Crystal structure, Hirshfeld surface analysis and contact enrichment ratios of 1-(2,7-di­methyl­imidazo[1,2-a]pyridin-3-yl)-2-(1,3-di­thio­lan-2-yl­idene)ethanone monohydrate

Bibila Mayaya Bisseyou, Y.; Ouattara, M.; Soro, P.A.; Yao-Kakou, R.C.A.; Tenon, A.J.

doi:10.1107/S2056989019015755

research communications

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ISSN: 2056-9890

Volume 75| Part 12| December 2019| Pages 1934-1939

https://doi.org/10.1107/S2056989019015755

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Crystal structure, Hirshfeld surface analysis and contact enrichment ratios of 1-(2,7-dimethylimidazo[1,2-a]pyridin-3-yl)-2-(1,3-dithiolan-2-ylidene)ethanone monohydrate

Yvon Bibila Mayaya Bisseyou,^a ^* Mahama Ouattara,^b Pénétjiligué Adama Soro,^a R. C. A. Yao-Kakou ^a and Abodou Jules Tenon ^a

^aLaboratoire de Cristallographie et Physique Moléculaire, UFR des Sciences des Structures de la Matière et de Technologie, Université Félix Houphouët-Boigny, 01 BP V34 Abidjan, Côte d'Ivoire, and ^bDépartement de Chimie Thérapeutique et Chimie Organique Pharmaceutique, UFR Sciences Pharmaceutiques et Biologiques, Université Félix Houphouët-Boigny, 01 BP V34 Abidjan, Côte d'Ivoire
^*Correspondence e-mail: mayaya.bibila@univ-fhb.edu.ci

Edited by L. Van Meervelt, Katholieke Universiteit Leuven, Belgium (Received 17 October 2019; accepted 21 November 2019; online 29 November 2019)

In the title hydrated hybrid compound C₁₄H₁₄N₂OS₂·H₂O, the planar imidazo[1,2-a]pyridine ring system is linked to the 1,3-dithiolane moiety by an enone bridge. The atoms of the C—C bond in the 1,3-dithiolane ring are disordered over two positions with occupancies of 0.579 (14) and 0.421 (14) and both disordered rings adopt a half-chair conformation. The oxygen atom of the enone bridge is involved in a weak intramolecular C—H⋯O hydrogen bond, which generates an S(6) graph-set motif. In the crystal, the hybrid molecules are associated in R₂²(14) dimeric units by weak C—H⋯O interactions. O—H⋯O hydrogen bonds link the water molecules, forming infinite self-assembled chains along the b-axis direction to which the dimers are connected via O—H⋯N hydrogen bonding. Analysis of intermolecular contacts using Hirshfeld surface analysis and contact enrichment ratio descriptors indicate that hydrogen bonds induced by water molecules are the main driving force in the crystal packing formation.

Keywords: crystal structure; hybrid molecule; Hirshfeld surface analysis; enrichment contact; hydrogen bond.

CCDC reference: 1967239

1. Chemical context

The imidazo[1,2-a]pyridine ring system was described for the first time in 1925 (Chichibabin, 1925 ). Compounds with the imidazo[1,2-a]pyridine scaffold exhibit a plethora of biological activities, including acting as receptor ligands, anti-infectious agents, enzyme inhibitors etc. as well as being potential nitrogen heterobicycle therapeutic agents, as described by recent studies (Goel et al., 2016 ; Deep et al., 2017 ; Kuthyala et al., 2018 ). On the other hand, compounds containing the 1,3-dithiolan-2-ylidene moiety have been found to exhibit valuable pharmacological activities, including use as potent broad-spectrum fungicides (Tanaka et al., 1976 , Wang et al., 1994 ), antitumor agents (Huang et al., 2009 ), potent cephalosporinase inhibitors (Ohya et al., 1982 ) and anti-HIV agents (Nguyen-Ba et al., 1999 ; Besra et al., 2005 ). In light of the above, we have incorporated into our research into the design of new potentially bioactive compounds the currently attractive molecular hybridization strategy, which consists of the combination of at least two pharmacophoric moieties of different bioactive substances to produce a new hybrid compound that is medically more effective than its individual components (Viegas-Junior et al. 2007 ; Meunier, 2008 ). Yang et al. (2012 ) have shown that this approach is an effective way to develop novel and potent drugs for different targets.

