yl)-5-[3-(4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5-ylsulfonyl) thiophen-2-yl]-1,3,4-oxadiazole (Fun et al., 2011b ▸).
Synthesis and crystallization
To a solution of methyl 1-(2,4-dichlorobenzyl)-5-methyl-1H-pyrazole-3-carboxylate (200 mg, 0.70 mmol, 1 equiv.) in dichloromethane (DCM) were added 2-thiophenesulfonamide (126 mg, 0. 77 mmol, 1.1 equiv.), 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide (EDC; 148 mg, 0.77 mmol, 1.1 equiv.) and 4-dimethyl-aminopyridine (DMAP; 17.8 mg, 0.14 mmol, 0.2 equiv.), and the resulting mixture was stirred overnight at room temperature. Upon completion of the reaction, the reaction mixture was partitioned between DCM and water. The collected organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give the crude compound, which was purified with automated-flash chromatography (120.6 mg, 39.95%). The obtained product was recrystallized from hexane and ethyl acetate (4:1), m.p. 464.8–465.3 K. 1H NMR (CDCl3): δ 2.24 (3H, s), 5.33 (2H, s), 6.64 (2H, m), 7.12 (1H, m), 7.21 (1H, dd, J = 8.4, 2.1 Hz), 7.45 (1H, d, J = 2.1 Hz), 7.69 (1H, dd, J = 5.1, 1.2 Hz), 7.97 (1H, dd, J = 3.9, 1.2 Hz), 9.29 (1H, bs); 13C NMR (CDCl3): 11.2, 50.5, 107.6, 127.3, 127.9, 129.1, 129.6, 131.7, 132.9, 133.8, 134.8, 135.1, 139.2, 142.0, 143.5, 158.4. HRMS m/z calculated for C16H13Cl2N3O3S2 [M + H]+ 429.9854; found: 429.9857.
Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All H atoms bound to carbon atoms were positioned geometrically and treated as riding with C—H = 0.93-0.97 Å and U
iso(H) = 1.2U
eq(C) or 1.5U
eq(C) for methyl H atoms. A rotating model was used for the methyl group. The nitrogen-bound H atom (H1N) was located in a difference-Fourier map and refined with the constraint N1—H1N = 0.84 (3) Å and U
iso(H) = 1.2U
eq(N). The thiophene ring is rotationally disordered by approximately 180° over two positions, the ratio of refined occupancies being 0.762 (3):0.238 (3). The dichlorobenzene group of the title compound is also disordered over two sets of sites with the same occupancy ratio. The disordered dicholorobenzene groups (C: C11–C16 and C′: C11A–C16A) were refined as rigid hexagons with bond lengths of 1.39 Å. The displacement ellipsoids for the corresponding carbon atoms in the disordered dicholorobenzene groups were constrained by using the EADP command. Six outliers (633, 
30, 
30, 515, 5
1, 520) were omitted in the final cycles of refinement.
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C16H13Cl2N3O3S2 |
| M r | 430.31 |
| Crystal system, space group | Triclinic, P
|
| Temperature (K) | 296 |
| a, b, c (Å) | 8.2706 (4), 8.7726 (4), 13.6433 (7) |
| α, β, γ (°) | 76.091 (2), 74.610 (2), 87.970 (2) |
| V (Å3) | 925.98 (8) |
