Crystal structures and Hirshfeld surface analyses of two precursors of the etoxazole metabolite ‘R8’

Sowbhagya, C.; Mohan Kumar, T.M.; Bhavya, P.; Shankara Prasad, H.J.; Harish Chinthal, C.; Yathirajan, H.S.; Parkin, S.

doi:10.1107/S2056989026004329

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 82| Part 5| May 2026| Pages 530-533

https://doi.org/10.1107/S2056989026004329

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Crystal structures and Hirshfeld surface analyses of two precursors of the etoxazole metabolite ‘R8’

Chaluvarangaiah Sowbhagya,^a Thaluru M. Mohan Kumar,^a Papegowda Bhavya,^b Holehundi J. Shankara Prasad,^c C. Harish Chinthal,^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 Applied Sciences, New Horizon College of Engineering, Bengaluru-560 103, India, ^cChemistry Department, Morarji Desai Residential Science PU College, Parshwaganahalli-513 101, India, ^dChemistry Department, Vidyanidhi PU College, Tumkur-572 101, 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: [email protected]

Edited by X. Hao, Institute of Chemistry, Chinese Academy of Sciences (Received 15 April 2026; accepted 24 April 2026; online 29 April 2026)

Etoxazole is an agricultural pesticide that degrades into potentially hazardous metabolites, necessitating a thorough understanding of their chemical properties for accurate environmental and health risk assessments. This study reports the synthesis and structural characterization of two precursors of an etoxazole metabolite designated ‘R8’: 1-(4-tert-butyl-2-ethoxyphenyl)-2-hydroxyethan-1-one, C₁₄H₂₀O₃ (I), and 1-(4-tert-butyl-2-ethoxyphenyl)ethan-1-one, C₁₄H₂₀O₂ (II). Compound I crystallizes with the symmetry of space group Pnma, while II crystallizes as P2₁/m. In both structures, the molecules lie on crystallographic mirror planes (Z′ = 1/2) and exhibit a high degree of conformational similarity, differing primarily in the torsion angle of the tert-butyl group. The crystal packing in both structures is consolidated by weak C—H⋯π contacts that assemble the molecules into columns parallel to the crystallographic b axes. Hirshfeld-surface analyses show that the intermolecular interactions in both compounds are overwhelmingly dominated by contacts involving hydrogen atoms.

Keywords: crystal structure; Hirshfeld surface; etoxazole metabolite R8; acaricide; insecticide.

CCDC references: 2549023; 2549022

1. Chemical context

Etoxazole is a diphenyl oxazoline acaricide/insecticide, widely used to control mites and ticks on crops, fruits, vegetables, and ornamental plants (Wei et al., 2014 ). It works by inhibiting chitin biosynthesis and causing adult pests to lay sterile eggs (Nauen et al., 2006 ). In both environmental and biological systems, etoxazole degrades through hydrolysis, oxidation, photodegradation, and microbial transformation. In rat and human liver microsomes specifically, it undergoes enantioselective metabolism, with each enantiomer degrading at a different rate (Yao et al., 2016 ). These degradation processes form several metabolites that are not yet fully understood. Some may pose environmental and health risks, potentially exhibiting similar or higher toxicity than etoxazole itself (Sun et al., 2019 ). Detailed study of these metabolites is therefore imperative for accurate risk assessment.

One significant metabolite has been designated ‘R8’ (FAO/WHO, 2011 ), systematic name 2-amino-2-(4-tert-butyl-2-ethoxyphenyl)ethan-1-ol, C₁₄H₂₃NO₂. Understanding the environmental behaviour, toxicity, and persistence of R8 and related compounds is critical for the remediation and risk assessment of etoxazole-related chemicals. The title compounds of this study, namely 1-(4-tert-butyl-2-ethoxyphenyl)-2-hydroxyethan-1-one (I) and 1-(4-tert-butyl-2-ethoxyphenyl)ethan-1-one (II), C₁₄H₂₀O₃ and C₁₄H₂₀O₂ are precursors isolated during the synthesis of the R8 metabolite.

