Crystal structure and Hirshfeld surface analysis of 6-[4-(1-cyclo­hexyl-1H-tetra­zol-5-yl)but­oxy]-8-nitro-3,4-di­hydro­quinolin-2(1H)-one

Dutta, A.; Dhasmana, Y.; Mohan, T.P.; Selvakumar, B.; Chopra, D.

doi:10.1107/S2056989025001793

research communications

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ISSN: 2056-9890

Volume 81| Part 4| April 2025| Pages 284-288

https://doi.org/10.1107/S2056989025001793

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Crystal structure and Hirshfeld surface analysis of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-8-nitro-3,4-dihydroquinolin-2(1H)-one

Arnab Dutta,^a Yogesh Dhasmana,^a T. P. Mohan,^b B. Selvakumar ^b and Deepak Chopra ^a ^*

^aDepartment of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhauri Bhopal 462066, India, and ^bBioneeds India Private Limited, P-3, Peenya Industrial Area, 1st Main Road, Peenya 1st stage, Bangalore 560094, Karnataka., India
^*Correspondence e-mail: dchopra@iiserb.ac.in

Edited by B. Therrien, University of Neuchâtel, Switzerland (Received 3 February 2025; accepted 25 February 2025; online 4 March 2025)

The crystal structure of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-8-nitro-3,4-dihydroquinolin-2(1H)-one, C₂₀H₂₆N₆O₄ (I), was characterized by single-crystal X-ray diffraction. The primary focus was to establish the position of the nitro group, the molecular conformation, and the role of intermolecular interactions towards the crystal packing of I. The crystalline structure is mainly consolidated by π–π, C—H⋯O, C—H⋯N, N⋯C(π) and O⋯C(π) interactions. The contributions of different interactions towards the crystal packing were further analyzed using Hirshfeld surface and fingerprint plots.

Keywords: crystal structure; intermolecular interaction; crystal packing; molecular conformation; Hirshfeld surface.

CCDC reference: 2426771

1. Introduction

Cilostazol is an important active pharmaceutical ingredient used to treat intermittent claudication associated with peripheral vascular disease (Lauters & Wilkin, 2002 ). However, cilostazol has the potential to generate nitroso impurities. The pharmaceutical industry is subject to stringent regulations to control genotoxic nitrosamine impurities in medications, as these compounds pose significant health risks (Vikram et al., 2024 ). Therefore, investigating the presence of nitrosamine impurities is crucial.

Given the possibility of nitroso impurity formation, it is essential to identify the specific site on cilostazol where nitrosation may occur. In this study, we attempted to synthesize N-nitroso cilostazol using a standard method (Lopez-Rodriguez et al., 2020 ). Unexpectedly, instead of obtaining the anticipated product – 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-1-nitroso-3,4-dihydroquinolin-2(1H)-one (N-nitroso cilostazol) – we isolated a different compound, referred to as I. This compound was fully characterized using ¹H NMR and LC-MS, spectroscopy and single-crystal X-ray diffraction.

2. Structural commentary

The molecular structure features a dihydroquinolinone moiety (N2/C1–C9/O3) and a tetrazole moiety composed of two fused six-membered rings (C1–C6, B, and C1/C6–C9/N2, A) and a five-membered ring (C14/N3/N15/N16/N4, C), respectively (Fig. 1). The dihedral angle between the plane through ring B and atoms O4, C10, C11 and the mean plane through ring C and atoms C13, C12, C11 is 82.46 (6)°. The butoxy chain exhibits rotational freedom, contributing to the conformational flexibility of the molecule. The various torsions of the butoxy chain are represented by τ₂, τ₃, τ₄, τ₅, and τ₆, and listed in Table 1. The C2 and C4 carbon atoms are connected to the nitro and alkoxy substituents, respectively, and the presence of two sp³-hybridized carbon atoms (C7 and C8) makes ring A non-planar. The puckering parameters (Cremer & Pople, 1975 ) generated by PLATON (Spek, 2020 ) were obtained for the different rings. For ring A, the puckering parameters are Q = 0.420 (2) Å, θ = 65.9 (3)° and φ = 25.1 (3)°, the value of θ indicating a screw-boat conformation (Boeyens, 1978 ). Atom N4 of ring C is linked to the cyclohexyl ring (C17–C22, D) [Q = 0.582 (3) Å, θ = 1.1 (3)° and φ = 138 (11)°]. The value of θ is very close to zero, thus indicating a chair conformation for ring D. The most acidic hydrogen atom (H2) is involved in the formation of an intramolecular hydrogen bond with the O1 atom of the nitro group [N2⋯O1 = 2.650 (3) Å, ∠N—H⋯O = 128°].

