Crystal structure and Hirshfeld-surface analysis of an etoxazole metabolite designated R13

Mohan Kumar, T.M.; Bhaskar, B.L.; Priyanka, P.; Divakara, T.R.; Yathirajan, H.S.; Parkin, S.

doi:10.1107/S2056989024010600

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ISSN: 2056-9890

Volume 80| Part 12| December 2024|

https://doi.org/10.1107/S2056989024010600

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Crystal structure and Hirshfeld-surface analysis of an etoxazole metabolite designated R13

Thaluru M. Mohan Kumar,^a Besagarahally L. Bhaskar,^b Prabhakar Priyanka,^c Thayamma R. Divakara,^d Hemmige S. Yathirajan ^e ^* and Sean Parkin ^f

^aDepartment of Physical Sciences, Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Bengaluru-560 035, India, ^bDepartment of Physical Sciences, Amrita School of Engineering, Amrita Vishwa Vidyapeetham, Bengaluru-560 035, India, ^cNational Hill View Public School, Bengaluru-560 098, India, ^dDepartment of Chemistry, T. John Institute of Technology, Bengaluru-560 083, India, ^eDepartment of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru-570 006, India, and ^fDepartment of Chemistry, University of Kentucky, Lexington, KY, 40506-0055, USA
^*Correspondence e-mail: yathirajan@hotmail.com

Edited by X. Hao, Institute of Chemistry, Chinese Academy of Sciences (Received 30 October 2024; accepted 2 November 2024; online 8 November 2024)

The etoxazole metabolite R13, systematic name 4-(4-tert-butyl-2-ethoxyphenyl)-2-(2,6-difluorophenyl)oxazole (C₂₁H₂₁F₂NO₂), results from the oxidation of etoxazole, a chitin synthesis inhibitor belonging to the oxazoline class, widely used as an insecticide/acaricide since 1998. The structure of R13 features a central oxazole ring with attached 2,6-difluorophenyl and 4-t-butyl-2-ethoxyphenyl moieties. The overall conformation gives dihedral angles between these rings and the oxazole of 24.91 (5)° (with difluorophenyl) and 15.30 (6)° (with t-butyl-ethoxyphenyl), indicating an overall deviation from planarity. Additionally, torsion angles of the ethoxy and t-butyl groups define the orientation of these substituents relative to their benzene ring. In the crystal packing, no significant hydrogen bonds are present, but a Hirshfeld surface analysis highlights weak intermolecular contacts leading to π–π-stacked dimers linked by weak C—H⋯N contacts. The packing analysis confirms that most intermolecular interactions involve hydrogen atoms.

Keywords: etoxazole metabolite R13; insecticide; acaricide; Hirshfeld surface analysis; crystal structure.

CCDC reference: 2397916

1. Chemical context

The etoxazole metabolite designated R13, systematic name 4-(4-t-butyl-2-ethoxyphenyl)-2-(2,6-difluorophenyl)oxazole (C₂₁H₂₁F₂NO₂), is derived from etoxazole (C₂₁H₂₃F₂NO₂), an organofluorine chitin synthesis inhibitor. Etoxazole is a member of the oxazoline class of insecticides, having been developed as a new-generation insecticide and acaricide (Li et al., 2014 ). It has been used globally since 1998 (Park et al., 2020 ). Etoxazole is readily absorbed by plants and translocates locally within leaves. The insecticidal mode of action of etoxazole is via the inhibition of chitin biosynthesis. A comprehensive review of the biological activities of oxazole derivatives was published by Kakkar & Narasimhan (2019 ), while Joshi et al. (2023 ) provided a detailed review of their chemistry. Recent research has also assessed the risks of oxidative stress and multiple toxicities induced by etoxazole (Macar et al., 2022 ). The synthesis and activity of novel acaricidal/insecticidal 2,4-diphenyl-1,3-oxazolines were reported by Suzuki et al. (2002 ). It is well established that the key transformation of etoxazole in plants and animals involves oxidation of the oxazole ring, leading to the formation of the R13 metabolite (APVMA, 2024 ).

We have recently reported the crystal structures of phenylpyrazole-based insecticides (Priyanka et al., 2022 ; Vinaya et al., 2023 ). The crystal structure of 2-(3-methyl-2-nitrophenyl)-4,5-dihydro-1,3-oxazole, an intermediate in the synthesis of anthranilamide insecticides, was reported by Lei et al. (2009 ). Additionally, the crystal structure of ethyl 3-(4-chlorophenyl)-5-[(E)-2-(dimethylamino)ethenyl]-1,2-oxazole-4-carboxylate was described by Efimov et al. (2015 ), and the structure of the insecticide fipronil was published by Park et al. (2017 ). Given the significance of etoxazole, we present in this paper the crystal structure of its metabolite, R13.