2. Structural commentary

The molecular structures of both I and II consist of 4-tert-butyl-2-ethoxyphenyl moieties substituted at the 1-position by 2-hydroxyethan-1-one in I and ethan-1-one in II. In both structures, the majority of atoms lie on crystallographic mirror planes. The molecular structures are shown in Figs. 1 and 2. The space group of I is Pnma, while that of II is P2₁/m, with both having Z′ = 0.5. There are no unusual bond lengths or angles in either structure. Given the similarity of the two molecules and the fact that they each lie on crystallographic mirror planes, there is a remarkable degree of superpositional overlap, as evident from the least-squares overlay in Fig. 3. For the fitted atoms (O2, O3, C2–C12), the r.m.s. deviation is only 0.0528 Å. The most obvious conformational difference lies in the torsion of the tert-butyl group. In I, the C6—C7—C12—C13 torsion is 180°, while in II it is 0°, with both angles being constrained by their respective mirror planes. Structure I includes an intramolecular hydrogen bond [O1—H1O⋯O3, d_D⋯A = 2.5518 (16) Å], which forms an S(5) ring motif (Etter et al., 1990 ).

Figure 1
An ellipsoid plot of I (50% probability). Hydrogen atoms are drawn as small arbitrary spheres. An intramolecular hydrogen bond is shown as a dashed line.

Figure 2
An ellipsoid plot of II (50% probability). Hydrogen atoms are drawn as small arbitrary spheres.

Figure 3
A least-squares-fit superposition of I (blue) and II (orange). The r.m.s. deviation of fitted atoms (i.e., all atoms except the tert-butyl methyls is 0.0528 Å (grey spheres, left) and hydroxyl oxygen (red sphere, right).

3. Supramolecular features

There are no conventional intermolecular hydrogen bonds in either I or II. The geometric criteria in SHELXL (Sheldrick, 2015b ) flag C11—H11A⋯O1ⁱ [symmetry code: (i) x, y, z − 1] in I and C8—H8⋯O3ⁱⁱ [symmetry code: (ii) x − 1, y, z] in II as ‘potential hydrogen bonds', but the geometries involved (see Tables 1 and 2) suggest that these would be very weak.

Table 1
Hydrogen bonds and close contacts (Å, °) in I

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O3	0.88 (2)	1.94 (2)	2.5518 (16)	125.1 (18)
C11—H11A⋯O1ⁱ	0.98	2.60	3.3885 (19)	137.2

C—H⋯centroid
C2—H2⋯Cg_C4–C9ⁱⁱ			2.647 (12)
Symmetry codes: (i) x, y, z − 1; (ii) 1 − x, 1 − y, 1 − z.

Table 2
Close contacts (Å, °) in II

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8⋯O3ⁱ	0.95	2.51	3.4535 (15)	175.5

C—H⋯centroid
C11—H11B⋯Cg_C4–C9ⁱⁱ			2.736 (17)
Symmetry codes: (i) x − 1, y, z; (ii) 1 − x, 1 − y, 1 − z.

In spite of the presence of benzene rings constrained to lie within planes parallel to ac in both I and II, neither structure has any π–π stacking. They do, however, each exhibit C—H⋯π contacts, as shown in Figs. 4 and 5, which lead to columns parallel to their respective b axes.

Figure 4
A perspective partial packing plot of I viewed slightly off the c-axis. C—H⋯π contacts are drawn as thin dashed lines, which connect the molecules into columns that extend parallel to the b-axis.

Figure 5
A perspective partial packing plot of II viewed slightly off the a axis. C—H⋯π contacts are drawn as thin dashed lines, which connect the molecules into columns that extend parallel to the b axis.

Hirshfeld surface analyses using CrystalExplorer (Spackman et al., 2021 ) show that virtually all atom–atom contacts in both I and II involve hydrogen: 96.2% in I, 99.99% in II, with 66.1% and 71.3% being H⋯H contacts in I and II, respectively. These, along with H⋯O/O⋯H and H⋯C/C⋯H are shown pairwise by type for the two structures in Fig. 6.

Figure 6
Hirshfeld-surface fingerprint plots of the most abundant types of atom-atom contacts in I and II. (a), (b) H⋯H contacts, (c), (d) H⋯O/O⋯H, (e), (f) H⋯C/C⋯H.

4. Database survey

A search of the Cambridge Structural Database (CSD v6.0, April 2025: Groom et al., 2016 ) on the common elements of structures I and II returned six hits, but only two bear any particular similarity to I and II. CSD refcode XILJIP (Bai et al., 2023 ) is a flavone: 7-tert-butyl-2-phenyl-4H-1-benzopyran-4-one (C₁₉H₁₈O₂), and ZIYLAU (Kataeva et al., 1995 ) is (6H)-12-oxo-3-tert-butyl-dibenzo[d,g](1,3)dioxocine, C₁₈H₁₈O₃, an eight-membered cyclic acetal. More recently, the crystal structures of etoxazole (C₂₁H₂₃F₂NO₂, CSD deposition 2422554; Sowbhagya et al., 2025a ) and several metabolites and related compounds have been reported: ‘R4’ (C₂₁H₂₅F₂NO₃, CSD deposition 2487064; Sowbhagya et al., 2025b ); ‘R13’ (C₂₁H₂₁F₂NO₂, CSD deposition 2397916; Mohan Kumar et al., 2024 ); and the bromide and fumarate salts of ‘R7’ (C₂₁H₂₆BrF₂NO₃ and C₂₅H₂₉F₂NO₇, CSD depositions 2533697 and 2533698; Mohan Kumar et al., 2026 ).