Herein we report the synthesis, crystal and molecular structure of the title compound, an hybrid compound containing both imidazo[1,2-a]pyridine and 1,3-dithiolane scaffolds. Moreover, since this compound crystallizes as a hydrate, the presence of water molecules in the crystal structure is likely to alter its thermodynamic activity, which would impact its pharmacodynamic properties such as bioavailability and product performance (Khankari & Grant, 1995 ). From a crystallographic point of view, the intrusion of water molecules into a solid state modifies the network of intermolecular interactions between host molecules by incorporating additional bonds between the organic host molecules and water molecules on the one hand, and between water molecules on the other. To gain a better insight into the cohesive forces between host molecules and intrusive water molecules, and to highlight favored contacts likely to be the crystal driving force, an analysis of intermolecular interactions was carried out using contact enrichment ratios (Jelsch et al., 2014 ), a descriptor obtained from Hirshfeld surface analysis (Spackman & McKinnon, 2002 ), which allows an in-depth analysis of the atom–atom contacts in molecular crystals, providing key information on their distribution and is a powerful tool for understanding the most important forces in intermolecular interactions (Jelsch & Bibila Mayaya Bisseyou, 2017 ).

2. Structural commentary

Fig. 1 shows the asymmetric unit of the title compound, which crystallizes as monohydrate in the orthorhombic space group I4₁cd. The hybrid molecule consists of imidazo[1,2-a]pyridine and 1,3-dithiolane scaffolds linked by an —CO—CH= enone bridge. The imidazo[1,2-a]pyridine ring system is essentially planar with a maximum deviation of 0.008 (1) Å for atom N1. Its geometrical parameters are similar to those found for 1-(2-methylimidazo[1,2-a]pyridin-3-yl)-3,3-bis(methylsulfanyl)prop-2-enone (Bibila Mayaya Bisseyou et al., 2009 ), as illustrated by the overlay of the structures shown in Fig. 2. In the 1,3-dithiolane moiety, the C11 and C12 atoms of the C—C bond of the ring exhibit occupational disorder over two positions, with relative occupancies of 0.579 (14) and 0.421 (14) for the major and minor components, respectively. This disorder in the 1,3-dithiolane skeleton is not uncommon and has been observed previously (Yang et al., 2007 ; Liu et al., 2008 ). Conformational analysis of the five-membered rings based on puckering parameters reveals a half-chair form for both disorder components [Q(2) = 0.419 (7)/0.443 (9) Å, φ(2) = 303.2 (9)/128.9 (11)° for the major and minor components, respectively]. The oxygen atom of the linker moiety is involved in a weak intramolecular C6—H6⋯O1 hydrogen bond (Table 1), which generates an S(6) graph-set motif.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯O1	0.93	2.24	2.812 (3)	119
O2W—H2W⋯N1	0.97 (1)	1.99 (2)	2.949 (3)	170 (6)
C5—H5⋯O1ⁱ	0.93	2.71	3.560 (3)	153
O2W—H1W⋯O2Wⁱⁱ	0.97 (1)	1.92 (2)	2.837 (2)	157 (4)
C12A—H12B⋯O2Wⁱⁱⁱ	0.97	2.66	3.577 (11)	157
Symmetry codes: (i) -x+1, -y, z; (ii) $[-y+1, x-{\script{1\over 2}}, z+{\script{1\over 4}}]$ ; (iii) $[-x+1, y, z-{\script{1\over 2}}]$ .

Figure 1
Molecular structure of the title compound with atomic labelling. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius. The minor component of the disordered moiety is drawn with open bonds. Hydrogen bonds are shown as dashed lines.

Figure 2
An overlay diagram of the title structure (red) with 1-(2-methylimidazo[1,2–a]pyridin-3-yl)-3,3-bis(methylsulfanyl)prop-2-enone structure (blue). H atoms and disordered moiety are excluded for clarity.

3. Supramolecular features

In the crystal, the host molecules form inversion dimers via pairwise weak C—H⋯O interactions [H5⋯O1ⁱ = 2.71 Å; symmetry code as in Table 1, Fig. 3] with an R₂²(14) ring motif. Salient intermolecular interactions in the crystal packing are induced by the water molecule. Each water molecule is linked to two neighbouring water molecules by O2W—H1W⋯O2Wⁱⁱ hydrogen bonds, generating an infinite self-assembled chain of water molecules in a helical fashion along the b axis around which the host molecules are linked via O2W—H2W⋯N1 hydrogen bonds and weak C12—H12D⋯O2Wⁱⁱ interactions (Fig. 4). The host molecules are stacked on top of each other in alternating orientations along the c-axis direction (Fig. 5) and each is further involved in a cooperative contact with its adjacent homologue through a C—H⋯S interaction (H5⋯S1ⁱ = 3.00 Å).

