N-(3,5-Di­chloro-4-hy­droxy­phen­yl)acetamide

Uppu, R.M.; Fronczek, F.R.

doi:10.1107/S2414314626000751

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 11| Part 1| January 2026| x260075

https://doi.org/10.1107/S2414314626000751

Open

access

N-(3,5-Dichloro-4-hydroxyphenyl)acetamide

Rao M. Uppu ^a ^* and Frank R. Fronczek ^b

^aDepartment of Environmental Toxicology, Southern University and A&M College, Baton Rouge, Louisiana 70813, USA, and ^bDepartment of Chemistry, Louisiana State University, Baton Rouge, Louisiana, 70803, USA
^*Correspondence e-mail: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 22 January 2026; accepted 25 January 2026; online 29 January 2026)

The title compound, C₈H₇Cl₂NO₂, crystallizes in the triclinic space group P1 with three molecules in the asymmetric unit. Two of them are essentially planar, with mean deviations of 13 non-hydrogen atoms of 0.029 and 0.030 Å, and differ only in the conformation of the O—H hydrogen atom. The third molecule is quite nonplanar, with the CCNO acetamide plane forming a dihedral angle of 67.56 (5)° with the remainder of the molecule. In the extended structure, the two almost planar molecules form antiparallel hydrogen-bonded chains through N—H⋯O interactions of the acetamide substituents. The N—H group of the nonplanar molecule donates a bifurcated hydrogen bond to the O—H group and a Cl substituent of one of the planar molecules. The O—H groups of all molecules form intermolecular hydrogen bonds to other O—H groups or carbonyl O atoms. Together, the hydrogen bonds generate a three-dimensional network.

Keywords: crystal structure; acetaminophen; chlorinated acetaminophen.

CCDC reference: 2525665

Structure description

The title compound, C₈H₇Cl₂NO₂ (I), is one of the two well characterized chlorination products formed when acetaminophen [N-(4-hydroxyphenyl)acetamide, C₈H₉NO₂], also known as paracetamol, reacts with hypochlorous acid–hypochlorite (HOCl/⁻OCl; pK_a ≃ 7.5) under mildly oxidative, near-neutral pH conditions (Bedner & MacCrehan, 2006 ). Ring-chlorinated products of this type have been detected when wastewater and surface water samples spiked with environmentally relevant concentrations of acetaminophen were subjected to chlorine-based disinfection (Cao et al., 2016 ; Kolpin et al., 2002 ; Paíga et al., 2025 ). Although the trichlorinated derivative of acetaminophen does not form under these conditions, the mono- and dichloro-substituted products are typically accompanied by p-benzoquinone imine, p-benzoquinone, and several high-molecular-weight species with m/z values between 320 and 610 (Bedner & MacCrehan, 2006; Glassmeyer & Shoemaker, 2005 ; Li et al., 2022 ). These transformation products, particularly p-benzoquinone imine and p-benzoquinone, are generally perceived to possess greater toxicological potency, prompting the adoption of combined and advanced oxidation processes for their efficient removal and detoxification in treated wastewaters (Dahlin & Nelson, 1982 ; Postigo & Richardson, 2014 ; Qutob et al., 2022 ; Phong Vo et al., 2019 ).

Similar to those described for HOCl/⁻OCl-mediated oxidations (Bedner & MacCrehan, 2006), the myeloperoxidase–H₂O₂–Cl⁻-acetaminophen system may generate various chlorinated products, including the title compound (Van Zyl et al., 1989 ). While N-(3,5-dichloro-4-hydroxyphenyl)acetamide may serve as a biomarker of chlorination, the compound itself could also pose a significant toxicological concern. Based on linear free-energy relationships and Hammett substituent principles, pK_a of (I) is predicted to be approximately 2.0–2.3 units lower than that of acetaminophen (pK_a ≃ 9.5), since each chlorine substituent in the ortho position to the phenolic –OH typically lowers the pK_a by about 1.0–1.2 units through strong inductive (–I) effects and stabilization of the phenoxide anion (Hansch et al., 1991 ; Perrin et al., 1981 ). Accordingly, with an expected pK_a in the range of 7.2–7.5, the title compound falls squarely within the classical ‘uncoupler window' (pK_a 4–8; Heytler & Prichard, 1962 ). Thus, at physiological pH (7.4), roughly half of the molecules would be deprotonated and half protonated; the likely membrane-permeable properties of (I) would therefore favor its behavior as a protonophoric uncoupler, capable of dissipating the mitochondrial protonmotive force that drives ATP synthesis from ADP and inorganic phosphate.