| Z | 2 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.60 |
| Crystal size (mm) | 0.99 × 0.68 × 0.52 |
| Data collection | |
| Diffractometer | Bruker APEXII CCD |
| Absorption correction | Multi-scan (SADABS; Bruker, 2007 ▸) |
| T min, T max | 0.60, 0.75 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 19595, 4598, 4134 |
| R int | 0.024 |
| (sin θ/λ)max (Å−1) | 0.668 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.056, 0.155, 1.03 |
| No. of reflections | 4598 |
| No. of parameters | 216 |
| No. of restraints | 14 |
| H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
| Δρmax, Δρmin (e Å−3) | 1.20, −0.82 |
Supplementary Material
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989018006242/rz5232sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018006242/rz5232Isup3.hkl
Supporting information file. DOI: 10.1107/S2056989018006242/rz5232Isup4.cml
Checkcif Report. DOI: 10.1107/S2056989018006242/rz5232sup4.pdf
CCDC reference: 1839201
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
The authors acknowledge the Aksaray University, Science and Technology Application and Research Center, Aksaray, Turkey, for the use of the Bruker SMART BREEZE CCD diffractometer (purchased under grant No. 2010 K120480 of the State of Planning Organization)
supplementary crystallographic information
Crystal data
| C16H13Cl2N3O3S2 | Z = 2 |
| Mr = 430.31 | F(000) = 440 |
| Triclinic, P1 | Dx = 1.543 Mg m−3 |
| Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
| a = 8.2706 (4) Å | Cell parameters from 9888 reflections |
| b = 8.7726 (4) Å | θ = 2.4–28.3° |
| c = 13.6433 (7) Å | µ = 0.60 mm−1 |
| α = 76.091 (2)° | T = 296 K |
| β = 74.610 (2)° | Prism, translucent light white |
| γ = 87.970 (2)° | 0.99 × 0.68 × 0.52 mm |
| V = 925.98 (8) Å3 |
Data collection
| Bruker APEXII CCD diffractometer | 4598 independent reflections |
| Radiation source: sealed tube | 4134 reflections with I > 2σ(I) |
| Graphite monochromator | Rint = 0.024 |
| φ and ω scans | θmax = 28.4°, θmin = 1.6° |
| Absorption correction: multi-scan (SADABS; Bruker, 2007) | h = −10→11 |
| Tmin = 0.60, Tmax = 0.75 | k = −11→11 |
| 19595 measured reflections | l = −17→18 |
Refinement
| Refinement on F2 | 14 restraints |
| Least-squares matrix: full | Hydrogen site location: mixed |
| R[F2 > 2σ(F2)] = 0.056 | H atoms treated by a mixture of independent and constrained refinement |
| wR(F2) = 0.155 | w = 1/[σ2(Fo2) + (0.082P)2 + 0.8819P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.03 | (Δ/σ)max < 0.001 |
| 4598 reflections | Δρmax = 1.20 e Å−3 |
| 216 parameters | Δρmin = −0.82 e Å−3 |
Special details
| Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles |
| Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > 2sigma(F2) is used only for calculating -R-factor-obs 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 | Occ. (<1) | |
| C1 | 1.0018 (3) | 0.5302 (5) | 0.6433 (2) | 0.0643 (8) | |
| H1 | 1.109594 | 0.540142 | 0.650187 | 0.077* | |
| C2 | 0.9085 (4) | 0.6538 (4) | 0.6217 (3) | 0.0615 (8) | |
| H2 | 0.943899 | 0.757761 | 0.609474 | 0.074* | |
| C3 | 0.7555 (6) | 0.6082 (6) | 0.6199 (4) | 0.0426 (11) | 0.762 (3) |
| H3 | 0.670625 | 0.678061 | 0.610153 | 0.051* | 0.762 (3) |
| S1 | 0.91332 (19) | 0.35743 (15) | 0.65722 (17) | 0.0492 (3) | 0.762 (3) |
| C3A | 0.901 (2) | 0.382 (2) | 0.655 (2) | 0.0426 (11) | 0.238 (3) |
| H3A | 0.933907 | 0.278893 | 0.670858 | 0.051* | 0.238 (3) |
| S1A | 0.7356 (7) | 0.6272 (6) | 0.6034 (4) | 0.0492 (3) | 0.238 (3) |
| C4 | 0.7359 (3) | 0.4413 (3) | 0.63434 (16) | 0.0334 (4) | |
| C5 | 0.7050 (3) | 0.1354 (2) | 0.52207 (17) | 0.0330 (4) | |
| C6 | 0.7152 (3) | 0.0968 (2) | 0.42142 (16) | 0.0313 (4) | |
| C7 | 0.8307 (3) | 0.0022 (3) | 0.37032 (19) | 0.0375 (5) | |
| H7 | 0.916655 | −0.053427 | 0.393564 | 0.045* | |
| C8 | 0.7892 (3) | 0.0094 (3) | 0.27811 (18) | 0.0361 (4) | |
| C9 | 0.8648 (4) | −0.0637 (4) | 0.1890 (2) | 0.0529 (6) | |
| H9A | 0.794588 | −0.150751 | 0.192409 | 0.079* | |
| H9B | 0.974150 | −0.100242 | 0.193074 | 0.079* | |
| H9C | 0.874250 | 0.012686 | 0.124042 | 0.079* | |
| C10 | 0.5646 (3) | 0.1512 (3) | 0.19870 (18) | 0.0397 (5) | |
| H10A | 0.448790 | 0.169220 | 0.231841 | 0.048* | |
| H10B | 0.565068 | 0.066145 | 0.164493 | 0.048* | |
| C11 | 0.6400 (5) | 0.2998 (3) | 0.1159 (2) | 0.0466 (3) | 0.762 (3) |
| C12 | 0.6577 (4) | 0.4311 (3) | 0.15290 (16) | 0.0466 (3) | 0.762 (3) |
| H12 | 0.629582 | 0.423813 | 0.224578 | 0.056* | 0.762 (3) |
| C13 | 0.7173 (4) | 0.5732 (3) | 0.08277 (18) | 0.0466 (3) | 0.762 (3) |
| H13 | 0.729125 | 0.660962 | 0.107532 | 0.056* | 0.762 (3) |
| C14 | 0.7593 (4) | 0.5840 (2) | −0.02436 (17) | 0.0466 (3) | 0.762 (3) |
| C15 | 0.7416 (5) | 0.4528 (3) | −0.06137 (17) | 0.0466 (3) | 0.762 (3) |
| H15 | 0.769664 | 0.460061 | −0.133046 | 0.056* | 0.762 (3) |
| C16 | 0.6819 (6) | 0.3107 (3) | 0.0088 (3) | 0.0466 (3) | 0.762 (3) |
| Cl1 | 0.8269 (3) | 0.7564 (2) | −0.11887 (17) | 0.0835 (5) | 0.762 (3) |
| Cl2 | 0.6424 (5) | 0.1501 (4) | −0.0388 (2) | 0.0805 (7) | 0.762 (3) |
| C11A | 0.6465 (15) | 0.3022 (11) | 0.1193 (7) | 0.0466 (3) | 0.238 (3) |
| C12A | 0.7063 (12) | 0.4320 (11) | 0.1423 (5) | 0.0466 (3) | 0.238 (3) |
| H12A | 0.696770 | 0.433593 | 0.211501 | 0.056* | 0.238 (3) |
| C13A | 0.7802 (12) | 0.5595 (9) | 0.0618 (6) | 0.0466 (3) | 0.238 (3) |
| H13A | 0.820202 | 0.646324 | 0.077136 | 0.056* | 0.238 (3) |
| C14A | 0.7945 (12) | 0.5571 (9) | −0.0417 (5) | 0.0466 (3) | 0.238 (3) |