Figure 3
A partial packing diagram for the title compound showing the R₂²(14) graph-set motif generated by weak C—H⋯O hydrogen bonds plotted as dashed lines. H atoms not involved in the hydrogen bonding have been omitted for clarity.

Figure 4
A view along b axis showing hydrogen-bonded self-assembled chain of water molecules with the hydrogen bonds between the water and host molecules shown as dashed lines. For clarity, the atoms in the host molecules not involved in hydrogen bonds have been omitted.

Figure 5
A view along the c axis of the crystal packing, showing the stacking of the host molecules, with hydrogen bonds between water molecules, and between water molecules and host molecules (dashed lines). For clarity, weak hydrogen contacts and some H atoms not involved in hydrogen bonding have been omitted.

4. Hirshfeld surface analysis

The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ) and two-dimensional fingerprint plots (McKinnon et al., 2007 ) were generated using CrystalExplorer (Turner et al., 2017 ). The Hirshfeld surface (HS) mapped over d_norm in the range −0.5072 to 1.2974 a.u. and shape-index (range −1.0 to 1.0 a.u.) are displayed in Figs. 6 and 7, respectively. The red spot on the HS indicates the O2W—H2W⋯N1 hydrogen bond while the pale-red spot near H12B illustrates the weak C—H⋯O2W interaction. The white spots represent H⋯O, H⋯S and H⋯H contacts. On the shape-index surface, convex blue regions indicate hydrogen-donor groups, while concave red regions indicate hydrogen-acceptor groups and S⋯N and S⋯C contacts and O⋯C interactions. The fingerprint plots show the contribution of different types of intermolecular interactions (Fig. 8). The largest contribution (46.9%) is from the weak van der Waals H⋯H contacts, followed by S⋯H/H⋯S (14.3%), C⋯H/H⋯C (12.4%) and O⋯H/H⋯O (6.3%) interactions. The fingerprint plot for the N⋯H/H⋯N contacts (5.9% contribution) shows a sharp spike pointing toward the origin of the plot, which highlights the strong hydrogen-bonding between the host molecule and water molecule. The C⋯C contacts, with a V-shaped distribution of points, contribute 5.7%.

Figure 6
The three-dimensional Hirshfeld surface representation of the title compound plotted over d_norm in the range −0.5086 to 1.2492 a.u.

Figure 7
The three-dimensional Hirshfeld surface mapped over shape-index.

Figure 8
(a) The overall two-dimensional fingerprint plot for title compound and (b)–(g) those delineated into H⋯H, S⋯H/H⋯S, C⋯H/H⋯C, O⋯H/H⋯O, N⋯H/H⋯N, C⋯C/C⋯C contacts, respectively.

In order to detect favoured contacts and highlight the crystal driving force, enrichment ratios were computed with MoProViewer (Guillot et al., 2014 ). The enrichment ratio E_XY of a chemical element pair (X, Y) is defined as the ratio between the proportion of actual crystal contacts between the different chemical species (X, Y) and the theoretical proportion of random equiprobable contacts (Jelsch et al., 2014). The asymmetric unit of the title compound is composed of two entities and in order to analyse all contacts present in the crystal, the host molecule and a neighboring water molecule not in contact each other were selected in order to obtain the integral Hirshfeld surfaces of each entity for the computation of the enrichment ratios. In addition, the hydrophobic Hc atoms bound to carbon were distinguished from the more polar Ho water hydrogen atoms and oxygen atoms were also differentiated (O = ketone oxygen atom and OW = water oxygen atom). The results obtained are summarized in Table 2. The hydrophobic Hc atoms, which constitute the largest part of the Hirshfeld surface, exhibit Hc⋯Hc self-contacts with an enrichment ratio equal to 1.0. The hydrophobic C⋯Hc interactions are unprivileged with E_CHc = 0.76 and correspond to weak C—H⋯C interactions. These interactions are under-represented because competition with the S⋯Hc, OW⋯Hc and weak O⋯Hc hydrogen bonds, the first two of which appear favoured with enrichment values of 1.35 and 1.14, respectively, and the last slightly under-represented with an enrichment ratio of 0.98. The C⋯C contacts are privileged and display an enrichment value of 1.85, which highlight molecules stacking one on top of the other as shown in Fig. 5. This type of stacking interaction is generally favoured in heterocyclic compounds because of the favourable electrostatic complementary orientations of molecules in the crystal packing. This result is in agreement to the findings reported by Jelsch et al. (2014). These stacking interactions induce N⋯S, O⋯C and S⋯C contacts displaying enrichment ratios of 1.58, 2.08 and 1.33, respectively. The N⋯Ho and OW⋯Ho polar contacts with the highest enrichment ratios of 5.03 and 5.19, respectively, are the most favoured contacts. These contacts correspond to the strong O2W—H2W⋯N1 and O2W—H1W⋯O2W hydrogen bonds (Table 1) observed in the crystal structure. Although crystallization is the result of concerted actions of all of the different interactions present within the crystal, the high enrichment value of the N⋯Ho and OW⋯Ho polar contacts reveal that these intermolecular interactions are the main driving force in the crystal packing formation of the title compound.

