Crystal structure and Hirshfeld surface analysis of 1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium 2,5-di­hydroxy­benzoate propan-2-ol monosolvate

Natchimuthu, V.; Sharmila, N.; Ravi, S.

doi:10.1107/S205698902000818X

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 76| Part 7| July 2020| Pages 1168-1172

https://doi.org/10.1107/S205698902000818X

Open

access

Crystal structure and Hirshfeld surface analysis of 1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium 2,5-dihydroxybenzoate propan-2-ol monosolvate

V. Natchimuthu,^a ^* N. Sharmila ^b and S. Ravi ^c

^aDepartment of Physics, M.Kumarasamy College of Engineering, Karur 639113, Tamil Nadu, India, ^bDepartment of Physics, Shrimati Indira Gandhi College, Tiruchirappalli 620 002, Tamilnadu, India, and ^cPostgraduate and Research Department of Physics, National College (Autonomous), Tiruchirappalli 620 001, Tamilnadu, India
^*Correspondence e-mail: natchimuthu88@gmail.com

Edited by J. T. Mague, Tulane University, USA (Received 21 May 2020; accepted 19 June 2020; online 30 June 2020)

The asymmetric unit of the title salt, C₁₇H₂₁N₄S⁺·C₇H₅O₄⁻·C₃H₇OH, consists of an olanzapinium cation, an independent 2,5-dihydroxybenzoate anion and a solvent isopropyl alcohol molecule. The central seven-membered heterocycle is in a boat conformation, while the piperazine ring displays a distorted chair conformation. The dihedral angle between the benzene and thiene rings flanking the diazepine ring is 52.58 (19)°. In the crystal, the anions and cations are connected by N—H⋯O and O—H⋯O hydrogen bonds, forming a three-dimensional network.

Keywords: crystal structure; olanzapine; salt; hydrogen bond; Hirshfeld surface.

CCDC reference: 2010899

1. Chemical context

Olanzapine is an atypical antipsychotic with indications for the treatment of schizophrenia, acute mania and the prevention of relapse in bipolar disorder. Olanzapine is structurally similar to clozapine, but is classified as a thienobenzodiazepine. Reviews on olanzapine in the management of bipolar disorders (Narasimhan et al., 2007 ) and olanzapine-associated toxicity and fatality in overdose (Chue & Singer, 2003 ) have been published. Olanzapine, the pharmaceutically active component of the title compound, a thienobenzodiazepine derivative, along with clozapine, quetiapine, risperidone and ziprasidone, belongs to the newer generation of atypical antipsychotic agents (Chakrabarti et al., 1980 ; Callaghan et al., 1999 ; Kennedy et al., 2001 ; Tandon & Jibson, 2003 ).

These atypical antipsychotic agents, in comparison with the older generation, show greater efficacy against both positive and negative symptoms of schizophrenia (a debilitating mental disorder) as well as associated cognitive deficits and are virtually devoid of extrapyramidal symptoms (Tandon, 2002 ). The therapeutic action of olanzapine against the symptoms of schizophrenia is thought to be due to its high affinity for dopaminergic D2 and serotonergic 5-HT2A receptor systems implicated in the pathogenesis of this disease (Bever & Perry, 1998 ).

The crystal structures of 2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine methanol solvate monohydrate (Capuano et al., 2003 ), polymorphic form II of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine (Wawrzycka-Gorczyca et al., 2004a ), 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine methanol solvate (Wawrzycka-Gorczyca et al., 2004b ), olazipinium nicotinate (Ravikumar et al., 2005 ), olanzapine and its solvates (Wawrzycka-Gorczyca et al., 2007 ), highly soluble olanzapinium maleate crystalline salts (Thakuria & Nangia, 2011a ) and polymorphic form IV of olanzapine (Thakuria & Nangia, 2011b ) have been reported. In view of the importance of olanzapine, this paper reports the crystal structure of the title salt, C₁₇H₂₁N₄S⁺·C₇H₅O₄⁻·C₃H₇OH, (I)

2. Structural commentary

A perspective view of (I), with the atomic numbering scheme, is illustrated in Fig. 1. The asymmetric unit comprises an olanzapinium cation, an independent 2,5-dihydroxybenzoate anion and a solvent isopropyl alcohol molecule. The central seven-membered (N1/C11/C6/N2/C5/C4/C12) heterocycle is in a boat conformation with puckering parameter Q = 0.715 (3) Å while the six-membered piperazine ring, N3/C13/C14/N4/C15/C16, adopts a distorted chair conformation with puckering parameters Q = 0.564 (3) Å, θ = 175.3 (3)°, φ = 200 (4)°. The dihedral angle between the benzene and thiene rings flanking the diazepine ring is 52.58 (19)°. This is similar to the values observed in the related structure olanzapinium dipicrate (II) [58.7 (9)°] . The dihedral angles between the plane of the four C atoms in the piperazine ring and the planes of the benzene and thiophene rings are 27.04 (13) and 33.36 (18)°, respectively. In the 2,5-dihydroxybenzoate, the mean plane of the C18–O1–O2 group is twisted by 4.7 (5)° from that of the benzene ring (C19–C24). The bond lengths and bond angles of the thiene and piperazine rings of compound (I) are also comparable with the values observed for related structures (Kavitha et al., 2013 ; Ravikumar et al., 2005).

Figure 1
The molecular structure of (I)

, with displacement ellipsoids for the non-H atoms drawn at the 30% probability level. Hydrogen bonds (Table 1

) are shown as dashed lines.

