2-[(2,4,6-Tri­methyl­benzene)­sulfon­yl]phthalazin-1(2H)-one: crystal structure, Hirshfeld surface analysis and computational study

Izuogu, D.C.; Asegbeloyin, J.N.; Jotani, M.M.; Tiekink, E.R.T.

doi:10.1107/S2056989020005101

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ISSN: 2056-9890

Volume 76| Part 5| May 2020| Pages 697-702

https://doi.org/10.1107/S2056989020005101

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2-[(2,4,6-Trimethylbenzene)sulfonyl]phthalazin-1(2H)-one: crystal structure, Hirshfeld surface analysis and computational study

David Chukwuma Izuogu,^a,^b,^c Jonnie Niyi Asegbeloyin,^a ‡ Mukesh M. Jotani ^d and Edward R. T. Tiekink ^e ^*

^aDepartment of Pure and Industrial Chemistry, University of Nigeria, Nsukka 410001, Enugu State, Nigeria, ^bDepartment of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aza-aoba, Aramaki, Sendai 980-8578, Japan, ^cDepartment of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, UK, ^dDepartment of Physics, Bhavan's Sheth R. A. College of Science, Ahmedabad, Gujarat 380001, India, and ^eResearch Centre for Crystalline Materials, School of Science and Technology, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
^*Correspondence e-mail: edwardt@sunway.edu.my

Edited by A. J. Lough, University of Toronto, Canada (Received 6 April 2020; accepted 11 April 2020; online 21 April 2020)

The X-ray crystal structure of the title phthalazin-1-one derivative, C₁₇H₁₆N₂O₃S {systematic name: 2-[(2,4,6-trimethylbenzene)sulfonyl]-1,2-dihydrophthalazin-1-one}, features a tetrahedral sulfoxide-S atom, connected to phthalazin-1-one and mesityl residues. The dihedral angle [83.26 (4)°] between the organic substituents is consistent with the molecule having the shape of the letter V. In the crystal, phthalazinone-C₆-C—H⋯O(sulfoxide) and π(phthalazinone-N₂C₄)–π(phthalazinone-C₆) stacking [inter-centroid distance = 3.5474 (9) Å] contacts lead to a linear supramolecular tape along the a-axis direction; tapes assemble without directional interactions between them. The analysis of the calculated Hirshfeld surfaces confirm the importance of the C—H⋯O and π-stacking interactions but, also H⋯H and C—H⋯C contacts. The calculation of the interaction energies indicate the importance of dispersion terms with the greatest energies calculated for the C—H⋯O and π-stacking interactions.

Keywords: crystal structure; phthalazinone; Hirshfeld surface analysis.

CCDC reference: 1996401

1. Chemical context

Phthalazin-1(2H)-one derivatives are a group of diazaheterobicycles that are noteworthy for their interesting medicinal applications. Thus, this class of compound has been reported to possess a wide variety of biological properties such as anti-diabetic (Mylari et al., 1992 ), anti-cancer (Menear et al., 2008 ), anti-inflammatory and analgesic (Pakulska et al., 2009 ), anti-histamine (Procopiou et al., 2011 ), anti-hypertensive and anti-thrombotic (Cherkez et al., 1986 ) activities. Some N-substituted phthalazinones have attracted attention as a result of their potential role as anti-asthmatic agents (Ukita et al., 1999 ), their ability to inhibit thromboxane A2 (TXA2) synthetase and to induce bronchodialation (Yamaguchi et al., 1993 ). At the present time, a number of phthalazin-1(2H)-one-based drugs are in use (Wu et al., 2012 ; Teran et al., 2019 ). A number of reaction pathways to the phthalazinone skeleton are known, notable among which include multi-step reactions involving cyclocondensation reactions of phthalic anhydrides, phthalimides, phthalaldehydic acid or 2-acylbenzoic acids with substituted hydrazines, in the presence of appropriate catalysts (Haider & Holzer, 2004 ). The conversion of phthalimides via Friedel–Crafts conditions or with organometallics to 2-keto benzoic acid hydrazides or 3,3-disubstituted indolinones, which are viable intermediates to substituted phthalazin-1(2H)-ones, have also been reported (Ismail et al., 1984 ; Chun et al., 2004 ) . Several other synthetic routes, involving various intermediates, have also been reported (Mylari et al., 1991 ; Yamaguchi et al., 1993; Acosta et al., 1995 ; Bele & Darabantu, 2003 ; Mahmoodi & Salehpour, 2003 ; Cockcroft et al., 2006 ; Del Olmo et al., 2006 ). In an earlier communication (Asegbeloyin et al., 2018 ), the dysprosium(III)-catalysed conversion of 2-{[2-(phenylsulfonyl)hydrazinylidene] methyl}benzoic acid to 2-(phenylsulfonyl)phthalazin-1-(2H)-one was described. In the present study, the title compound, 2-[(2,4,6-trimethylbenzene)sulfonyl]-1,2-dihydrophthalazin-1-one, (I), was obtained by the catalytic conversion of 2-{[2-(2,4,6-trimethylphenylsulfonyl)hydrazinylidene]methyl}benzoic acid. Herein, the crystal and molecular structures of (I) are described as is a detailed analysis of the molecular packing by an evaluation of the calculated Hirshfeld surfaces augmented by a computational chemistry study.