In essence, the stabilization of the phenoxide anion by the two Cl substituents through inductive and intramolecular hydrogen-bonding effects, together with their likely enhanced lipophilicity and minimal steric hindrance, could render this compound an effective mitochondrial uncoupler. To provide an unambiguous structural basis for these chemical and biological considerations, single crystals of (I) were grown from aqueous solution and analyzed by single-crystal X-ray diffraction.

Compound (I) crystallizes in the triclinic space group P $[\overline{1}]$ with three independent molecules in the asymmetric unit (Fig. 1). Two of these molecules, containing atoms N2 and N3, are essentially planar, with mean deviations of their 13 non-hydrogen atoms of 0.029 and 0.030 Å, respectively, and are nearly parallel, forming a dihedral angle of 7.51 (4)°. They differ only in the conformation of the OH hydrogen atom (C14—C9—O3—H30H = 3.09°; C18—C17—O5—H50H = −6.9°). The third molecule containing atom N1 is distinctly nonplanar, with the C7/C8/N1/O2 acetamide plane forming a dihedral angle of 67.56 (5)° with the remainder of the molecule. In the three molecules, the C—Cl distances range from 1.7197 (17) to 1.7381 (18) Å (mean 1.7311 Å), and the C—OH distances range from 1.351 (2) to 1.359 (2) Å (mean 1.354 Å).

Figure 1
The molecular structure of (I), shown with displacement ellipsoids at the 50% probability level.

In the extended structure of (I), the molecules are linked by numerous hydrogen bonds (Table 1). Among these, the two planar molecules form antiparallel hydrogen-bonded chains through N—H⋯O interactions of the acetamide substituents. The third, nonplanar molecule links adjacent chains via additional bifurcated O—H⋯(O,Cl) interactions, generating a three-dimensional hydrogen-bonded network that consolidates the crystal packing (Fig. 2). Figs. 3 and 4 show, respectively, selected bifurcated hydrogen-bonding motifs and a view of the unit cell along the a-axis direction.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H10H⋯O2ⁱ	0.83 (2)	1.94 (2)	2.6776 (18)	148 (2)
N1—H1N⋯Cl3ⁱⁱ	0.84 (2)	2.78 (2)	3.3925 (17)	131 (2)
N1—H1N⋯O3ⁱⁱ	0.84 (2)	2.60 (2)	3.401 (2)	161 (2)
C8—H8C⋯O1ⁱⁱ	0.98	2.60	3.521 (2)	157
O3—H30H⋯O1	0.81 (2)	2.03 (2)	2.7602 (18)	149 (3)
O3—H30H⋯Cl4	0.81 (2)	2.59 (2)	3.0528 (14)	118 (2)
N2—H2N⋯O6ⁱⁱⁱ	0.84 (2)	2.09 (2)	2.920 (2)	172 (2)
C13—H13⋯O4	0.95	2.26	2.866 (2)	121
O5—H50H⋯O2ⁱ	0.81 (2)	2.22 (2)	2.9546 (18)	150 (3)
O5—H50H⋯Cl5	0.81 (2)	2.51 (2)	2.9949 (14)	119 (2)
N3—H3N⋯O4^iv	0.84 (2)	2.08 (2)	2.913 (2)	176 (2)
C21—H21⋯O6	0.95	2.24	2.853 (2)	121
C24—H24A⋯O4^iv	0.98	2.59	3.464 (2)	149
Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

Figure 2
Intermolecular hydrogen-bonding network in the crystal structure of (I).

Figure 3
Detail of the bifurcated O—H⋯(O,Cl) hydrogen-bonding motif observed in the crystal packing of (I).

Figure 4
View of the unit cell of (I) along the a-axis direction.

Synthesis and crystallization

The title compound was synthesized by acetylation of 4-amino-2,6-phenol (CAS 5930–28-9; purity: 97%) using acetic anhydride in acetic acid solvent: 1.78 g (10 mmol) of 4-amino-2,6-phenol in 10 ml of glacial acetic was allowed to react with 1.23 g (12 mmol) of acetic anhydride for 24–48 h at room temperature. The reaction mixture was stirred continuously during the reaction. In the end, the mixture was dried under vacuum, and the residue was purified by recrystallization once from aqueous solution. Single crystals of (I) in the form of colorless needles were grown in water by slow cooling of a hot and nearly saturated solution.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₈H₇Cl₂NO₂
M_r	220.05
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	100
a, b, c (Å)	9.6844 (14), 9.8884 (16), 14.976 (3)
α, β, γ (°)	85.181 (10), 76.43 (1), 74.769 (7)
V (Å³)	1344.8 (4)
Z	6
Radiation type	Cu Kα
μ (mm⁻¹)	6.24
Crystal size (mm)	0.20 × 0.15 × 0.01