The superimposed fit (Gans & Shalloway, 2001 ) of the olazapine group of (I) (atoms C1–C8, N1, O1 and O2) gives an r.m.s deviation of 1.179 Å with olanzapinium dipicrate (II) (Kavitha et al., 2013) (Fig. 2) and 1.175 Å with olazipinium nicotinate (III) (Ravikumar et al., 2005) (Fig. 3). The larger r.m.s deviation with the related structure may be due to the different substitution of groups on the olanzapinium cation.

Figure 2
A superimposed fit of (I)

(red) and the related structure (II) (blue).

Figure 3
A superimposed fit of (I)

(red) and the related structure (III) (green).

3. Supramolecular features

In the crystal, the anions and cations are connected by C—H⋯O, N—H⋯O and O—H⋯O hydrogen bonds (Table 1), forming a three-dimensional network. The interaction between C1—O1 and C10—O1 via atoms H1A and H10 encloses an R₄² (22) ring motif. In addition, the interaction between C1—O1 and C13—O4 via atoms H1A and H13A forms an R₂² (15) ring motif and that between C17—O2 and N4—O1 via atoms H17B and H4N encloses an R₂² (7) ring motif (Fig. 4). The atoms O2 and O3, O4, O5 and O3, O5 are connected through H3A, H4A and H5, forming an intermolecular ring motif. The contact between atoms N4 and O1 via H4N generates parallel chains to form a three dimensional network (Fig. 5).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1A⋯O1ⁱ	0.96	2.64	3.579 (4)	168
C10—H10⋯O1ⁱⁱ	0.93	2.52	3.316 (4)	143
C13—H13A⋯O4ⁱ	0.97	2.62	3.233 (4)	122
C17—H17B⋯O2	0.96	2.63	3.216 (4)	120
N2—H2⋯O4ⁱⁱⁱ	0.87 (3)	2.28 (3)	3.088 (4)	156 (3)
N4—H4⋯O1	0.89 (4)	1.77 (4)	2.660 (3)	178 (4)
O3—H3A⋯O2	0.89 (4)	1.63 (4)	2.479 (3)	156 (4)
O4—H4A⋯O5^iv	0.85 (4)	1.84 (4)	2.682 (3)	173 (4)
O5—H5⋯O3^v	0.88 (4)	1.88 (4)	2.764 (3)	178 (3)
Symmetry codes: (i) x-1, y, z; (ii) -x+1, -y+1, -z; (iii) -x+1, -y+1, -z+1; (iv) x+1, y, z; (v) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Figure 4
Crystal packing of (I)

, showing the C—H⋯O hydrogen bonds [R₄² (22) ring motif, R₂² (15) and R₂² (7) ring motifs; Table 1

] as dashed lines. H atoms not involved in these interactions have been omitted for clarity.

Figure 5
Crystal packing of (I)

, showing the O—H⋯O and N—H⋯O hydrogen bonds (Table 1

) as dashed lines; the shortest contacts between O2 and O3 give rise to an R(6) motif. H atoms not involved in these interactions have been omitted for clarity.

4. Database survey

A search of the Cambridge Crystallographic Database (CSD version 5.41, last update March 2020; Groom et al., 2016 ) gave only twenty-two entries based on the olanzapine drug molecule. They include salts with gallic acid: {CSD refcodes SUKPEW, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl)piperazin-1-ium 2,4,6-trihydroxybenzoate, and SUKPOG, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl)piperazin-1-ium 3,4,5-trihydroxybenzoate dihydrate; Sarmah et al., 2020 }, with mono and dihydroxy benzoic acid {FABJUQ, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl) piperazin-1-ium 4-hydroxybenzoate acetonitrile solvate, FABJIE, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl) piperazin-1-ium 2,5dihydroxybenzoate, FABJEA, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl)piperazin-1-ium 2,4-dihydroxybenzoate and FABJOK, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl) piperazin-1-ium 2,6dihydroxybenzoate; Sarmah et al., 2016 }, with nicotinic acid {TAQNUV, 1-methyl-4-(2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-yl) hexahydropyrazin-1-ium nicotinate; Ravikumar et al., 2005}, with pyrazinoic acid (SUKPAS; Sarmah et al., 2020) and with other carboxylic acids (AMIYUR and AMIZAY; Thakuria et al., 2011a and Sarmah et al., 2020; FABKAX and FABKEB; Sarmah et al., 2016; FHIRYUE, HIRZAL, HIRZEP and HIRZIT; Thakuria et al., 2013 ; JIXROY; Sridhar & Ravikumar, 2007 ; LESQIL; Kavitha et al., 2013; PEWPUF, PEWQAM and PEWQEQ; Sarmah et al., 2018 ; TAQNUV; Ravikumar et al., 2005). Among them, the crystal structures of PEWQEQ, PEWQAM, HIRZIT, FABJUQ, SUKPIA, SUKPOG, FABKEB, HIRZEP and PEWQAM contain solvent molecules.