2. Structural commentary

The molecule of (I), Fig. 1, may be conveniently described as a central SO₂ residue with mesityl and phthalazin-1-one substituents. The geometry about the S1 atom is distorted tetrahedral with the range of angles subtended at S1 being a narrow 103.58 (6)° for N1—S1—C1, involving the singly-bonded N1 and C1 atoms, to a wide 118.39 (6)°, for O1—S1—O2, involving the doubly-bonded sulfoxide-O1, O2 atoms. The organic residues lie to the opposite side of the molecule to the SO₂ residue, forming dihedral angles of 67.35 (4)° [phthalazin-1-one with r.m.s. deviation = 0.0105 Å] and 49.79 (6)° [mesityl]. The dihedral angle between the organic residues of 83.26 (4)° indicates a close to orthogonal relationship. The N2—N1—C10—O3 torsion angle of −179.88 (12)° indicates a co-planar arrangement for these atoms, which allows for the close approach of the N2 and O3 atoms, i.e. 2.6631 (15) Å, suggestive of a stabilizing contact (Nakanishi et al., 2007 ). Globally, the molecule has the shape of the letter V. Within the hetero-ring of the phthalazin-1-one substituent, the N1—N2 bond length is 1.3808 (15) Å and C10—N1 = 1.4003 (17) Å. In each of the C17=N2 [1.2911 (18) Å] and C10=O3 [1.2175 (15) Å] bonds, double-bond character is noted. The bond angles about the N1 atom are non-symmetric, with the endocyclic N2—N1—C10 angle of 126.97 (11) Å being significantly wider than the exocyclic N2—N1—S1 [113.93 (9) Å] and C10—N1—S1 [118.89 (8) Å] angles.

Figure 1
The molecular structures of (I)

showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.

3. Supramolecular features

The formation of a supramolecular tape sustained by phthalazinone-C₆-C—H⋯O(sulfoxide) contacts, Table 1, and π(phthalazinone)–π(phthalazinone) stacking is the main feature of the molecular packing in the crystal of (I), Fig. 2(a). The π-stacking occurs between centrosymmetrically related phthalazinone rings, i.e. between the N₂C₄ and C₆ⁱ rings with an inter-centroid distance = 3.5474 (9) Å, angle of inclination = 1.17 (7)° for symmetry operation (i) 1 − x, 1 − y, 2 − z. As shown in Fig. 2(b), the tapes inter-digitate along the c-axis direction allowing for putative π-stacking between mesityl rings but, the inter-centroid separation is long at 4.1963 (8) Å. The assemblies shown in Fig. 2(b) stack along the a-axis direction, again without directional interactions between them, Fig. 2(c).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C12—H12⋯O2ⁱ	0.95	2.49	3.3395 (18)	149
Symmetry code: (i) x, y-1, z.

Figure 2
Molecular packing in the crystal of (I)

: (a) supramolecular tape sustained by phthalazinone-C—H⋯O(sulfoxide) and π(phthalazinone)–π(phthalazinone) stacking interactions shown as orange and purple dashed lines, respectively, (b) a view of the unit-cell contents down the a axis showing the inter-digitation of tapes and (c) a view of the unit-cell contents down the c axis showing the stacking of assemblies of (b) along the a-axis direction.

4. Hirshfeld surface analysis

In order to probe the interactions between molecules of (I) in the crystal, the Hirshfeld surfaces and two-dimensional fingerprint plots were calculated with the program Crystal Explorer 17 (Turner et al., 2017 ) using established procedures described by Tan et al. (2019 ). In addition to the bright-red spots appearing near the sulfoxide-O2 and phthalazinone-H12 atoms on the Hirshfeld surface in Fig. 3(a),(b), the presence of diminutive red spots near methyl-C7 and benzene-H5 are indicative of intermolecular C—H⋯C contacts as C—H⋯π contacts are not preferred because of the V-shaped molecular geometry of (I). Also, the group of faint-red spots near alternate carbon atoms C10, C12, C14 and C16 of the phthalazinone-C₆ ring on the d_norm-mapped Hirshfeld surface in Fig. 3(b) is indicative of short intra-chain C⋯C contacts [Table 2 and Fig. 2(a)] and is consistent with the significant contribution from π–π stacking between centrosymmetrically related phthalazinone-N₂C₄ and C₆ rings, encompassing connections between phthalazinone-C₆ rings [3.6657 (9) Å with angle of inclination = 0.03 (7)°]. The involvement of the methyl-C8 atom in C—H⋯O [to provide links between the chains shown in Fig. 2(b)] and C—H⋯C contacts, Table 2, is highlighted in Fig. 3(c). The blue and red regions corresponding to positive and negative electrostatic potentials, respectively, on the Hirshfeld surface mapped over electrostatic potential shown in Fig. 4 represent the involvement of different atoms in the intermolecular interactions in the crystal.

Table 2
A summary of short interatomic contacts (Å) in (I)^a

Contact	Distance	Symmetry operation
C10⋯C14	3.345 (2)	1 − x, 1 − y, 2 − z
C12⋯C16	3.351 (2)	1 − x, 1 − y, 2 − z
O1⋯H9C	2.58	1 + x, y, z
O1⋯H14	2.61	1 − x, 1 − y, 2 − z
O3⋯H8A	2.60	−x, 1 − y, 1 − z
C5⋯H7C	2.78	1 − x, 2 − y, 1 − z
C7⋯H5	2.61	1 + x, y, z
C10⋯H8A	2.79	−x, 1 − y, 1 − z
H12⋯H9A	2.20	x, −1 + y, z
Notes: (a) The interatomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X—H bond lengths are adjusted to their neutron values; (b) these interactions correspond to conventional hydrogen bonds.