Table 2
Intermolecular contacts and enrichment ratios (%) on the Hirshfeld surface by atom type

The top part of the table gives the surface contribution S_X of each chemical type X to the Hirshfeld surface. The next part shows the percentage contributions C_XY of the actual contact types to the surface and the lower part of the table shows the E_XY enrichment contact ratios. E_XY ratios larger than unity are enriched contacts and those lower than unity are impoverished.

Atom type	Ho	C	N	O	S	Hc	Ow
Surface	7.70	23.26	3.69	2.77	14.46	43.96	4.17

Contact
Ho
C		9.40
N	3.20
O	0.00	3.00
S	0.70	9.00	2.00
Hc	8.40	15.00	2.40	3.00	17.60	18.70
OW	3.50	0.00	0.00	0.00	0.00	4.10	0.00

Enrichment
OW	5.19
N	5.03
S	0.27	1.33	1.58
C	0.00	1.85	0.00	2.08
Hc	1.19	0.76	0.72	0.98	1.35	1.00	1.14

5. Database survey

A search of the Cambridge Structural Database (WebCSD; Thomas et al., 2010 ) gave 66 hits for structures having an imidazo[1,2-a]pyridin-3-yl moiety and 157 entries for structures containing an 1,3-dithiolan-2-ylidene scaffold. No structure containing both fragments simultaneously has been determined to date. However, there is one imidazo[1,2-a]pyridin-3-yl derivative monohydrate that closely resembles the title compound viz. 1-(2-methylimidazo[1,2-a]pyridin-3-yl)-3,3-bis(methylsulfanyl)prop-2-∊none monohydrate (CSD refcode FOVROY; Bibila Mayaya Bisseyou et al., 2009).

6. Synthesis and crystallization

1-(2,7-Dimethylimidazol[1,2-a]pyridin-3-yl)ethanone (6.2 mmol) was dissolved in distilled dimethyl sulfoxide (15 ml), and the carbon disulfide (1.1 molar equivalents, 6.82 mmol) was added. After cooling the mixture to 273 K, sodium hydride (2.5 molar equivalents, 15.5 mmol) was added. After stirring for 30 min. at 273 K, the mixture was stirred at ambient temperature for 4 h. The solution was then cooled at 273 K and 1,2-dichloro ethane (2.5 molar equivalents, 15.5 mmol) was added dropwise. The resulting mixture was then stirred for 24 h and then poured into 50 ml of ice-cold water. The precipitate was filtered and recrystallized from a mixture of water–dioxane (2:1) to obtain brown single crystals of the title compound suitable for X-ray diffraction analysis (yield 76%; m.p. 453 K).

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. Water H atoms were located in difference-Fourier maps and OW—H bond lengths were restrained to the target value of the neutron diffraction distance. All other H atoms were positioned geometrically (C—H = 0.93–0.97 Å) and were refined using a riding model with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(C-methyl). In the 1,3-dithiolane ring, the carbon atoms of the C—C bond are disordered over two positions with refined occupancy factors of 0.579 (14) and 0.421 (14). C—C bond lengths in both disordered components were restrained to the target value of 1.513 Å (Allen et al., 1987 ).