Table 1
Torsion angles (°) of the butoxy chain in I, IA, IC (see Database survey)

Torsion angle	I	IA	IC
τ₁	177.7 (2)	−7.9 (2)	4.1 (2)
τ₂	−179.4 (2)	174.6 (1)	175.8 (1)
τ₃	−74.1 (2)	174.8 (1)	−174.7 (1)
τ₄	−171.1 (2)	70.9 (1)	178.5 (1)
τ₅	176.1 (2)	179.6 (1)	−64.6 (2)
τ₆	168.9 (2)	−111.7 (1)	−94.9 (2)

Figure 1
The molecular structure of I with 50% probability level ellipsoids. The dotted line indicates the intramolecular N2—H2⋯O1 interaction.

3. Supramolecular features

The crystal packing was further analysed by Mercury (Version 2024.1.0; Macrae et al., 2020 ). The crystal packing along the a-axis shows that the molecules form three motifs by inversion symmetry, I, II and III, respectively (Fig. 2 , Table 2). The motifs I and II are consolidated by π–π stacking, N(π-hole)⋯C(π) and C—H⋯O hydrogen-bonding interactions, while motif III contains onlyC—H⋯N hydrogen bonds (involving H17 and N15 and H13A with N15). The π–π stacking occurs in a parallel offset fashion between B rings in both motifs I and II, the latter one consisting of a very short π–π interaction between C3(π)⋯C1(π) with a distance of 3.2067 (3) Å. In the MESP map (Fig. 4a), the electropositive blue region over N1 (0.0332 a.u.) shows the π hole for the N1⋯C5 interaction. In motif III, ring C forms C—H⋯N interactions with the butoxy chain and cyclohexyl ring D, which propagate along the a-axis direction.

Table 2
Intermolecular interactions (Å, °) present in I

Motif	D—X⋯Y	D—X	X⋯Y	D⋯Y	∠D—X⋯Y
I^vi	C8—H8A⋯O2—N1	0.99	2.71	3.467 (2)	133
	C3(π)⋯C1(π)	–	3.261 (3)	–	–
	N1⋯C5(π)	–	3.230 (3)	–	–
	C12—H12B⋯O3—C9	0.99	2.62	3.553 (3)	157
IIⁱⁱⁱ	C10—H10B⋯O1—N1	0.99	2.74	3.526 (3)	136
	C3(π)⋯C1(π)	–	3.207 (3)	–	–
	N1⋯C5(π)	–	3.241 (3)	–	–
IIIⁱⁱ	C17—H17⋯N15	1.00	2.73	3.705 (3)	165
	C13—H13A⋯N15	0.99	2.80	3.646 (3)	144
IV^vii	C18—H18A⋯O1—N1	0.99	2.59	3.527 (3)	157
	C14(π)⋯O2	–	3.146 (3)	–	–
Vⁱ	C3—H3⋯O3—C9	0.95	2.75	3.681 (3)	168
	O4⋯C8—H8B	0.99	2.55	3.453 (3)	151
VI^v	C8—H8A⋯O3—C9	0.99	2.57	3.409 (3)	142
VII^iv	C7—H7A⋯O3—C9	0.99	2.35	3.170 (2)	140
Symmetry codes: (i) x, y + 1, z; (ii) x − 1, y, z; (iii) −x, −y, −z + 1; (iv) −x, −1 − y, 1 − z; (v) −x + 1, −y − 1, −z + 1; (vi) −x + 1, −y, −z + 1; (vii) −x + 1, −y + 1, −z + 1.

Figure 2
Crystal packing extending along the a-axis via π–π stacking, N(π-hole)⋯C(π), C—H⋯O and C—H⋯N interactions.

Figure 3
Crystal packing of I along the bc plane showing C—H⋯O and O⋯C(π) interactions.

Figure 4
The molecular electrostatic potential map (a) and Hirshfeld surface mapped over d_norm (b, c, d). Non-covalent interactions are indicated by dashed lines.

Along the bc plane (Fig. 3), motif IV forms a centrosymmetric dimer through C—H⋯O and O⋯C(π) interactions, while motif V consists of C3—H3⋯O3 and C8—H8B⋯O4 interactions. Motif V utilizes translation symmetry along the b-axis direction for the packing of molecules in the crystal. The remaining motifs VI and VII are also involved in the formation of C—H⋯O hydrogen bonds, the latter one shows a significant short contact [C7⋯O3 = 3.170 (2) Å]. It is noteworthy that atoms H3 and H17, which are attached to hybridized sp² carbons, form the most directional C—H⋯O and C—H⋯N hydrogen bonds in the crystal packing.