2. Structural commentary

The crystal structure of R13 is monoclinic, space-group type C2/c. The molecular structure (Fig. 1) consists of three substituted rings: a central oxazole ring flanked by a 2,6-difluorophenyl ring attached to the oxazole carbon between the nitrogen and oxygen atoms, and a 4-t-butyl-2-ethoxyphenyl group attached to the oxazole carbon on the opposite side of the nitrogen. There are no unusual bond lengths or angles within the molecule.

Figure 1
An ellipsoid plot of R13 (50% probability). Hydrogen atoms are shown as circles of arbitrary radius.

The overall conformation is primarily defined by the dihedral angles between the oxazole and difluorophenyl rings [24.91 (5)°], and between the oxazole and t-butyl-2-ethoxyphenyl rings [15.30 (6)°]. The dihedral angle between the two benzene rings is 11.56 (6)°. These values indicate that the molecule deviates from planarity, mostly due to the tilt of the oxazole ring relative to its attached substituents. An intramolecular close contact between H2 and O2 (Table 1) is flagged as a ‘potential’ hydrogen bond by SHELXL (Sheldrick, 2015b ), but not by Mercury (Macrae et al., 2020 ).

Table 1
Close contacts (Å, °) for R13

Weak hydrogen bonds
D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2⋯O2	0.95	2.29	2.7807 (12)	111.1
C19ⁱ—H19ⁱ⋯N	0.95	2.61	3.3494 (14)	134.7
π–π stacks
Ring 1⋯ring 2		Distance	Dihedral angle
Ox⋯Oxⁱⁱ(interplanar)		3.3426 (11)	0 (parallel)
Cg(Ox)⋯Cg(Ox)ⁱⁱ		3.3894 (11)	0 (parallel)
Cg(C4–C9)⋯Cg(C16–C21)ⁱⁱ		3.9439 (11)	11.56 (6)
Abbreviations: Ox = oxazole; Cg = centroid. Symmetry codes: (i) = $[{1\over 2}]$ − x, $[{1\over 2}]$ + y, $[{1\over 2}]$ − z; (ii) = $[{1\over 2}]$ − x, $[{3\over 2}]$ − y, 1 − z.

Further degrees of freedom in the structure are characterized by torsion angles, specifically the positioning of the ethoxy group, defined by C4—C9—O2—C10 [176.53 (9)°] and C9—O2—C10—C11 [174.49 (9)°], and the relative orientation of the t-butyl group to its attached benzene ring, indicated by torsion C6—C7—C12—C13 [−177.08 (9)°].

3. Supramolecular features

There are no especially strong intermolecular interactions in the crystal packing of R13. The default geometric search for hydrogen-bond type contacts in SHELXL (Sheldrick, 2015b) and Mercury (Macrae et al., 2020) suggests no potential intermolecular hydrogen bonds. A plot of the Hirshfeld surface (HS) mapped over d_norm (Fig. 2a) in CrystalExplorer21 (Spackman et al., 2021 ), however, reveals a pair of small red spots representing close contacts of the form C19ⁱ—H19ⁱ⋯N1 [symmetry code: (i) = $[{1\over 2}]$ − x, $[{1\over 2}]$ + y, $[{1\over 2}]$ − z]. These are necessarily weak, as evident from the D⋯A distance and D—H⋯A angle given in Table 1. The remainder of the HS mapped over d_norm is a largely featureless expanse of blue and white (contact distances larger than and equal to the sum of van der Waals radii, respectively). The HS mapped over ‘shape index’ (Fig. 2b), however, reveals pairs of juxtaposed, roughly triangular, blue and red regions that are a characteristic signature of π–π-stacking interactions (Tan et al., 2019 ). The interplanar separation of oxazole ring N1–C1–O1–C2–C3 to its inversion-related counterpart [via symmetry operation (ii) $[{1\over 2}]$ − x, $[{3\over 2}]$ − y, 1 − z] is 3.3426 (11) Å. Mutual overlap of benzene rings C4–C9 and C16ⁱⁱ–C21ⁱⁱ (and vice versa) is less distinct; the centroid–centroid distance is 3.9439 (11) Å and the rings are not parallel, but mis-aligned by 11.56 (6)° (Table 1). The manner in which these π–π interactions as well as the weak hydrogen-bond-like contacts combine in the crystal packing is shown in Fig. 3. Hirshfeld surface fingerprint plots quantifying the atom–atom contact coverages are given in Fig. 4, showing that the vast majority of intermolecular contacts involve hydrogen.

