Synthesis and redetermination of the crystal structure of salicyl­aldehyde N(4)-morpholino­thio­semi­carbazone

Tran Buu, D.; Duong Ba, V.; Khoi Nguyen Hoang, M.; Vu Quoc, T.; Duong Khanh, L.; Oanh Doan Thi, Y.; Van Meervelt, L.

doi:10.1107/S2056989019011812

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 75| Part 9| September 2019| Pages 1389-1393

https://doi.org/10.1107/S2056989019011812

Open

access

Synthesis and redetermination of the crystal structure of salicylaldehyde N(4)-morpholinothiosemicarbazone

Dang Tran Buu,^a Vu Duong Ba,^a Minh Khoi Nguyen Hoang,^b Trung Vu Quoc,^c ^* Linh Duong Khanh,^c Yen Oanh Doan Thi ^d and Luc Van Meervelt ^e ^*

^aFaculty of Chemistry, Ho Chi Minh City University of Education, 280 An Duong Vuong Street, District No. 5, Ho Chi Minh City, Vietnam, ^bVietnam National University, Ho Chi Minh City High School for the Gifted, 153 Nguyen Chi Thanh, District 5, Ho Chi Minh City, Vietnam, ^cFaculty of Chemistry, Hanoi National University of Education, 136 Xuan Thuy, Cau Giay, Hanoi, Vietnam, ^dPublishing House for Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam, and ^eDepartment of Chemistry, KU Leuven, Biomolecular Architecture, Celestijnenlaan 200F, Leuven (Heverlee), B-3001, Belgium
^*Correspondence e-mail: trungvq@hnue.edu.vn, luc.vanmeervelt@kuleuven.be

Edited by J. T. Mague, Tulane University, USA (Received 5 August 2019; accepted 27 August 2019; online 30 August 2019)

The structure of the title compound (systematic name: N-{[(2-hydroxyphenyl)methylidene]amino}morpholine-4-carbothioamide), C₁₂H₁₅N₃O₂S, was previously determined (Koo et al., 1977 ) using multiple-film equi-inclination Weissenberg data, but has been redetermined with higher precision to explore its conformation and the hydrogen-bonding patterns and supramolecular interactions. The molecular structure shows intramolecular O—H⋯N and C—H⋯S interactions. The configuration of the C=N bond is E. The molecule is slightly twisted about the central N—N bond. The best planes through the phenyl ring and the morpholino ring make an angle of 43.44 (17)°. In the crystal, the molecules are connected into chains by N—H⋯O and C—H⋯O hydrogen bonds, which combine to generate sheets lying parallel to (002). The most prominent contribution to the surface contacts are H⋯H contacts (51.6%), as concluded from a Hirshfeld surface analysis.

Keywords: crystal structure; thiosemicarbazone; hydrogen bonding; Hirshfeld analysis.

CCDC reference: 1949697

1. Chemical context

For many years, scientific studies on cancer have attracted a lot of attention, especially in the field of antitumor drugs. Cisplatin is well known as an effective therapy to prohibit the proliferation of tumor cells (Berners-Price, 2011 ). However, this drug has some unforeseen side effects with detrimental effects on the patient's health (Lévi et al., 2000 ; Go & Adjei, 1999 ; Harbour et al., 1996 ). In a search for antitumour drugs with fewer harmful side effects, thiosemicarbazides were examined since this organic class of thiourea derivatives was known to possess a diversity of biological activities such as antitumoral, antibacterial, and antifungal activities owing to presence of the N—N—C=S system (Dilović et al., 2008 ; Liberta & West, 1992 ). Many mechanisms have been advanced to probe the role of this conjugated system. In general, thiosemicarbazones can bind to nucleotides of tumour cells by the nitrogen and sulfur atoms, which prevents the distorted DNA from translation and encryption for their growth (Dilović et al., 2008).

Thiosemicarbazones are synthesized by the condensation between an aldehyde or ketone and an N(4)-substituted thiosemicarbazide. Many reports have demonstrated that N(4)-aromatic or heterocyclic substituted thiosemicarbazides are biologically more active than thiosemicarbazones without substituted groups (Dilović et al., 2008; Chen et al., 2004 ; Shi et al., 2009 ). In addition, salicylaldehyde is a key compound in the synthesis of a variety of potential therapeutic products (Bindu et al., 1998 ).