4. Hirshfeld surface analysis and fingerprint plots

Hirshfeld surface analysis was performed to investigate and visualize the intermolecular interactions present between molecules and most importantly to quantify the individual contributions of different interactions involved in the crystal packing (Spackman et al., 2021 ). The Hirshfeld surface and the 2D fingerprint plots (Spackman & McKinnon, 2002 ) were generated using CrystalExplorer (version: 21.5) over electrostatic potential range −0.02 a.u. to +0.02 a.u., as depicted in Figs. 4 and 5, respectively. The red spots on the Hirshfeld surface (plotted over d_norm) (Fig. 4b,c,d) indicate the presence of intermolecular π–π stacking, C—H⋯N, C—H⋯O, O⋯C(π) and N⋯C(π) short contacts. In the crystal packing, the relative contributions of the interactions are: O⋯H/H⋯O (22.2%), N⋯H/H⋯N (17.1%), C(π)⋯C(π) (3.7%), O⋯C(π)/C(π)⋯O (2.6%) and N⋯C(π)/C(π)⋯N (2.3%).

Figure 5
The fingerprint plot showing the overall contribution of all contacts and a diagram showing the percentage of individual contributions in the crystal packing.

5. Database survey

A CSD (Groom et al., 2016 ) survey for the cilostazol molecule was performed using CCDC ConQuest (version 2024.1.0). The five resulting hits with refcodes OCIKIX, OCIKOD, OCIKUJ (Yoshimura et al., 2017 ) and XOSGUH, XOSGUH01 (Whittall et al., 2002 ) report co-crystals of cilostazol and the structures of polymorphic forms of cilostazol.

OCIKIX, OCIKOD and OCIKUJ (Yoshimura et al., 2017) are three co-crystals of cilostazol. Cilostazol is a poorly soluble compound, and in order to increase the solubility, co-crystals of cilostazol with 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid (1:1 stoichiometric ratio) have been prepared for different pharmaceutical applications.

XOSGUH and XOSGUH01 (Whittall et al., 2002) feature two unique conformational polymorphic forms of cilostazol. The study shows how the conformational differences can possibly influence the intermolecular forces and packing of the molecules during crystallization. As a result of the conformational flexibility of the butoxy chain, cilostazol crystallizes in two different space groups, P2₁/n (IC) and Pbca (IA). It is observed that I exists in two different conformations for the two reported polymorphs of cilostazol. Conformational variations were analysed by generating a molecular overlay diagram, keeping the tetrazole rings fixed for the three molecules (Fig. 6). It is found that I and IC have similar conformations but differ significantly from IA. The magnitudes of the torsion angles (Table 1) indicate that the most significant conformational differences are observed in the butoxy chains.

Figure 6
An overlay of structures I, IA and IC.

6. Synthesis and crystallization

Cilostazol (1.00 g, 2.7 mmol) was stirred in 5 mL of dichloroethane for 15 min. Isoamyl nitrite (0.32 g, 2.7 mmol) was added at 273–278 K. The reaction mixture was slowly brought to 298 K and allowed to stir for 1h. The reaction mixture was diluted with water and extracted with dichloromethane twice (2 × 50 mL) and concentrated to dryness to afford 1 g of crude product. The crude product was purified by flash chromatography using 2% methanol:dichloromethane eluent system to afford the title compound (0.35 g, 33%). ¹H NMR (400 MHz, dimethyl sulfoxide): δ 9.70 (s, 1H), 7.47–7.48 (d, J = 2.8 Hz, 1H), 7.36 (d, J = 2.8 Hz, 1H), 4.41–4.42 (m, 1H), 4.08–4.11 (m, 2H), 2.97–3.04 (m, 4H), 2.51–2.58 (m, 2H), 1.67–1.98 (m, 11H), 1.42-1.46 (m, 2H), 1.24–1.28 (m, 1H), LC/MS (ESI) m/e 415.2 [M + H]⁺ calculated for C₂₀H₂₇N₆O₄. The crude product was dissolved in isooctane-chloroform (1:1 mixture) and kept at low temperature. After a week, single crystals were obtained.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. All of the hydrogen atoms, except H2 (attached to N2), which was located from a difference-Fourier map, were placed at their geometrically calculated positions and refined using a riding model with U_i_so(H) = 1.2U_eq(C) or 1.5U_eq(C-methyl).

