2,3-Di­chloro-3′,4′-di­hydroxy­biphen­yl

Dhakal, R.; Parkin, S.; Lehmler, H.-J.

doi:10.1107/S241431461900662X

organic compounds

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ISSN: 2414-3146

Volume 4| Part 5| May 2019| x190662

https://doi.org/10.1107/S241431461900662X

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2,3-Dichloro-3′,4′-dihydroxybiphenyl

Ram Dhakal,^a Sean Parkin ^b and Hans-Joachim Lehmler ^a ^*

^aThe University of Iowa, Department of Occupational and Environmental Health, University of Iowa, Research Park, IREH, Iowa City, IA, 52242, USA, and ^bDepartment of Chemistry, University of Kentucky, 117a Chemistry-Physics Bldg, Lexington, KY, 40506-0055, USA
^*Correspondence e-mail: hans-joachim-lehmler@uiowa.edu

Edited by J. Simpson, University of Otago, New Zealand (Received 5 May 2019; accepted 8 May 2019; online 14 May 2019)

The title compound [systematic name: 4-(2,3-Dichlorophenyl)benzene-1,2-diol], C₁₂H₈Cl₂O₂, is a putative dihydroxylated metabolite of 2,3-dichlorobiphenyl (PCB 5). The title structure displays intramolecular O—H⋯O hydrogen bonding, and the π–π stacking distance between inversion-related chlorinated benzene rings of the title compound is 3.371 (3) Å. The dihedral angle between two benzene rings is 59.39 (8)°.

Keywords: crystal structure; polychlorinated biphenyls (PCBs); metabolites; hydroxylated compound.

CCDC reference: 1914945

Structure description

Polychlorinated biphenyls (PCBs) are a class of environmental pollutants banned under the Stockholm Convention on Persistent Organic Pollutants (Stockholm Convention, 2008 ). Exposure to PCBs is associated with a range of adverse health effects, for example cancer and adverse neurotoxic outcomes (ATSDR, 2000 ; IARC, 2017 ). Cytochrome P450 enzymes oxidize PCB congeners in two steps to dihydroxylated metabolites (Lu et al., 2013 ; McLean et al., 1996 ). PCB metabolites with ortho- or para-substituted hydroxyl groups can be further oxidized to reactive and highly toxic PCB quinones (Dhakal et al., 2018 ; Grimm et al., 2015 ). Only a few solid-state structures of dihydroxylated PCBs have been reported to date (Lehmler et al., 2001a ; McKinney & Singh, 1988 ). 2,3-Dichloro-3′,4′-dihydroxybiphenyl is a putative metabolite of PCB 5, a minor constituent of technical PCB mixtures, such as Aroclor 1221 (Frame, 1997 ). The present study reports the solid-state structure of this dihydroxylated PCB metabolite, thus adding to the number of available crystal structures of this important class of PCB metabolites.

2,3-Dichloro-3′,4′-dihydroxybiphenyl crystallizes in the monoclinic P2₁/n space group. The dihedral angle between the least-squares planes of the two benzene rings, an important determinant of the three-dimensional structure of PCB derivatives, is 59.39 (8)°. Similarly, the solid-state dihedral angle of other mono ortho-chlorine-substituted PCB derivatives ranges from 47.34 (5) to 59.92 (9)° (Boyarskiy et al., 2010 ; Kania-Korwel et al. 2004 ; Lehmler et al. 2001b ; Li et al. 2010 ; Luthe et al. 2007 ; van der Sluis et al., 1990 ; Sutherland & Ali-Adib, 1987 ; Vyas et al., 2006 ). In the crystal, the title compound displays intra and intermolecular O—H⋯O hydrogen bonds involving both of the two hydroxy groups (Figs. 1 and 2). The intramolecular bond distance for O1—H1⋯O2 is 2.763 (2) Å, while that for O2—H2⋯O1 is 2.677 (2) Å, Table 1. The π–π stacking distance between inversion-related C1–C6 rings of the title compound is 3.371 (3) Å.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯O2ⁱ	0.79	1.98	2.763 (2)	168
O2—H2O⋯O1	0.79	2.24	2.677 (2)	116
Symmetry code: (i) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

Figure 1
View of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. The intramolecular hydrogen bond (Table 1

) is shown as a dashed line.