Figure 2
Two views of the Hirshfeld surface of R13 showing: (a) the surface rendered as d_norm, highlighting close contacts of the form C19ⁱ—H19ⁱ⋯N1 [symmetry code: (i) $[{1\over 2}]$ − x, $[{1\over 2}]$ + y, $[{1\over 2}]$ − z] as small red spots; (b) the surface rendered by ‘shape index’, which provides evidence of π–π stacking as opposing blue and red roughly triangular regions at each of the oxazole and benzene rings.

Figure 3
A partial packing plot of R13 showing dimers resulting from the π–π stacking (indicated by dotted lines), and close C—H⋯N contacts between dimers (dashed lines).

Figure 4
Two-dimensional fingerprint plots quantifying the various atom–atom contact coverages present in the crystal packing: (a) H⋯H = 46.5%; (b) H⋯F/F⋯H = 18.1%; (c) H⋯C/C⋯H = 16.6%; (d) C⋯C = 5.6%; (e) H⋯O/O⋯H = 5.4%; (f) H⋯N/N⋯H = 3.3%.

4. Database survey

A search of the CSD (v5.45 with updates as of March 2024; Groom et al., 2016 ) using a fragment consisting of the three rings of R13, but with the fluorine, ethoxy, and t-butyl substituents removed and the double bonds of the oxazole ring specified as ‘any’ type of bond, returned 336 hits. The latter criterion ensures that entries with both oxazole and dihydro-oxazole five-membered rings would be caught. A pared-down fragment without ethoxy or t-butyl, but with the two fluorine atoms included gave just two matches, CSD refcodes DOGMEV and LIYZUS. Structure DOGMEV (Roque et al., 2023 ), or 4-(4-t-butyl-2-ethoxyphenyl)-2-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2,6-difluorophenyl]-4,5-dihydro-1,3-oxazole, has a dimethyldioxaborinanyl group attached at the 4-position of the difluorinated benzene ring and a dihydro-oxazole five-membered ring (i.e., just one double bond, as in etoxazole). Structure LIYZUS (Saha et al., 2023 ) is 5-ethoxy-2-(pentafluorophenyl)-4-phenyl-1,3-oxazole, which has an oxazole ring (i.e., two double bonds) as per R13, but with a pentafluorophenyl ring at the oxazole 2-position, an unsubstituted phenyl at the 4-position and an ethoxy group at the 5-position.

5. Synthesis and crystallization

5.0 g of etoxazole were placed in a 100 mL round-bottom flask and heated in a controlled manner at 2 K min⁻¹ to 377 K, i.e., just past its melting point (374–375 K). After cooling to RT, the resulting solid was dissolved in 10 ml of 100% hexane. The resulting solution containing about 40% etoxazole, 40% of the R13 metabolite, and 20% unknown products was purified by column chromatography using 100% hexane as the mobile phase and 60-120 mesh size silica gel as the stationary phase. It was then recrystallized from 100% hexane, giving crystals of R13 suitable for X-ray analysis.

NMR spectra were recorded on an SA-AGILENT 400 MHz NMR spectrometer: ¹H NMR: CDCl₃ (400 MHz, δ ppm): 1.310–1.313 [s, 9H, C(CH₃)₃]; 1.524–1.559 (t, 3H, J = 6.8 Hz, CH₃); 4.176–4.228 (q, 2H, J = 7.2 Hz, CH₂); 6.96–7.09 (m, 4H, aromatic); 7.375–7.417 (m, 1H, aromatic); 8.116–8.135 (d, 1H, aromatic); 8.326 (s, 1H, oxazole).