Figure 3
(a)–(c) Three views of Hirshfeld surface mapped over d_norm for (I)

in the range −0.128 to + 1.298 arbitrary units. The intermolecular C-H⋯O and short interatomic C⋯C contacts are represented with black dashed lines, and the short interatomic H⋯H, O⋯H/H⋯O and C⋯H/H⋯C contacts with sky-blue, yellow and red dashed lines, respectively.

Figure 4
(a) and (b) Two views of the calculated electrostatic potential mapped onto the Hirshfeld surface within the isosurface range −0.093 to 0.040 atomic units. The red and blue regions represent negative and positive electrostatic potentials, respectively.

The overall two-dimensional fingerprint plots for (I) and those delineated into H⋯H, O⋯H/H⋯O, C⋯H/H⋯C and C⋯C contacts are illustrated in Fig. 5(a)–(e), respectively; the percentage contributions from the different interatomic contacts to the Hirshfeld surfaces are summarized in Table 3. A short interatomic H⋯H contact involving the phthalazinone-H12 and methyl-H9A atoms, Table 2, appears as a small peak at d_e + d_i ∼2.2 Å in the fingerprint plot delineated into H⋯H contacts, Fig. 5(b). In the fingerprint plot delineated into O⋯H/H⋯O contacts illustrated in Fig. 5(c), a pair of forceps-like tips at d_e + d_i ∼2.3 Å, indicate the intermolecular C—H⋯O interaction involving the phthalazinone-H12 and sulfoxide-O2 atoms, whereas the other interatomic O⋯H/H⋯O contacts are merged within the plot and appear as a pair of intense blue spikes at d_e + d_i ∼2.8 Å. Despite the observation that intermolecular C—H⋯π contacts are usually preferred by methyl groups, none are found involving those substituted at (C1–C6) benzene ring in the crystal due to the V-shaped geometry. Rather, the involvement of methyl-C7 and H5A atoms, and benzene-C5 and H7C atoms [to provide links between the chains shown in Fig. 2(b)] in C—H⋯C interactions, Table 2, are characterized as the pair of forceps-like flat tips about d_e + d_i ∼2.8 Å in the fingerprint plot delineated into C⋯H/H⋯C contacts, Fig. 5(d). The presence of π–π stacking interactions between symmetry-related phthalazinone-N₂C₄ and C₆ rings is also evident as the arrow-shaped distribution of points around d_e, d_i ∼1.8 Å in the fingerprint plot delineated into C⋯C contacts, Fig. 5(e). The contribution from other interatomic contacts, summarized in Table 2, show a negligible effect on the calculated Hirshfeld surface of (I).

Table 3
Percentage contributions to intermolecular contacts on the Hirshfeld surface calculated for (I)

Contact	Percentage contribution
H⋯H	44.9
O⋯H/H⋯O	24.0
C⋯H/H⋯C	18.1
C⋯C	6.5
N⋯H/H⋯ N	4.0
C⋯O/O⋯C	1.1
C⋯N/N⋯C	0.7
N⋯N	0.4
C⋯S/S⋯C	0.2

Figure 5
(a) The overall two-dimensional fingerprint plots for (I)

, and those delineated into (b) H⋯H, (c) O⋯H/H⋯O, (d) C⋯H/H⋯C and (e) C⋯C contacts.

5. Computational chemistry

The pairwise interaction energies between the molecules within the crystal of (I) were calculated by summing up four energy components, comprising electrostatic (E_ele), polarization (E_pol), dispersion (E_dis) and exchange–repulsion (E_rep) following Turner et al. (2017). The energies were obtained by using the wave function calculated at the B3LYP/6-31G(d,p) level of theory. The nature and strength of the intermolecular interactions in terms of their energies are quantitatively summarized in Table 4, where it is clear that the dispersive component makes the major contribution to the interaction energies in the crystal in the absence of conventional hydrogen bonding. It is revealed from the interaction energies listed in Table 4, that the π–π stacking interaction between phthalazinone-N₂C₄ and C₆ rings and the short interatomic O1⋯H14 contact have the greatest energy. The short interatomic C5⋯H7C, O3⋯H8A and C10⋯H8A contacts also have significant interaction energies due to their participation in inversion-related contacts. Lower energies, compared to above interactions, are calculated for the H12⋯H9A, C7⋯H5 and O1⋯H9C contacts.

Table 4
A summary of interaction energies (kJ mol⁻¹) calculated for (I)

Contact	R (Å)	E_ele	E_pol	E_dis	E_rep	E_tot
Cg(N₂C₄)⋯Cg(C₆)ⁱ +
Cg(C₆)⋯Cg(C₆)ⁱ +	8.12	−28.9	−5.0	−64.7	48.2	−60.8
O1⋯H14ⁱ
C5⋯H7Cⁱⁱ	7.84	−21.3	−5.5	−60.9	43.5	−52.8
O3 ⋯H8Aⁱⁱⁱ +
C10 ⋯H8Aⁱⁱⁱ	7.54	−10.7	−2.0	−56.8	32.6	−42.1
C12—H12⋯O2^iv +
H12⋯H9A^iv	8.17	−4.4	−4.6	−20.5	18.0	−14.8
O1⋯H9C^v +
C7⋯H5^v	7.98	−3.1	−2.0	−16.9	14.2	−10.6
Symmetry codes: (i) 1 − x, 1 − y, 2 − z; (ii) 1 − x, 2 − y, 1 − z; (iii) − x, 1 − y, 1 − z; (iv) x, −1 + y, z; (v) 1 + x, y, z.