| C15A | 0.7347 (15) | 0.4273 (11) | −0.0646 (6) | 0.0466 (3) | 0.238 (3) |
| H15A | 0.744229 | 0.425767 | −0.133838 | 0.056* | 0.238 (3) |
| C16A | 0.6608 (17) | 0.2999 (11) | 0.0159 (9) | 0.0466 (3) | 0.238 (3) |
| Cl1A | 0.8896 (10) | 0.7355 (9) | −0.1136 (7) | 0.0835 (5) | 0.238 (3) |
| Cl2A | 0.6826 (18) | 0.1514 (15) | −0.0300 (9) | 0.0805 (7) | 0.238 (3) |
| N1 | 0.6005 (2) | 0.2605 (2) | 0.53833 (15) | 0.0363 (4) | |
| H1N | 0.571 (4) | 0.317 (3) | 0.4869 (18) | 0.044* | |
| N2 | 0.6550 (2) | 0.1036 (2) | 0.27928 (14) | 0.0340 (4) | |
| N3 | 0.6080 (2) | 0.1593 (2) | 0.36579 (14) | 0.0334 (4) | |
| O1 | 0.5273 (2) | 0.2101 (2) | 0.73271 (13) | 0.0479 (4) | |
| O2 | 0.4310 (2) | 0.4460 (2) | 0.62514 (13) | 0.0412 (4) | |
| O3 | 0.7814 (2) | 0.0698 (2) | 0.58384 (14) | 0.0473 (4) | |
| S2 | 0.55880 (6) | 0.33499 (6) | 0.64141 (4) | 0.03159 (15) |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| Cl1 | 0.1094 (16) | 0.0562 (7) | 0.0754 (7) | −0.0290 (10) | −0.0317 (10) | 0.0150 (5) |
| Cl1A | 0.1094 (16) | 0.0562 (7) | 0.0754 (7) | −0.0290 (10) | −0.0317 (10) | 0.0150 (5) |
| Cl2 | 0.144 (2) | 0.0649 (5) | 0.0438 (7) | −0.0339 (10) | −0.0276 (8) | −0.0255 (5) |
| Cl2A | 0.144 (2) | 0.0649 (5) | 0.0438 (7) | −0.0339 (10) | −0.0276 (8) | −0.0255 (5) |
| S1 | 0.0461 (5) | 0.0507 (7) | 0.0605 (6) | 0.0166 (4) | −0.0260 (4) | −0.0205 (6) |
| S1A | 0.0461 (5) | 0.0507 (7) | 0.0605 (6) | 0.0166 (4) | −0.0260 (4) | −0.0205 (6) |
| S2 | 0.0325 (3) | 0.0336 (3) | 0.0302 (3) | 0.0020 (2) | −0.0086 (2) | −0.0102 (2) |
| O1 | 0.0609 (11) | 0.0441 (9) | 0.0348 (8) | −0.0091 (8) | −0.0098 (7) | −0.0038 (7) |
| O2 | 0.0342 (8) | 0.0474 (9) | 0.0468 (9) | 0.0105 (7) | −0.0122 (7) | −0.0204 (7) |
| O3 | 0.0556 (10) | 0.0487 (10) | 0.0485 (10) | 0.0187 (8) | −0.0304 (8) | −0.0160 (8) |
| N1 | 0.0458 (10) | 0.0360 (9) | 0.0336 (9) | 0.0126 (8) | −0.0186 (8) | −0.0135 (7) |
| N2 | 0.0386 (9) | 0.0332 (8) | 0.0323 (9) | 0.0031 (7) | −0.0116 (7) | −0.0099 (7) |
| N3 | 0.0366 (9) | 0.0338 (8) | 0.0330 (9) | 0.0061 (7) | −0.0125 (7) | −0.0108 (7) |
| C1 | 0.0361 (12) | 0.105 (3) | 0.0567 (17) | −0.0026 (14) | −0.0139 (11) | −0.0267 (17) |
| C2 | 0.0577 (16) | 0.0581 (17) | 0.0667 (19) | −0.0200 (14) | −0.0091 (14) | −0.0164 (14) |
| C3 | 0.0345 (19) | 0.0394 (19) | 0.051 (2) | −0.0035 (14) | −0.0204 (15) | 0.0060 (15) |
| C3A | 0.0345 (19) | 0.0394 (19) | 0.051 (2) | −0.0035 (14) | −0.0204 (15) | 0.0060 (15) |
| C4 | 0.0306 (9) | 0.0381 (10) | 0.0336 (10) | 0.0034 (8) | −0.0096 (7) | −0.0122 (8) |
| C5 | 0.0344 (10) | 0.0310 (9) | 0.0369 (10) | 0.0036 (7) | −0.0137 (8) | −0.0103 (8) |
| C6 | 0.0332 (9) | 0.0285 (9) | 0.0344 (10) | 0.0027 (7) | −0.0119 (8) | −0.0088 (8) |