The crystal and molecular structure of salicylaldehyde N(4)-morpholinothiosemicarbazone was published previously (Koo et al., 1977) based on multiple-film equi-inclination Weissenberg data using Cu Kα radiation and refined to an R value of 0.11. In this study, we present the synthesis of salicylaldehyde N(4)-morpholinothiosemicarbazone (3) together with its structural characteristics and crystal structure redetermination using present-day technology.

2. Structural commentary

The title compound crystallizes in the orthorhombic space group Pna2₁ with one molecule in the asymmetric unit (Fig. 1). The N9—N10 and C11=N10 bond lengths are 1.371 (3) and 1.275 (3) Å, respectively (compared to 1.40 and 1.30 Å in the previous structure determination; Koo et al., 1977). The configuration of the C11=N10 bond is E [the N9—N10—C11—C12 torsion angle is −179.9 (3)°], which gives rise to an intramolecular O18—H18⋯N10 hydrogen bond with an S₁¹(6) graph-set motif (Table 1). The planes of the phenyl ring (r.m.s. deviation = 0.0020 Å) and the thiosemicarbazone function (N1/C7–C11; r.m.s. deviation = 0.0911 Å) make an angle of 16.26 (5)°. The molecule is slightly twisted about the N9—N10 bond [torsion angle C7—N9—N10—C11 is 162.4 (3)°; +ap conformation].

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N9—H9⋯O4ⁱ	0.86 (3)	2.33 (3)	3.141 (3)	157 (3)
O18—H18⋯N10	0.80 (4)	1.91 (5)	2.597 (3)	145 (4)
C6—H6A⋯S8	0.97	2.62	3.121 (3)	112
C15—H15⋯O18ⁱⁱ	0.93	2.48	3.404 (4)	176
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z]$ ; (ii) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, z]$ .

Figure 1
A view of the molecular structure of (3), with atom labels and displacement ellipsoids drawn at the 50% probability level. H atoms are shown as small circles of arbitrary radii and the intramolecular O—H⋯N and C—H⋯S interactions, respectively, by blue and grey dashed lines.

The morpholino ring adopts a chair conformation [puckering parameters Q = 0.554 (3) Å, θ = 173.2 (3)° and φ = 214 (3)°] with the thiosemicarbazone function in an equatorial position. The plane of the phenyl ring forms a dihedral angle of 43.44 (17)° with the best plane through the morpholino ring. A second intramolecular C6—H6A⋯S8 interaction is observed (Table 1).

3. Supramolecular features

The crystal packing of (3) is dominated by N9—H9⋯O4 hydrogen bonds (Table 1), resulting in the formation of chains of molecules with graph-set motif C₁¹(7) propagating along the a-axis direction (Fig. 2). Furthermore, a second parallel chain of molecules with graph-set motif C₁¹(5) running along the a-axis direction is formed by C15—H15⋯O18 interactions (Fig. 3). These two chain motifs combine to generate a sheet lying parallel to (002). No voids or π–π stackings are observed in the crystal packing of (3).

Figure 2
Partial crystal packing of (3), showing the N—H⋯O interactions (red dashed lines) resulting in chain formation in the a-axis direction [see Table 1

; symmetry code: (i) x + $[{1\over 2}]$ , −y + $[{1\over 2}]$ , z].

Figure 3
Partial crystal packing of (3), showing the C—H⋯O interactions (red dashed lines) resulting in chain formation in the a-direction [see Table 1

; symmetry code: (ii) x + $[{1\over 2}]$ , −y + $[{3\over 2}]$ , z].

A Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ) and the associated two-dimensional fingerprint plots (McKinnon et al., 2007 ) were performed in order to further investigate the supramolecular network. The Hirshfeld surface calculated using CrystalExplorer (Turner et al., 2017 ) and mapped over d_norm is given in Fig. 4. The bright-red spots near atoms O4 and N9 in Fig. 4a refer to the N9—H9⋯O4 hydrogen bond, and near atoms C15 and O18 in Fig. 4b to the C15—H15⋯O18 hydrogen bond. The faint-red spots near atoms C5 and S8 illustrate a short contact in the crystal packing of (3) (H5B⋯S8 = 2.913 Å). The fingerprint plots (Fig. 5) further indicate a major contribution by H⋯H contacts, corresponding to 51.6% of the two-dimensional fingerprint plot (Fig. 5b). Significant contributions by reciprocal O⋯H/H⋯O (13.4%) and S⋯H/H⋯S (12.5%) contacts appear as two symmetrical spikes at d_e + d_i ≃ 2.2 and 2.8 Å, respectively (Fig. 5c,d). Smaller contributions are from C⋯H/H⋯C (11.7%, Fig. 5e), N⋯C/C⋯N (5.3%, Fig. 5f), C⋯C (3.2%), N⋯H/H⋯N (1.6%), C⋯O/O⋯C (0.3%), C⋯S/S⋯C (0.3%) and O⋯O contacts (0.1%).

Figure 4
The Hirshfeld surface mapped over d_norm for (3) in the range −0.3153 to 1.2662 a.u.

Figure 5
Full two-dimensional fingerprint plots for (3), showing (a) all interactions, and delineated into (b) H⋯H, (c) O⋯H/H⋯O, (d) S⋯H/H⋯S, (e) C⋯H/H⋯C and (f) N⋯C/C⋯N interactions. The d_i and d_e values are the closest internal and external distances (in Å) from a given point on the Hirshfeld surface.

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.40, update of May 2019; Groom et al., 2016 ) for the central N—C(=S)—NH—N=C moiety (Fig. 6a) present in the title compound gave 583 hits. Fig. 6b,c illustrate the histograms of the distribution of torsion angles τ₁ and τ₂. The histogram of τ₁ shows a major preference for the −sp/+sp (or cis) conformation and a minor preference for the −ap/+ap (or trans) conformation. For torsion angle τ₂, only one region is preferred: a narrow spread in the region −ap/+ap (or trans). For (3), the torsion angles τ₁ and τ₂ are both in the +ap region [τ₁ = 173.8 (3) and τ₂ = 162.4 (3)°].

Figure 6
(a) Fragment used for a search in the CSD. (b),(c) Histograms of torsion angles τ₁ and τ₂. The vertical pink lines show the torsion angle observed in (3).

The most similar compound present in the CSD is the 2-hydroxynaphthaldehyde-based thiosemicarbazone (refcode IDEQAM; Aneesrahman et al., 2018 ). The asymmetric unit contains two molecules (one morpholino ring shows disorder). The mean plane of the non-disordered morpholino ring makes an angle of 36.9 (7)° with the naphthalene ring system. The torsion angles τ₁ [175.89 (15) and −175.97 (15)°] and τ₂ [166.51 (16) and −174.99 (16)°] are similar to those observed for the title compound. An intramolecular hydrogen bond similar to O18—H18⋯N10 is also observed.

5. Synthesis and crystallization

The reaction scheme for the synthesis of (3) is given in Fig. 7.

Figure 7
Reaction scheme for the synthesis of (3).

Synthesis of 2-((morpholine-4-carbonothioyl)thio)acetic acid (1):

A mixture consisting of carbon disulfide (0.2 mol) and concentrated ammonia (25 mL) was stirred to form a homogeneous solution at 278 K. Then, morpholine (0.2 mol) was added dropwise to this solution. The yellow solid that separated from the solution was filtered off and immediately dissolved in deionized water (300 mL) at room temperature to generate a yellow solution. Sodium chloroacetate (0.2 mol) was added to this solution and the reaction mixture maintained for 6 h at room temperature. The yellowish solution was acidified with concentrated hydrochloric acid and the resulting white precipitate was filtered off and recrystallized from ethanol.

Synthesis of N(4)-morpholinothiosemicarbazide (2):

A mixture composed of (1) (50 mmol), deionized water (10 mL) and hydrazine hydrate (25 mL) was refluxed for 30 minutes at 353 K. The white solid which precipitated from the transparent solution was filtered off and recrystallized from ethanol to give (2).