5. Synthesis and crystallization

The samples of compounds I and II were received as a gift from Honeychem Pharma Research Pvt. Ltd. They were purified by column chromatography and recrystallized from hexane by slow evaporation to obtain colourless crystals.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3. Carbon-bound hydrogen atoms were found in difference-Fourier maps, but most were subsequently included in the refinement using riding models, with constrained distances set to 0.95 Å (Csp²—H), 0.98 Å (R—CH₃) and 0.99 Å (R₂—CH₂). The methylene hydrogen atom H2 in I and the methyl hydrogen atoms H11A/B/C were refined in order to obtain standard uncertainties for the C—H⋯π distances (Tables 1 and 2). The hydroxyl hydrogen coordinates in I were refined. U_iso(H) parameters were set to values of either 1.2U_eq or 1.5U_eq (R—CH₃, O–H) of the attached atom. Restraints (SHELXL command SADI) were used to ensure satisfactory refinement of methyl hydrogen atoms across the mirror plane of P2₁/m in II. The numbering schemes start at ‘C2’ (I and II) and ‘O2’ (II) for carbon and oxygen to ensure correspondence with the published structures of etoxazole (Sowbhagya et al., 2025a) and its ‘R4’ (Sowbhagya et al., 2025b), ‘R7’ (Mohan Kumar et al., 2026), and ‘R13’ metabolites (Mohan Kumar et al., 2024).

Table 3
Experimental details

	I	II
Crystal data
Chemical formula	C₁₄H₂₀O₃	C₁₄H₂₀O₂
M_r	236.30	220.30
Crystal system, space group	Orthorhombic, Pnma	Monoclinic, P2₁/m
Temperature (K)	100	100
a, b, c (Å)	22.0186 (7), 6.8796 (3), 8.4858 (3)	8.0183 (3), 7.0193 (2), 11.5258 (4)
α, β, γ (°)	90, 90, 90	90, 94.469 (1), 90
V (Å³)	1285.42 (8)	646.73 (4)
Z	4	2
Radiation type	Mo Kα	Mo Kα
μ (mm⁻¹)	0.08	0.07
Crystal size (mm)	0.27 × 0.20 × 0.19	0.28 × 0.27 × 0.20

Data collection
Diffractometer	Bruker D8 Venture dual source	Bruker D8 Venture dual source
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )	Multi-scan (SADABS;Krause et al., 2015)
T_min, T_max	0.883, 0.971	0.884, 0.971
No. of measured, independent and observed [I > 2σ(I)] reflections	18796, 1592, 1391	12368, 1596, 1387
R_int	0.028	0.022
(sin θ/λ)_max (Å⁻¹)	0.650	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.072, 1.12	0.031, 0.077, 1.06
No. of reflections	1592	1596
No. of parameters	107	111
No. of restraints	0	18
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.18	0.24, −0.18
Computer programs: APEX5 (Bruker, 2023 ), SHELXT (Sheldrick, 2015a ), SHELXL2025/1 (Sheldrick, 2015b), PrimeXP (Parkin, 2026 ), Overlay (Parkin, 2025 ), SHELX (Sheldrick, 2008 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC references: 2549023; 2549022

Crystal structure: contains datablocks I, II, global. DOI: https://doi.org/10.1107/S2056989026004329/nx2035sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989026004329/nx2035Isup2.hkl

Structure factors: contains datablock II. DOI: https://doi.org/10.1107/S2056989026004329/nx2035IIsup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989026004329/nx2035Isup4.cml

Supporting information file. DOI: https://doi.org/10.1107/S2056989026004329/nx2035IIsup5.cml

checkCIF report

Computing details top

1-(4-tert-Butyl-2-ethoxyphenyl)-2-hydroxyethan-1-one (I) top

Crystal data top

C₁₄H₂₀O₃	D_x = 1.221 Mg m⁻³
M_r = 236.30	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pnma	Cell parameters from 9900 reflections
a = 22.0186 (7) Å	θ = 2.6–27.5°
b = 6.8796 (3) Å	µ = 0.08 mm⁻¹
c = 8.4858 (3) Å	T = 100 K
V = 1285.42 (8) Å³	Cut block, colourless
Z = 4	0.27 × 0.20 × 0.19 mm
F(000) = 512

