3-(3,5-Di­chloro­phen­yl)benzene-1,2-diol

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

doi:10.1107/S2414314619012021

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 4| Part 9| September 2019| x191202

https://doi.org/10.1107/S2414314619012021

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3-(3,5-Dichlorophenyl)benzene-1,2-diol

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, Iowa City, IA 52242, USA, and ^bDepartment of Chemistry, University of Kentucky, Chemistry-Physics Bldg, Lexington, KY 40506-0055, USA
^*Correspondence e-mail: hans-joachim-lehmler@uiowa.edu

Edited by A. J. Lough, University of Toronto, Canada (Received 26 August 2019; accepted 30 August 2019; online 6 September 2019)

The title structure, C₁₂H₈Cl₂O₂, is a putative metabolite of 3,5-dichlorobiphenyl (PCB 14). The dihedral angle between the two benzene rings of the title compounds is 58.86 (4)°. In the crystal, it displays intra- and intermolecular O—H⋯O hydrogen bonding and intermolecular O—H⋯Cl hydrogen⋯chlorine interactions. The intermolecular interactions form a two-dimensional network parallel to (010).

Keywords: dihedral angle; hydroxylated compound; metabolite; polychlorinated biphenyl; PCB; crystal structure.

CCDC reference: 1950307

Structure description

Humans are exposed to polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, via their diet (Schecter et al., 2010 ; Shin et al., 2015 ) and by inhalation (Dhakal et al., 2014 ; Hu et al., 2010 ). In particular, lower chlorinated PCBs are oxidized by cytochrome P450 enzymes to the corresponding monohydroxylated and further to dihydroxylated compounds (Grimm et al., 2015 ; Kania-Korwel & Lehmler, 2016 ). Dihydroxylated PCBs can be oxidized to reactive PCB quinones. Both dihydroxylated PCBs and the corresponding quinones are highly toxic, for example because they can promote oxidative stress or bind to nucleophilic sites on cellular macromolecules (Grimm et al., 2015). To better understand the mechanism(s) of toxicity of these molecules in living organisms, it is important to characterize the three-dimensional structure of these PCB metabolites (Lehmler, Parkin et al., 2002 ; Shaikh et al., 2008 ).

3-(3,5-Dichlorophenyl)benzene-1,2-diol (Fig. 1) is a putative metabolite of PCB 14 (3,5-dichlorobiphenyl). The dihedral angle between the least-squares planes of the two benzene rings is 58.84 (4)°. For comparison, the dihedral angle of other PCB derivatives with one OH group ortho to the phenyl–phenyl bond ranges from 48 to 59.5° (Lehmler, Robertson et al., 2002 ; Perrin et al., 1987 ). Dihedral angles of PCB derivatives without any ortho chlorine substituents are in the range 4.9 to 43.9° (Dhakal et al., 2019a ), whereas PCB derivatives with one ortho chlorine substituent range from 47.34 to 59.92° (Dhakal et al., 2019b ). The title compound crystallizes in the monoclinic space group P2₁/c and displays intra- and intermolecular molecular O—H⋯O hydrogen bonding (Fig. 2, Table 1) and intermolecular O—H⋯Cl interactions (Fig. 3, Table 1). The intermolecular interactions lead to the formation of a two-dimensional network parallel to (010).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1O⋯Cl2ⁱ	0.79	2.73	3.2538 (12)	126
O1—H1O⋯O2	0.79	2.20	2.6459 (16)	117
O2—H2O⋯O1ⁱⁱ	0.77	2.02	2.7708 (16)	169
Symmetry codes: (i) $[x+1, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ .

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 is shown as a dashed line. For information regarding the hydrogen-bond geometry, see Table 1

Figure 2
A packing plot viewed approximately along the a axis. Intra- and intermolecular hydrogen bonds are drawn as thick dashed lines. For information regarding the hydrogen-bond geometry, see Table 1

Figure 3
A packing plot viewed approximately along the b axis. Intermolecular hydrogen⋯chlorine interactions are drawn as thin dashed lines. For information regarding the hydrogen-bond geometry, see Table 1

Synthesis and crystallization

The title compound was synthesized via a Suzuki cross-coupling reaction of 1-bromo-3,5-dichlorobenzene with 2,3-dimethoxyphenyl boronic 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 ). Crystals suitable for crystal-structure analysis were obtained by recrystallization from diethyl ether:hexanes (approximately 1:3, v/v) as described by Bauer et al. (1995).