Data collection
Diffractometer	Bruker D8 Venture DUO with Photon III C14
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.625, 0.940
No. of measured, independent and observed [I > 2σ(I)] reflections	31306, 5786, 5206
R_int	0.053
(sin θ/λ)_max (Å⁻¹)	0.640

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.089, 1.06
No. of reflections	5786
No. of parameters	373
No. of restraints	6
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.55, −0.39
Computer programs: APEX5 and SAINT (Bruker, 2016 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2019/1 (Sheldrick, 2015b ) and Mercury (Macrae et al., 2020 ).

Structural data

CCDC reference: 2525665

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314626000751/hb4553sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314626000751/hb4553Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314626000751/hb4553Isup3.cml

checkCIF report

Computing details top

N-(3,5-Dichloro-4-hydroxyphenyl)acetamide top

Crystal data top

C₈H₇Cl₂NO₂	Z = 6
M_r = 220.05	F(000) = 672
Triclinic, P1	D_x = 1.630 Mg m⁻³
a = 9.6844 (14) Å	Cu Kα radiation, λ = 1.54184 Å
b = 9.8884 (16) Å	Cell parameters from 9884 reflections
c = 14.976 (3) Å	θ = 3.0–79.7°
α = 85.181 (10)°	µ = 6.24 mm⁻¹
β = 76.43 (1)°	T = 100 K
γ = 74.769 (7)°	Plate, colourless
V = 1344.8 (4) Å³	0.20 × 0.15 × 0.01 mm

Data collection top

Bruker D8 Venture DUO with Photon III C14 diffractometer	5206 reflections with I > 2σ(I)
Radiation source: IµS 3.0 microfocus	R_int = 0.053
φ and ω scans	θ_max = 80.5°, θ_min = 3.0°
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	h = −12→12
T_min = 0.625, T_max = 0.940	k = −12→12
31306 measured reflections	l = −18→19
5786 independent reflections

Refinement top

Refinement on F²	6 restraints
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) = 0.089	w = 1/[σ²(F_o²) + (0.0476P)² + 0.6745P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max = 0.001
5786 reflections	Δρ_max = 0.55 e Å⁻³
373 parameters	Δρ_min = −0.39 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.

Refinement. All non-H atoms were refined anisotropically. H atoms were treated by a mixed independent and riding model.