5. Hirshfeld surface (HS) analysis

The HS analysis (McKinnon et al., 1998 , 2004 , 2007 ; Spackman & Jayatilaka, 2009 ) was performed to understand the intermolecular interactions in the crystal structure of (I) and was constructed in the crystal environment using CrystalExplorer 17.5 (Turner et al., 2017 ). The various non-covalent interactions are quantified with decomposed, two-dimensional fingerprint plots (Spackman & McKinnon, 2002 ). The HS plotted over d_norm is shown in Fig. 6 with red areas indicating distances shorter (in closer contact) and blue those longer (distant contact) than the van der Waals radii. The contacts with distances equal to the sum of van der Waals radii are indicated in white (Venkatesan et al., 2016 ). From Fig. 6, the bright-red spots appearing near the hydrogen atoms H2N, H4N, H10, and H13 in the cation indicate that these hydrogen atoms are involved in the intermolecular interactions. The shape-index (SI) diagram, a tool to visualize π–π stacking interactions, for the cation, anion and solvent molecule is shown in Fig. 7. No adjacent red and blue triangles are seen, indicating that no π–π interactions are present, which is in agreement with the experimental findings. The overall two-dimensional fingerprint (2D–FP) plots are illustrated in Fig. 6. The H⋯H contacts make the highest contribution (53.8%) to the total crystal packing (broad peaks at d_e+ d_i = ∼2.3 Å). The second highest contribution is from H⋯C/C⋯H contacts (21.8%) and is indicated by the broad wing-like structure at d_e+ d_i = ∼2.6 Å. The symmetrical sharp spikes at d_e+ d_i = ∼1.6 Å are attributed to H⋯O/O⋯H contacts (14.3%).

Figure 6
Views of the Hirshfeld surfaces of title compound (I)

mapped with d_norm in two different orientations. The HS is plotted in the range −0.1500 to 1.4938 a.u.

Figure 7
Views of the shape-index diagram of title compound (I)

6. Synthesis and crystallization

Olanzapine (156 mg, 0.5 mmol) and 2,5-dihydroxybenzoic acid (77 mg, 0.5 mmol) were dissolved in 20 mL of isopropyl alcohol and stirred magnetically for 5 h at 330 K. The mixture was kept aside for two days at room temperature and the salt formed was filtered off and dried. The compound was recrystallized from (1:1) isopropyl alcohol/DMF by slow evaporation at room temperature (m.p. 373–375 K).

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The N-bound and O-bound H atoms were located in a difference-Fourier map and freely refined. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.93–0.97 Å with U_iso(H) = 1.5U_eq(C) for methyl H atoms and = 1.2U_eq(C) for other H atoms.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₇H₂₁N₄S⁺·C₇H₅O₄⁻·C₃H₈O
M_r	526.64
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	294
a, b, c (Å)	8.4867 (6), 29.764 (2), 10.6334 (8)
β (°)	94.381 (1)
V (Å³)	2678.1 (3)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.17
Crystal size (mm)	0.15 × 0.14 × 0.06

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2008 )
T_min, T_max	0.96, 0.98
No. of measured, independent and observed [I > 2σ(I)] reflections	25175, 4560, 4081
R_int	0.040
(sin θ/λ)_max (Å⁻¹)	0.588

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.069, 0.143, 1.31
No. of reflections	4560
No. of parameters	358
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.32, −0.21
Computer programs: SMART (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008 ), SHELXL2018/3 (Sheldrick, 2015 ), QMOL (Gans & Shalloway, 2001), Mercury (Macrae et al., 2020 ), ORTEPIII (Burnett & Johnson, 1996 ), WinGX publication routines (Farrugia, 2012 ) and PLATON (Spek, 2020 ).

Supporting information

CCDC reference: 2010899

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S205698902000818X/mw2162sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S205698902000818X/mw2162Isup2.hkl

checkCIF report

Computing details top

Data collection: SMART (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2018); molecular graphics: QMOL (Gans & Shalloway, 2001), Mercury (Macrae et al., 2020); software used to prepare material for publication: ORTEPIII (Burnett & Johnson, 1996), WinGX publication routines (Farrugia, 2012) and PLATON (Spek, 2020).

1-Methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazin-1-ium 2,5-dihydroxybenzoate propan-2-ol monosolvate top

Crystal data top

C₁₇H₂₁N₄S⁺·C₇H₅O₄⁻·C₃H₈O	F(000) = 1120
M_r = 526.64	D_x = 1.306 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 8.4867 (6) Å	Cell parameters from 4689 reflections
b = 29.764 (2) Å	θ = 2.3–24.2°
c = 10.6334 (8) Å	µ = 0.17 mm⁻¹
β = 94.381 (1)°	T = 294 K
V = 2678.1 (3) Å³	Solid, white
Z = 4	0.15 × 0.14 × 0.06 mm