Fig. 6 illustrates the magnitudes of intermolecular energies represented graphically by energy frameworks to highlight the supramolecular architecture of the crystal through cylinders joining the centroids of molecular pairs using red, green and blue colour codes for the components E_ele, E_disp and E_tot, respectively. The images emphasize the importance of dispersion interactions in the molecular packing.

Figure 6
Perspective views of the energy frameworks calculated for (I)

, showing the (a) electrostatic force, (b) dispersion force and (c) total energy. The radii of the cylinders are proportional to the relative strength of the corresponding energies and were adjusted to the same scale factor of 50 with a cut-off value of 3 kJ mol⁻¹ within 4 × 4 × 4 unit cells.

6. Database survey

There is only a single direct analogue to (I) in the crystallographic literature, namely 2-(phenylsulfonyl)phthalazin-1(2H)-one (Asegbeloyin et al., 2018), (II). A comparison of key geometric parameters for (I) and (II) is given in Table 5. The data in Table 5 confirm the closeness of the salient bond lengths, but also show significant differences in the torsion angles about the N1—S1 and C1—S1 bonds, i.e. by up to 18 and 8°, respectively. These conformational differences are highlighted in the overlay diagram of Fig. 7 and in the dihedral angles between the aromatic residues of 83.26 (4) and 78.12 (4)° for (I) and (II), respectively.

Table 5
A comparison of key geometric parameters (Å, °) for (I) and (II)

	(I)	(II)
N1—N2	1.3808 (15)	1.384 (2)
C10—O3	1.2175 (15	1.212 (3)
C10—N1	1.4003 (17)	1.406 (2)
C17—N2	1.2911 (18)	1.283 (2)
N2⋯O2	2.6631 (15)	2.6394 (19)
N2—N1—S1—O1	120.33 (10)	138.71 (12)
N2—N1—S1—O2	−5.52 (11)	9.59 (13)
N1—S1—C1—C2	−111.55 (11)	−103.95 (16)
N1—S1—C1—C6	69.70 (11)	76.49 (17)

Figure 7
An overlay diagram for (I)

(red image) and (II) (blue). The molecules have been overlapped so the hetero-rings are coincident.

7. Synthesis and crystallization

2-{[2-(2,4,6-Trimethylphenylsulfonyl)hydrazinylidene]methyl}benzoic acid (III) was obtained by a method reported earlier (Asegbeloyin et al., 2018). Compound (I) was obtained from the following reaction. An ethanol solution (10 ml) of Dy(O₂CCH₃)₃·4H₂O (Wako Chemicals, Japan; 1 mmol, 411.692 mg) was added with constant stirring to an ethanol solution (20 ml) of (III) (1,039.2 mg, 3 mmol). The resulting mixture was refluxed for 3 h in an oil bath. The obtained colourless solution was concentrated to afford a colourless precipitate, which was filtered, dried under suction and further dried in vacuo over CaCl₂. The precipitates were dissolved in ethanol, the resultant colourless solution was filtered and left at room temperature for 48 h to obtain colourless crystals of (I).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 6. The carbon-bound H atoms were placed in calculated positions (C—H = 0.95–0.98 Å) and were included in the refinement in the riding-model approximation, with U_iso(H) set to 1.2–1.5U_eq(C).

Table 6
Experimental details

Crystal data
Chemical formula	C₁₇H₁₆N₂O₃S
M_r	328.38
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	100
a, b, c (Å)	7.9782 (4), 8.1711 (5), 12.6661 (7)
α, β, γ (°)	92.214 (2), 93.423 (1), 114.274 (1)
V (Å³)	749.55 (7)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.23
Crystal size (mm)	0.38 × 0.12 × 0.08

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996 )
T_min, T_max	0.924, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	11665, 5913, 4625
R_int	0.027
(sin θ/λ)_max (Å⁻¹)	0.804

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.048, 0.122, 1.02
No. of reflections	5913
No. of parameters	211
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.59, −0.39
Computer programs: APEX2 and SAINT (Bruker, 2002 ), SHELXT (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), ORTEP-3 for Windows (Farrugia, 2012 ), DIAMOND (Brandenburg, 2006 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1996401

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989020005101/lh5956sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020005101/lh5956Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989020005101/lh5956Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); program(s) used to solve structure: SHELXS (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

2-[(2,4,6-Trimethylbenzene)sulfonyl]phthalazin-1(2H)-one top

Crystal data top

C₁₇H₁₆N₂O₃S	Z = 2
M_r = 328.38	F(000) = 344
Triclinic, P1	D_x = 1.455 Mg m⁻³
a = 7.9782 (4) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.1711 (5) Å	Cell parameters from 5241 reflections
c = 12.6661 (7) Å	θ = 2.7–34.7°
α = 92.214 (2)°	µ = 0.23 mm⁻¹
β = 93.423 (1)°	T = 100 K
γ = 114.274 (1)°	Prism, colourless
V = 749.55 (7) Å³	0.38 × 0.12 × 0.08 mm

Data collection top

Bruker APEXII CCD diffractometer	4625 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.027
ω scans	θ_max = 34.9°, θ_min = 1.6°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −12→12
T_min = 0.924, T_max = 1.000	k = −13→7
11665 measured reflections	l = −19→19
5913 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.122	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0579P)² + 0.3671P] where P = (F_o² + 2F_c²)/3
5913 reflections	(Δ/σ)_max < 0.001
211 parameters	Δρ_max = 0.59 e Å⁻³
0 restraints	Δρ_min = −0.39 e Å⁻³