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

	x	y	z	U_iso*/U_eq
Cl1	0.35134 (4)	0.53881 (4)	−0.05637 (3)	0.01871 (10)
Cl2	−0.13004 (4)	0.52183 (4)	0.20588 (3)	0.01605 (10)
O1	0.09880 (13)	0.65297 (12)	0.08713 (8)	0.0140 (2)
H10H	0.0124 (19)	0.696 (2)	0.1091 (16)	0.021*
O2	0.13322 (14)	0.12695 (13)	−0.12814 (8)	0.0169 (3)
N1	0.17559 (17)	0.08975 (15)	0.01623 (10)	0.0161 (3)
H1N	0.204 (3)	0.029 (2)	0.0552 (15)	0.019*
C1	0.11189 (18)	0.51671 (17)	0.07256 (11)	0.0124 (3)
C2	0.23029 (18)	0.44736 (18)	0.00553 (12)	0.0141 (3)
C3	0.25114 (19)	0.30765 (18)	−0.01319 (12)	0.0151 (3)
H3	0.332077	0.262650	−0.059234	0.018*
C4	0.15275 (19)	0.23420 (17)	0.03591 (12)	0.0143 (3)
C5	0.03595 (19)	0.29868 (18)	0.10440 (11)	0.0142 (3)
H5	−0.030199	0.247607	0.138824	0.017*
C6	0.01692 (19)	0.43888 (18)	0.12201 (11)	0.0134 (3)
C7	0.17477 (18)	0.04592 (18)	−0.06649 (12)	0.0143 (3)
C8	0.2294 (2)	−0.10968 (18)	−0.07887 (12)	0.0171 (3)
H8A	0.329501	−0.141133	−0.068846	0.026*
H8B	0.229353	−0.131997	−0.141389	0.026*
H8C	0.165136	−0.157433	−0.034474	0.026*
Cl3	0.40021 (5)	1.01733 (5)	0.16640 (3)	0.02288 (11)
Cl4	0.33207 (4)	0.48954 (4)	0.21640 (3)	0.01722 (10)
O3	0.28764 (15)	0.78676 (14)	0.13405 (9)	0.0186 (3)
H30H	0.254 (3)	0.722 (2)	0.1269 (18)	0.028*
O4	0.65977 (15)	0.44791 (13)	0.43476 (9)	0.0194 (3)
N2	0.63076 (16)	0.68011 (15)	0.39607 (10)	0.0150 (3)
H2N	0.652 (3)	0.754 (2)	0.4057 (16)	0.018*
C9	0.37032 (18)	0.75224 (18)	0.19782 (11)	0.0147 (3)
C10	0.43264 (19)	0.85323 (18)	0.22059 (12)	0.0151 (3)
C11	0.51803 (18)	0.82759 (18)	0.28510 (12)	0.0144 (3)
H11	0.558929	0.898799	0.298694	0.017*
C12	0.54439 (18)	0.69736 (18)	0.33037 (12)	0.0136 (3)
C13	0.48653 (18)	0.59321 (18)	0.30858 (12)	0.0142 (3)
H13	0.504517	0.503491	0.338150	0.017*
C14	0.40183 (18)	0.62223 (18)	0.24281 (12)	0.0144 (3)
C15	0.68395 (18)	0.56115 (18)	0.44264 (12)	0.0146 (3)
C16	0.7786 (2)	0.57841 (19)	0.50564 (13)	0.0194 (4)
H16A	0.781445	0.676874	0.504637	0.029*
H16B	0.878336	0.519833	0.484830	0.029*
H16C	0.737581	0.549727	0.568375	0.029*
Cl5	−0.00475 (5)	0.72743 (4)	0.31367 (3)	0.01681 (10)
Cl6	0.03404 (6)	1.25666 (4)	0.32909 (3)	0.02303 (11)
O5	−0.05222 (15)	1.03136 (13)	0.25812 (9)	0.0190 (3)
H50H	−0.069 (3)	0.965 (2)	0.2380 (18)	0.028*
O6	0.32528 (15)	1.05309 (13)	0.56203 (10)	0.0208 (3)
N3	0.28449 (16)	0.85184 (15)	0.52262 (10)	0.0152 (3)
H3N	0.298 (3)	0.766 (2)	0.5329 (16)	0.018*
C17	0.02825 (19)	0.98609 (18)	0.32290 (11)	0.0149 (3)
C18	0.06138 (19)	0.84906 (18)	0.35663 (12)	0.0141 (3)
C19	0.14531 (19)	0.80609 (18)	0.42180 (12)	0.0141 (3)
H19	0.166334	0.710941	0.442481	0.017*
C20	0.19856 (18)	0.90281 (18)	0.45676 (11)	0.0136 (3)
C21	0.16516 (19)	1.04206 (18)	0.42647 (12)	0.0150 (3)
H21	0.200021	1.109642	0.450257	0.018*
C22	0.0804 (2)	1.08122 (18)	0.36118 (12)	0.0160 (3)
C23	0.34095 (19)	0.92514 (19)	0.57035 (12)	0.0162 (3)
C24	0.4274 (2)	0.8378 (2)	0.63615 (14)	0.0233 (4)
H24A	0.427483	0.739182	0.632890	0.035*
H24B	0.382235	0.870236	0.698858	0.035*