| C7 | 0.0361 (10) | 0.0351 (10) | 0.0468 (12) | 0.0078 (8) | −0.0157 (9) | −0.0158 (9) |
| C8 | 0.0372 (10) | 0.0317 (10) | 0.0411 (11) | 0.0031 (8) | −0.0091 (8) | −0.0139 (8) |
| C9 | 0.0538 (14) | 0.0576 (15) | 0.0525 (15) | 0.0090 (12) | −0.0087 (12) | −0.0298 (13) |
| C10 | 0.0471 (12) | 0.0413 (11) | 0.0348 (11) | −0.0009 (9) | −0.0173 (9) | −0.0094 (9) |
| C11 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C11A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C12 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C12A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C13 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C13A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C14 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C14A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C15 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C15A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C16 | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
| C16A | 0.0639 (8) | 0.0396 (6) | 0.0367 (6) | −0.0054 (6) | −0.0098 (5) | −0.0130 (5) |
Geometric parameters (Å, º)
| Cl1—C14 | 1.733 (3) | C10—C11 | 1.530 (4) |
| Cl1A—C14A | 1.723 (12) | C11—C12 | 1.391 (4) |
| Cl2—C16 | 1.760 (5) | C11—C16 | 1.390 (5) |
| Cl2A—C16A | 1.561 (17) | C11A—C16A | 1.389 (15) |
| S1—C4 | 1.688 (3) | C11A—C12A | 1.391 (14) |
| S1—C1 | 1.654 (4) | C12—C13 | 1.390 (4) |
| S1A—C4 | 1.583 (6) | C12A—C13A | 1.390 (11) |
| S1A—C2 | 1.550 (7) | C13—C14 | 1.390 (3) |
| S2—O2 | 1.4362 (18) | C13A—C14A | 1.391 (10) |
| S2—N1 | 1.641 (2) | C14—C15 | 1.390 (3) |
| S2—C4 | 1.733 (3) | C14A—C15A | 1.390 (13) |
| S2—O1 | 1.4184 (18) | C15—C16 | 1.390 (4) |
| O3—C5 | 1.210 (3) | C15A—C16A | 1.390 (14) |
| N1—C5 | 1.396 (3) | C1—H1 | 0.9300 |
| N2—N3 | 1.343 (3) | C2—H2 | 0.9300 |
| N2—C8 | 1.359 (3) | C3—H3 | 0.9300 |
| N2—C10 | 1.461 (3) | C3A—H3A | 0.9300 |
| N3—C6 | 1.336 (3) | C7—H7 | 0.9300 |
| C1—C2 | 1.329 (5) | C9—H9A | 0.9600 |
| C1—C3A | 1.522 (19) | C9—H9C | 0.9600 |
| N1—H1N | 0.84 (3) | C9—H9B | 0.9600 |
| C2—C3 | 1.349 (6) | C10—H10A | 0.9700 |
| C3—C4 | 1.439 (6) | C10—H10B | 0.9700 |
| C3A—C4 | 1.516 (19) | C12—H12 | 0.9300 |
| C5—C6 | 1.472 (3) | C12A—H12A | 0.9300 |
| C6—C7 | 1.399 (3) | C13—H13 | 0.9300 |
| C7—C8 | 1.376 (3) | C13A—H13A | 0.9300 |
| C8—C9 | 1.491 (4) | C15—H15 | 0.9300 |
| C10—C11A | 1.540 (10) | C15A—H15A | 0.9300 |
| C1—S1—C4 | 91.91 (16) | Cl1—C14—C15 | 115.95 (18) |
| C2—S1A—C4 | 96.3 (4) | C13—C14—C15 | 120.0 (2) |
| O1—S2—N1 | 108.73 (10) | Cl1A—C14A—C13A | 104.5 (7) |
| O1—S2—C4 | 108.83 (11) | Cl1A—C14A—C15A | 135.5 (6) |
| O1—S2—O2 | 120.05 (10) | C13A—C14A—C15A | 120.0 (7) |
| O2—S2—C4 | 107.17 (12) | C14—C15—C16 | 120.0 (2) |