Figure 2
A packing plot viewed approximately along the c axis. Hydrogen bonds (Table 1

) are drawn as solid dashed lines, and the π–π interactions are depicted as dashed open lines between the centroids of stacked rings.

Synthesis and crystallization

The title compound was synthesized via a Suzuki cross-coupling reaction of 4-bromo-1,2-dimethoxybenzene with 2,3-dichlorophenylboronic acid in the presence of Pd(PPh₃)₄, and a 2 M aqueous solution of Na₂CO₃ followed by demethylation with BBr₃ (Bauer et al., 1995 ; Lehmler & Robertson, 2001 ). Crystals suitable for crystal-structure analysis were obtained by recrystallization of the title compound from diethyl ether: hexanes (approximately 1:3, v/v) as previously described (Bauer et al., 1995; Lehmler & Robertson, 2001).

Refinement

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

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₈Cl₂O₂
M_r	255.08
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	90
a, b, c (Å)	6.8542 (4), 19.9526 (11), 7.6704 (4)
β (°)	95.762 (3)
V (Å³)	1043.7 (1)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.60
Crystal size (mm)	0.25 × 0.15 × 0.10

Data collection
Diffractometer	Nonius KappaCCD
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 2006 )
T_min, T_max	0.865, 0.942
No. of measured, independent and observed [I > 2σ(I)] reflections	6305, 1834, 1333
R_int	0.078
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.074, 1.05
No. of reflections	1834
No. of parameters	149
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.35
Computer programs: COLLECT (Nonius, 1998 ), SCALEPACK and DENZO-SMN (Otwinowski & Minor, 2006), SHELXS, XP in SHELXTL and SHELX (Sheldrick, 2008 ), SHELXL2018/1 (Sheldrick, 2015 ) and CIFFIX (Parkin, 2013 ).

Structural data

CCDC reference: 1914945

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S241431461900662X/sj4205sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S241431461900662X/sj4205Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S241431461900662X/sj4205Isup3.cml

checkCIF report

Computing details top

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 2006); data reduction: DENZO-SMN (Otwinowski & Minor, 2006); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/1 (Sheldrick, 2015); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX (Sheldrick, 2008) and CIFFIX (Parkin, 2013).

4-(2,3-Dichlorophenyl)benzene-1,2-diol top

Crystal data top

C₁₂H₈Cl₂O₂	F(000) = 520
M_r = 255.08	D_x = 1.623 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 6.8542 (4) Å	Cell parameters from 7512 reflections
b = 19.9526 (11) Å	θ = 1.0–25.3°
c = 7.6704 (4) Å	µ = 0.60 mm⁻¹
β = 95.762 (3)°	T = 90 K
V = 1043.7 (1) Å³	Block, colourless
Z = 4	0.25 × 0.15 × 0.10 mm

Data collection top

Nonius KappaCCD diffractometer	1834 independent reflections
Radiation source: fine-focus sealed-tube	1333 reflections with I > 2σ(I)
Detector resolution: 9.1 pixels mm^-1	R_int = 0.078
φ and ω scans at fixed χ = 55°	θ_max = 25.0°, θ_min = 2.0°
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 2006)	h = −8→8
T_min = 0.865, T_max = 0.942	k = −23→23
6305 measured reflections	l = −9→9

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)] = 0.046	Hydrogen site location: difference Fourier map
wR(F²) = 0.074	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ²(F_o²) + (0.0177P)² + 0.1242P] where P = (F_o² + 2F_c²)/3
1834 reflections	(Δ/σ)_max = 0.001
149 parameters	Δρ_max = 0.37 e Å⁻³
0 restraints	Δρ_min = −0.35 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 90K, which is standard practice in this laboratory for the majority of flash-cooled crystals.