H24C	0.528572	0.847223	0.619395	0.035*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0173 (2)	0.0159 (2)	0.0224 (2)	−0.00726 (15)	0.00099 (15)	−0.00318 (15)
Cl2	0.01757 (19)	0.01529 (19)	0.01441 (19)	−0.00439 (15)	−0.00074 (15)	−0.00249 (14)
O1	0.0149 (6)	0.0111 (6)	0.0170 (6)	−0.0038 (5)	−0.0042 (5)	−0.0025 (4)
O2	0.0232 (6)	0.0122 (6)	0.0165 (6)	−0.0030 (5)	−0.0086 (5)	−0.0007 (5)
N1	0.0260 (8)	0.0093 (7)	0.0143 (7)	−0.0043 (6)	−0.0075 (6)	0.0002 (5)
C1	0.0144 (8)	0.0112 (8)	0.0143 (8)	−0.0035 (6)	−0.0077 (6)	−0.0007 (6)
C2	0.0154 (8)	0.0135 (8)	0.0152 (8)	−0.0060 (6)	−0.0047 (6)	0.0008 (6)
C3	0.0167 (8)	0.0148 (8)	0.0138 (8)	−0.0034 (6)	−0.0040 (6)	−0.0012 (6)
C4	0.0209 (8)	0.0103 (8)	0.0145 (8)	−0.0041 (6)	−0.0088 (7)	−0.0011 (6)
C5	0.0184 (8)	0.0144 (8)	0.0131 (8)	−0.0076 (6)	−0.0065 (6)	0.0011 (6)
C6	0.0162 (8)	0.0150 (8)	0.0102 (7)	−0.0040 (6)	−0.0049 (6)	−0.0009 (6)
C7	0.0146 (8)	0.0140 (8)	0.0152 (8)	−0.0056 (6)	−0.0028 (6)	−0.0012 (6)
C8	0.0216 (9)	0.0125 (8)	0.0190 (8)	−0.0052 (7)	−0.0062 (7)	−0.0019 (6)
Cl3	0.0330 (2)	0.0166 (2)	0.0271 (2)	−0.01274 (18)	−0.01799 (19)	0.00836 (16)
Cl4	0.0192 (2)	0.0145 (2)	0.0218 (2)	−0.00792 (15)	−0.00755 (16)	−0.00149 (15)
O3	0.0243 (7)	0.0177 (6)	0.0196 (6)	−0.0108 (5)	−0.0112 (5)	0.0022 (5)
O4	0.0244 (7)	0.0116 (6)	0.0251 (7)	−0.0050 (5)	−0.0113 (5)	0.0020 (5)
N2	0.0179 (7)	0.0115 (7)	0.0182 (7)	−0.0054 (6)	−0.0073 (6)	−0.0010 (6)
C9	0.0143 (8)	0.0170 (8)	0.0134 (8)	−0.0048 (6)	−0.0031 (6)	−0.0021 (6)
C10	0.0168 (8)	0.0130 (8)	0.0164 (8)	−0.0048 (6)	−0.0045 (6)	0.0003 (6)
C11	0.0151 (8)	0.0133 (8)	0.0163 (8)	−0.0052 (6)	−0.0042 (6)	−0.0012 (6)
C12	0.0126 (7)	0.0129 (8)	0.0147 (8)	−0.0020 (6)	−0.0028 (6)	−0.0020 (6)
C13	0.0141 (8)	0.0115 (8)	0.0164 (8)	−0.0037 (6)	−0.0015 (6)	−0.0013 (6)
C14	0.0143 (8)	0.0129 (8)	0.0170 (8)	−0.0056 (6)	−0.0016 (6)	−0.0029 (6)
C15	0.0145 (8)	0.0139 (8)	0.0152 (8)	−0.0034 (6)	−0.0031 (6)	−0.0001 (6)
C16	0.0224 (9)	0.0170 (9)	0.0221 (9)	−0.0062 (7)	−0.0116 (7)	0.0039 (7)
Cl5	0.0224 (2)	0.01470 (19)	0.01636 (19)	−0.00743 (15)	−0.00643 (15)	−0.00220 (14)
Cl6	0.0402 (3)	0.01053 (19)	0.0213 (2)	−0.00473 (17)	−0.01516 (19)	0.00195 (15)
O5	0.0283 (7)	0.0134 (6)	0.0187 (6)	−0.0043 (5)	−0.0130 (5)	−0.0001 (5)
O6	0.0262 (7)	0.0128 (6)	0.0278 (7)	−0.0062 (5)	−0.0127 (6)	−0.0017 (5)
N3	0.0190 (7)	0.0089 (7)	0.0190 (7)	−0.0031 (6)	−0.0074 (6)	−0.0001 (5)
C17	0.0173 (8)	0.0153 (8)	0.0119 (7)	−0.0031 (7)	−0.0034 (6)	−0.0014 (6)
C18	0.0161 (8)	0.0142 (8)	0.0127 (7)	−0.0055 (6)	−0.0011 (6)	−0.0039 (6)
C19	0.0154 (8)	0.0114 (8)	0.0146 (8)	−0.0029 (6)	−0.0019 (6)	−0.0007 (6)
C20	0.0157 (8)	0.0134 (8)	0.0118 (7)	−0.0036 (6)	−0.0029 (6)	−0.0009 (6)
C21	0.0193 (8)	0.0122 (8)	0.0142 (8)	−0.0052 (6)	−0.0033 (6)	−0.0016 (6)
C22	0.0219 (8)	0.0109 (8)	0.0147 (8)	−0.0035 (7)	−0.0038 (7)	−0.0005 (6)
C23	0.0174 (8)	0.0147 (8)	0.0175 (8)	−0.0040 (7)	−0.0052 (7)	−0.0018 (6)
C24	0.0298 (10)	0.0171 (9)	0.0274 (10)	−0.0048 (8)	−0.0158 (8)	−0.0007 (7)