Data collection top

Bruker SMART CCD area-detector diffractometer	4081 reflections with I > 2σ(I)
Radiation source: fine focus sealed tube	R_int = 0.040
ω and φ scan	θ_max = 24.7°, θ_min = 2.0°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −9→9
T_min = 0.96, T_max = 0.98	k = −35→35
25175 measured reflections	l = −12→12
4560 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)] = 0.069	Hydrogen site location: mixed
wR(F²) = 0.143	H atoms treated by a mixture of independent and constrained refinement
S = 1.31	w = 1/[σ²(F_o²) + (0.0423P)² + 1.7858P] where P = (F_o² + 2F_c²)/3
4560 reflections	(Δ/σ)_max = 0.001
358 parameters	Δρ_max = 0.32 e Å⁻³
0 restraints	Δρ_min = −0.21 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
C1	−0.3762 (4)	0.47317 (12)	0.3380 (4)	0.0585 (9)
H1A	−0.390099	0.447460	0.283753	0.088*
H1B	−0.459922	0.494268	0.317993	0.088*
H1C	−0.378228	0.463851	0.424267	0.088*
C2	−0.2208 (3)	0.49488 (10)	0.3192 (3)	0.0406 (7)
C3	−0.1143 (3)	0.48603 (10)	0.2353 (3)	0.0385 (7)
H3	−0.128823	0.463584	0.174715	0.046*
C4	0.0236 (3)	0.51399 (9)	0.2470 (3)	0.0352 (7)
C5	0.0161 (3)	0.54454 (9)	0.3420 (3)	0.0350 (7)
C6	0.1609 (3)	0.60738 (10)	0.2772 (3)	0.0366 (7)
C7	0.1472 (4)	0.65330 (10)	0.2934 (3)	0.0430 (7)
H7	0.110794	0.664279	0.367734	0.052*
C8	0.1862 (4)	0.68310 (11)	0.2016 (3)	0.0489 (8)
H8	0.176887	0.713877	0.214109	0.059*
C9	0.2390 (4)	0.66693 (11)	0.0915 (3)	0.0524 (9)
H9	0.264640	0.686670	0.028400	0.063*
C10	0.2537 (4)	0.62100 (11)	0.0749 (3)	0.0467 (8)
H10	0.290372	0.610411	0.000239	0.056*
C11	0.2157 (3)	0.59022 (10)	0.1660 (3)	0.0379 (7)
C12	0.1630 (3)	0.51169 (10)	0.1725 (3)	0.0374 (7)
C13	0.1896 (4)	0.42917 (9)	0.2035 (3)	0.0395 (7)
H13A	0.108954	0.432885	0.262627	0.047*
H13B	0.290178	0.424550	0.251401	0.047*
C14	0.1511 (4)	0.38905 (10)	0.1209 (3)	0.0446 (8)
H14A	0.149251	0.362254	0.172674	0.054*
H14B	0.047123	0.392826	0.077708	0.054*
C15	0.2881 (4)	0.42556 (11)	−0.0459 (3)	0.0491 (8)
H15A	0.192261	0.430932	−0.099538	0.059*
H15B	0.374372	0.422019	−0.099854	0.059*
C16	0.3204 (4)	0.46547 (10)	0.0388 (3)	0.0440 (8)
H16A	0.422192	0.461909	0.085780	0.053*
H16B	0.323924	0.492549	−0.011672	0.053*
C17	0.2321 (5)	0.34478 (12)	−0.0581 (4)	0.0658 (11)
H17A	0.130021	0.349145	−0.101715	0.099*
H17B	0.231500	0.317686	−0.009157	0.099*
H17C	0.310467	0.342428	−0.118316	0.099*
N1	0.2492 (3)	0.54488 (8)	0.1415 (2)	0.0422 (6)
N2	0.1266 (3)	0.57751 (9)	0.3767 (2)	0.0401 (6)
H2	0.104 (3)	0.5922 (10)	0.443 (3)	0.038 (9)*
N3	0.1973 (3)	0.46954 (8)	0.1257 (2)	0.0401 (6)
N4	0.2699 (3)	0.38349 (9)	0.0266 (2)	0.0426 (6)
H4	0.359 (4)	0.3785 (12)	0.075 (3)	0.062 (11)*
S1	−0.15686 (9)	0.53903 (3)	0.41676 (8)	0.0417 (2)
C18	0.5648 (4)	0.32953 (11)	0.1890 (3)	0.0392 (7)
C19	0.7193 (3)	0.31664 (9)	0.2566 (3)	0.0323 (6)
C20	0.8224 (3)	0.34904 (9)	0.3104 (3)	0.0333 (6)
H20	0.795966	0.379278	0.302211	0.040*
C21	0.9623 (3)	0.33711 (9)	0.3753 (3)	0.0332 (6)
C22	1.0032 (4)	0.29233 (10)	0.3851 (3)	0.0431 (8)
H22	1.098573	0.284064	0.427658	0.052*
C23	0.9038 (4)	0.25982 (10)	0.3322 (3)	0.0466 (8)
H23	0.932732	0.229732	0.338820	0.056*
C24	0.7613 (3)	0.27150 (10)	0.2692 (3)	0.0380 (7)
O1	0.5341 (2)	0.37036 (7)	0.1732 (2)	0.0469 (6)
O2	0.4736 (3)	0.29822 (8)	0.1504 (2)	0.0603 (7)
O3	0.6639 (3)	0.23843 (8)	0.2203 (3)	0.0571 (7)
H3A	0.581 (5)	0.2537 (13)	0.186 (4)	0.071 (13)*
O4	1.0557 (3)	0.37078 (7)	0.4286 (2)	0.0442 (5)