| N1—S2—C4 | 107.33 (10) | C14A—C15A—C16A | 120.0 (8) |
| O2—S2—N1 | 104.06 (10) | Cl2—C16—C11 | 120.2 (3) |
| S2—N1—C5 | 126.32 (16) | Cl2—C16—C15 | 119.6 (3) |
| N3—N2—C8 | 112.91 (18) | C11—C16—C15 | 120.0 (3) |
| N3—N2—C10 | 119.06 (18) | C11A—C16A—C15A | 120.0 (10) |
| C8—N2—C10 | 128.01 (19) | Cl2A—C16A—C11A | 126.3 (10) |
| N2—N3—C6 | 104.17 (16) | Cl2A—C16A—C15A | 107.6 (9) |
| S1—C1—C2 | 115.5 (2) | S1—C1—H1 | 122.00 |
| C2—C1—C3A | 108.6 (7) | C2—C1—H1 | 122.00 |
| S2—N1—H1N | 113.9 (18) | C3A—C1—H1 | 129.00 |
| C5—N1—H1N | 118.5 (18) | S1A—C2—H2 | 116.00 |
| C1—C2—C3 | 110.9 (4) | C1—C2—H2 | 125.00 |
| S1A—C2—C1 | 118.7 (4) | C3—C2—H2 | 125.00 |
| C2—C3—C4 | 113.7 (4) | C2—C3—H3 | 123.00 |
| C1—C3A—C4 | 104.5 (12) | C4—C3—H3 | 123.00 |
| S1—C4—C3 | 107.9 (3) | C4—C3A—H3A | 128.00 |
| S2—C4—C3A | 129.1 (7) | C1—C3A—H3A | 128.00 |
| S1A—C4—S2 | 119.4 (3) | C8—C7—H7 | 128.00 |
| S2—C4—C3 | 128.3 (3) | C6—C7—H7 | 128.00 |
| S1—C4—S2 | 123.50 (17) | C8—C9—H9A | 109.00 |
| S1A—C4—C3A | 111.6 (8) | H9A—C9—H9B | 109.00 |
| O3—C5—C6 | 124.5 (2) | C8—C9—H9B | 110.00 |
| O3—C5—N1 | 122.7 (2) | C8—C9—H9C | 110.00 |
| N1—C5—C6 | 112.78 (19) | H9B—C9—H9C | 109.00 |
| C5—C6—C7 | 128.2 (2) | H9A—C9—H9C | 109.00 |
| N3—C6—C7 | 111.90 (19) | N2—C10—H10B | 109.00 |
| N3—C6—C5 | 119.91 (19) | C11—C10—H10A | 109.00 |
| C6—C7—C8 | 104.9 (2) | C11A—C10—H10A | 110.00 |
| C7—C8—C9 | 131.6 (3) | C11A—C10—H10B | 111.00 |
| N2—C8—C9 | 122.3 (2) | C11—C10—H10B | 109.00 |
| N2—C8—C7 | 106.1 (2) | N2—C10—H10A | 109.00 |
| N2—C10—C11A | 110.0 (5) | H10A—C10—H10B | 108.00 |
| N2—C10—C11 | 113.2 (2) | C13—C12—H12 | 120.00 |
| C10—C11—C12 | 116.2 (2) | C11—C12—H12 | 120.00 |
| C10—C11—C16 | 123.7 (3) | C13A—C12A—H12A | 120.00 |
| C12—C11—C16 | 120.0 (2) | C11A—C12A—H12A | 120.00 |
| C10—C11A—C12A | 126.4 (7) | C14—C13—H13 | 120.00 |
| C10—C11A—C16A | 113.6 (8) | C12—C13—H13 | 120.00 |
| C12A—C11A—C16A | 120.0 (9) | C14A—C13A—H13A | 120.00 |
| C11—C12—C13 | 120.0 (2) | C12A—C13A—H13A | 120.00 |
| C11A—C12A—C13A | 120.0 (7) | C16—C15—H15 | 120.00 |
| C12—C13—C14 | 120.0 (2) | C14—C15—H15 | 120.00 |
| C12A—C13A—C14A | 120.0 (8) | C14A—C15A—H15A | 120.00 |
| Cl1—C14—C13 | 123.98 (18) | C16A—C15A—H15A | 120.00 |
| C1—S1—C4—S2 | −176.25 (16) | C2—C3—C4—S1 | 3.8 (5) |
| C1—S1—C4—C3 | −2.0 (3) | C2—C3—C4—S2 | 177.7 (3) |
| C4—S1—C1—C2 | −0.1 (3) | O3—C5—C6—C7 | −12.2 (4) |
| O1—S2—N1—C5 | −44.1 (2) | N1—C5—C6—N3 | −11.7 (3) |
| O2—S2—N1—C5 | −173.15 (18) | N1—C5—C6—C7 | 166.0 (2) |
| C4—S2—N1—C5 | 73.5 (2) | O3—C5—C6—N3 | 170.1 (2) |
| O2—S2—C4—S1 | 175.63 (16) | N3—C6—C7—C8 | 0.1 (3) |
| N1—S2—C4—S1 | −73.11 (18) | C5—C6—C7—C8 | −177.8 (2) |
| O1—S2—C4—C3 | −128.6 (3) | C6—C7—C8—C9 | 179.3 (3) |