6. Refinement

Crystal data, data collection, and structure refinement details are given in Table 2. All hydrogens were present in difference-Fourier maps, but were subsequently included in the refinement using riding models, with constrained distances of 0.95 Å (R₂CH), 0.99 Å (R₂CH₂) and 0.98 Å (RCH₃). U_iso(H) parameters were set to either 1.2U_eq or 1.5U_eq (RCH₃ only) of the attached carbon.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₁H₂₁F₂NO₂
M_r	357.39
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	100
a, b, c (Å)	18.4793 (6), 10.4036 (3), 18.5669 (7)
β (°)	93.035 (1)
V (Å³)	3564.5 (2)
Z	8
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.20 × 0.19 × 0.11

Data collection
Diffractometer	Bruker D8 Venture dual source
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.904, 0.959
No. of measured, independent and observed [I > 2σ(I)] reflections	41370, 4095, 3558
R_int	0.061
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.085, 1.07
No. of reflections	4095
No. of parameters	239
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.22
Computer programs: APEX5 (Bruker, 2023 ), SHELXT (Sheldrick, 2015a ), SHELXL2019/2 (Sheldrick, 2015b), XP in SHELXTL (Sheldrick, 2008 ), SHELX (Sheldrick, 2008) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2397916

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989024010600/nx2015sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989024010600/nx2015Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989024010600/nx2015Isup3.cml

checkCIF report

Computing details top

4-(4-tert-Butyl-2-ethoxyphenyl)-2-(2,6-difluorophenyl)oxazole top

Crystal data top

C₂₁H₂₁F₂NO₂	F(000) = 1504
M_r = 357.39	D_x = 1.332 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 18.4793 (6) Å	Cell parameters from 9910 reflections
b = 10.4036 (3) Å	θ = 2.3–27.5°
c = 18.5669 (7) Å	µ = 0.10 mm⁻¹
β = 93.035 (1)°	T = 100 K
V = 3564.5 (2) Å³	Cut block, colourless
Z = 8	0.20 × 0.19 × 0.11 mm

Data collection top

Bruker D8 Venture dual source diffractometer	4095 independent reflections
Radiation source: microsource	3558 reflections with I > 2σ(I)
Detector resolution: 7.41 pixels mm^-1	R_int = 0.061
φ and ω scans	θ_max = 27.5°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −23→23
T_min = 0.904, T_max = 0.959	k = −13→13
41370 measured reflections	l = −24→24

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)] = 0.033	Hydrogen site location: difference Fourier map
wR(F²) = 0.085	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0317P)² + 1.7737P] where P = (F_o² + 2F_c²)/3
4095 reflections	(Δ/σ)_max < 0.001
239 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Special details top

Experimental. The crystal was mounted using polyisobutene oil on the tip of a fine glass fibre, which was fastened in a copper mounting pin with electrical solder. It was placed directly into the cold gas stream of a liquid-nitrogen based cryostat (Hope, 1994; Parkin & Hope, 1998).

Diffraction data were collected with the crystal at 100K.

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.

Refinement. Refinement progress was checked using Platon (Spek, 2020) and by an R-tensor (Parkin, 2000). The final model was further checked with the IUCr utility checkCIF.