Data collection top

Bruker D8 Venture dual source diffractometer	1592 independent reflections
Radiation source: microsource	1391 reflections with I > 2σ(I)
Detector resolution: 7.41 pixels mm^-1	R_int = 0.028
φ and ω scans	θ_max = 27.5°, θ_min = 2.6°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −28→26
T_min = 0.883, T_max = 0.971	k = −8→8
18796 measured reflections	l = −11→11

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.032	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.072	w = 1/[σ²(F_o²) + (0.0104P)² + 0.6298P] where P = (F_o² + 2F_c²)/3
S = 1.12	(Δ/σ)_max < 0.001
1592 reflections	Δρ_max = 0.29 e Å⁻³
107 parameters	Δρ_min = −0.18 e Å⁻³
0 restraints	Extinction correction: SHELXL-2025/1 (Sheldrick 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0042 (10)

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	Occ. (<1)
O1	0.40136 (5)	0.250000	0.80021 (13)	0.0255 (3)
H1O	0.4318 (9)	0.250000	0.867 (2)	0.038*
O2	0.46532 (4)	0.250000	0.34710 (11)	0.0189 (2)
O3	0.51720 (5)	0.250000	0.80930 (12)	0.0280 (3)
C5	0.60380 (7)	0.250000	0.57638 (17)	0.0193 (3)
H5	0.615895	0.250000	0.683843	0.023*
C6	0.64763 (7)	0.250000	0.46117 (17)	0.0190 (3)
H6	0.689280	0.250000	0.490378	0.023*
C7	0.63182 (6)	0.250000	0.30110 (17)	0.0168 (3)
C8	0.57029 (6)	0.250000	0.26240 (17)	0.0164 (3)
H8	0.558521	0.250000	0.154695	0.020*
C9	0.52563 (6)	0.250000	0.37944 (17)	0.0156 (3)
C10	0.44505 (6)	0.250000	0.18579 (16)	0.0183 (3)
H10A	0.459919	0.133001	0.129884	0.022*	0.5
H10B	0.459919	0.366999	0.129884	0.022*	0.5
C11	0.37648 (7)	0.250000	0.19426 (18)	0.0226 (3)
H11A	0.359668	0.250000	0.087337	0.034*
H11B	0.362664	0.133690	0.250476	0.034*	0.5
H11C	0.362664	0.366310	0.250476	0.034*	0.5
C12	0.68190 (6)	0.250000	0.17624 (17)	0.0182 (3)
C13	0.65627 (7)	0.250000	0.00871 (17)	0.0237 (3)
H13A	0.689793	0.250000	−0.067248	0.036*
H13B	0.631291	0.133690	−0.006987	0.036*	0.5
H13C	0.631291	0.366310	−0.006987	0.036*	0.5
C14	0.72128 (5)	0.43293 (17)	0.19745 (13)	0.0241 (2)
H14A	0.753264	0.434623	0.117157	0.036*
H14B	0.739798	0.431616	0.302466	0.036*
H14C	0.695857	0.549033	0.186255	0.036*
C2	0.43015 (7)	0.250000	0.65125 (17)	0.0187 (3)
H2	0.4181 (5)	0.3657 (17)	0.5896 (13)	0.022*
C3	0.49835 (7)	0.250000	0.67329 (17)	0.0186 (3)
C4	0.54169 (6)	0.250000	0.53968 (16)	0.0166 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0260 (6)	0.0333 (6)	0.0172 (5)	0.000	0.0060 (5)	0.000
O2	0.0146 (5)	0.0291 (6)	0.0131 (5)	0.000	−0.0009 (4)	0.000
O3	0.0278 (6)	0.0418 (7)	0.0146 (5)	0.000	0.0000 (4)	0.000
C5	0.0235 (7)	0.0191 (7)	0.0155 (7)	0.000	−0.0036 (6)	0.000
C6	0.0171 (7)	0.0191 (7)	0.0209 (7)	0.000	−0.0038 (6)	0.000
C7	0.0182 (7)	0.0136 (7)	0.0186 (7)	0.000	0.0005 (6)	0.000
C8	0.0185 (7)	0.0162 (7)	0.0145 (6)	0.000	−0.0008 (5)	0.000
C9	0.0156 (7)	0.0137 (6)	0.0177 (7)	0.000	−0.0016 (5)	0.000
C10	0.0185 (7)	0.0245 (8)	0.0118 (6)	0.000	−0.0016 (5)	0.000
C11	0.0181 (7)	0.0301 (8)	0.0195 (7)	0.000	−0.0017 (6)	0.000
C12	0.0158 (7)	0.0198 (7)	0.0191 (7)	0.000	0.0006 (5)	0.000
C13	0.0191 (7)	0.0333 (9)	0.0188 (7)	0.000	0.0027 (6)	0.000
C14	0.0207 (5)	0.0246 (6)	0.0270 (5)	−0.0029 (4)	0.0020 (4)	0.0007 (5)
C2	0.0223 (7)	0.0190 (7)	0.0147 (7)	0.000	0.0039 (6)	0.000
C3	0.0248 (7)	0.0143 (7)	0.0165 (7)	0.000	−0.0004 (6)	0.000
C4	0.0197 (7)	0.0144 (7)	0.0159 (7)	0.000	−0.0001 (6)	0.000