Synthesis of salicylaldehyde N(4)-morpholinothiosemicarbazone (3):

After dissolving (2) in hot ethanol, the solution was added to an equivalent amount of salicylaldehyde. The final solution was refluxed at 353 K for 2 h in the presence of acetic acid as a catalyst. The resulting solution was gradually reduced in volume at room temperature overnight. The needle-shaped crystals that formed were filtered off and recrystallized from ethanol to give (3) in the form of transparent crystals (yield 60%), m.p. 461–463 K. FT–IR (cm⁻¹): 3436 (O—H), 3279 (N—H), 1617 (C_Ar—H), 1540 (C=N), 1061 (N—N), 1348 and 959 (C=S). ¹H NMR [Bruker 500 MHz, d₆-DMSO, δ (ppm), J (Hz)]: 3.67 (4H, t, H2 and H6); 3.92 (4H, t, H3 and H5); 6.90 (2H, m, H14 and H16); 7.28 (1H, m, J = 7.5, H15); 7.41 (1H, d, J = 7.0, H17); 8.47 (1H, s, H11); 11.49 (1H, br, N—H); 11.55 (1H, br, O—H). ¹³C NMR [Bruker 125 MHz, d₆-DMSO, δ (ppm)]: 49.4 (C2 and C6), 66.2 (C3 and C5), 117.0 (C14), 118.9 (C12), 119.5 (C16), 130.4 (C17), 131.3 (C15), 146.9 (C13), 157.6 (C11), 180.1 (C7). UV–Vis (ethanol, nm): 200 (π→π*); 300 and 350 (n→π*).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. Both H atoms H9 and H18 were located from difference electron density maps and refined freely. The other H atoms were placed in idealized positions and included as riding contributions with U_iso(H) values 1.2U_eq of the parent atoms, with C—H distances of 0.93 (aromatic, CH=N) and 0.97 Å (CH₂). In the final cycles of refinement, 4 outliers were omitted.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₅N₃O₂S
M_r	265.33
Crystal system, space group	Orthorhombic, Pna2₁
Temperature (K)	293
a, b, c (Å)	11.7579 (4), 15.0584 (5), 7.1103 (3)
V (Å³)	1258.92 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.26
Crystal size (mm)	0.5 × 0.2 × 0.1

Data collection
Diffractometer	Rigaku Oxford Diffraction SuperNova, Single source at offset/far, Eos
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, UK.]$ )
T_min, T_max	0.483, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	12278, 2565, 2314
R_int	0.025
(sin θ/λ)_max (Å⁻¹)	0.625

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.034, 0.087, 1.07
No. of reflections	2565
No. of parameters	171
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.17, −0.17
Absolute structure	Flack x determined using 938 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.02 (3)
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, UK.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 1949697

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989019011812/mw2147sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019011812/mw2147Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989019011812/mw2147Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2018); cell refinement: CrysAlis PRO (Rigaku OD, 2018); data reduction: CrysAlis PRO (Rigaku OD, 2018); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

N-{[(2-Hydroxyphenyl)methylidene]amino}morpholine-4-carbothioamide top

Crystal data top

C₁₂H₁₅N₃O₂S	D_x = 1.400 Mg m⁻³
M_r = 265.33	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna2₁	Cell parameters from 5842 reflections
a = 11.7579 (4) Å	θ = 3.2–27.3°
b = 15.0584 (5) Å	µ = 0.26 mm⁻¹
c = 7.1103 (3) Å	T = 293 K
V = 1258.92 (8) Å³	Block, colourless
Z = 4	0.5 × 0.2 × 0.1 mm
F(000) = 560