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
O1	0.3278 (3)	0.25608 (9)	−0.0075 (2)	0.0178 (5)
H1O	0.257 (3)	0.2624 (10)	0.067 (3)	0.027*
O2	0.6024 (3)	0.23958 (9)	−0.2285 (2)	0.0175 (5)
H2O	0.497 (4)	0.2241 (11)	−0.228 (2)	0.026*
Cl1	0.74285 (10)	0.52729 (3)	0.06782 (8)	0.0204 (2)
Cl2	0.77595 (10)	0.63119 (3)	0.37417 (9)	0.0218 (2)
C1	0.7234 (3)	0.43053 (13)	0.3178 (3)	0.0113 (6)
C2	0.7451 (3)	0.49894 (13)	0.2822 (3)	0.0131 (7)
C3	0.7609 (3)	0.54586 (12)	0.4169 (3)	0.0143 (7)
C4	0.7593 (3)	0.52551 (13)	0.5897 (3)	0.0166 (7)
H4	0.773622	0.557486	0.681882	0.020*
C5	0.7366 (3)	0.45841 (13)	0.6266 (3)	0.0159 (7)
H5	0.733444	0.444169	0.744443	0.019*
C6	0.7184 (3)	0.41181 (13)	0.4922 (3)	0.0154 (7)
H6	0.702020	0.365856	0.519651	0.018*
C1'	0.6972 (4)	0.37913 (12)	0.1762 (3)	0.0113 (6)
C2'	0.5271 (4)	0.33991 (12)	0.1597 (3)	0.0136 (7)
H2'	0.433327	0.344812	0.241955	0.016*
C3'	0.4945 (4)	0.29424 (13)	0.0252 (3)	0.0124 (7)
C4'	0.6346 (4)	0.28487 (13)	−0.0917 (3)	0.0116 (7)
C5'	0.8067 (4)	0.32105 (13)	−0.0734 (3)	0.0146 (7)
H5'	0.904134	0.313550	−0.151069	0.018*
C6'	0.8374 (4)	0.36868 (12)	0.0594 (3)	0.0145 (7)
H6'	0.954896	0.394255	0.070420	0.017*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0186 (12)	0.0175 (11)	0.0187 (12)	−0.0056 (10)	0.0087 (9)	−0.0050 (9)
O2	0.0185 (13)	0.0189 (12)	0.0158 (11)	−0.0048 (9)	0.0055 (10)	−0.0055 (9)
Cl1	0.0275 (5)	0.0166 (4)	0.0177 (4)	−0.0023 (3)	0.0051 (3)	0.0032 (3)
Cl2	0.0258 (5)	0.0112 (4)	0.0286 (5)	−0.0007 (3)	0.0040 (4)	−0.0003 (3)
C1	0.0078 (15)	0.0107 (16)	0.0158 (17)	0.0006 (12)	0.0029 (12)	−0.0023 (13)
C2	0.0096 (16)	0.0192 (17)	0.0107 (16)	0.0020 (13)	0.0018 (13)	0.0009 (13)
C3	0.0112 (17)	0.0107 (16)	0.0210 (18)	0.0000 (13)	0.0019 (13)	−0.0001 (14)
C4	0.0128 (17)	0.0161 (17)	0.0207 (18)	0.0000 (13)	0.0012 (13)	−0.0086 (15)
C5	0.0154 (17)	0.0208 (18)	0.0112 (16)	0.0019 (14)	−0.0001 (13)	0.0015 (14)
C6	0.0181 (17)	0.0107 (16)	0.0176 (17)	0.0000 (13)	0.0026 (13)	0.0020 (14)
C1'	0.0141 (16)	0.0083 (15)	0.0112 (16)	0.0031 (13)	−0.0001 (13)	0.0052 (12)
C2'	0.0174 (17)	0.0115 (16)	0.0130 (16)	0.0019 (13)	0.0067 (13)	0.0007 (13)
C3'	0.0117 (16)	0.0113 (16)	0.0141 (16)	0.0000 (13)	0.0017 (13)	0.0024 (13)
C4'	0.0190 (17)	0.0070 (15)	0.0084 (15)	0.0038 (13)	0.0001 (13)	0.0000 (13)
C5'	0.0120 (17)	0.0199 (17)	0.0124 (16)	0.0015 (14)	0.0034 (13)	0.0022 (14)
C6'	0.0142 (16)	0.0131 (17)	0.0161 (17)	−0.0027 (13)	0.0006 (13)	0.0044 (13)

Geometric parameters (Å, º) top

O1—C3'	1.375 (3)	C5—C6	1.385 (3)
O1—H1O	0.79 (2)	C5—H5	0.9500
O2—C4'	1.386 (3)	C6—H6	0.9500
O2—H2O	0.79 (2)	C1'—C6'	1.394 (3)
Cl1—C2	1.737 (3)	C1'—C2'	1.399 (3)
Cl2—C3	1.739 (3)	C2'—C3'	1.378 (3)
C1—C6	1.393 (3)	C2'—H2'	0.9500
C1—C2	1.403 (3)	C3'—C4'	1.391 (3)
C1—C1'	1.492 (3)	C4'—C5'	1.378 (3)
C2—C3	1.391 (3)	C5'—C6'	1.394 (3)
C3—C4	1.387 (3)	C5'—H5'	0.9500
C4—C5	1.380 (3)	C6'—H6'	0.9500
C4—H4	0.9500