| O2—S2—C4—C3 | 2.6 (3) | C6—C7—C8—N2 | −0.5 (3) |
| N1—S2—C4—C3 | 113.9 (3) | N2—C10—C11—C12 | −55.0 (4) |
| O1—S2—C4—S1 | 44.39 (19) | N2—C10—C11—C16 | 128.4 (4) |
| S2—N1—C5—C6 | 179.75 (16) | C10—C11—C12—C13 | −176.8 (3) |
| S2—N1—C5—O3 | −2.0 (3) | C16—C11—C12—C13 | 0.0 (6) |
| C8—N2—C10—C11 | −88.0 (3) | C10—C11—C16—Cl2 | 2.2 (6) |
| C8—N2—N3—C6 | −0.6 (2) | C10—C11—C16—C15 | 176.6 (4) |
| N3—N2—C8—C7 | 0.7 (3) | C12—C11—C16—Cl2 | −174.4 (3) |
| N3—N2—C10—C11 | 90.2 (2) | C12—C11—C16—C15 | 0.0 (7) |
| C10—N2—C8—C7 | 178.9 (2) | C11—C12—C13—C14 | 0.0 (5) |
| C10—N2—N3—C6 | −179.01 (19) | C12—C13—C14—Cl1 | 177.4 (3) |
| C10—N2—C8—C9 | −0.8 (4) | C12—C13—C14—C15 | 0.0 (5) |
| N3—N2—C8—C9 | −179.1 (2) | Cl1—C14—C15—C16 | −177.6 (3) |
| N2—N3—C6—C5 | 178.40 (18) | C13—C14—C15—C16 | 0.0 (6) |
| N2—N3—C6—C7 | 0.3 (2) | C14—C15—C16—Cl2 | 174.4 (3) |
| S1—C1—C2—C3 | 2.4 (4) | C14—C15—C16—C11 | 0.0 (7) |
| C1—C2—C3—C4 | −4.0 (5) |
Hydrogen-bond geometry (Å, º)
Cg1 is the centroid of the major component (S1/C1–C4) of the disordered thiophene ring.
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1N···N3 | 0.84 (3) | 2.35 (3) | 2.694 (3) | 105 (2) |
| N1—H1N···O2i | 0.84 (3) | 2.27 (3) | 3.029 (3) | 150 (3) |
| C7—H7···O3ii | 0.93 | 2.59 | 3.437 (3) | 152 |
| C10—H10B···Cl2 | 0.97 | 2.60 | 3.134 (4) | 115 |
| C10—H10B···Cl2A | 0.97 | 2.50 | 3.012 (12) | 112 |
| C10—H10B···O1iii | 0.97 | 2.52 | 3.141 (3) | 122 |
| C12—H12···N3 | 0.93 | 2.61 | 3.224 (3) | 124 |
| C12—H12···O2i | 0.93 | 2.51 | 3.348 (3) | 150 |
| C15—H15···Cg1iv | 0.93 | 2.97 | 3.893 (3) | 174 |
| C15A—H15A···Cg1iv | 0.93 | 2.95 | 3.836 (8) | 159 |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y, −z+1; (iii) −x+1, −y, −z+1; (iv) x, y, z−1.
References
- Akkurt, M., Öztürk Yıldırım, S., Bogdanov, M. G., Kandinska, M. I. & Büyükgüngör, O. (2008). Acta Cryst. E64, o1955–o1956. [DOI] [PMC free article] [PubMed]
- Asiri, A. M., Akkurt, M., Khan, S. A., Arshad, M. N., Khan, I. U. & Sharif, H. M. A. (2009). Acta Cryst. E65, o1246–o1247. [DOI] [PMC free article] [PubMed]
- Banoğlu, E., Akoğlu, Ç., Ünlü, S., Ergün, B., Küpeli, E., Yeşilada, E. & Şahin, M. (2005). Arzneimittelforschung, 55, 520–527. [DOI] [PubMed]
- Baraldi, P. G., Beria, I., Cozzi, P., Geroni, C., Espinosa, A., Gallo, M. A., Entrena, A., Bingham, J. P., Hartley, J. A. & Romagnoli, R. (2004). Bioorg. Med. Chem. 12, 3911–3921. [DOI] [PubMed]
- Bruker (2007). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
- Çalışkan, B., Luderer, S., Özkan, Y., Werz, O. & Banoğlu, E. (2011). Eur. J. Med. Chem. 46, 5021–5033. [DOI] [PubMed]
- Çalışkan, B., Yılmaz, A., Evren, İ., Menevşe, S., Uludag, O. & Banoğlu, E. (2013). Med. Chem. Res. 22, 782–793.