H4A	1.127 (5)	0.3588 (13)	0.478 (4)	0.071 (13)*
C25	0.4829 (5)	0.37490 (14)	0.5193 (4)	0.0740 (12)
H25A	0.463666	0.400651	0.570276	0.111*
H25B	0.421761	0.377329	0.439808	0.111*
H25C	0.593185	0.373497	0.505130	0.111*
C26	0.4367 (4)	0.33350 (12)	0.5852 (3)	0.0519 (9)
H26	0.493746	0.332991	0.668868	0.062*
C27	0.4755 (6)	0.29132 (15)	0.5177 (4)	0.0808 (13)
H27A	0.426807	0.292136	0.433192	0.121*
H27B	0.436502	0.265885	0.561363	0.121*
H27C	0.587968	0.288851	0.515149	0.121*
O5	0.2703 (3)	0.33712 (9)	0.6017 (2)	0.0548 (6)
H5	0.238 (4)	0.3130 (12)	0.641 (3)	0.058 (11)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.046 (2)	0.052 (2)	0.078 (3)	−0.0084 (16)	0.0086 (18)	−0.0055 (19)
C2	0.0369 (17)	0.0321 (16)	0.0523 (19)	0.0018 (13)	−0.0002 (14)	0.0041 (14)
C3	0.0413 (17)	0.0286 (15)	0.0445 (17)	0.0018 (13)	−0.0032 (14)	−0.0019 (13)
C4	0.0381 (17)	0.0292 (15)	0.0377 (16)	0.0041 (12)	−0.0004 (13)	0.0056 (13)
C5	0.0369 (16)	0.0324 (16)	0.0353 (16)	0.0010 (13)	0.0001 (13)	0.0057 (13)
C6	0.0335 (16)	0.0379 (17)	0.0378 (16)	−0.0064 (13)	−0.0003 (13)	0.0048 (13)
C7	0.0422 (18)	0.0393 (18)	0.0476 (18)	−0.0023 (14)	0.0044 (14)	−0.0037 (15)
C8	0.0488 (19)	0.0377 (18)	0.061 (2)	0.0000 (15)	0.0075 (16)	0.0042 (16)
C9	0.058 (2)	0.0422 (19)	0.058 (2)	−0.0043 (16)	0.0106 (17)	0.0165 (16)
C10	0.051 (2)	0.047 (2)	0.0431 (18)	−0.0029 (15)	0.0104 (15)	0.0032 (15)
C11	0.0324 (16)	0.0384 (17)	0.0429 (17)	−0.0023 (13)	0.0021 (13)	0.0042 (14)
C12	0.0416 (17)	0.0363 (17)	0.0336 (16)	0.0058 (14)	−0.0014 (13)	0.0027 (13)
C13	0.0405 (17)	0.0361 (17)	0.0424 (17)	0.0082 (13)	0.0064 (14)	0.0051 (14)
C14	0.0391 (17)	0.0388 (17)	0.055 (2)	0.0058 (14)	0.0006 (15)	−0.0009 (15)
C15	0.057 (2)	0.054 (2)	0.0368 (17)	0.0186 (17)	0.0026 (15)	0.0040 (15)
C16	0.0481 (19)	0.0451 (19)	0.0397 (17)	0.0075 (15)	0.0088 (14)	0.0053 (14)
C17	0.077 (3)	0.057 (2)	0.060 (2)	0.012 (2)	−0.017 (2)	−0.0209 (19)
N1	0.0428 (15)	0.0379 (15)	0.0469 (15)	0.0026 (12)	0.0090 (12)	0.0031 (12)
N2	0.0490 (16)	0.0389 (15)	0.0321 (14)	−0.0091 (12)	0.0011 (12)	−0.0037 (12)
N3	0.0484 (15)	0.0334 (14)	0.0396 (14)	0.0055 (11)	0.0096 (12)	0.0037 (11)
N4	0.0431 (15)	0.0422 (15)	0.0408 (15)	0.0124 (12)	−0.0072 (13)	−0.0056 (12)
S1	0.0447 (5)	0.0361 (4)	0.0455 (5)	−0.0030 (3)	0.0105 (4)	−0.0033 (3)
C18	0.0372 (17)	0.0459 (19)	0.0346 (16)	0.0043 (15)	0.0032 (13)	−0.0043 (14)
C19	0.0315 (15)	0.0368 (16)	0.0294 (14)	0.0039 (12)	0.0063 (12)	−0.0023 (12)
C20	0.0379 (16)	0.0268 (14)	0.0354 (15)	0.0050 (12)	0.0047 (13)	0.0017 (12)
C21	0.0363 (16)	0.0327 (16)	0.0307 (14)	−0.0023 (12)	0.0028 (12)	0.0000 (12)
C22	0.0397 (17)	0.0405 (18)	0.0472 (18)	0.0078 (14)	−0.0085 (14)	0.0035 (14)
C23	0.0491 (19)	0.0253 (16)	0.064 (2)	0.0052 (14)	−0.0056 (16)	−0.0023 (15)
C24	0.0359 (16)	0.0348 (16)	0.0430 (17)	−0.0012 (13)	0.0022 (13)	−0.0060 (13)
O1	0.0411 (12)	0.0462 (14)	0.0518 (13)	0.0106 (10)	−0.0059 (10)	0.0003 (10)
O2	0.0412 (13)	0.0572 (15)	0.0789 (18)	−0.0010 (12)	−0.0182 (12)	−0.0084 (13)
O3	0.0453 (14)	0.0362 (13)	0.0874 (19)	−0.0014 (11)	−0.0101 (13)	−0.0156 (12)
O4	0.0440 (13)	0.0357 (12)	0.0507 (13)	−0.0039 (10)	−0.0116 (11)	0.0016 (10)
C25	0.051 (2)	0.083 (3)	0.089 (3)	−0.008 (2)	0.006 (2)	0.022 (2)
C26	0.0376 (18)	0.065 (2)	0.052 (2)	−0.0007 (16)	−0.0038 (15)	0.0092 (17)
C27	0.087 (3)	0.077 (3)	0.083 (3)	−0.001 (2)	0.034 (3)	−0.006 (2)
O5	0.0398 (13)	0.0617 (16)	0.0624 (16)	−0.0048 (11)	−0.0001 (11)	0.0184 (13)