Geometric parameters (Å, º) top

O1—C2	1.4141 (17)	C10—H10B	0.9900
O1—H1O	0.88 (2)	C11—H11A	0.9800
O2—C9	1.3562 (16)	C11—H11B	0.9800
O2—C10	1.4397 (16)	C11—H11C	0.9800
O3—C3	1.2265 (18)	C12—C13	1.530 (2)
C5—C6	1.374 (2)	C12—C14	1.5389 (13)
C5—C4	1.403 (2)	C12—C14ⁱ	1.5389 (13)
C5—H5	0.9500	C13—H13A	0.9800
C6—C7	1.402 (2)	C13—H13B	0.9800
C6—H6	0.9500	C13—H13C	0.9800
C7—C8	1.394 (2)	C14—H14A	0.9800
C7—C12	1.529 (2)	C14—H14B	0.9800
C8—C9	1.398 (2)	C14—H14C	0.9800
C8—H8	0.9500	C2—C3	1.513 (2)
C9—C4	1.4049 (19)	C2—H2	0.989 (12)
C10—C11	1.511 (2)	C3—C4	1.482 (2)
C10—H10A	0.9900

C2—O1—H1O	103.6 (13)	H11B—C11—H11C	109.5
C9—O2—C10	119.73 (11)	C7—C12—C13	112.21 (12)
C6—C5—C4	121.80 (13)	C7—C12—C14	108.98 (8)
C6—C5—H5	119.1	C13—C12—C14	108.46 (8)
C4—C5—H5	119.1	C7—C12—C14ⁱ	108.98 (8)
C5—C6—C7	121.00 (13)	C13—C12—C14ⁱ	108.46 (8)
C5—C6—H6	119.5	C14—C12—C14ⁱ	109.72 (12)
C7—C6—H6	119.5	C12—C13—H13A	109.5
C8—C7—C6	118.00 (13)	C12—C13—H13B	109.5
C8—C7—C12	122.52 (13)	H13A—C13—H13B	109.5
C6—C7—C12	119.48 (13)	C12—C13—H13C	109.5
C7—C8—C9	121.09 (13)	H13A—C13—H13C	109.5
C7—C8—H8	119.5	H13B—C13—H13C	109.5
C9—C8—H8	119.5	C12—C14—H14A	109.5
O2—C9—C8	123.04 (13)	C12—C14—H14B	109.5
O2—C9—C4	116.25 (12)	H14A—C14—H14B	109.5
C8—C9—C4	120.72 (13)	C12—C14—H14C	109.5
O2—C10—C11	105.33 (11)	H14A—C14—H14C	109.5
O2—C10—H10A	110.7	H14B—C14—H14C	109.5
C11—C10—H10A	110.7	O1—C2—C3	109.53 (12)
O2—C10—H10B	110.7	O1—C2—H2	110.7 (7)
C11—C10—H10B	110.7	C3—C2—H2	109.3 (7)
H10A—C10—H10B	108.8	O3—C3—C4	120.14 (14)
C10—C11—H11A	109.5	O3—C3—C2	116.88 (13)
C10—C11—H11B	109.5	C4—C3—C2	122.98 (13)
H11A—C11—H11B	109.5	C5—C4—C9	117.40 (13)
C10—C11—H11C	109.5	C5—C4—C3	117.26 (13)
H11A—C11—H11C	109.5	C9—C4—C3	125.34 (13)