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

	x	y	z	U_iso*/U_eq
F1	0.31274 (3)	0.82135 (6)	0.32509 (3)	0.02734 (16)
F2	0.05890 (3)	0.81737 (7)	0.34205 (4)	0.03608 (19)
O1	0.14316 (4)	0.71474 (7)	0.44635 (4)	0.02199 (17)
O2	0.19533 (4)	0.41164 (7)	0.58364 (4)	0.02220 (17)
N1	0.24848 (5)	0.64149 (8)	0.41010 (5)	0.02001 (18)
C1	0.19516 (5)	0.72003 (9)	0.39718 (5)	0.0190 (2)
C2	0.16811 (6)	0.62314 (10)	0.49472 (6)	0.0216 (2)
H2	0.144270	0.596124	0.536213	0.026*
C3	0.23218 (5)	0.57765 (9)	0.47364 (5)	0.0189 (2)
C4	0.28343 (5)	0.48460 (9)	0.50675 (5)	0.0190 (2)
C5	0.35428 (6)	0.47979 (10)	0.48489 (6)	0.0216 (2)
H5	0.368284	0.535977	0.447771	0.026*
C6	0.40484 (6)	0.39551 (10)	0.51568 (6)	0.0229 (2)
H6	0.452820	0.395248	0.499675	0.028*
C7	0.38619 (5)	0.31068 (9)	0.57009 (5)	0.0196 (2)
C8	0.31520 (5)	0.31386 (9)	0.59192 (5)	0.0197 (2)
H8	0.301032	0.255850	0.628094	0.024*
C9	0.26455 (5)	0.40030 (9)	0.56181 (5)	0.0190 (2)
C10	0.17146 (6)	0.3233 (1)	0.63687 (6)	0.0222 (2)
H10A	0.205099	0.324699	0.680171	0.027*
H10B	0.169803	0.234787	0.617268	0.027*
C11	0.09681 (6)	0.36551 (12)	0.65605 (6)	0.0294 (3)
H11A	0.063603	0.360211	0.613215	0.044*
H11B	0.098855	0.454391	0.673527	0.044*
H11C	0.079477	0.309378	0.693857	0.044*
C12	0.44366 (5)	0.22003 (10)	0.60412 (6)	0.0216 (2)
C13	0.41297 (6)	0.12946 (11)	0.65984 (6)	0.0283 (2)
H13A	0.373991	0.077640	0.636764	0.043*
H13B	0.393756	0.180052	0.699046	0.043*
H13C	0.451514	0.072699	0.679385	0.043*
C14	0.50460 (6)	0.30006 (12)	0.64139 (7)	0.0315 (3)
H14A	0.525169	0.357895	0.606173	0.047*
H14B	0.542537	0.242579	0.661459	0.047*
H14C	0.484974	0.350789	0.680327	0.047*
C15	0.47507 (6)	0.13723 (11)	0.54504 (6)	0.0282 (2)
H15A	0.435806	0.090190	0.519134	0.042*
H15B	0.509964	0.075983	0.567013	0.042*
H15C	0.499521	0.192584	0.511211	0.042*
C16	0.18637 (5)	0.81374 (9)	0.33852 (5)	0.0192 (2)
C17	0.24577 (5)	0.86239 (10)	0.30370 (5)	0.0203 (2)
C18	0.23993 (6)	0.95121 (10)	0.24873 (6)	0.0227 (2)
H18	0.281992	0.981741	0.226916	0.027*
C19	0.17194 (6)	0.99543 (10)	0.22567 (6)	0.0241 (2)
H19	0.167056	1.057008	0.187945	0.029*
C20	0.11108 (6)	0.94965 (11)	0.25776 (6)	0.0264 (2)
H20	0.064166	0.978656	0.241898	0.032*
C21	0.11937 (6)	0.86175 (10)	0.31282 (6)	0.0237 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0184 (3)	0.0327 (3)	0.0312 (3)	0.0040 (3)	0.0041 (2)	0.0080 (3)
F2	0.0179 (3)	0.0475 (4)	0.0429 (4)	−0.0016 (3)	0.0019 (3)	0.0198 (3)
O1	0.0204 (4)	0.0240 (4)	0.0219 (4)	0.0021 (3)	0.0036 (3)	0.0044 (3)
O2	0.0174 (3)	0.0247 (4)	0.0250 (4)	0.0020 (3)	0.0051 (3)	0.0068 (3)
N1	0.0217 (4)	0.0190 (4)	0.0194 (4)	0.0001 (3)	0.0017 (3)	0.0007 (3)
C1	0.0186 (5)	0.0191 (5)	0.0193 (5)	−0.0016 (4)	0.0020 (4)	−0.0013 (4)
C2	0.0225 (5)	0.0223 (5)	0.0199 (5)	0.0006 (4)	0.0020 (4)	0.0042 (4)
C3	0.0208 (5)	0.0178 (4)	0.0181 (5)	−0.0025 (4)	0.0009 (4)	−0.0005 (4)
C4	0.0202 (5)	0.0176 (4)	0.0191 (5)	0.0000 (4)	0.0008 (4)	−0.0013 (4)
C5	0.0235 (5)	0.0208 (5)	0.0209 (5)	−0.0008 (4)	0.0040 (4)	0.0020 (4)
C6	0.0184 (5)	0.0252 (5)	0.0254 (5)	0.0005 (4)	0.0036 (4)	0.0005 (4)
C7	0.0197 (5)	0.0195 (5)	0.0195 (5)	0.0009 (4)	0.0004 (4)	−0.0028 (4)
C8	0.0211 (5)	0.0190 (5)	0.0190 (5)	−0.0004 (4)	0.0018 (4)	0.0001 (4)
C9	0.0178 (5)	0.0201 (5)	0.0193 (5)	−0.0010 (4)	0.0019 (4)	−0.0019 (4)
C10	0.0217 (5)	0.0223 (5)	0.0227 (5)	−0.0011 (4)	0.0026 (4)	0.0056 (4)
C11	0.0224 (5)	0.0364 (6)	0.0297 (6)	0.0012 (5)	0.0049 (4)	0.0118 (5)
C12	0.0193 (5)	0.0239 (5)	0.0216 (5)	0.0028 (4)	0.0008 (4)	0.0000 (4)
C13	0.0254 (5)	0.0316 (6)	0.0282 (6)	0.0072 (5)	0.0031 (4)	0.0078 (5)
C14	0.0239 (6)	0.0360 (6)	0.0337 (6)	0.0001 (5)	−0.0053 (5)	−0.0009 (5)
C15	0.0284 (6)	0.0287 (6)	0.0277 (6)	0.0084 (5)	0.0048 (4)	0.0001 (4)
C16	0.0218 (5)	0.0180 (5)	0.0179 (5)	0.0001 (4)	0.0008 (4)	−0.0011 (4)
C17	0.0188 (5)	0.0212 (5)	0.0210 (5)	0.0023 (4)	0.0014 (4)	−0.0025 (4)
C18	0.0249 (5)	0.0224 (5)	0.0212 (5)	−0.0011 (4)	0.0055 (4)	−0.0005 (4)
C19	0.0305 (6)	0.0210 (5)	0.0209 (5)	0.0011 (4)	0.0010 (4)	0.0021 (4)
C20	0.0233 (5)	0.0281 (5)	0.0276 (6)	0.0037 (4)	−0.0017 (4)	0.0041 (4)
C21	0.0195 (5)	0.0255 (5)	0.0265 (5)	−0.0020 (4)	0.0032 (4)	0.0023 (4)