Table 3
Experimental details

Crystal data
Chemical formula	C₂₀H₂₆N₆O₄
M_r	414.47
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	100
a, b, c (Å)	6.4597 (8), 9.2666 (11), 17.382 (2)
α, β, γ (°)	104.113 (5), 96.645 (5), 99.656 (5)
V (Å³)	981.3 (2)
Z	2
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.24 × 0.13 × 0.05

Data collection
Diffractometer	Bruker D8 Quest
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.683, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	16058, 5647, 4069
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.705

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.069, 0.141, 1.08
No. of reflections	5647
No. of parameters	275
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.36, −0.39
Computer programs: APEX2 and SAINT (Bruker, 2016 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2426771

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989025001793/tx2094sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989025001793/tx2094Isup5.hkl

checkCIF report

Computing details top

6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-8-nitro-3,4-dihydroquinolin-2(1H)-one top

Crystal data top

C₂₀H₂₆N₆O₄	Z = 2
M_r = 414.47	F(000) = 440
Triclinic, P1	D_x = 1.403 Mg m⁻³
a = 6.4597 (8) Å	Mo Kα radiation, λ = 0.71073 Å
b = 9.2666 (11) Å	Cell parameters from 4187 reflections
c = 17.382 (2) Å	θ = 2.5–30.0°
α = 104.113 (5)°	µ = 0.10 mm⁻¹
β = 96.645 (5)°	T = 100 K
γ = 99.656 (5)°	Plate, yellow
V = 981.3 (2) Å³	0.24 × 0.13 × 0.05 mm

Data collection top

Bruker D8 Quest diffractometer	5647 independent reflections
Radiation source: microfocus sealed X-ray tube, Incoatec Iµs	4069 reflections with I > 2σ(I)
Mirror optics monochromator	R_int = 0.043
Detector resolution: 7.9 pixels mm^-1	θ_max = 30.1°, θ_min = 2.3°
ω and φ scans	h = −9→9
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −12→13
T_min = 0.683, T_max = 0.746	l = −24→24
16058 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.069	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.141	w = 1/[σ²(F_o²) + (0.036P)² + 1.0039P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
5647 reflections	Δρ_max = 0.36 e Å⁻³
275 parameters	Δρ_min = −0.39 e Å⁻³
0 restraints