Data collection top

Rigaku Oxford Diffraction SuperNova, Single source at offset/far, Eos diffractometer	2565 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Mo) X-ray Source	2314 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.025
Detector resolution: 15.9631 pixels mm^-1	θ_max = 26.4°, θ_min = 2.7°
ω scans	h = −14→14
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2018)	k = −18→18
T_min = 0.483, T_max = 1.000	l = −8→8
12278 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.087	w = 1/[σ²(F_o²) + (0.0434P)² + 0.1653P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
2565 reflections	Δρ_max = 0.17 e Å⁻³
171 parameters	Δρ_min = −0.17 e Å⁻³
1 restraint	Absolute structure: Flack x determined using 938 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013)
Primary atom site location: dual space	Absolute structure parameter: 0.02 (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
N1	0.12956 (17)	0.37994 (13)	0.5311 (5)	0.0441 (5)
C2	0.1602 (2)	0.28850 (18)	0.4815 (5)	0.0438 (7)
H2A	0.174911	0.254390	0.594672	0.053*
H2B	0.228621	0.288274	0.405192	0.053*
C3	0.0625 (3)	0.2474 (2)	0.3728 (5)	0.0552 (8)
H3A	0.050961	0.280351	0.257136	0.066*
H3B	0.081833	0.186795	0.339747	0.066*
O4	−0.04027 (17)	0.24774 (14)	0.4794 (3)	0.0545 (6)
C5	−0.0710 (2)	0.3379 (2)	0.5178 (7)	0.0615 (9)
H5A	−0.141436	0.338728	0.588879	0.074*
H5B	−0.084419	0.368531	0.399814	0.074*
C6	0.0177 (3)	0.3860 (2)	0.6249 (6)	0.0597 (9)
H6A	−0.003873	0.447934	0.636901	0.072*
H6B	0.023218	0.361089	0.750398	0.072*
C7	0.2028 (2)	0.44909 (15)	0.5299 (5)	0.0388 (6)
S8	0.16206 (6)	0.55578 (4)	0.54532 (17)	0.0552 (2)
N9	0.31482 (18)	0.42656 (14)	0.5168 (4)	0.0406 (6)
H9	0.337 (2)	0.3724 (19)	0.521 (6)	0.044 (8)*
N10	0.39379 (18)	0.49289 (14)	0.4965 (3)	0.0384 (6)
C11	0.4978 (2)	0.47549 (15)	0.5317 (5)	0.0366 (5)
H11	0.519030	0.418814	0.569994	0.044*
C12	0.5829 (2)	0.54502 (15)	0.5115 (4)	0.0353 (6)
C13	0.5532 (2)	0.63316 (17)	0.4666 (4)	0.0394 (6)
C14	0.6374 (3)	0.69733 (19)	0.4546 (5)	0.0512 (8)
H14	0.617815	0.755628	0.426000	0.061*
C15	0.7497 (3)	0.6758 (2)	0.4845 (4)	0.0542 (8)
H15	0.805097	0.719608	0.475521	0.065*
C16	0.7811 (2)	0.5896 (2)	0.5277 (6)	0.0537 (7)
H16	0.857037	0.575138	0.547403	0.064*
C17	0.6977 (2)	0.52566 (18)	0.5408 (6)	0.0466 (6)
H17	0.718495	0.467720	0.570242	0.056*
O18	0.44378 (18)	0.65822 (14)	0.4336 (4)	0.0513 (6)
H18	0.402 (3)	0.617 (3)	0.446 (6)	0.073 (13)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0326 (10)	0.0409 (10)	0.0590 (14)	−0.0031 (9)	0.0038 (14)	−0.0046 (15)
C2	0.0354 (13)	0.0407 (13)	0.0551 (19)	−0.0024 (11)	0.0056 (13)	−0.0046 (13)
C3	0.0576 (18)	0.0553 (18)	0.0528 (19)	−0.0181 (15)	0.0075 (16)	−0.0038 (15)
O4	0.0436 (11)	0.0530 (11)	0.0670 (16)	−0.0148 (9)	0.0020 (11)	0.0020 (11)
C5	0.0376 (14)	0.0584 (17)	0.088 (3)	−0.0044 (13)	−0.0064 (19)	0.014 (2)
C6	0.0370 (16)	0.0545 (17)	0.088 (3)	−0.0016 (14)	0.0139 (17)	−0.0090 (18)
C7	0.0360 (12)	0.0418 (12)	0.0387 (14)	−0.0009 (10)	−0.0011 (15)	0.0015 (15)
S8	0.0481 (4)	0.0396 (3)	0.0780 (6)	0.0056 (3)	0.0010 (5)	−0.0010 (5)
N9	0.0333 (11)	0.0329 (10)	0.0556 (16)	−0.0031 (8)	0.0009 (12)	0.0040 (12)
N10	0.0336 (11)	0.0359 (10)	0.0458 (15)	−0.0050 (9)	−0.0004 (10)	0.0032 (10)
C11	0.0388 (13)	0.0329 (10)	0.0380 (13)	−0.0003 (9)	−0.0010 (14)	0.0021 (14)
C12	0.0353 (12)	0.0354 (11)	0.0353 (16)	−0.0029 (9)	0.0002 (12)	−0.0007 (12)
C13	0.0418 (14)	0.0356 (12)	0.0408 (15)	0.0001 (11)	0.0026 (12)	−0.0019 (12)
C14	0.0605 (19)	0.0351 (13)	0.0581 (19)	−0.0111 (13)	0.0005 (16)	0.0001 (14)
C15	0.0534 (17)	0.0585 (17)	0.0507 (19)	−0.0249 (15)	−0.0003 (15)	−0.0007 (15)
C16	0.0363 (14)	0.0681 (17)	0.0567 (18)	−0.0104 (13)	−0.0022 (17)	0.0016 (19)
C17	0.0389 (14)	0.0465 (13)	0.0545 (16)	−0.0001 (11)	−0.0039 (18)	0.0019 (18)
O18	0.0448 (11)	0.0349 (10)	0.0744 (15)	0.0042 (9)	−0.0019 (11)	0.0049 (10)