Geometric parameters (Å, º) top

Cl1—C2	1.7197 (17)	C10—C11	1.380 (2)
Cl2—C6	1.7311 (17)	C11—C12	1.395 (2)
O1—C1	1.351 (2)	C11—H11	0.9500
O1—H10H	0.833 (16)	C12—C13	1.388 (2)
O2—C7	1.240 (2)	C13—C14	1.391 (2)
N1—C7	1.349 (2)	C13—H13	0.9500
N1—C4	1.432 (2)	C15—C16	1.508 (2)
N1—H1N	0.838 (18)	C16—H16A	0.9800
C1—C6	1.394 (2)	C16—H16B	0.9800
C1—C2	1.398 (2)	C16—H16C	0.9800
C2—C3	1.386 (2)	Cl5—C18	1.7317 (17)
C3—C4	1.386 (2)	Cl6—C22	1.7303 (18)
C3—H3	0.9500	O5—C17	1.359 (2)
C4—C5	1.387 (2)	O5—H50H	0.812 (17)
C5—C6	1.389 (2)	O6—C23	1.233 (2)
C5—H5	0.9500	N3—C23	1.347 (2)
C7—C8	1.502 (2)	N3—C20	1.414 (2)
C8—H8A	0.9800	N3—H3N	0.835 (18)
C8—H8B	0.9800	C17—C18	1.388 (2)
C8—H8C	0.9800	C17—C22	1.395 (2)
Cl3—C10	1.7381 (18)	C18—C19	1.384 (2)
Cl4—C14	1.7357 (17)	C19—C20	1.387 (2)
O3—C9	1.353 (2)	C19—H19	0.9500
O3—H30H	0.814 (17)	C20—C21	1.391 (2)
O4—C15	1.223 (2)	C21—C22	1.387 (3)
N2—C15	1.359 (2)	C21—H21	0.9500
N2—C12	1.407 (2)	C23—C24	1.511 (3)
N2—H2N	0.836 (18)	C24—H24A	0.9800
C9—C14	1.395 (2)	C24—H24B	0.9800
C9—C10	1.396 (2)	C24—H24C	0.9800

C1—O1—H10H	112.4 (17)	C12—C13—C14	118.97 (16)
C7—N1—C4	123.14 (15)	C12—C13—H13	120.5
C7—N1—H1N	118.3 (17)	C14—C13—H13	120.5
C4—N1—H1N	117.9 (17)	C13—C14—C9	123.16 (16)
O1—C1—C6	124.18 (15)	C13—C14—Cl4	117.92 (13)
O1—C1—C2	118.36 (15)	C9—C14—Cl4	118.92 (14)
C6—C1—C2	117.44 (15)	O4—C15—N2	123.95 (16)
C3—C2—C1	121.68 (16)	O4—C15—C16	121.55 (16)
C3—C2—Cl1	119.26 (13)	N2—C15—C16	114.50 (15)
C1—C2—Cl1	119.05 (13)	C15—C16—H16A	109.5
C2—C3—C4	119.35 (16)	C15—C16—H16B	109.5
C2—C3—H3	120.3	H16A—C16—H16B	109.5
C4—C3—H3	120.3	C15—C16—H16C	109.5
C3—C4—C5	120.55 (15)	H16A—C16—H16C	109.5
C3—C4—N1	118.90 (16)	H16B—C16—H16C	109.5
C5—C4—N1	120.54 (16)	C17—O5—H50H	109.9 (19)
C4—C5—C6	119.17 (16)	C23—N3—C20	128.15 (15)
C4—C5—H5	120.4	C23—N3—H3N	118.5 (16)
C6—C5—H5	120.4	C20—N3—H3N	113.3 (16)
C5—C6—C1	121.77 (15)	O5—C17—C18	124.46 (16)
C5—C6—Cl2	119.79 (13)	O5—C17—C22	119.62 (15)
C1—C6—Cl2	118.43 (13)	C18—C17—C22	115.91 (16)
O2—C7—N1	123.09 (16)	C19—C18—C17	122.96 (16)
O2—C7—C8	122.14 (15)	C19—C18—Cl5	119.16 (13)
N1—C7—C8	114.77 (15)	C17—C18—Cl5	117.88 (13)
C7—C8—H8A	109.5	C18—C19—C20	119.59 (16)
C7—C8—H8B	109.5	C18—C19—H19	120.2
H8A—C8—H8B	109.5	C20—C19—H19	120.2
C7—C8—H8C	109.5	C19—C20—C21	119.39 (16)
H8A—C8—H8C	109.5	C19—C20—N3	116.74 (15)
H8B—C8—H8C	109.5	C21—C20—N3	123.87 (16)
C9—O3—H30H	110.7 (19)	C22—C21—C20	119.35 (16)
C15—N2—C12	128.27 (15)	C22—C21—H21	120.3
C15—N2—H2N	118.2 (16)	C20—C21—H21	120.3
C12—N2—H2N	113.5 (16)	C21—C22—C17	122.76 (16)
O3—C9—C14	125.72 (15)	C21—C22—Cl6	118.03 (13)
O3—C9—C10	118.25 (15)	C17—C22—Cl6	119.18 (14)
C14—C9—C10	116.03 (16)	O6—C23—N3	123.84 (17)
C11—C10—C9	122.28 (16)	O6—C23—C24	121.59 (16)
C11—C10—Cl3	118.96 (13)	N3—C23—C24	114.58 (16)
C9—C10—Cl3	118.76 (14)	C23—C24—H24A	109.5
C10—C11—C12	120.13 (16)	C23—C24—H24B	109.5
C10—C11—H11	119.9	H24A—C24—H24B	109.5
C12—C11—H11	119.9	C23—C24—H24C	109.5
C13—C12—C11	119.41 (16)	H24A—C24—H24C	109.5
C13—C12—N2	123.90 (16)	H24B—C24—H24C	109.5
C11—C12—N2	116.70 (15)