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
O4	0.3538 (2)	0.31868 (16)	0.63879 (8)	0.0143 (3)
O3	0.2010 (2)	−0.53087 (16)	0.43484 (9)	0.0182 (3)
O1	0.1523 (3)	−0.15696 (17)	0.33108 (8)	0.0196 (3)
O2	0.2294 (2)	0.08708 (17)	0.35239 (9)	0.0189 (3)
N1	0.2034 (3)	−0.0266 (2)	0.37737 (10)	0.0127 (3)
N2	0.1868 (3)	−0.28422 (19)	0.45172 (10)	0.0120 (3)
N3	1.0704 (3)	0.8204 (2)	0.79866 (10)	0.0163 (4)
N4	0.9390 (3)	1.01503 (19)	0.85030 (10)	0.0132 (3)
N15	1.2241 (3)	0.9502 (2)	0.81932 (11)	0.0195 (4)
N16	1.1471 (3)	1.0679 (2)	0.85096 (11)	0.0184 (4)
C4	0.3116 (3)	0.1701 (2)	0.59483 (11)	0.0113 (4)
C6	0.2611 (3)	−0.1011 (2)	0.58111 (11)	0.0107 (4)
C3	0.2731 (3)	0.1415 (2)	0.51206 (11)	0.0115 (4)
H3	0.272801	0.223263	0.488058	0.014*
C1	0.2277 (3)	−0.1325 (2)	0.49707 (11)	0.0108 (4)
C5	0.3044 (3)	0.0472 (2)	0.62909 (11)	0.0114 (4)
H5	0.329520	0.066015	0.685933	0.014*
C2	0.2347 (3)	−0.0072 (2)	0.46401 (11)	0.0109 (4)
C14	0.8946 (3)	0.8632 (2)	0.81830 (11)	0.0132 (4)
C9	0.2296 (3)	−0.4038 (2)	0.48070 (12)	0.0130 (4)
C17	0.7998 (3)	1.1125 (2)	0.88721 (12)	0.0137 (4)
H17	0.650785	1.068434	0.858439	0.016*
C10	0.3854 (3)	0.3463 (2)	0.72468 (11)	0.0147 (4)
H10A	0.507798	0.304216	0.742582	0.018*
H10B	0.257221	0.295982	0.741387	0.018*
C7	0.2393 (3)	−0.2331 (2)	0.61839 (12)	0.0129 (4)
H7A	0.088266	−0.265566	0.622944	0.015*
H7B	0.323372	−0.199896	0.673263	0.015*
C13	0.6805 (3)	0.7660 (2)	0.81081 (13)	0.0178 (4)
H13A	0.572194	0.814652	0.787945	0.021*
H13B	0.653491	0.763306	0.865403	0.021*
C11	0.4277 (3)	0.5164 (2)	0.76270 (12)	0.0150 (4)
H11A	0.408954	0.534190	0.819755	0.018*
H11B	0.319495	0.559413	0.735488	0.018*
C8	0.3162 (3)	−0.3673 (2)	0.56840 (12)	0.0145 (4)
H8A	0.473662	−0.343760	0.575942	0.017*
H8B	0.272399	−0.457746	0.588016	0.017*
C18	0.8604 (4)	1.2733 (2)	0.87864 (13)	0.0184 (4)
H18A	0.849021	1.270559	0.820994	0.022*
H18B	1.009626	1.318310	0.904730	0.022*
C12	0.6491 (3)	0.6027 (2)	0.75913 (12)	0.0156 (4)
H12A	0.759748	0.552795	0.779382	0.019*
H12B	0.661840	0.602030	0.702839	0.019*
C22	0.8051 (4)	1.1126 (2)	0.97530 (13)	0.0178 (4)
H22A	0.762243	1.007088	0.978963	0.021*
H22B	0.951825	1.153979	1.004952	0.021*
C21	0.6549 (4)	1.2086 (3)	1.01333 (13)	0.0198 (5)
H21A	0.663914	1.210730	1.070855	0.024*
H21B	0.506652	1.162545	0.986406	0.024*
C20	0.7128 (4)	1.3703 (3)	1.00564 (13)	0.0204 (5)
H20A	0.609442	1.429620	1.028136	0.024*
H20B	0.855917	1.419567	1.036988	0.024*
C19	0.7118 (4)	1.3706 (3)	0.91805 (13)	0.0212 (5)
H19A	0.756991	1.476331	0.915033	0.025*
H19B	0.565143	1.331179	0.888035	0.025*
H2	0.150 (3)	−0.304 (2)	0.3988 (13)	0.009 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O4	0.0222 (8)	0.0082 (7)	0.0122 (7)	0.0025 (6)	0.0026 (6)	0.0022 (5)
O3	0.0195 (8)	0.0090 (7)	0.0240 (8)	0.0019 (6)	0.0062 (6)	0.0001 (6)
O1	0.0264 (9)	0.0162 (8)	0.0129 (7)	0.0035 (7)	0.0015 (6)	−0.0008 (6)
O2	0.0257 (9)	0.0179 (8)	0.0157 (7)	0.0047 (7)	0.0037 (6)	0.0092 (6)
N1	0.0091 (8)	0.0150 (8)	0.0137 (8)	0.0029 (7)	0.0016 (6)	0.0031 (6)
N2	0.0133 (8)	0.0093 (8)	0.0116 (8)	0.0009 (6)	0.0013 (6)	0.0009 (6)
N3	0.0156 (9)	0.0174 (9)	0.0159 (8)	0.0055 (7)	0.0039 (7)	0.0023 (7)
N4	0.0120 (8)	0.0123 (8)	0.0151 (8)	0.0027 (7)	0.0035 (6)	0.0024 (6)
N15	0.0168 (9)	0.0205 (10)	0.0203 (9)	0.0049 (8)	0.0061 (7)	0.0019 (7)
N16	0.0123 (9)	0.0189 (9)	0.0225 (9)	0.0002 (7)	0.0046 (7)	0.0039 (7)
C4	0.0090 (9)	0.0095 (9)	0.0160 (9)	0.0032 (7)	0.0033 (7)	0.0032 (7)
C6	0.0088 (9)	0.0110 (9)	0.0143 (9)	0.0035 (7)	0.0045 (7)	0.0049 (7)
C3	0.0095 (9)	0.0110 (9)	0.0156 (9)	0.0020 (7)	0.0033 (7)	0.0059 (7)
C1	0.0077 (9)	0.0100 (9)	0.0151 (9)	0.0015 (7)	0.0038 (7)	0.0033 (7)
C5	0.0108 (9)	0.0128 (9)	0.0106 (8)	0.0013 (8)	0.0025 (7)	0.0033 (7)
C2	0.0075 (9)	0.0139 (10)	0.0112 (9)	0.0014 (7)	0.0014 (7)	0.0035 (7)
C14	0.0168 (10)	0.0118 (9)	0.0100 (8)	0.0037 (8)	0.0013 (7)	0.0010 (7)
C9	0.0093 (9)	0.0093 (9)	0.0215 (10)	0.0020 (7)	0.0066 (8)	0.0046 (8)
C17	0.0120 (10)	0.0110 (9)	0.0172 (9)	0.0035 (8)	0.0031 (8)	0.0009 (7)
C10	0.0205 (11)	0.0117 (10)	0.0111 (9)	0.0021 (8)	0.0025 (8)	0.0026 (7)
C7	0.0165 (10)	0.0083 (9)	0.0141 (9)	0.0012 (8)	0.0030 (8)	0.0042 (7)
C13	0.0150 (11)	0.0139 (10)	0.0213 (10)	0.0015 (8)	0.0043 (8)	−0.0008 (8)
C11	0.0197 (11)	0.0116 (10)	0.0131 (9)	0.0034 (8)	0.0041 (8)	0.0014 (7)
C8	0.0157 (10)	0.0108 (9)	0.0186 (10)	0.0025 (8)	0.0040 (8)	0.0064 (8)
C18	0.0255 (12)	0.0153 (10)	0.0179 (10)	0.0070 (9)	0.0080 (9)	0.0066 (8)
C12	0.0185 (11)	0.0104 (9)	0.0174 (10)	0.0043 (8)	0.0041 (8)	0.0016 (8)
C22	0.0225 (11)	0.0137 (10)	0.0216 (10)	0.0065 (9)	0.0092 (9)	0.0083 (8)
C21	0.0213 (12)	0.0216 (11)	0.0209 (11)	0.0097 (9)	0.0086 (9)	0.0077 (9)
C20	0.0277 (12)	0.0163 (11)	0.0186 (10)	0.0118 (9)	0.0045 (9)	0.0021 (8)
C19	0.0309 (13)	0.0162 (11)	0.0203 (10)	0.0096 (10)	0.0065 (9)	0.0078 (9)