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
S1	0.52952 (4)	0.91549 (4)	0.73039 (2)	0.00972 (8)
O1	0.70758 (13)	0.91524 (14)	0.72487 (8)	0.01414 (19)
O2	0.51875 (14)	1.07825 (13)	0.76724 (7)	0.01422 (19)
O3	0.45530 (14)	0.53580 (14)	0.72961 (7)	0.01357 (19)
N1	0.42015 (15)	0.76225 (15)	0.82277 (8)	0.0107 (2)
N2	0.36966 (17)	0.83676 (16)	0.90820 (9)	0.0138 (2)
C1	0.38648 (17)	0.82486 (17)	0.61201 (9)	0.0097 (2)
C2	0.44783 (17)	0.75451 (17)	0.52613 (10)	0.0103 (2)
C3	0.32852 (18)	0.69064 (18)	0.43396 (10)	0.0116 (2)
H3	0.367189	0.643377	0.375142	0.014*
C4	0.15518 (18)	0.69371 (18)	0.42516 (10)	0.0126 (2)
C5	0.09886 (18)	0.76139 (19)	0.51177 (10)	0.0133 (2)
H5	−0.020289	0.761710	0.506665	0.016*
C6	0.21077 (18)	0.82878 (18)	0.60579 (10)	0.0116 (2)
C7	0.63166 (18)	0.7437 (2)	0.52408 (11)	0.0141 (2)
H7A	0.636640	0.683730	0.456594	0.021*
H7B	0.647194	0.675014	0.582699	0.021*
H7C	0.730720	0.865470	0.531622	0.021*
C8	0.0315 (2)	0.6274 (2)	0.32396 (11)	0.0190 (3)
H8A	−0.094563	0.608096	0.337969	0.028*
H8B	0.032099	0.513741	0.296720	0.028*
H8C	0.076289	0.717057	0.271317	0.028*
C9	0.1341 (2)	0.9043 (2)	0.69211 (11)	0.0190 (3)
H9A	0.184991	1.035634	0.691039	0.028*
H9B	0.168371	0.871735	0.761207	0.028*
H9C	−0.000599	0.854423	0.680026	0.028*
C10	0.40551 (17)	0.58589 (17)	0.80886 (10)	0.0099 (2)
C11	0.32443 (17)	0.47264 (18)	0.89581 (10)	0.0106 (2)
C12	0.30524 (18)	0.29500 (18)	0.89276 (10)	0.0132 (2)
H12	0.343082	0.246095	0.834285	0.016*
C13	0.23047 (19)	0.19062 (19)	0.97587 (11)	0.0153 (3)
H13	0.216814	0.069423	0.974185	0.018*
C14	0.17479 (19)	0.2621 (2)	1.06236 (11)	0.0160 (3)
H14	0.123129	0.189023	1.118763	0.019*
C15	0.19460 (19)	0.4382 (2)	1.06607 (11)	0.0154 (3)
H15	0.157015	0.486375	1.124986	0.018*
C16	0.27053 (18)	0.54625 (18)	0.98247 (10)	0.0118 (2)
C17	0.2996 (2)	0.73194 (19)	0.98264 (10)	0.0145 (2)
H17	0.264466	0.781298	1.042086	0.017*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.00989 (13)	0.01011 (14)	0.00894 (13)	0.00401 (11)	0.00008 (10)	0.00083 (10)
O1	0.0094 (4)	0.0174 (5)	0.0147 (4)	0.0047 (4)	0.0002 (3)	0.0018 (4)
O2	0.0193 (5)	0.0103 (4)	0.0128 (4)	0.0061 (4)	0.0007 (4)	−0.0004 (3)
O3	0.0168 (5)	0.0153 (5)	0.0105 (4)	0.0083 (4)	0.0033 (3)	0.0004 (3)
N1	0.0139 (5)	0.0110 (5)	0.0083 (4)	0.0060 (4)	0.0022 (4)	0.0010 (4)
N2	0.0203 (6)	0.0139 (5)	0.0094 (4)	0.0093 (5)	0.0019 (4)	−0.0013 (4)
C1	0.0105 (5)	0.0107 (5)	0.0082 (5)	0.0046 (4)	0.0002 (4)	0.0007 (4)
C2	0.0109 (5)	0.0109 (5)	0.0106 (5)	0.0054 (4)	0.0030 (4)	0.0023 (4)
C3	0.0139 (5)	0.0121 (6)	0.0094 (5)	0.0059 (5)	0.0025 (4)	0.0006 (4)
C4	0.0121 (5)	0.0128 (6)	0.0113 (5)	0.0035 (5)	−0.0001 (4)	0.0009 (4)
C5	0.0107 (5)	0.0176 (6)	0.0130 (5)	0.0073 (5)	0.0002 (4)	0.0008 (5)
C6	0.0115 (5)	0.0143 (6)	0.0107 (5)	0.0071 (5)	0.0010 (4)	0.0005 (4)
C7	0.0118 (5)	0.0181 (6)	0.0151 (5)	0.0086 (5)	0.0035 (5)	0.0016 (5)
C8	0.0167 (6)	0.0226 (7)	0.0134 (6)	0.0050 (6)	−0.0036 (5)	−0.0036 (5)
C9	0.0186 (6)	0.0309 (8)	0.0138 (6)	0.0172 (6)	0.0002 (5)	−0.0043 (5)
C10	0.0091 (5)	0.0112 (5)	0.0094 (5)	0.0045 (4)	−0.0012 (4)	−0.0005 (4)
C11	0.0100 (5)	0.0122 (6)	0.0094 (5)	0.0044 (4)	0.0004 (4)	0.0010 (4)
C12	0.0140 (6)	0.0125 (6)	0.0132 (5)	0.0059 (5)	0.0001 (4)	−0.0003 (4)
C13	0.0143 (6)	0.0119 (6)	0.0185 (6)	0.0041 (5)	0.0009 (5)	0.0038 (5)
C14	0.0135 (6)	0.0188 (7)	0.0149 (6)	0.0052 (5)	0.0024 (5)	0.0069 (5)
C15	0.0148 (6)	0.0207 (7)	0.0116 (5)	0.0079 (5)	0.0031 (5)	0.0020 (5)
C16	0.0114 (5)	0.0137 (6)	0.0108 (5)	0.0060 (5)	0.0003 (4)	0.0006 (4)
C17	0.0195 (6)	0.0167 (6)	0.0103 (5)	0.0104 (5)	0.0025 (5)	−0.0008 (4)