C4—C5—C6—C7	0.000 (1)	C8—C7—C12—C14ⁱ	−120.14 (8)
C5—C6—C7—C8	0.000 (1)	C6—C7—C12—C14ⁱ	59.86 (8)
C5—C6—C7—C12	180.000 (1)	O1—C2—C3—O3	0.000 (1)
C6—C7—C8—C9	0.000 (1)	O1—C2—C3—C4	180.000 (1)
C12—C7—C8—C9	180.000 (1)	C6—C5—C4—C9	0.000 (1)
C10—O2—C9—C8	0.000 (1)	C6—C5—C4—C3	180.000 (1)
C10—O2—C9—C4	180.000 (1)	O2—C9—C4—C5	180.000 (1)
C7—C8—C9—O2	180.000 (1)	C8—C9—C4—C5	0.000 (1)
C7—C8—C9—C4	0.000 (1)	O2—C9—C4—C3	0.000 (1)
C9—O2—C10—C11	180.0	C8—C9—C4—C3	180.000 (1)
C8—C7—C12—C13	0.000 (1)	O3—C3—C4—C5	0.000 (1)
C6—C7—C12—C13	180.0	C2—C3—C4—C5	180.000 (1)
C8—C7—C12—C14	120.14 (8)	O3—C3—C4—C9	180.000 (1)
C6—C7—C12—C14	−59.86 (8)	C2—C3—C4—C9	0.000 (1)

Symmetry code: (i) x, −y+1/2, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O3	0.88 (2)	1.94 (2)	2.5518 (16)	125 (2)
C11—H11A···O1ⁱⁱ	0.98	2.60	3.3885 (19)	137

Symmetry code: (ii) x, y, z−1.

1-(4-tert-Butyl-2-ethoxyphenyl)ethan-1-one (II) top

Crystal data top

C₁₄H₂₀O₂	F(000) = 240
M_r = 220.30	D_x = 1.131 Mg m⁻³
Monoclinic, P2₁/m	Mo Kα radiation, λ = 0.71073 Å
a = 8.0183 (3) Å	Cell parameters from 8769 reflections
b = 7.0193 (2) Å	θ = 2.6–27.4°
c = 11.5258 (4) Å	µ = 0.07 mm⁻¹
β = 94.469 (1)°	T = 100 K
V = 646.73 (4) Å³	Wedge-shaped block, colourless
Z = 2	0.28 × 0.27 × 0.20 mm

Data collection top

Bruker D8 Venture dual source diffractometer	1596 independent reflections
Radiation source: microsource	1387 reflections with I > 2σ(I)
Detector resolution: 7.41 pixels mm^-1	R_int = 0.022
φ and ω scans	θ_max = 27.5°, θ_min = 2.6°
Absorption correction: multi-scan (SADABS;Krause et al., 2015)	h = −10→10
T_min = 0.884, T_max = 0.971	k = −8→9
12368 measured reflections	l = −14→14

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)] = 0.031	Hydrogen site location: mixed
wR(F²) = 0.077	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ²(F_o²) + (0.0258P)² + 0.178P] where P = (F_o² + 2F_c²)/3
1596 reflections	(Δ/σ)_max < 0.001
111 parameters	Δρ_max = 0.24 e Å⁻³
18 restraints	Δρ_min = −0.18 e Å⁻³

Special details top

Diffraction data were collected with the crystal at 100K.