Geometric parameters (Å, º) top

O4—C4	1.366 (2)	C10—H10B	0.9900
O4—C10	1.436 (2)	C10—C11	1.517 (3)
O3—C9	1.221 (2)	C7—H7A	0.9900
O1—N1	1.243 (2)	C7—H7B	0.9900
O2—N1	1.228 (2)	C7—C8	1.526 (3)
N1—C2	1.458 (2)	C13—H13A	0.9900
N2—C1	1.398 (2)	C13—H13B	0.9900
N2—C9	1.379 (2)	C13—C12	1.526 (3)
N2—H2	0.89 (2)	C11—H11A	0.9900
N3—N15	1.367 (3)	C11—H11B	0.9900
N3—C14	1.319 (3)	C11—C12	1.533 (3)
N4—N16	1.349 (2)	C8—H8A	0.9900
N4—C14	1.348 (3)	C8—H8B	0.9900
N4—C17	1.470 (3)	C18—H18A	0.9900
N15—N16	1.301 (3)	C18—H18B	0.9900
C4—C3	1.383 (3)	C18—C19	1.531 (3)
C4—C5	1.404 (3)	C12—H12A	0.9900
C6—C1	1.401 (3)	C12—H12B	0.9900
C6—C5	1.386 (3)	C22—H22A	0.9900
C6—C7	1.511 (3)	C22—H22B	0.9900
C3—H3	0.9500	C22—C21	1.523 (3)
C3—C2	1.391 (3)	C21—H21A	0.9900
C1—C2	1.412 (3)	C21—H21B	0.9900
C5—H5	0.9500	C21—C20	1.525 (3)
C14—C13	1.491 (3)	C20—H20A	0.9900
C9—C8	1.496 (3)	C20—H20B	0.9900
C17—H17	1.0000	C20—C19	1.522 (3)
C17—C18	1.524 (3)	C19—H19A	0.9900
C17—C22	1.527 (3)	C19—H19B	0.9900
C10—H10A	0.9900