Geometric parameters (Å, º) top

S1—O1	1.4273 (10)	C7—H7C	0.9800
S1—O2	1.4300 (10)	C8—H8A	0.9800
S1—N1	1.7422 (11)	C8—H8B	0.9800
S1—C1	1.7646 (12)	C8—H8C	0.9800
O3—C10	1.2175 (15)	C9—H9A	0.9800
N1—N2	1.3808 (15)	C9—H9B	0.9800
N1—C10	1.4003 (17)	C9—H9C	0.9800
N2—C17	1.2911 (18)	C10—C11	1.4694 (18)
C1—C6	1.4130 (18)	C11—C12	1.3943 (19)
C1—C2	1.4142 (17)	C11—C16	1.4034 (18)
C2—C3	1.3975 (18)	C12—C13	1.3847 (19)
C2—C7	1.5066 (18)	C12—H12	0.9500
C3—C4	1.3913 (19)	C13—C14	1.400 (2)
C3—H3	0.9500	C13—H13	0.9500
C4—C5	1.3883 (18)	C14—C15	1.380 (2)
C4—C8	1.5055 (19)	C14—H14	0.9500
C5—C6	1.3917 (18)	C15—C16	1.4059 (19)
C5—H5	0.9500	C15—H15	0.9500
C6—C9	1.5125 (18)	C16—C17	1.438 (2)
C7—H7A	0.9800	C17—H17	0.9500
C7—H7B	0.9800

O1—S1—O2	118.39 (6)	C4—C8—H8B	109.5
O1—S1—N1	106.22 (6)	H8A—C8—H8B	109.5
O2—S1—N1	104.37 (6)	C4—C8—H8C	109.5
O1—S1—C1	112.48 (6)	H8A—C8—H8C	109.5
O2—S1—C1	110.28 (6)	H8B—C8—H8C	109.5
N1—S1—C1	103.58 (6)	C6—C9—H9A	109.5
N2—N1—C10	126.97 (11)	C6—C9—H9B	109.5
N2—N1—S1	113.93 (9)	H9A—C9—H9B	109.5
C10—N1—S1	118.89 (8)	C6—C9—H9C	109.5
C17—N2—N1	116.47 (12)	H9A—C9—H9C	109.5
C6—C1—C2	121.56 (11)	H9B—C9—H9C	109.5
C6—C1—S1	117.50 (9)	O3—C10—N1	120.86 (12)
C2—C1—S1	120.94 (10)	O3—C10—C11	124.94 (12)
C3—C2—C1	117.37 (12)	N1—C10—C11	114.19 (11)
C3—C2—C7	116.62 (11)	C12—C11—C16	120.62 (12)
C1—C2—C7	126.01 (11)	C12—C11—C10	120.00 (11)
C4—C3—C2	122.42 (12)	C16—C11—C10	119.36 (12)
C4—C3—H3	118.8	C13—C12—C11	119.31 (12)
C2—C3—H3	118.8	C13—C12—H12	120.3
C5—C4—C3	118.48 (12)	C11—C12—H12	120.3
C5—C4—C8	120.39 (12)	C12—C13—C14	120.60 (13)
C3—C4—C8	121.12 (12)	C12—C13—H13	119.7
C4—C5—C6	122.33 (12)	C14—C13—H13	119.7
C4—C5—H5	118.8	C15—C14—C13	120.31 (13)
C6—C5—H5	118.8	C15—C14—H14	119.8
C5—C6—C1	117.83 (11)	C13—C14—H14	119.8
C5—C6—C9	116.57 (12)	C14—C15—C16	119.85 (13)
C1—C6—C9	125.58 (12)	C14—C15—H15	120.1
C2—C7—H7A	109.5	C16—C15—H15	120.1
C2—C7—H7B	109.5	C11—C16—C15	119.30 (13)
H7A—C7—H7B	109.5	C11—C16—C17	117.99 (12)
C2—C7—H7C	109.5	C15—C16—C17	122.69 (12)
H7A—C7—H7C	109.5	N2—C17—C16	125.01 (12)
H7B—C7—H7C	109.5	N2—C17—H17	117.5
C4—C8—H8A	109.5	C16—C17—H17	117.5