Table 3
Experimental details

Crystal data
Chemical formula	C₁₄H₁₄N₂OS₂·H2O
M_r	308.41
Crystal system, space group	Tetragonal, I4₁cd
Temperature (K)	293
a, c (Å)	28.3247 (7), 7.2820 (2)
V (Å³)	5842.3 (3)
Z	16
Radiation type	Mo Kα
μ (mm⁻¹)	0.37
Crystal size (mm)	0.35 × 0.20 × 0.15

Data collection
Diffractometer	Nonius KappaCCD
Absorption correction	Multi-scan (Blessing, 1995 )
T_min, T_max	0.927, 0.963
No. of measured, independent and observed [I > 2σ(I)] reflections	22803, 3672, 2765
R_int	0.044

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.102, 1.04
No. of reflections	3672
No. of parameters	211
No. of restraints	43
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.29
Absolute structure	Flack x determined using 1012 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al. 2013 )
Absolute structure parameter	−0.01 (4)
Computer programs: COLLECT (Nonius, 1997 ), DENZO/SCALEPACK (Otwinowski & Minor, 1997 ), SHELXS97 (Sheldrick, 2008 ), SHELXL2014 (Sheldrick, 2015 ), ORTEP-3 for Windows and WinGX (Farrugia, 2012 ), PLATON (Spek, 2009 ), OLEX2 (Dolomanov et al., 2009 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1967239

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989019015755/vm2224sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2056989019015755/vm2224Isup2.cml

checkCIF report

Computing details top

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997), PLATON (Spek, 2009) and OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

1-(2,7-Dimethylimidazo[1,2-a]pyridin-3-yl)-2-(1,3-dithiolan-2-ylidene)ethanone monohydrate top

Crystal data top

C₁₄H₁₄N₂OS₂·H2O	D_x = 1.403 Mg m⁻³
M_r = 308.41	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, I4₁cd	Cell parameters from 22217 reflections
a = 28.3247 (7) Å	θ = 1.4–30.0°
c = 7.2820 (2) Å	µ = 0.37 mm⁻¹
V = 5842.3 (3) Å³	T = 293 K
Z = 16	Parallelepiped, brown
F(000) = 2592	0.35 × 0.20 × 0.15 mm

Data collection top

Nonius KappaCCD diffractometer	2765 reflections with I > 2σ(I)
phi and ω scan	R_int = 0.044
Absorption correction: multi-scan (Blessing, 1995)	θ_max = 30.0°, θ_min = 2.0°
T_min = 0.927, T_max = 0.963	h = −37→30
22803 measured reflections	k = −39→37
3672 independent reflections	l = −9→7

Refinement top

Refinement on F²	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ²(F_o²) + (0.0537P)² + 1.6604P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.036	(Δ/σ)_max = 0.001
wR(F²) = 0.102	Δρ_max = 0.22 e Å⁻³
S = 1.04	Δρ_min = −0.29 e Å⁻³
3672 reflections	Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
211 parameters	Extinction coefficient: 0.0024 (6)
43 restraints	Absolute structure: Flack x determined using 1012 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al. 2013)
Hydrogen site location: mixed	Absolute structure parameter: −0.01 (4)