Geometric parameters (Å, º) top

N1—C2	1.466 (3)	N9—H9	0.86 (3)
N1—C6	1.478 (4)	N9—N10	1.371 (3)
N1—C7	1.351 (3)	N10—C11	1.275 (3)
C2—H2A	0.9700	C11—H11	0.9300
C2—H2B	0.9700	C11—C12	1.456 (3)
C2—C3	1.516 (4)	C12—C13	1.409 (3)
C3—H3A	0.9700	C12—C17	1.396 (4)
C3—H3B	0.9700	C13—C14	1.386 (4)
C3—O4	1.426 (3)	C13—O18	1.361 (3)
O4—C5	1.432 (4)	C14—H14	0.9300
C5—H5A	0.9700	C14—C15	1.376 (4)
C5—H5B	0.9700	C15—H15	0.9300
C5—C6	1.481 (5)	C15—C16	1.383 (4)
C6—H6A	0.9700	C16—H16	0.9300
C6—H6B	0.9700	C16—C17	1.377 (4)
C7—S8	1.680 (2)	C17—H17	0.9300
C7—N9	1.364 (3)	O18—H18	0.80 (4)

C2—N1—C6	112.7 (2)	N1—C7—N9	115.1 (2)
C7—N1—C2	124.4 (2)	N9—C7—S8	121.17 (18)
C7—N1—C6	121.5 (2)	C7—N9—H9	121.8 (18)
N1—C2—H2A	110.0	C7—N9—N10	118.7 (2)
N1—C2—H2B	110.0	N10—N9—H9	119.5 (18)
N1—C2—C3	108.6 (2)	C11—N10—N9	118.6 (2)
H2A—C2—H2B	108.4	N10—C11—H11	120.3
C3—C2—H2A	110.0	N10—C11—C12	119.5 (2)
C3—C2—H2B	110.0	C12—C11—H11	120.3
C2—C3—H3A	109.3	C13—C12—C11	121.9 (2)
C2—C3—H3B	109.3	C17—C12—C11	120.0 (2)
H3A—C3—H3B	107.9	C17—C12—C13	118.1 (2)
O4—C3—C2	111.7 (3)	C14—C13—C12	119.5 (3)
O4—C3—H3A	109.3	O18—C13—C12	122.3 (2)
O4—C3—H3B	109.3	O18—C13—C14	118.1 (3)
C3—O4—C5	108.6 (2)	C13—C14—H14	119.6
O4—C5—H5A	109.1	C15—C14—C13	120.7 (3)
O4—C5—H5B	109.1	C15—C14—H14	119.6
O4—C5—C6	112.6 (2)	C14—C15—H15	119.6
H5A—C5—H5B	107.8	C14—C15—C16	120.8 (3)
C6—C5—H5A	109.1	C16—C15—H15	119.6
C6—C5—H5B	109.1	C15—C16—H16	120.6
N1—C6—C5	111.4 (3)	C17—C16—C15	118.7 (3)
N1—C6—H6A	109.4	C17—C16—H16	120.6
N1—C6—H6B	109.4	C12—C17—H17	118.9
C5—C6—H6A	109.4	C16—C17—C12	122.1 (3)
C5—C6—H6B	109.4	C16—C17—H17	118.9
H6A—C6—H6B	108.0	C13—O18—H18	110 (3)
N1—C7—S8	123.73 (19)