- Cankara Pirol, Ş., Çalışkan, B., Durmaz, İ., Atalay, R. & Banoğlu, E. (2014). Eur. J. Med. Chem. 87, 140–149. [DOI] [PubMed]
- Comber, R. N., Gray, R. J. & Secrist, J. A. (1992). Carbohydr. Res. 216, 441–452. [DOI] [PubMed]
- Ding, X. L., Zhang, H. Y., Qi, L., Zhao, B. X., Lian, S., Lv, H. S. & Miao, J. Y. (2009). Bioorg. Med. Chem. Lett. 19, 5325–5328. [DOI] [PubMed]
- Ergün, B. C., Nuñez, M. T., Labeaga, L., Ledo, F., Darlington, J., Bain, G., Cakir, B. & Banoğlu, E. (2010). Arzneimittelforschung, 60, 497–505. [DOI] [PubMed]
- Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.
- Fun, H.-K., Hemamalini, M., Rai, S., Isloor, A. M. & Shetty, P. (2011a). Acta Cryst. E67, o2743–o2744. [DOI] [PMC free article] [PubMed]
- Fun, H.-K., Hemamalini, M., Rai, S., Isloor, A. M. & Shetty, P. (2011b). Acta Cryst. E67, o2781–o2782. [DOI] [PMC free article] [PubMed]
- Hirshfeld, H. L. (1977). Theor. Chim. Acta, 44, 129–138.
- Küçükgüzel, Ş. G. & Şenkardeş, S. (2015). Eur. J. Med. Chem. 97, 786–815. [DOI] [PubMed]
- Levent, S., Çalışkan, B., Çiftçi, M., Özkan, Y., Yenicesu, İ., Ünver, H. & Banoğlu, E. (2013). Eur. J. Med. Chem. 64, 42–53. [DOI] [PubMed]
- Mustafa, G., Khan, I. U., Khan, F. M. & Akkurt, M. (2012). Acta Cryst. E68, o1305. [DOI] [PMC free article] [PubMed]
- Mustafa, G., Muhmood, T., Khan, I. U. & Akkurt, M. (2012). Acta Cryst. E68, o1388. [DOI] [PMC free article] [PubMed]
- Palaska, E., Aydin, F., Uçar, G. & Erol, D. (2008). Arch. Pharm. Chem. Life Sci. 341, 209–215. [DOI] [PubMed]
- Parkin, A., Barr, G., Dong, W., Gilmore, C. J., Jayatilaka, D., McKinnon, J. J., Spackman, M. A. & Wilson, C. C. (2007). CrystEngComm, 9, 648–652.
- Rohl, A. L., Moret, M., Kaminsky, W., Claborn, K., McKinnon, J. J. & Kahr, B. (2008). Cryst. Growth Des. 8, 4517–4525.
- Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.
- Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.
- Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32.
- Spek, A. L. (2009). Acta Cryst. D65, 148–155. [DOI] [PMC free article] [PubMed]
- Şüküroğlu, M., Ergün, B. Ç., Ünlü, S., Sahin, M. F., Küpeli, E., Yesilada, E. & Banoğlu, E. (2005). Arch. Pharm. Res. 28, 509–517. [DOI] [PubMed]
- Sun, J. & Zhou, Y. (2015). Molecules, 20, 4383–4394. [DOI] [PMC free article] [PubMed]
- Turner, M. J., MacKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17.5. University of Western Australia.
- Yan, Z., Liu, A., Huang, M., Liu, M., Pei, H., Huang, L., Yi, H., Liu, W. & Hu, A. (2018). Eur. J. Med. Chem. 149, 170–181. [DOI] [PubMed]
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) global, I. DOI: 10.1107/S2056989018006242/rz5232sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018006242/rz5232Isup3.hkl
Supporting information file. DOI: 10.1107/S2056989018006242/rz5232Isup4.cml
Checkcif Report. DOI: 10.1107/S2056989018006242/rz5232sup4.pdf
CCDC reference: 1839201
Additional supporting information: crystallographic information; 3D view; checkCIF report