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
S1	0.38738 (2)	0.12434 (2)	0.85051 (16)	0.0539 (2)
S2	0.39148 (2)	0.22768 (2)	0.85799 (17)	0.0626 (2)
O1	0.47583 (6)	0.09202 (6)	0.8604 (5)	0.0651 (6)
N2	0.57546 (6)	0.09070 (6)	0.8622 (5)	0.0402 (4)
N1	0.62625 (6)	0.15130 (7)	0.8534 (4)	0.0419 (4)
C1	0.58159 (8)	0.16831 (8)	0.8543 (6)	0.0413 (5)
C2	0.62206 (7)	0.10414 (8)	0.8578 (5)	0.0392 (5)
C3	0.65720 (8)	0.06930 (8)	0.8584 (5)	0.0445 (5)
H3	0.6888	0.0781	0.8543	0.053*
C4	0.64537 (8)	0.02258 (8)	0.8648 (6)	0.0474 (6)
C5	0.59688 (9)	0.01044 (9)	0.8715 (6)	0.0559 (8)
H5	0.5883	−0.0212	0.8775	0.067*
C6	0.56270 (9)	0.04398 (9)	0.8694 (7)	0.0539 (7)
H6	0.5310	0.0354	0.8727	0.065*
C7	0.54822 (8)	0.13206 (7)	0.8609 (5)	0.0414 (5)
C8	0.49691 (9)	0.13052 (7)	0.8601 (7)	0.0451 (5)
C9	0.47020 (8)	0.17414 (8)	0.8611 (6)	0.0480 (6)
H9	0.4863	0.2028	0.8650	0.058*
C10	0.42253 (8)	0.17425 (8)	0.8563 (6)	0.0432 (5)
C11A	0.3325 (3)	0.1573 (3)	0.8856 (14)	0.0577 (19)	0.579 (14)
H11A	0.3064	0.1402	0.8309	0.069*	0.579 (14)
H11B	0.3264	0.1604	1.0161	0.069*	0.579 (14)
C12A	0.3362 (3)	0.2057 (3)	0.7998 (15)	0.0585 (18)	0.579 (14)
H12A	0.3115	0.2262	0.8466	0.070*	0.579 (14)
H12B	0.3330	0.2035	0.6674	0.070*	0.579 (14)
C11B	0.3315 (4)	0.1526 (4)	0.792 (2)	0.054 (2)	0.421 (14)
H11C	0.3288	0.1570	0.6607	0.065*	0.421 (14)
H11D	0.3051	0.1337	0.8344	0.065*	0.421 (14)
C12B	0.3324 (4)	0.1995 (4)	0.8896 (19)	0.058 (3)	0.421 (14)
H12C	0.3262	0.1950	1.0194	0.069*	0.421 (14)
H12D	0.3080	0.2199	0.8400	0.069*	0.421 (14)
C13	0.57437 (9)	0.22043 (8)	0.8531 (7)	0.0545 (6)
H13A	0.6044	0.2360	0.8444	0.082*
H13B	0.5589	0.2299	0.9644	0.082*
H13C	0.5552	0.2290	0.7496	0.082*
C14	0.68205 (9)	−0.01559 (9)	0.8647 (6)	0.0587 (7)
H14A	0.7128	−0.0017	0.8536	0.088*
H14B	0.6766	−0.0364	0.7629	0.088*
H14C	0.6802	−0.0331	0.9773	0.088*
O2W	0.70594 (8)	0.21823 (9)	0.8393 (5)	0.0750 (7)
H1W	0.7256 (13)	0.2168 (16)	0.948 (4)	0.097 (15)*
H2W	0.6805 (13)	0.1956 (14)	0.859 (9)	0.131 (19)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0382 (3)	0.0429 (3)	0.0806 (5)	0.0006 (2)	0.0015 (4)	0.0037 (5)
S2	0.0479 (4)	0.0417 (3)	0.0982 (6)	0.0122 (3)	−0.0040 (5)	0.0009 (5)
O1	0.0367 (9)	0.0391 (9)	0.1197 (18)	−0.0002 (7)	−0.0006 (14)	−0.0017 (14)
N2	0.0334 (9)	0.0334 (9)	0.0539 (11)	0.0013 (7)	−0.0004 (12)	−0.0002 (12)
N1	0.0379 (10)	0.0359 (10)	0.0518 (11)	−0.0018 (7)	−0.0011 (13)	0.0002 (13)
C1	0.0394 (12)	0.0370 (11)	0.0474 (13)	−0.0004 (9)	−0.0002 (16)	0.0010 (15)
C2	0.0327 (11)	0.0389 (11)	0.0460 (13)	−0.0011 (8)	−0.0006 (14)	−0.0010 (15)
C3	0.0341 (11)	0.0439 (12)	0.0555 (14)	0.0026 (9)	0.0009 (14)	−0.0031 (15)
C4	0.0396 (12)	0.0434 (12)	0.0591 (16)	0.0080 (9)	−0.0002 (16)	−0.0025 (15)
C5	0.0454 (13)	0.0365 (13)	0.086 (2)	0.0029 (9)	0.0000 (19)	−0.002 (2)
C6	0.0356 (12)	0.0372 (12)	0.089 (2)	−0.0026 (9)	0.0004 (17)	0.0012 (17)
C7	0.0361 (11)	0.0348 (10)	0.0532 (14)	0.0037 (8)	−0.0006 (14)	0.0014 (15)
C8	0.0355 (10)	0.0414 (10)	0.0583 (14)	0.0024 (10)	−0.0007 (13)	0.000 (2)
C9	0.0378 (11)	0.0371 (11)	0.0692 (16)	0.0029 (9)	−0.0037 (17)	0.0002 (15)
C10	0.0401 (11)	0.0391 (11)	0.0504 (13)	0.0050 (10)	0.0012 (18)	0.0013 (15)
C11A	0.035 (2)	0.062 (3)	0.075 (5)	−0.001 (2)	0.003 (4)	−0.006 (4)
C12A	0.042 (3)	0.067 (4)	0.066 (4)	0.012 (3)	−0.005 (4)	−0.003 (3)
C11B	0.035 (4)	0.062 (4)	0.066 (5)	0.010 (3)	0.006 (5)	−0.003 (5)
C12B	0.043 (4)	0.060 (5)	0.070 (6)	0.012 (3)	0.009 (4)	−0.006 (5)
C13	0.0470 (13)	0.0363 (12)	0.0802 (19)	0.0001 (10)	−0.0017 (18)	0.0023 (18)
C14	0.0458 (13)	0.0488 (14)	0.082 (2)	0.0125 (10)	0.000 (2)	−0.005 (2)
O2W	0.0606 (13)	0.0720 (14)	0.092 (2)	−0.0131 (11)	−0.0092 (16)	0.0270 (17)