N1—C2—C3—O4	−58.7 (4)	N9—N10—C11—C12	−179.9 (3)
N1—C7—N9—N10	173.8 (3)	N10—C11—C12—C13	4.5 (5)
C2—N1—C6—C5	−50.2 (4)	N10—C11—C12—C17	−176.9 (3)
C2—N1—C7—S8	167.6 (3)	C11—C12—C13—C14	178.1 (3)
C2—N1—C7—N9	−13.0 (5)	C11—C12—C13—O18	−2.1 (4)
C2—C3—O4—C5	62.2 (4)	C11—C12—C17—C16	−178.5 (4)
C3—O4—C5—C6	−59.5 (4)	C12—C13—C14—C15	0.6 (5)
O4—C5—C6—N1	53.7 (4)	C13—C12—C17—C16	0.2 (5)
C6—N1—C2—C3	51.7 (4)	C13—C14—C15—C16	−0.2 (5)
C6—N1—C7—S8	−27.0 (5)	C14—C15—C16—C17	−0.2 (5)
C6—N1—C7—N9	152.5 (3)	C15—C16—C17—C12	0.2 (6)
C7—N1—C2—C3	−141.7 (3)	C17—C12—C13—C14	−0.6 (4)
C7—N1—C6—C5	142.7 (3)	C17—C12—C13—O18	179.3 (3)
C7—N9—N10—C11	162.4 (3)	O18—C13—C14—C15	−179.3 (3)
S8—C7—N9—N10	−6.7 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N9—H9···O4ⁱ	0.86 (3)	2.33 (3)	3.141 (3)	157 (3)
O18—H18···N10	0.80 (4)	1.91 (5)	2.597 (3)	145 (4)
C6—H6A···S8	0.97	2.62	3.121 (3)	112
C15—H15···O18ⁱⁱ	0.93	2.48	3.404 (4)	176

Symmetry codes: (i) x+1/2, −y+1/2, z; (ii) x+1/2, −y+3/2, z.

Acknowledgements

LVM thanks the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035.

References

Aneesrahman, K. N., Rohini, G., Bhuvanesh, N. S. P., Sundararaj, S., Musthafa, M. & Sreekanth, A. (2018). ChemistrySelect 3, 8118–8130. CrossRef CAS Google Scholar
Berners-Price, S. J. (2011). Angew. Chem. Int. Ed. 50, 804–805. CAS Google Scholar
Bindu, P., Kurup, M. R. P. & Satyakeerty, T. R. (1998). Polyhedron, 18, 321–331. CrossRef Google Scholar
Chen, J., Huang, Y. W., Liu, G., Afrasiabi, Z., Sinn, E., Padhye, S. & Ma, Y. (2004). Toxicol. Appl. Pharmacol. 197, 40–48. CrossRef PubMed CAS Google Scholar
Dilović, I., Rubcić, M., Vrdoljak, V., Kraljević Pavelić, S., Kralj, M., Piantanida, I. & Cindrić, M. (2008). Bioorg. Med. Chem. 16, 5189–5198. 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
Go, R. S. & Adjei, A. A. (1999). J. Clin. Oncol. 17, 409–422. CrossRef PubMed CAS Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Harbour, J. W., Murray, T. G., Hamasaki, D., Cicciarelli, N., Hernández, E., Smith, B., Windle, J. & O'Brien, J. M. (1996). Invest. Ophthalmol. Vis. Sci. 37, 1892–1898. CAS PubMed Google Scholar
Koo, C. H., Kim, H. S. & Ahn, C. H. (1977). J. Korean Chem. Soc. 21, 3–15. CAS Google Scholar
Lévi, F., Metzger, G., Massari, C. & Milano, G. (2000). Clin. Pharmacokinet. 38, 1–21. PubMed Google Scholar
Liberta, A. E. & West, D. X. (1992). Biometals, 5, 121–126. CrossRef PubMed CAS Web of Science Google Scholar
McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. 3814–3816. Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CrossRef CAS IUCr Journals Google Scholar
Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, UK. 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
Shi, L., Mao, W. J., Yang, Y. & Zhu, H. L. (2009). J. Coord. Chem. 62, 3471–3477. CrossRef CAS Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS 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

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.