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	Occ. (<1)
O2	0.54443 (10)	0.750000	0.51826 (7)	0.0200 (2)
O3	1.01603 (12)	0.750000	0.39884 (9)	0.0445 (3)
C2	0.88242 (16)	0.750000	0.57222 (12)	0.0304 (3)
H2A	0.8247 (18)	0.863 (2)	0.5989 (11)	0.046*	0.5
H2B	0.9971 (14)	0.750000	0.6077 (10)	0.046*
H2C	0.8247 (18)	0.637 (2)	0.5989 (11)	0.046*	0.5
C3	0.88279 (15)	0.750000	0.44258 (11)	0.0233 (3)
C4	0.72412 (15)	0.750000	0.36485 (10)	0.0193 (3)
C5	0.74016 (15)	0.750000	0.24516 (11)	0.0220 (3)
H5	0.849183	0.750000	0.218261	0.026*
C6	0.60365 (16)	0.750000	0.16426 (10)	0.0216 (3)
H6	0.620143	0.750000	0.083527	0.026*
C7	0.44184 (15)	0.750000	0.20052 (10)	0.0181 (2)
C8	0.42282 (14)	0.750000	0.3200 (1)	0.0177 (2)
H8	0.313385	0.750000	0.346210	0.021*
C9	0.56034 (14)	0.750000	0.40159 (10)	0.0168 (2)
C10	0.37896 (14)	0.750000	0.5582 (1)	0.0184 (2)
H10A	0.316638	0.635502	0.529387	0.022*	0.5
H10B	0.316638	0.864498	0.529387	0.022*	0.5
C11	0.39854 (16)	0.750000	0.68936 (11)	0.0222 (3)
H11A	0.2880 (14)	0.750000	0.7205 (9)	0.033*
H11B	0.4598 (17)	0.637 (2)	0.7182 (10)	0.033*	0.5
H11C	0.4598 (17)	0.863 (2)	0.7182 (10)	0.033*	0.5
C12	0.28480 (16)	0.750000	0.11559 (10)	0.0218 (3)
C13	0.32689 (18)	0.750000	−0.01188 (11)	0.0299 (3)
H13A	0.223093	0.750000	−0.062750	0.045*
H13B	0.392239	0.863995	−0.027190	0.045*	0.5
H13C	0.392239	0.636005	−0.027190	0.045*	0.5
C14	0.18143 (12)	0.57111 (15)	0.13709 (8)	0.0296 (2)
H14A	0.081042	0.569519	0.082847	0.044*
H14B	0.148547	0.572309	0.217212	0.044*
H14C	0.248705	0.457326	0.124919	0.044*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O2	0.0179 (4)	0.0284 (5)	0.0137 (4)	0.000	0.0006 (3)	0.000
O3	0.0184 (5)	0.0828 (9)	0.0325 (6)	0.000	0.0020 (4)	0.000
C2	0.0202 (6)	0.0447 (9)	0.0254 (7)	0.000	−0.0046 (5)	0.000
C3	0.0187 (6)	0.0240 (6)	0.0272 (7)	0.000	0.0012 (5)	0.000
C4	0.0191 (6)	0.0182 (6)	0.0206 (6)	0.000	0.0011 (4)	0.000
C5	0.0204 (6)	0.0231 (6)	0.0231 (6)	0.000	0.0056 (5)	0.000
C6	0.0268 (6)	0.0218 (6)	0.0167 (6)	0.000	0.0048 (5)	0.000
C7	0.0231 (6)	0.0146 (5)	0.0166 (5)	0.000	0.0008 (4)	0.000
C8	0.0182 (5)	0.0177 (6)	0.0173 (5)	0.000	0.0018 (4)	0.000
C9	0.0201 (6)	0.0147 (5)	0.0156 (5)	0.000	0.0012 (4)	0.000
C10	0.0182 (6)	0.0203 (6)	0.0169 (5)	0.000	0.0021 (4)	0.000
C11	0.0269 (6)	0.0235 (6)	0.0164 (6)	0.000	0.0021 (5)	0.000
C12	0.0247 (6)	0.0245 (6)	0.0157 (6)	0.000	−0.0014 (4)	0.000
C13	0.0341 (7)	0.0393 (8)	0.0157 (6)	0.000	−0.0017 (5)	0.000
C14	0.0308 (5)	0.0349 (5)	0.0220 (4)	−0.0084 (4)	−0.0052 (3)	−0.0009 (4)

Geometric parameters (Å, º) top

O2—C9	1.3607 (14)	C8—H8	0.9500
O2—C10	1.4379 (14)	C10—C11	1.5076 (16)
O3—C3	1.2163 (15)	C10—H10A	0.9900
C2—C3	1.4945 (18)	C10—H10B	0.9900
C2—H2A	0.979 (11)	C11—H11A	0.982 (10)
C2—H2B	0.977 (11)	C11—H11B	0.978 (10)
C2—H2C	0.979 (11)	C11—H11C	0.978 (10)
C3—C4	1.4978 (16)	C12—C13	1.5329 (17)
C4—C5	1.3955 (17)	C12—C14ⁱ	1.5353 (12)
C4—C9	1.4109 (16)	C12—C14	1.5353 (12)
C5—C6	1.3815 (17)	C13—H13A	0.9800
C5—H5	0.9500	C13—H13B	0.9800
C6—C7	1.3937 (17)	C13—H13C	0.9800
C6—H6	0.9500	C14—H14A	0.9800
C7—C8	1.3973 (16)	C14—H14B	0.9800
C7—C12	1.5335 (16)	C14—H14C	0.9800
C8—C9	1.3923 (16)