Geometric parameters (Å, º) top

S1—C10	1.729 (3)	C1—C7	1.396 (3)
S1—C11B	1.824 (11)	C1—C13	1.491 (3)
S1—C11A	1.831 (8)	C2—C3	1.402 (3)
S2—C12A	1.739 (8)	C3—C4	1.366 (3)
S2—C10	1.750 (2)	C4—C5	1.417 (3)
S2—C12B	1.868 (12)	C4—C14	1.500 (3)
O1—C8	1.243 (3)	C5—C6	1.356 (3)
N2—C6	1.373 (3)	C7—C8	1.454 (3)
N2—C2	1.374 (3)	C8—C9	1.449 (3)
N2—C7	1.403 (3)	C9—C10	1.351 (3)
N1—C2	1.342 (3)	C11A—C12A	1.509 (9)
N1—C1	1.354 (3)	C11B—C12B	1.506 (10)

C10—S1—C11B	98.4 (3)	C5—C4—C14	119.8 (2)
C10—S1—C11A	93.9 (3)	C6—C5—C4	121.4 (2)
C12A—S2—C10	98.1 (3)	C5—C6—N2	119.2 (2)
C10—S2—C12B	94.7 (4)	C1—C7—N2	104.01 (19)
C6—N2—C2	121.39 (19)	C1—C7—C8	134.3 (2)
C6—N2—C7	131.3 (2)	N2—C7—C8	121.7 (2)
C2—N2—C7	107.28 (19)	O1—C8—C9	119.8 (2)
C2—N1—C1	105.76 (18)	O1—C8—C7	120.4 (2)
N1—C1—C7	111.77 (19)	C9—C8—C7	119.8 (2)
N1—C1—C13	118.7 (2)	C10—C9—C8	121.6 (2)
C7—C1—C13	129.5 (2)	C9—C10—S1	125.03 (19)
N1—C2—N2	111.18 (19)	C9—C10—S2	120.27 (19)
N1—C2—C3	129.7 (2)	S1—C10—S2	114.69 (14)
N2—C2—C3	119.2 (2)	C12A—C11A—S1	110.3 (6)
C4—C3—C2	120.5 (2)	C11A—C12A—S2	106.6 (6)
C3—C4—C5	118.3 (2)	C12B—C11B—S1	105.2 (9)
C3—C4—C14	121.9 (2)	C11B—C12B—S2	109.6 (7)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O1	0.93	2.24	2.812 (3)	119
O2W—H2W···N1	0.97 (1)	1.99 (2)	2.949 (3)	170 (6)
C5—H5···O1ⁱ	0.93	2.71	3.560 (3)	153
O2W—H1W···O2Wⁱⁱ	0.97 (1)	1.92 (2)	2.837 (2)	157 (4)
C12A—H12B···O2Wⁱⁱⁱ	0.97	2.66	3.577 (11)	157

Symmetry codes: (i) −x+1, −y, z; (ii) −y+1, x−1/2, z+1/4; (iii) −x+1, y, z−1/2.

Intermolecular contacts and enrichment ratios (%) on the Hirshfeld surface by atom type top

Atom type	Ho	C	N	O	S	Hc	Ow
Surface	7.70	23.26	3.69	2.77	14.46	43.96	4.17

Contact
Ho
C		9.40
N	3.20
O	0.00	3.00
S	0.70	9.00	2.00
Hc	8.40	15.00	2.40	3.00	17.60	18.70
OW	3.50	0.00	0.00	0.00	0.00	4.10	0.00

Enrichment
OW	5.19
N	5.03
S	0.27	1.33	1.58
C	0.00	1.85	0.00	2.08
Hc	1.19	0.76	0.72	0.98	1.35	1.00	1.14

Acknowledgements

The authors thank the Spectropôle Service of the Faculty of Sciences and Techniques of Saint Jérôme (France) for the use of their diffractometer.