Geometric parameters (Å, º) top

C1—C2	1.496 (4)	C16—N3	1.452 (4)
C1—H1A	0.9600	C16—H16A	0.9700
C1—H1B	0.9600	C16—H16B	0.9700
C1—H1C	0.9600	C17—N4	1.483 (4)
C2—C3	1.343 (4)	C17—H17A	0.9600
C2—S1	1.736 (3)	C17—H17B	0.9600
C3—C4	1.434 (4)	C17—H17C	0.9600
C3—H3	0.9300	N2—H2	0.87 (3)
C4—C5	1.365 (4)	N4—H4	0.89 (4)
C4—C12	1.474 (4)	C18—O1	1.252 (4)
C5—N2	1.388 (4)	C18—O2	1.260 (4)
C5—S1	1.729 (3)	C18—C19	1.496 (4)
C6—C7	1.383 (4)	C19—C24	1.394 (4)
C6—C11	1.400 (4)	C19—C20	1.395 (4)
C6—N2	1.429 (4)	C20—C21	1.373 (4)
C7—C8	1.378 (4)	C20—H20	0.9300
C7—H7	0.9300	C21—O4	1.373 (3)
C8—C9	1.372 (5)	C21—C22	1.379 (4)
C8—H8	0.9300	C22—C23	1.376 (4)
C9—C10	1.385 (4)	C22—H22	0.9300
C9—H9	0.9300	C23—C24	1.381 (4)
C10—C11	1.388 (4)	C23—H23	0.9300
C10—H10	0.9300	C24—O3	1.363 (4)
C11—N1	1.408 (4)	O3—H3A	0.89 (4)
C12—N1	1.287 (4)	O4—H4A	0.85 (4)
C12—N3	1.389 (4)	C25—C26	1.485 (5)
C13—N3	1.463 (4)	C25—H25A	0.9600
C13—C14	1.503 (4)	C25—H25B	0.9600
C13—H13A	0.9700	C25—H25C	0.9600
C13—H13B	0.9700	C26—O5	1.440 (4)
C14—N4	1.484 (4)	C26—C27	1.495 (5)
C14—H14A	0.9700	C26—H26	0.9800
C14—H14B	0.9700	C27—H27A	0.9600
C15—N4	1.485 (4)	C27—H27B	0.9600
C15—C16	1.503 (4)	C27—H27C	0.9600
C15—H15A	0.9700	O5—H5	0.88 (4)
C15—H15B	0.9700

C2—C1—H1A	109.5	N4—C17—H17A	109.5
C2—C1—H1B	109.5	N4—C17—H17B	109.5
H1A—C1—H1B	109.5	H17A—C17—H17B	109.5
C2—C1—H1C	109.5	N4—C17—H17C	109.5
H1A—C1—H1C	109.5	H17A—C17—H17C	109.5
H1B—C1—H1C	109.5	H17B—C17—H17C	109.5
C3—C2—C1	130.5 (3)	C12—N1—C11	124.2 (3)
C3—C2—S1	110.5 (2)	C5—N2—C6	114.5 (2)
C1—C2—S1	119.1 (2)	C5—N2—H2	113 (2)
C2—C3—C4	114.5 (3)	C6—N2—H2	111 (2)
C2—C3—H3	122.7	C12—N3—C16	119.0 (2)
C4—C3—H3	122.7	C12—N3—C13	121.3 (2)
C5—C4—C3	111.5 (3)	C16—N3—C13	110.9 (2)
C5—C4—C12	120.9 (3)	C17—N4—C14	111.8 (3)
C3—C4—C12	127.6 (3)	C17—N4—C15	111.5 (3)
C4—C5—N2	126.8 (3)	C14—N4—C15	111.1 (2)
C4—C5—S1	111.5 (2)	C17—N4—H4	111 (2)
N2—C5—S1	121.7 (2)	C14—N4—H4	103 (2)
C7—C6—C11	120.1 (3)	C15—N4—H4	109 (2)
C7—C6—N2	119.9 (3)	C5—S1—C2	91.97 (14)
C11—C6—N2	119.9 (3)	O1—C18—O2	123.9 (3)
C8—C7—C6	121.4 (3)	O1—C18—C19	118.6 (3)
C8—C7—H7	119.3	O2—C18—C19	117.5 (3)
C6—C7—H7	119.3	C24—C19—C20	118.6 (3)
C9—C8—C7	119.4 (3)	C24—C19—C18	120.1 (3)
C9—C8—H8	120.3	C20—C19—C18	121.3 (3)
C7—C8—H8	120.3	C21—C20—C19	121.2 (3)
C8—C9—C10	119.5 (3)	C21—C20—H20	119.4
C8—C9—H9	120.2	C19—C20—H20	119.4
C10—C9—H9	120.2	O4—C21—C20	117.9 (3)
C9—C10—C11	122.3 (3)	O4—C21—C22	122.7 (3)
C9—C10—H10	118.8	C20—C21—C22	119.4 (3)
C11—C10—H10	118.8	C23—C22—C21	120.4 (3)
C10—C11—C6	117.3 (3)	C23—C22—H22	119.8
C10—C11—N1	116.3 (3)	C21—C22—H22	119.8
C6—C11—N1	126.2 (3)	C22—C23—C24	120.5 (3)
N1—C12—N3	117.6 (3)	C22—C23—H23	119.7
N1—C12—C4	126.6 (3)	C24—C23—H23	119.7
N3—C12—C4	115.7 (3)	O3—C24—C23	119.1 (3)
N3—C13—C14	109.8 (2)	O3—C24—C19	121.1 (3)
N3—C13—H13A	109.7	C23—C24—C19	119.8 (3)
C14—C13—H13A	109.7	C24—O3—H3A	103 (2)
N3—C13—H13B	109.7	C21—O4—H4A	108 (3)
C14—C13—H13B	109.7	C26—C25—H25A	109.5
H13A—C13—H13B	108.2	C26—C25—H25B	109.5
N4—C14—C13	110.8 (2)	H25A—C25—H25B	109.5
N4—C14—H14A	109.5	C26—C25—H25C	109.5
C13—C14—H14A	109.5	H25A—C25—H25C	109.5
N4—C14—H14B	109.5	H25B—C25—H25C	109.5
C13—C14—H14B	109.5	O5—C26—C25	107.0 (3)
H14A—C14—H14B	108.1	O5—C26—C27	112.0 (3)
N4—C15—C16	112.1 (3)	C25—C26—C27	113.2 (3)
N4—C15—H15A	109.2	O5—C26—H26	108.1
C16—C15—H15A	109.2	C25—C26—H26	108.1
N4—C15—H15B	109.2	C27—C26—H26	108.1
C16—C15—H15B	109.2	C26—C27—H27A	109.5
H15A—C15—H15B	107.9	C26—C27—H27B	109.5
N3—C16—C15	109.9 (3)	H27A—C27—H27B	109.5
N3—C16—H16A	109.7	C26—C27—H27C	109.5
C15—C16—H16A	109.7	H27A—C27—H27C	109.5
N3—C16—H16B	109.7	H27B—C27—H27C	109.5
C15—C16—H16B	109.7	C26—O5—H5	110 (2)
H16A—C16—H16B	108.2