O1—C1—C2—C3	179.89 (15)	C11—C12—C13—C14	−0.9 (2)
C6—C1—C2—C3	1.7 (3)	N2—C12—C13—C14	179.62 (16)
O1—C1—C2—Cl1	−1.1 (2)	C12—C13—C14—C9	−0.7 (3)
C6—C1—C2—Cl1	−179.35 (13)	C12—C13—C14—Cl4	179.54 (13)
C1—C2—C3—C4	−0.3 (3)	O3—C9—C14—C13	−179.34 (16)
Cl1—C2—C3—C4	−179.28 (13)	C10—C9—C14—C13	1.7 (2)
C2—C3—C4—C5	−1.2 (3)	O3—C9—C14—Cl4	0.4 (2)
C2—C3—C4—N1	−179.79 (16)	C10—C9—C14—Cl4	−178.52 (13)
C7—N1—C4—C3	−61.8 (2)	C12—N2—C15—O4	−1.8 (3)
C7—N1—C4—C5	119.65 (19)	C12—N2—C15—C16	177.56 (16)
C3—C4—C5—C6	1.3 (3)	O5—C17—C18—C19	179.13 (16)
N1—C4—C5—C6	179.84 (15)	C22—C17—C18—C19	−2.3 (3)
C4—C5—C6—C1	0.1 (3)	O5—C17—C18—Cl5	−0.2 (2)
C4—C5—C6—Cl2	178.90 (13)	C22—C17—C18—Cl5	178.36 (13)
O1—C1—C6—C5	−179.70 (15)	C17—C18—C19—C20	0.7 (3)
C2—C1—C6—C5	−1.6 (2)	Cl5—C18—C19—C20	−179.88 (13)
O1—C1—C6—Cl2	1.5 (2)	C18—C19—C20—C21	0.8 (2)
C2—C1—C6—Cl2	179.64 (13)	C18—C19—C20—N3	−179.53 (15)
C4—N1—C7—O2	−10.9 (3)	C23—N3—C20—C19	−175.73 (17)
C4—N1—C7—C8	168.63 (16)	C23—N3—C20—C21	3.9 (3)
O3—C9—C10—C11	179.73 (16)	C19—C20—C21—C22	−0.6 (3)
C14—C9—C10—C11	−1.3 (3)	N3—C20—C21—C22	179.69 (16)
O3—C9—C10—Cl3	0.2 (2)	C20—C21—C22—C17	−1.0 (3)
C14—C9—C10—Cl3	179.25 (13)	C20—C21—C22—Cl6	177.07 (13)
C9—C10—C11—C12	−0.2 (3)	O5—C17—C22—C21	−178.93 (16)
Cl3—C10—C11—C12	179.27 (13)	C18—C17—C22—C21	2.4 (3)
C10—C11—C12—C13	1.3 (3)	O5—C17—C22—Cl6	3.0 (2)
C10—C11—C12—N2	−179.14 (15)	C18—C17—C22—Cl6	−175.66 (13)
C15—N2—C12—C13	6.5 (3)	C20—N3—C23—O6	−0.6 (3)
C15—N2—C12—C11	−172.98 (16)	C20—N3—C23—C24	179.64 (17)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H10H···O2ⁱ	0.83 (2)	1.94 (2)	2.6776 (18)	148 (2)
N1—H1N···Cl3ⁱⁱ	0.84 (2)	2.78 (2)	3.3925 (17)	131 (2)
N1—H1N···O3ⁱⁱ	0.84 (2)	2.60 (2)	3.401 (2)	161 (2)
C8—H8C···O1ⁱⁱ	0.98	2.60	3.521 (2)	157
O3—H30H···O1	0.81 (2)	2.03 (2)	2.7602 (18)	149 (3)
O3—H30H···Cl4	0.81 (2)	2.59 (2)	3.0528 (14)	118 (2)
N2—H2N···O6ⁱⁱⁱ	0.84 (2)	2.09 (2)	2.920 (2)	172 (2)
C13—H13···O4	0.95	2.26	2.866 (2)	121
O5—H50H···O2ⁱ	0.81 (2)	2.22 (2)	2.9546 (18)	150 (3)
O5—H50H···Cl5	0.81 (2)	2.51 (2)	2.9949 (14)	119 (2)
N3—H3N···O4^iv	0.84 (2)	2.08 (2)	2.913 (2)	176 (2)
C21—H21···O6	0.95	2.24	2.853 (2)	121
C24—H24A···O4^iv	0.98	2.59	3.464 (2)	149