O1—S1—N1—N2	120.33 (10)	C2—C1—C6—C5	−0.2 (2)
O2—S1—N1—N2	−5.52 (11)	S1—C1—C6—C5	178.53 (10)
C1—S1—N1—N2	−120.99 (10)	C2—C1—C6—C9	−178.71 (14)
O1—S1—N1—C10	−54.70 (11)	S1—C1—C6—C9	0.02 (19)
O2—S1—N1—C10	179.45 (10)	N2—N1—C10—O3	−179.88 (12)
C1—S1—N1—C10	63.98 (11)	S1—N1—C10—O3	−5.57 (17)
C10—N1—N2—C17	−0.8 (2)	N2—N1—C10—C11	0.98 (18)
S1—N1—N2—C17	−175.38 (10)	S1—N1—C10—C11	175.29 (9)
O1—S1—C1—C6	−176.04 (10)	O3—C10—C11—C12	2.1 (2)
O2—S1—C1—C6	−41.49 (12)	N1—C10—C11—C12	−178.79 (11)
N1—S1—C1—C6	69.70 (11)	O3—C10—C11—C16	−179.23 (12)
O1—S1—C1—C2	2.71 (13)	N1—C10—C11—C16	−0.13 (17)
O2—S1—C1—C2	137.26 (11)	C16—C11—C12—C13	0.6 (2)
N1—S1—C1—C2	−111.55 (11)	C10—C11—C12—C13	179.29 (12)
C6—C1—C2—C3	0.74 (19)	C11—C12—C13—C14	−0.1 (2)
S1—C1—C2—C3	−177.95 (10)	C12—C13—C14—C15	−0.3 (2)
C6—C1—C2—C7	179.99 (13)	C13—C14—C15—C16	0.2 (2)
S1—C1—C2—C7	1.30 (19)	C12—C11—C16—C15	−0.75 (19)
C1—C2—C3—C4	−0.3 (2)	C10—C11—C16—C15	−179.40 (12)
C7—C2—C3—C4	−179.65 (12)	C12—C11—C16—C17	177.93 (12)
C2—C3—C4—C5	−0.6 (2)	C10—C11—C16—C17	−0.72 (18)
C2—C3—C4—C8	178.73 (13)	C14—C15—C16—C11	0.3 (2)
C3—C4—C5—C6	1.2 (2)	C14—C15—C16—C17	−178.29 (13)
C8—C4—C5—C6	−178.16 (13)	N1—N2—C17—C16	−0.2 (2)
C4—C5—C6—C1	−0.8 (2)	C11—C16—C17—N2	0.9 (2)
C4—C5—C6—C9	177.86 (14)	C15—C16—C17—N2	179.58 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12···O2ⁱ	0.95	2.49	3.3395 (18)	149

Symmetry code: (i) x, y−1, z.

A summary of short interatomic contacts (Å) in (I)^a top

Contact	Distance	Symmetry operation
C10···C14	3.345 (2)	1 - x, 1 - y, 2 - z
C12···C16	3.351 (2)	1 - x, 1 - y, 2 - z
O1···H9C	2.58	1 + x, y, z
O1···H14	2.61	1 - x, 1 - y, 2 - z
O3···H8A	2.60	- x, 1 - y, 1 - z
C5···H7C	2.78	1 - x, 2 - y, 1 - z
C7···H5	2.61	1 + x, y, z
C10···H8A	2.79	- x, 1 - y, 1 - z
H12···H9A	2.20	x, -1 + y, z

Notes: (a) The interatomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X—H bond lengths are adjusted to their neutron values; (b) these interactions correspond to conventional hydrogen bonds.

Percentage contributions to intermolecular contacts on the Hirshfeld surface calculated for (I) top

Contact	Percentage contribution
H···H	44.9
O···H/H···O	24.0
C···H/H···C	18.1
C···C	6.5
N···H/H··· N	4.0
C···O/O···C	1.1
C···N/N···C	0.7
N···N	0.4
C···S/S···C	0.2

A summary of interaction energies (kJ mol^-1) calculated for (I) top

Contact	R (Å)	E_ele	E_pol	E_dis	E_rep	E_tot
Cg(N₂C₄)···Cg(C₆)ⁱ +
Cg(C₆)···Cg(C₆)ⁱ +	8.12	-28.9	-5.0	-64.7	48.2	-60.8
O1···H14ⁱ
C5···H7Cⁱⁱ	7.84	-21.3	-5.5	-60.9	43.5	-52.8
O3 ···H8Aⁱⁱⁱ +
C10 ···H8Aⁱⁱⁱ	7.54	-10.7	-2.0	-56.8	32.6	-42.1
C12—H12···O2^iv +
H12···H9A^iv	8.17	-4.4	-4.6	-20.5	18.0	-14.8
O1···H9C^v +
C7···H5^v	7.98	-3.1	-2.0	-16.9	14.2	-10.6

Symmetry codes: (i) 1 - x, 1 - y, 2 - z; (ii) 1 - x, 2 - y, 1 - z; (iii) - x, 1 - y, 1 - z; (iv) x, -1 + y, z; (v) 1 + x, y, z.

A comparison of key geometric parameters (Å; °) for (I) and (II) top

N1—N2	1.3808 (15)	1.384 (2)
C10—O3	1.2175 (15	1.212 (3)
C10—N1	1.4003 (17)	1.406 (2)
C17—N2	1.2911 (18)	1.283 (2)
N2···O2	2.6631 (15)	2.6394 (19)
N2—N1—S1—O1	120.33 (10)	138.71 (12)
N2—N1—S1—O2	-5.52 (11)	9.59 (13)
N1—S1—C1—C2	-111.55 (11)	-103.95 (16)
N1—S1—C1—C6	69.70 (11)	76.49 (17)

Footnotes

‡Additional correspondence author, e-mail: niyi.asegbeloyin@unn.edu.ng.

Acknowledgements

The authors are grateful to Professor Masahiro Yamashita of the Department of Chemistry, Tohoku University, for the X-ray intensity data.