C1—C2—C3—C4	−179.3 (3)	N1—C12—N3—C16	−3.9 (4)
S1—C2—C3—C4	0.6 (3)	C4—C12—N3—C16	172.5 (3)
C2—C3—C4—C5	−0.6 (4)	N1—C12—N3—C13	140.6 (3)
C2—C3—C4—C12	177.8 (3)	C4—C12—N3—C13	−42.9 (4)
C3—C4—C5—N2	−178.0 (3)	C15—C16—N3—C12	−152.5 (3)
C12—C4—C5—N2	3.5 (4)	C15—C16—N3—C13	59.5 (3)
C3—C4—C5—S1	0.3 (3)	C14—C13—N3—C12	151.8 (3)
C12—C4—C5—S1	−178.3 (2)	C14—C13—N3—C16	−61.1 (3)
C11—C6—C7—C8	0.1 (5)	C13—C14—N4—C17	−178.6 (3)
N2—C6—C7—C8	177.0 (3)	C13—C14—N4—C15	−53.4 (3)
C6—C7—C8—C9	0.4 (5)	C16—C15—N4—C17	177.9 (3)
C7—C8—C9—C10	−0.7 (5)	C16—C15—N4—C14	52.5 (4)
C8—C9—C10—C11	0.5 (5)	C4—C5—S1—C2	0.1 (2)
C9—C10—C11—C6	0.0 (5)	N2—C5—S1—C2	178.4 (2)
C9—C10—C11—N1	−174.7 (3)	C3—C2—S1—C5	−0.4 (2)
C7—C6—C11—C10	−0.3 (4)	C1—C2—S1—C5	179.6 (3)
N2—C6—C11—C10	−177.2 (3)	O1—C18—C19—C24	−176.1 (3)
C7—C6—C11—N1	173.8 (3)	O2—C18—C19—C24	3.3 (4)
N2—C6—C11—N1	−3.1 (5)	O1—C18—C19—C20	5.2 (4)
C5—C4—C12—N1	−34.3 (4)	O2—C18—C19—C20	−175.4 (3)
C3—C4—C12—N1	147.5 (3)	C24—C19—C20—C21	−0.4 (4)
C5—C4—C12—N3	149.7 (3)	C18—C19—C20—C21	178.3 (3)
C3—C4—C12—N3	−28.6 (4)	C19—C20—C21—O4	−178.3 (2)
N3—C13—C14—N4	57.4 (3)	C19—C20—C21—C22	1.5 (4)
N4—C15—C16—N3	−55.2 (3)	O4—C21—C22—C23	178.6 (3)
N3—C12—N1—C11	170.5 (3)	C20—C21—C22—C23	−1.1 (5)
C4—C12—N1—C11	−5.5 (5)	C21—C22—C23—C24	−0.4 (5)
C10—C11—N1—C12	−144.3 (3)	C22—C23—C24—O3	−178.5 (3)
C6—C11—N1—C12	41.5 (5)	C22—C23—C24—C19	1.5 (5)
C4—C5—N2—C6	56.1 (4)	C20—C19—C24—O3	178.9 (3)
S1—C5—N2—C6	−121.9 (3)	C18—C19—C24—O3	0.2 (4)
C7—C6—N2—C5	125.9 (3)	C20—C19—C24—C23	−1.1 (4)
C11—C6—N2—C5	−57.2 (4)	C18—C19—C24—C23	−179.7 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1A···O1ⁱ	0.96	2.64	3.579 (4)	168
C10—H10···O1ⁱⁱ	0.93	2.52	3.316 (4)	143
C13—H13A···O4ⁱ	0.97	2.62	3.233 (4)	122
C17—H17B···O2	0.96	2.63	3.216 (4)	120
N2—H2···O4ⁱⁱⁱ	0.87 (3)	2.28 (3)	3.088 (4)	156 (3)
N4—H4···O1	0.89 (4)	1.77 (4)	2.660 (3)	178 (4)
O3—H3A···O2	0.89 (4)	1.63 (4)	2.479 (3)	156 (4)
O4—H4A···O5^iv	0.85 (4)	1.84 (4)	2.682 (3)	173 (4)
O5—H5···O3^v	0.88 (4)	1.88 (4)	2.764 (3)	178 (3)

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

Acknowledgements

VN thanks Dr K. Ravikumar of the Indian Institute of Chemical Technology, Hyderabad, for his kind help and useful discussions.