Geometric parameters (Å, º) top

F1—C17	1.3489 (12)	C11—H11A	0.9800
F2—C21	1.3495 (12)	C11—H11B	0.9800
O1—C1	1.3611 (12)	C11—H11C	0.9800
O1—C2	1.3725 (12)	C12—C13	1.5303 (15)
O2—C9	1.3671 (12)	C12—C15	1.5328 (15)
O2—C10	1.4361 (12)	C12—C14	1.5355 (15)
N1—C1	1.2927 (13)	C13—H13A	0.9800
N1—C3	1.4004 (13)	C13—H13B	0.9800
C1—C16	1.4644 (14)	C13—H13C	0.9800
C2—C3	1.3521 (14)	C14—H14A	0.9800
C2—H2	0.9500	C14—H14B	0.9800
C3—C4	1.4664 (14)	C14—H14C	0.9800
C4—C5	1.3919 (14)	C15—H15A	0.9800
C4—C9	1.4049 (14)	C15—H15B	0.9800
C5—C6	1.3827 (15)	C15—H15C	0.9800
C5—H5	0.9500	C16—C21	1.3955 (15)
C6—C7	1.3983 (14)	C16—C17	1.3978 (14)
C6—H6	0.9500	C17—C18	1.3768 (14)
C7—C8	1.3938 (14)	C18—C19	1.3843 (15)
C7—C12	1.5314 (14)	C18—H18	0.9500
C8—C9	1.3934 (14)	C19—C20	1.3848 (16)
C8—H8	0.9500	C19—H19	0.9500
C10—C11	1.5081 (15)	C20—C21	1.3741 (15)
C10—H10A	0.9900	C20—H20	0.9500
C10—H10B	0.9900