C9—O2—C10	118.45 (9)	O2—C10—H10A	110.3
C3—C2—H2A	110.6 (8)	C11—C10—H10A	110.3
C3—C2—H2B	110.1 (8)	O2—C10—H10B	110.3
H2A—C2—H2B	108.7 (10)	C11—C10—H10B	110.3
C3—C2—H2C	110.6 (8)	H10A—C10—H10B	108.5
H2A—C2—H2C	108.0 (9)	C10—C11—H11A	109.9 (7)
H2B—C2—H2C	108.7 (10)	C10—C11—H11B	110.5 (8)
O3—C3—C2	118.99 (11)	H11A—C11—H11B	108.6 (9)
O3—C3—C4	118.99 (12)	C10—C11—H11C	110.5 (8)
C2—C3—C4	122.02 (11)	H11A—C11—H11C	108.6 (9)
C5—C4—C9	117.15 (11)	H11B—C11—H11C	108.6 (8)
C5—C4—C3	116.87 (11)	C13—C12—C7	112.38 (10)
C9—C4—C3	125.99 (11)	C13—C12—C14ⁱ	108.46 (7)
C6—C5—C4	122.55 (11)	C7—C12—C14ⁱ	108.89 (6)
C6—C5—H5	118.7	C13—C12—C14	108.46 (7)
C4—C5—H5	118.7	C7—C12—C14	108.89 (6)
C5—C6—C7	120.32 (11)	C14ⁱ—C12—C14	109.74 (11)
C5—C6—H6	119.8	C12—C13—H13A	109.5
C7—C6—H6	119.8	C12—C13—H13B	109.5
C6—C7—C8	118.11 (11)	H13A—C13—H13B	109.5
C6—C7—C12	123.08 (10)	C12—C13—H13C	109.5
C8—C7—C12	118.81 (10)	H13A—C13—H13C	109.5
C9—C8—C7	121.61 (11)	H13B—C13—H13C	109.5
C9—C8—H8	119.2	C12—C14—H14A	109.5
C7—C8—H8	119.2	C12—C14—H14B	109.5
O2—C9—C8	122.49 (10)	H14A—C14—H14B	109.5
O2—C9—C4	117.24 (10)	C12—C14—H14C	109.5
C8—C9—C4	120.27 (10)	H14A—C14—H14C	109.5
O2—C10—C11	107.12 (9)	H14B—C14—H14C	109.5

O3—C3—C4—C5	0.000 (1)	C7—C8—C9—O2	180.000 (1)
C2—C3—C4—C5	180.000 (1)	C7—C8—C9—C4	0.000 (1)
O3—C3—C4—C9	180.000 (1)	C5—C4—C9—O2	180.000 (1)
C2—C3—C4—C9	0.000 (1)	C3—C4—C9—O2	0.000 (1)
C9—C4—C5—C6	0.000 (1)	C5—C4—C9—C8	0.000 (1)
C3—C4—C5—C6	180.000 (1)	C3—C4—C9—C8	180.000 (1)
C4—C5—C6—C7	0.000 (1)	C9—O2—C10—C11	180.000 (1)
C5—C6—C7—C8	0.000 (1)	C6—C7—C12—C13	0.000 (1)
C5—C6—C7—C12	180.000 (1)	C8—C7—C12—C13	180.000 (1)
C6—C7—C8—C9	0.000 (1)	C6—C7—C12—C14ⁱ	−120.18 (7)
C12—C7—C8—C9	180.000 (1)	C8—C7—C12—C14ⁱ	59.82 (7)
C10—O2—C9—C8	0.000 (1)	C6—C7—C12—C14	120.18 (7)
C10—O2—C9—C4	180.000 (1)	C8—C7—C12—C14	−59.82 (7)

Symmetry code: (i) x, −y+3/2, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8···O3ⁱⁱ	0.95	2.51	3.4535 (15)	176

Symmetry code: (ii) x−1, y, z.

Hydrogen bonds and close contacts (Å, °) in I top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O3	0.88 (2)	1.94 (2)	2.5518 (16)	125.1 (18)
C11—H11A···O1ⁱ	0.98	2.60	3.3885 (19)	137.2
C—H···centroid
C2—H2···Cg_C4–C9ⁱⁱ			2.647 (12)

Symmetry codes: (i) x, y, z - 1; (ii) 1 - x, 1 - y, 1 - z.

Close contacts (Å, °) in II top

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8···O3ⁱ	0.95	2.51	3.4535 (15)	175.5
C—H···centroid
C11—H11B···Cg_C4–C9ⁱⁱ			2.736 (17)

Symmetry codes: (i) x - 1, y, z; (ii) 1 - x, 1 - y, 1 - z.

Acknowledgements

The D8 Venture diffractometer was funded by the NSF (MRI CHE1625732), and by the University of Kentucky. TMM and CS thank the Amritha School of Engineering for help and facilities.

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Volume 82| Part 5| May 2026| Pages 530-533

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

Crystal structures and Hirshfeld surface analyses of two precursors of the etoxazole metabolite ‘R8’

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