Funding information

Crystallographic research at Sunway University is supported by Sunway University Sdn Bhd (grant No. STR-RCTR-RCCM-001-2019).

References

Acosta, A., de la Cruz, P., De Miguel, P., Diez-Barra, E., de la Hoz, A., Langa, F., Loupy, A., Majdoub, M., Martin, N., Sanchez, C. & Seoane, C. (1995). Tetrahedron Lett. 36, 2165–2168. CrossRef CAS Google Scholar
Asegbeloyin, J. N., Izuogu, D. C., Oyeka, E. E., Okpareke, O. C. & Ibezim, A. (2018). J. Mol. Struct. 1175, 219–229. CSD CrossRef Google Scholar
Bele, C. & Darabantu, M. (2003). Heterocycl. Commun. 9, 641–646. CrossRef CAS Google Scholar
Brandenburg, K. (2006). DIAMOND. Crystal Impact GbR, Bonn, Germany. Google Scholar
Bruker (2002). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cherkez, S., Herzig, J. & Yellin, H. (1986). J. Med. Chem. 29, 947–959. CrossRef CAS PubMed Google Scholar
Chun, T. G., Kim, K. S., Lee, S., Jeong, T. S., Lee, H. Y., Kim, Y. H. & Lee, W. S. (2004). Synth. Commun. 34, 1301–1308. CrossRef CAS Google Scholar
Cockcroft, X. L., Dillon, K. J., Dixon, L., Drzewiecki, J., Kerrigan, F., Loh, V. M. Jr, Martin, N. M. B., Meneara, K. A. & Smith, G. C. M. (2006). Bioorg. Med. Chem. Lett. 16, 1040–1044. CrossRef PubMed CAS Google Scholar
Del Olmo, E., Barboza, B., Ybarra, M. I., Lopez-Perez, J. L., Carron, R., Sevilla, M. A., Bosellid, C. & San Feliciano, A. (2006). Bioorg. Med. Chem. Lett. 16, 2786–2790. PubMed CAS Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Haider, N. & Holzer, W. (2004). Science Synth. 16, 315–372. CAS Google Scholar
Ismail, M. F., El-Bassiouny, F. A. & Younes, H. A. (1984). Tetrahedron 40, 983–2984. Google Scholar
Mahmoodi, N. O. & Salehpour, M. J. (2003). Heterocycl. Chem. 40, 875–878. CrossRef CAS Google Scholar
Menear, K. A., Adcock, C., Boulter, R., Cockcroft, X., Copsey, L., Cranston, A., Dillon, K. J., Drzewiecki, J., Garman, S., Gomez, S., Javaid, H., Kerrigan, F., Knights, C., Lau, A., Loh, V. M. Jr, Matthews, I. T. W., Moore, S., O'Connor, M. J., Smith, G. C. M. & Martin, N. M. B. (2008). J. Med. Chem. 51, 6581–6591. CrossRef PubMed CAS Google Scholar
Mylari, B. L., Beyer, T. A., Scott, P. J., Aldinger, C. E., Dee, M. F., Siegel, T. W. & Zembrowski, W. J. (1992). J. Med. Chem. 35, 457–465. CrossRef PubMed CAS Google Scholar
Mylari, B. L., Larson, E. R., Beyer, T. A., Zembrowski, W. J., Aldinger, C. E., Dee, M. F., Siegel, T. W. & Singleton, D. H. (1991). J. Med. Chem. 34, 108–122. CSD CrossRef PubMed CAS Google Scholar
Nakanishi, W., Nakamoto, T., Hayashi, S., Sasamori, T. & Tokitoh, N. (2007). Chem. Eur. J. 13, 255–268. CSD CrossRef PubMed CAS Google Scholar
Pakulska, W., Malinowski, Z., Szczesniak, A. K., Czarnecka, E. & Epsztajn, J. (2009). Arch. Pharm. Chem. Life Sci. 342, 41–47. CrossRef CAS Google Scholar
Procopiou, P. A., Browning, C., Buckley, J. M., Clark, K. L., Fechner, L., Gore, P. M., Hancock, A. P., Hodgson, S. T., Holmes, D. S., Kranz, M., Looker, B. E., Morriss, K. M. L., Parton, D. L., Russell, L. J., Slack, R. J., Sollis, S. L., Vile, S. & Watts, C. J. (2011). J. Med. Chem. 54, 2183–2195. CrossRef CAS PubMed Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Tan, S. L., Jotani, M. M. & Tiekink, E. R. T. (2019). Acta Cryst. E75, 308–318. Web of Science CrossRef IUCr Journals Google Scholar
Teran, C., Besada, P., Vila, N. & Costa-Lago, M. C. (2019). Eur. J. Med. Chem. 161, 468–478. CAS PubMed Google Scholar
Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer 17. The University of Western Australia. Google Scholar
Ukita, T., Sugahara, M., Terakawa, Y., Kuroda, T., Wada, K., Nakata, A., Ohmachi, Y., Kikkawa, H., Ikezawa, K. & Naito, K. (1999). J. Med. Chem. 42, 1088-1099. CrossRef PubMed CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wu, X.-F., Neumann, H., Neumann, S. & Beller, M. (2012). Chem. Eur. J. 18, 8596-8599. CrossRef CAS PubMed Google Scholar
Yamaguchi, M., Kamei, K., Koga, T., Akima, M., Kuroki, T. & Ohi, N. (1993). J. Med. Chem. 36, 4052–4060. CrossRef CAS PubMed Google Scholar

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