C1—O1—C2	104.02 (8)	C13—C12—C7	112.60 (8)
C9—O2—C10	118.37 (8)	C13—C12—C15	107.80 (9)
C1—N1—C3	105.08 (8)	C7—C12—C15	109.36 (8)
N1—C1—O1	114.10 (9)	C13—C12—C14	108.56 (9)
N1—C1—C16	127.75 (9)	C7—C12—C14	109.15 (9)
O1—C1—C16	118.12 (9)	C15—C12—C14	109.32 (9)
C3—C2—O1	108.82 (9)	C12—C13—H13A	109.5
C3—C2—H2	125.6	C12—C13—H13B	109.5
O1—C2—H2	125.6	H13A—C13—H13B	109.5
C2—C3—N1	107.97 (9)	C12—C13—H13C	109.5
C2—C3—C4	131.74 (9)	H13A—C13—H13C	109.5
N1—C3—C4	120.22 (9)	H13B—C13—H13C	109.5
C5—C4—C9	117.61 (9)	C12—C14—H14A	109.5
C5—C4—C3	119.87 (9)	C12—C14—H14B	109.5
C9—C4—C3	122.51 (9)	H14A—C14—H14B	109.5
C6—C5—C4	121.84 (10)	C12—C14—H14C	109.5
C6—C5—H5	119.1	H14A—C14—H14C	109.5
C4—C5—H5	119.1	H14B—C14—H14C	109.5
C5—C6—C7	120.8 (1)	C12—C15—H15A	109.5
C5—C6—H6	119.6	C12—C15—H15B	109.5
C7—C6—H6	119.6	H15A—C15—H15B	109.5
C8—C7—C6	117.83 (9)	C12—C15—H15C	109.5
C8—C7—C12	122.52 (9)	H15A—C15—H15C	109.5
C6—C7—C12	119.65 (9)	H15B—C15—H15C	109.5
C9—C8—C7	121.41 (9)	C21—C16—C17	114.61 (9)
C9—C8—H8	119.3	C21—C16—C1	123.64 (9)
C7—C8—H8	119.3	C17—C16—C1	121.75 (9)
O2—C9—C8	123.77 (9)	F1—C17—C18	117.73 (9)
O2—C9—C4	115.73 (9)	F1—C17—C16	118.68 (9)
C8—C9—C4	120.49 (9)	C18—C17—C16	123.59 (10)
O2—C10—C11	107.11 (8)	C17—C18—C19	119.12 (10)
O2—C10—H10A	110.3	C17—C18—H18	120.4
C11—C10—H10A	110.3	C19—C18—H18	120.4
O2—C10—H10B	110.3	C18—C19—C20	119.8 (1)
C11—C10—H10B	110.3	C18—C19—H19	120.1
H10A—C10—H10B	108.5	C20—C19—H19	120.1
C10—C11—H11A	109.5	C21—C20—C19	119.2 (1)
C10—C11—H11B	109.5	C21—C20—H20	120.4
H11A—C11—H11B	109.5	C19—C20—H20	120.4
C10—C11—H11C	109.5	F2—C21—C20	117.70 (9)
H11A—C11—H11C	109.5	F2—C21—C16	118.60 (9)
H11B—C11—H11C	109.5	C20—C21—C16	123.68 (10)

C3—N1—C1—O1	−0.50 (11)	C3—C4—C9—C8	−179.69 (9)
C3—N1—C1—C16	177.39 (9)	C9—O2—C10—C11	174.49 (9)
C2—O1—C1—N1	0.39 (11)	C8—C7—C12—C13	3.86 (14)
C2—O1—C1—C16	−177.71 (9)	C6—C7—C12—C13	−177.08 (9)
C1—O1—C2—C3	−0.11 (11)	C8—C7—C12—C15	123.67 (10)
O1—C2—C3—N1	−0.18 (11)	C6—C7—C12—C15	−57.26 (12)
O1—C2—C3—C4	176.69 (10)	C8—C7—C12—C14	−116.78 (11)
C1—N1—C3—C2	0.40 (11)	C6—C7—C12—C14	62.29 (12)
C1—N1—C3—C4	−176.89 (9)	N1—C1—C16—C21	156.63 (11)
C2—C3—C4—C5	−162.47 (11)	O1—C1—C16—C21	−25.56 (14)
N1—C3—C4—C5	14.08 (14)	N1—C1—C16—C17	−23.42 (16)
C2—C3—C4—C9	15.99 (17)	O1—C1—C16—C17	154.39 (9)
N1—C3—C4—C9	−167.46 (9)	C21—C16—C17—F1	179.95 (9)
C9—C4—C5—C6	0.07 (15)	C1—C16—C17—F1	−0.01 (14)
C3—C4—C5—C6	178.60 (9)	C21—C16—C17—C18	0.45 (15)
C4—C5—C6—C7	0.45 (16)	C1—C16—C17—C18	−179.51 (9)
C5—C6—C7—C8	0.16 (15)	F1—C17—C18—C19	−179.85 (9)
C5—C6—C7—C12	−178.95 (9)	C16—C17—C18—C19	−0.35 (16)
C6—C7—C8—C9	−1.30 (15)	C17—C18—C19—C20	−0.28 (16)
C12—C7—C8—C9	177.78 (9)	C18—C19—C20—C21	0.77 (16)
C10—O2—C9—C8	−4.80 (14)	C19—C20—C21—F2	−178.85 (10)
C10—O2—C9—C4	176.53 (9)	C19—C20—C21—C16	−0.67 (17)
C7—C8—C9—O2	−176.75 (9)	C17—C16—C21—F2	178.24 (9)
C7—C8—C9—C4	1.86 (15)	C1—C16—C21—F2	−1.81 (16)
C5—C4—C9—O2	177.51 (9)	C17—C16—C21—C20	0.07 (16)
C3—C4—C9—O2	−0.98 (14)	C1—C16—C21—C20	−179.98 (10)
C5—C4—C9—C8	−1.20 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2	0.95	2.29	2.7807 (12)	111

Close contacts (Å, °) for R13 top

Abbreviations: Ox = oxazole; Cg = centroid.