C4—O4—C10	116.53 (15)	C14—C13—H13A	108.4
O1—N1—C2	119.39 (16)	C14—C13—H13B	108.4
O2—N1—O1	121.98 (17)	C14—C13—C12	115.69 (18)
O2—N1—C2	118.62 (17)	H13A—C13—H13B	107.4
C1—N2—H2	117.8 (14)	C12—C13—H13A	108.4
C9—N2—C1	124.94 (17)	C12—C13—H13B	108.4
C9—N2—H2	116.4 (14)	C10—C11—H11A	108.5
C14—N3—N15	105.82 (17)	C10—C11—H11B	108.5
N16—N4—C17	122.55 (17)	C10—C11—C12	114.99 (17)
C14—N4—N16	108.70 (17)	H11A—C11—H11B	107.5
C14—N4—C17	128.46 (18)	C12—C11—H11A	108.5
N16—N15—N3	110.93 (17)	C12—C11—H11B	108.5
N15—N16—N4	106.10 (17)	C9—C8—C7	112.55 (17)
O4—C4—C3	117.16 (17)	C9—C8—H8A	109.1
O4—C4—C5	123.72 (17)	C9—C8—H8B	109.1
C3—C4—C5	119.11 (18)	C7—C8—H8A	109.1
C1—C6—C7	118.46 (17)	C7—C8—H8B	109.1
C5—C6—C1	120.91 (18)	H8A—C8—H8B	107.8
C5—C6—C7	120.58 (17)	C17—C18—H18A	109.8
C4—C3—H3	120.1	C17—C18—H18B	109.8
C4—C3—C2	119.86 (18)	C17—C18—C19	109.59 (18)
C2—C3—H3	120.1	H18A—C18—H18B	108.2
N2—C1—C6	118.42 (17)	C19—C18—H18A	109.8
N2—C1—C2	124.44 (17)	C19—C18—H18B	109.8
C6—C1—C2	117.13 (18)	C13—C12—C11	108.81 (17)
C4—C5—H5	119.5	C13—C12—H12A	109.9
C6—C5—C4	120.92 (18)	C13—C12—H12B	109.9
C6—C5—H5	119.5	C11—C12—H12A	109.9
C3—C2—N1	116.24 (17)	C11—C12—H12B	109.9
C3—C2—C1	122.02 (17)	H12A—C12—H12B	108.3
C1—C2—N1	121.74 (17)	C17—C22—H22A	109.6
N3—C14—N4	108.44 (18)	C17—C22—H22B	109.6
N3—C14—C13	128.13 (19)	H22A—C22—H22B	108.1
N4—C14—C13	123.40 (18)	C21—C22—C17	110.43 (18)
O3—C9—N2	119.85 (19)	C21—C22—H22A	109.6
O3—C9—C8	123.46 (19)	C21—C22—H22B	109.6
N2—C9—C8	116.67 (17)	C22—C21—H21A	109.5
N4—C17—H17	108.0	C22—C21—H21B	109.5
N4—C17—C18	111.43 (17)	C22—C21—C20	110.50 (18)
N4—C17—C22	109.98 (17)	H21A—C21—H21B	108.1
C18—C17—H17	108.0	C20—C21—H21A	109.5
C18—C17—C22	111.33 (17)	C20—C21—H21B	109.5
C22—C17—H17	108.0	C21—C20—H20A	109.5
O4—C10—H10A	109.9	C21—C20—H20B	109.5
O4—C10—H10B	109.9	H20A—C20—H20B	108.0
O4—C10—C11	108.84 (16)	C19—C20—C21	110.93 (18)
H10A—C10—H10B	108.3	C19—C20—H20A	109.5
C11—C10—H10A	109.9	C19—C20—H20B	109.5
C11—C10—H10B	109.9	C18—C19—H19A	109.3
C6—C7—H7A	109.3	C18—C19—H19B	109.3
C6—C7—H7B	109.3	C20—C19—C18	111.82 (18)
C6—C7—C8	111.54 (16)	C20—C19—H19A	109.3
H7A—C7—H7B	108.0	C20—C19—H19B	109.3
C8—C7—H7A	109.3	H19A—C19—H19B	107.9
C8—C7—H7B	109.3