C3'—O1—H1O	109.5	C1—C6—H6	119.1
C4'—O2—H2O	109.5	C6'—C1'—C2'	118.7 (2)
C6—C1—C2	117.5 (2)	C6'—C1'—C1	122.0 (2)
C6—C1—C1'	120.2 (2)	C2'—C1'—C1	119.3 (2)
C2—C1—C1'	122.3 (2)	C3'—C2'—C1'	120.6 (2)
C3—C2—C1	120.8 (2)	C3'—C2'—H2'	119.7
C3—C2—Cl1	118.5 (2)	C1'—C2'—H2'	119.7
C1—C2—Cl1	120.7 (2)	O1—C3'—C2'	124.9 (2)
C4—C3—C2	120.4 (2)	O1—C3'—C4'	115.0 (2)
C4—C3—Cl2	118.2 (2)	C2'—C3'—C4'	120.1 (2)
C2—C3—Cl2	121.4 (2)	C5'—C4'—O2	119.2 (2)
C5—C4—C3	119.4 (2)	C5'—C4'—C3'	120.2 (2)
C5—C4—H4	120.3	O2—C4'—C3'	120.5 (2)
C3—C4—H4	120.3	C4'—C5'—C6'	119.8 (2)
C4—C5—C6	120.2 (2)	C4'—C5'—H5'	120.1
C4—C5—H5	119.9	C6'—C5'—H5'	120.1
C6—C5—H5	119.9	C5'—C6'—C1'	120.6 (2)
C5—C6—C1	121.7 (2)	C5'—C6'—H6'	119.7
C5—C6—H6	119.1	C1'—C6'—H6'	119.7

C6—C1—C2—C3	0.1 (4)	C6—C1—C1'—C2'	57.1 (3)
C1'—C1—C2—C3	177.2 (2)	C2—C1—C1'—C2'	−120.0 (3)
C6—C1—C2—Cl1	−177.37 (18)	C6'—C1'—C2'—C3'	−3.2 (4)
C1'—C1—C2—Cl1	−0.2 (4)	C1—C1'—C2'—C3'	176.9 (2)
C1—C2—C3—C4	1.2 (4)	C1'—C2'—C3'—O1	−176.3 (2)
Cl1—C2—C3—C4	178.69 (19)	C1'—C2'—C3'—C4'	2.5 (4)
C1—C2—C3—Cl2	−176.86 (19)	O1—C3'—C4'—C5'	179.1 (2)
Cl1—C2—C3—Cl2	0.6 (3)	C2'—C3'—C4'—C5'	0.2 (4)
C2—C3—C4—C5	−1.7 (4)	O1—C3'—C4'—O2	−0.3 (3)
Cl2—C3—C4—C5	176.45 (19)	C2'—C3'—C4'—O2	−179.3 (2)
C3—C4—C5—C6	0.9 (4)	O2—C4'—C5'—C6'	177.4 (2)
C4—C5—C6—C1	0.4 (4)	C3'—C4'—C5'—C6'	−2.1 (4)
C2—C1—C6—C5	−0.9 (4)	C4'—C5'—C6'—C1'	1.3 (4)
C1'—C1—C6—C5	−178.1 (2)	C2'—C1'—C6'—C5'	1.3 (4)
C6—C1—C1'—C6'	−122.7 (3)	C1—C1'—C6'—C5'	−178.9 (2)
C2—C1—C1'—C6'	60.2 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O2ⁱ	0.79	1.98	2.763 (2)	168
O2—H2O···O1	0.79	2.24	2.677 (2)	116

Symmetry code: (i) x−1/2, −y+1/2, z+1/2.

Acknowledgements

The KappaCCD diffractometer was funded by the University of Kentucky.

Funding information

Funding for this research was provided by: National Institute of Environmental Health Sciences (grant Nos. P42 ES013661; P30 ES005605 and R21 ES027169).

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