Weak hydrogen bonds
D—H···A	D—H	H···A	D···A	D—H···A
C2—H2···O2	0.95	2.29	2.7807 (12)	111.1
C19ⁱ—H19ⁱ···N	0.95	2.61	3.3494 (14)	134.7
π–π stacks
Ring 1···ring 2		Distance	Dihedral
Ox···Oxⁱⁱ(interplanar)		3.3426 (11)	0 (parallel)
Cg(Ox)···Cg(Ox)ⁱⁱ		3.3894 (11)	0 (parallel)
Cg(C4–C9)···Cg(C16–C21)ⁱⁱ		3.9439 (11)	11.56 (6)

Abbreviations: Ox = oxazole; Cg = centroid. Symmetry codes: (i) = 1/2 - x, 1/2 + y, 1/2 - z; (ii) = 1/2 - x, 3/2 - y, 1 - z.

Acknowledgements

The authors thank Honeychem Pharma Research Pvt. Ltd., Peenya Industrial Area, Bengaluru-560 058, India for a pure sample of etoxazole as a gift.

References

APVMA (2024). Australian Pesticide and Veterinary Medicines Authority, pp. 17–18. Google Scholar
Bruker (2023). APEX5. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Efimov, I., Slepukhin, P. & Bakulev, V. (2015). Acta Cryst. E71, o1028. Web of Science CSD CrossRef IUCr Journals 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
Joshi, S., Mehra, M., Singh, R. & Kakkar, S. (2023). Egypt. J. Basic Appl. Sci, 10, 218–239. Google Scholar
Kakkar, S. & Narasimhan, B. (2019). BMC Chem. 13, 16. Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Lei, D., Yang, H., Li, B. & Kang, Z. (2009). Acta Cryst. E65, o54. CrossRef IUCr Journals Google Scholar
Macar, O., Kalefetoğlu Macar, T., Çavuşoğlu, K. & Yalçın, E. (2022). Sci. Rep. 12, 20453. CrossRef PubMed 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
Park, H., Kim, J., Kwon, E. & Kim, T. H. (2017). Acta Cryst. E73, 1472–1474. Web of Science CSD CrossRef IUCr Journals Google Scholar
Park, W., Lim, W., Park, S., Whang, K.-Y. & Song, G. (2020). Environ. Pollut. 257, 113480. CrossRef PubMed Google Scholar
Priyanka, P., Jayanna, B. K., Sunil Kumar, Y. C., Shreenivas, M. T., Srinivasa, G. R., Divakara, T. R., Yathirajan, H. S. & Parkin, S. (2022). Acta Cryst. E78, 1084–1088. Web of Science CSD CrossRef IUCr Journals Google Scholar
Roque, J. B., Shimozono, A. M., Pabst, T. P., Hierlmeier, G., Peterson, P. O. & Chirik, P. J. (2023). Science, 382, 1165–1170. CrossRef CAS PubMed Google Scholar
Saha, A., Sen, C., Guin, S., Das, C., Maiti, D., Sen, S. & Maiti, D. (2023). Angew. Chem. Int. Ed. 62, e202308916. CrossRef Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals 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
Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006–1011. Web of Science CrossRef CAS IUCr Journals Google Scholar
Suzuki, J., Ishida, T., Kikuchi, Y., Ito, Y., Morikawa, C., Tsukidate, Y., Tanji, I., Ota, Y. & Toda, K. (2002). J. Pestic. Sci. 27, 1–8. CrossRef 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
Vinaya, Basavaraju, Y. B., Srinivasa, G. R., Shreenivas, M. T., Yathirajan, H. S. & Parkin, S. (2023). Acta Cryst. E79, 54–59. Web of Science CSD CrossRef IUCr Journals Google Scholar
Wei, L., Hua, R., Li, M., Huang, Y., Li, S., He, Y. & Shen, Z. (2014). J. Insect Sci. 14, 104. CrossRef PubMed Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

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research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Crystal structure and Hirshfeld-surface analysis of an etoxazole metabolite designated R13

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Database survey

5. Synthesis and crystallization

6. Refinement

Supporting information

Acknowledgements

References

research communications

3. Supramolecular features