References

Allen, F. H., Kennard, O. & Watson, D. G. (1987). J. Chem. Soc. Perkin Trans. II, S1-S19. CrossRef Google Scholar
Besra, R. C., Rudrawar, S. & Chakraborti, A. K. (2005). Tetrahedron Lett. 46, 6213–6217. CrossRef CAS Google Scholar
Bibila Mayaya Bisseyou, Y., Sissouma, D., Goulizan Bi, S. D., Ouattara, M. & Yao-Kakou, R. C. A. (2009). Acta Cryst. E65, o1698–o1699. CSD CrossRef IUCr Journals Google Scholar
Blessing, R. H. (1995). Acta Cryst. A51, 33–38. CrossRef CAS Web of Science IUCr Journals Google Scholar
Chichibabin, A. E. (1925). Chem. Ber. 58, 1704–1706. Google Scholar
Deep, A., Bhatia, R. K., Kaur, R., Kumar, S., Jain, U. K., Singh, H., Batra, S., Kaushik, D. & Deb, P. K. (2017). Curr. Top. Med. Chem. 17, 238–250. CrossRef CAS PubMed Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Goel, R., Luxami, V. & Paul, K. (2016). Curr. Top. Med. Chem. 16, 3590–3616. CrossRef CAS PubMed Google Scholar
Guillot, B., Enrique, E., Huder, L. & Jelsch, C. (2014). Acta Cryst. A70, C279. CrossRef IUCr Journals Google Scholar
Huang, F., Zhao, M., Zhang, X., Wang, C., Qian, K., Kuo, R. Y., Morris-Natschke, S., Lee, K. H. & Peng, S. (2009). Bioorg. Med. Chem. 17, 6085–6095. CrossRef PubMed CAS Google Scholar
Jelsch, C. & Bibila Mayaya Bisseyou, Y. (2017). IUCrJ, 4, 158–174. Web of Science CrossRef CAS PubMed IUCr Journals Google Scholar
Jelsch, C., Ejsmont, K. & Huder, L. (2014). IUCrJ, 1, 119–128. Web of Science CrossRef CAS PubMed IUCr Journals Google Scholar
Khankari, R. K. & Grant, D. J. W. (1995). Thermochim. Acta, 248, 61–79. CrossRef CAS Web of Science Google Scholar
Kuthyala, S., Nagaraja, G. K., Sheik, S., Hanumanthappa, M. & Kumar, S. M. (2018). J. Mol. Struct. pp. 381–390. Google Scholar
Liu, J.-F., Liu, X.-L. & Liu, Y.-H. (2008). Acta Cryst. E64, o1340. Web of Science CSD CrossRef IUCr Journals Google Scholar
McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814–3816. Web of Science CrossRef Google Scholar
Meunier, B. (2008). Acc. Chem. Res. 41, 69–77. Web of Science CrossRef PubMed CAS Google Scholar
Nguyen-Ba, N., Brown, W. L., Chan, L., Lee, N., Brasili, L., Lafleur, D. & Zacharie, B. (1999). Chem. Commun. pp. 1245–1246. Google Scholar
Nonius (1997). COLLECT. Nonius BV, Delft, The Netherlands. Google Scholar
Ohya, S., Miyadera, T. & Yamazaki, M. (1982). Antimicrob. Agents Chemother. 21, 613–617. CrossRef CAS PubMed Google Scholar
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press. Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS Google Scholar
Spackman, M. A. & McKinnon, J. J. (2002). CrystEngComm, 4, 378–392. Web of Science CrossRef CAS Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tanaka, H., Araki, F., Harada, T. & Kurono, H. (1976). Jpn Patent No. 51151326A. Google Scholar
Thomas, I. R., Bruno, I. J., Cole, J. C., Macrae, C. F., Pidcock, E. & Wood, P. A. (2010). J. Appl. Cryst. 43, 362–366. Web of Science CrossRef CAS IUCr Journals Google Scholar
Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17. University of Western Australia. https://hirshfeldsurface.net. Google Scholar
Viegas-Junior, C., Danuello, A., Bolzani, V. da S., Barreiro, E. J. & Fraga, C. A. M. (2007). Curr. Med. Chem. 14, 1829–1852. PubMed CAS Google Scholar
Wang, Y., Li, Z. H. & Gao, N. (1994). Yaoxue Xuebao, 29, 78–80. Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Yang, L.-J., Li, Z.-G., Liu, X.-L. & Liu, Y.-H. (2007). Acta Cryst. E63, o4501. Web of Science CSD CrossRef IUCr Journals Google Scholar
Yang, X.-D., Wan, W. C., Deng, X.-Y., Li, Y., Yang, L.-J., Li, L. & Zhang, H.-B. (2012). Bioorg. Med. Chem. Lett. 22, 2726–2729. CrossRef CAS PubMed Google Scholar

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