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

Funding information

This work was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant No. P20GM103424–21, by the US Department of Education under grant No. P031B040030 (Title III, Part B: Strengthening Historically Black Graduate Institutions), and by the National Science Foundation under grant No. 2418415 (RII FEC: Advancing Climate Neutrality in Farming Communities through Upcycling Natural Fiber–Reinforced Fireproof Vitrimer Composites). The diffractometer was purchased with support from the National Science Foundation MRI award CHE–1622215262. The authors are solely responsible for the content of this publication, which does not necessarily represent the official views of the NIH, NIGMS, NSF, or the US Department of Education.

References

Bedner, M. & MacCrehan, W. A. (2006). Environ. Sci. Technol. 40, 516–522. Web of Science CrossRef PubMed CAS Google Scholar
Bruker (2016). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cao, F., Zhang, M., Yuan, S., Feng, J., Wang, Q., Wang, W. & Hu, Z. (2016). Environ. Sci. Pollut. Res. 23, 12303–12311. Web of Science CrossRef CAS Google Scholar
Dahlin, D. C. & Nelson, S. D. (1982). J. Med. Chem. 25, 885–886. CrossRef CAS PubMed Web of Science Google Scholar
Glassmeyer, S. T. & Shoemaker, J. A. (2005). Bull. Environ. Contam. Toxicol. 74, 24–31. Web of Science CrossRef PubMed CAS Google Scholar
Hansch, C., Leo, A. J. & Taft, R. W. (1991). Chem. Rev. 91, 165–195. CrossRef CAS Google Scholar
Heytler, P. G. & Prichard, W. W. (1962). Biochem. Biophys. Res. Commun. 7, 272–275. CrossRef PubMed CAS Google Scholar
Kolpin, D. W., Furlong, E. T., Meyer, M. T., Thurman, E. M., Zaugg, S. D., Barber, L. B. & Buxton, H. T. (2002). Environ. Sci. Technol. 36, 1202–1211. Web of Science CrossRef PubMed CAS 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
Li, W. X., Zhang, X. R. & Han, J. R. (2022). Environ. Sci. Technol. 56, 16929–16939. Web of Science CrossRef CAS 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
Paíga, P., Figueiredo, S., Correia, M., André, M., Barbosa, R., Jorge, S. & Delerue-Matos, C. (2025). J. Xenobiot. 15, 78. Web of Science PubMed Google Scholar
Perrin, D. D., Dempsey, B. & Serjeant, E. P. (1981). pK_a Prediction for Organic Acids and Bases. London: Chapman and Hall. Google Scholar
Phong Vo, H. N., Le, G. K., Hong Nguyen, T. M., Bui, X.-T., Nguyen, K. H., Rene, E. R., Vo, T. D. H., Thanh Cao, N. D. & Mohan, R. (2019). Chemosphere 236, 124391. CrossRef PubMed Google Scholar
Postigo, C. & Richardson, S. D. (2014). J. Hazard. Mater. 279, 461–475. Web of Science CrossRef CAS PubMed Google Scholar
Qutob, M., Hussein, M. A., Alamry, K. A. & Rafatullah, M. (2022). RSC Adv. 12, 18373–18396. Web of Science CrossRef CAS PubMed 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
Van Zyl, J. M., Basson, K. & Van Der Walt, B. J. (1989). Biochem. Pharmacol. 38, 161–165. CrossRef CAS PubMed 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.