O4—C4—C3—C2	178.34 (18)	C1—N2—C9—C8	3.3 (3)
O4—C4—C5—C6	−179.89 (18)	C1—C6—C5—C4	1.3 (3)
O4—C10—C11—C12	−74.1 (2)	C1—C6—C7—C8	34.9 (2)
O3—C9—C8—C7	−151.93 (19)	C5—C4—C3—C2	−2.1 (3)
O1—N1—C2—C3	−174.48 (18)	C5—C6—C1—N2	179.37 (18)
O1—N1—C2—C1	6.0 (3)	C5—C6—C1—C2	−1.6 (3)
O2—N1—C2—C3	5.7 (3)	C5—C6—C7—C8	−147.74 (19)
O2—N1—C2—C1	−173.81 (18)	C14—N3—N15—N16	0.5 (2)
N2—C1—C2—N1	−1.5 (3)	C14—N4—N16—N15	0.6 (2)
N2—C1—C2—C3	179.02 (19)	C14—N4—C17—C18	−152.15 (19)
N2—C9—C8—C7	29.8 (2)	C14—N4—C17—C22	83.9 (2)
N3—N15—N16—N4	−0.7 (2)	C14—C13—C12—C11	176.09 (17)
N3—C14—C13—C12	−13.5 (3)	C9—N2—C1—C6	−17.8 (3)
N4—C14—C13—C12	168.87 (18)	C9—N2—C1—C2	163.28 (19)
N4—C17—C18—C19	−179.86 (17)	C17—N4—N16—N15	175.00 (17)
N4—C17—C22—C21	−177.90 (18)	C17—N4—C14—N3	−174.26 (18)
N15—N3—C14—N4	−0.1 (2)	C17—N4—C14—C13	3.8 (3)
N15—N3—C14—C13	−178.08 (19)	C17—C18—C19—C20	55.8 (3)
N16—N4—C14—N3	−0.3 (2)	C17—C22—C21—C20	−57.1 (2)
N16—N4—C14—C13	177.78 (18)	C10—O4—C4—C3	177.68 (17)
N16—N4—C17—C18	34.6 (3)	C10—O4—C4—C5	−1.9 (3)
N16—N4—C17—C22	−89.3 (2)	C10—C11—C12—C13	−171.11 (17)
C4—O4—C10—C11	−179.44 (17)	C7—C6—C1—N2	−3.3 (3)
C4—C3—C2—N1	−177.77 (17)	C7—C6—C1—C2	175.74 (17)
C4—C3—C2—C1	1.8 (3)	C7—C6—C5—C4	−175.97 (18)
C6—C1—C2—N1	179.61 (18)	C18—C17—C22—C21	58.1 (2)
C6—C1—C2—C3	0.1 (3)	C22—C17—C18—C19	−56.7 (2)
C6—C7—C8—C9	−47.1 (2)	C22—C21—C20—C19	56.3 (3)
C3—C4—C5—C6	0.5 (3)	C21—C20—C19—C18	−56.1 (3)
C1—N2—C9—O3	−175.10 (18)

Torsion angles (°) of the butoxy chain in I, IA, IC top

Torsion angle	I	IA	IC
τ₁	177.7 (2)	-7.9 (2)	4.1 (2)
τ₂	-179.4 (2)	174.6 (1)	175.8 (1)
τ₃	-74.1 (2)	174.8 (1)	-174.7 (1)
τ₄	-171.1 (2)	70.9 (1)	178.5 (1)
τ₅	176.1 (2)	179.6 (1)	-64.6 (2)
τ₆	168.9 (2)	-111.7 (1)	-94.9 (2)

Intermolecular interactions (Å, °) present in I top

Motif	D—X···Y	D—X	X···Y	D···Y	∠D—X···Y
I^vi	C8—H8A···O2—N1	0.99	2.71	3.467 (2)	133
	C3(π)···C1(π)	–	3.261 (3)	–	–
	N1···C5(π)	–	3.230 (3)	–	–
	C12—H12B···O3—C9	0.99	2.62	3.553 (3)	157
IIⁱⁱⁱ	C10—H10B···O1—N1	0.99	2.74	3.526 (3)	136
	C3(π)···C1(π)	–	3.207 (3)	–	–
	N1···C5(π)	–	3.241 (3)	–	–
IIIⁱⁱ	C17—H17···N15	1.00	2.73	3.705 (3)	165
	C13—H13A···N15	0.99	2.80	3.646 (3)	144
IV^vii	C18—H18A···O1—N1	0.99	2.59	3.527 (3)	157
	O2···C14(π)	–	3.146 (3)	–	–
Vⁱ	C3—H3···O3—C9	0.95	2.75	3.681 (3)	168
	C8—H8B···O4	0.99	2.55	3.453 (3)	151
VI^v	C8—H8A···O3—C9	0.99	2.57	3.409 (3)	142
VII^iv	C7—H7A···O3—C9	0.99	2.35	3.170 (2)	140

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

Acknowledgements

The authors are grateful to IISERB for research facilities and infrastructure. YD thanks DST-INSPIRE for the research fellowship.

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