References

Bever, K. A. & Perry, P. J. (1998). Am. J. Health Syst. Pharm. 55, 1003–1016. Web of Science CrossRef CAS PubMed Google Scholar
Bruker (2008). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL- 6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Callaghan, J. T., Bergstrom, R. F., Ptak, L. R. & Beasley, C. M. (1999). Clin. Pharmacokinet. 37, 177–193. CrossRef PubMed CAS Google Scholar
Capuano, B., Crosby, I. T., Fallon, G. D., Lloyd, E. J., Yuriev, E. & Egan, S. J. (2003). Acta Cryst. E59, o1367–o1369. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Chakrabarti, J. K., Horsman, L., Hotten, T. M., Pullar, I. A., Tupper, D. E. & Wright, F. C. (1980). J. Med. Chem. 23, 878–884. CrossRef CAS PubMed Web of Science Google Scholar
Chue, P. & Singer, P. (2003). J. Psychiatry Neurosci. 28, 253–261. PubMed Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Gans, J. & Shalloway, D. (2001). J. Mol. Graphics Modell. 19, 557–559. Web of Science CrossRef 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
Kavitha, C. N., Jasinski, J. P., Keeley, A. C., Yathirajan, H. S. & Dayananda, A. S. (2013). Acta Cryst. E69, o232–o233. CrossRef IUCr Journals Google Scholar
Kennedy, J. S., Bymaster, F. P., Schuh, L., Calligaro, D. O., Nomikos, G., Felder, C. C., Bernauer, M., Kinon, B. J., Baker, R. W., Hay, D., Roth, H. J., Dossenbach, M., Kaiser, C., Beasley, C. M., Holcombe, J. H., Effron, M. B. & Breier, A. (2001). Int. J. Geriat. Psychiatr. 16, S33–S61. CrossRef Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
McKinnon, J. J., Jayatilaka, D. & Spackman, M. A. (2007). Chem. Commun. pp. 3814–3816. Web of Science CrossRef Google Scholar
McKinnon, J. J., Mitchell, A. S. & Spackman, M. A. (1998). Chem. Eur. J. 4, 2136–2141. CrossRef CAS Google Scholar
McKinnon, J. J., Spackman, M. A. & Mitchell, A. S. (2004). Acta Cryst. B60, 627–668. Web of Science CrossRef CAS IUCr Journals Google Scholar
Narasimhan, M., Bruce, T. O. & Masand, P. (2007). Neuropsychiatr. Dis. Treat. 3, 579–587. PubMed CAS Google Scholar
Ravikumar, K., Swamy, G. Y. S. K., Sridhar, B. & Roopa, S. (2005). Acta Cryst. E61, o2720–o2723. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Sarmah, K. K., Nath, N., Rao, D. R. & Thakuria, R. (2020). CrystEngComm, 22, 1120–1130. CrossRef CAS Google Scholar
Sarmah, K. K., Sarma, A., Roy, K., Rao, D. R. & Thakuria, R. (2016). Cryst. Growth Des. 16, 1047–1055. Web of Science CSD CrossRef CAS Google Scholar
Sarmah, K. K., Sarma, P., Rao, D. R., Gupta, P., Nath, N. K., Arhangelskis, M. & Thakuria, R. (2018). Cryst. Growth Des. 18, 2138–2150. CrossRef CAS 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. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Sridhar, B. & Ravikumar, K. (2007). Zh. Strukt. Khim. 48, 194–202. Google Scholar
Tandon, R. (2002). Psychiatr. Q. 73, 297–311. Web of Science CrossRef PubMed Google Scholar
Tandon, R. & Jibson, M. D. (2003). Psychoneuroendocrinology, 28, 9–26. Web of Science CrossRef PubMed CAS Google Scholar
Thakuria, R. & Nangia, A. (2011a). CrystEngComm, 13, 1759–1764. Web of Science CSD CrossRef CAS Google Scholar
Thakuria, R. & Nangia, A. (2011b). Acta Cryst. C67, o461–o463. Web of Science CSD CrossRef IUCr Journals Google Scholar
Thakuria, R. & Nangia, A. (2013). Cryst. GrowthDes.13(8),3672-3680. Google Scholar
Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, M. A., Jayatilaka, D. & Spackman, M. A. (2017). Crystal Explorer. University of Western Australia. Google Scholar
Venkatesan, P., Thamotharan, S., Ilangovan, A., Liang, H. & Sundius, T. (2016). Spectrochim. Acta Part A, 153, 625–636. Web of Science CSD CrossRef CAS Google Scholar
Wawrzycka-Gorczyca, I., Borowski, P., Osypiuk-Tomasik, J., Mazur, L. & Koziol, A. E. (2007). J. Mol. Struct. 830, 188–197. CAS Google Scholar
Wawrzycka-Gorczyca, I., Koziol, A. E., Glice, M. & Cybulski, J. (2004a). Acta Cryst. E60, o66–o68. Web of Science CSD CrossRef IUCr Journals Google Scholar
Wawrzycka-Gorczyca, I., Mazur, L. & Koziol, A. E. (2004b). Acta Cryst. E60, o69–o71. Web of Science CSD CrossRef IUCr Journals 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.