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/c
Temperature (K)	90
a, b, c (Å)	6.2198 (3), 16.9271 (8), 10.4460 (5)
β (°)	101.013 (3)
V (Å³)	1079.53 (9)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.58
Crystal size (mm)	0.28 × 0.25 × 0.25

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 2006 )
T_min, T_max	0.855, 0.869
No. of measured, independent and observed [I > 2σ(I)] reflections	6641, 2470, 2029
R_int	0.037
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.074, 1.04
No. of reflections	2470
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)	0.31, −0.28
Computer programs: COLLECT (Nonius, 1998 ), SCALEPACK and DENZO-SMN (Otwinowski & Minor, 2006), XP in SHELXTL, SHELXS and SHELX (Sheldrick, 2008 ), SHELXL2018/3 (Sheldrick, 2015 ) and CIFFIX (Parkin, 2013 ).

Structural data

CCDC reference: 1950307

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314619012021/lh4050sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314619012021/lh4050Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314619012021/lh4050Isup3.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: SHELXL-2018/3 (Sheldrick, 2015); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX (Sheldrick, 2008) and CIFFIX (Parkin, 2013).

3-(3,5-Dichlorophenyl)benzene-1,2-diol top

Crystal data top

C₁₂H₈Cl₂O₂	F(000) = 520
M_r = 255.08	D_x = 1.569 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 6.2198 (3) Å	Cell parameters from 5954 reflections
b = 16.9271 (8) Å	θ = 1.0–27.5°
c = 10.4460 (5) Å	µ = 0.58 mm⁻¹
β = 101.013 (3)°	T = 90 K
V = 1079.53 (9) Å³	Block, colourless
Z = 4	0.28 × 0.25 × 0.25 mm

Data collection top

Nonius KappaCCD diffractometer	2470 independent reflections
Radiation source: fine-focus sealed-tube	2029 reflections with I > 2σ(I)
Detector resolution: 9.1 pixels mm^-1	R_int = 0.037
φ and ω scans at fixed χ = 55°	θ_max = 27.5°, θ_min = 2.3°
Absorption correction: multi-scan (Scalepack; Otwinowski & Minor, 2006)	h = −7→8
T_min = 0.855, T_max = 0.869	k = −21→21
6641 measured reflections	l = −11→13

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) = 0.074	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.0259P)² + 0.363P] where P = (F_o² + 2F_c²)/3
2470 reflections	(Δ/σ)_max = 0.001
149 parameters	Δρ_max = 0.31 e Å⁻³
0 restraints	Δρ_min = −0.28 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.

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.

Refinement. H atoms were found in difference Fourier maps. Carbon-bound H atoms were subsequently included in the refinement using riding models, with constrained distances set to 0.95 Å (C_sp2H). Hydroxyl O—H distances were refined. U_iso(H) parameters were set to values of either 1.2U_eq or 1.5U_eq (OH only) of the attached atom.

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

	x	y	z	U_iso*/U_eq
Cl1	1.06252 (7)	0.51040 (2)	0.70416 (4)	0.02025 (12)
Cl2	0.30147 (7)	0.35884 (3)	0.52162 (4)	0.02112 (13)
O1	0.98156 (18)	0.29232 (7)	1.03073 (11)	0.0180 (3)
H1O	1.064 (3)	0.2671 (12)	1.0814 (15)	0.027*
O2	0.98599 (18)	0.25308 (7)	1.27641 (11)	0.0189 (3)
H2O	0.9675 (16)	0.2391 (11)	1.343 (2)	0.028*
C1	0.6550 (3)	0.38712 (9)	0.88020 (16)	0.0151 (4)
C2	0.8333 (3)	0.43045 (9)	0.85610 (16)	0.0156 (4)
H2	0.948128	0.444585	0.926113	0.019*
C3	0.8430 (3)	0.45292 (10)	0.72976 (16)	0.0157 (4)
C4	0.6808 (3)	0.43163 (9)	0.62473 (16)	0.0165 (4)
H4	0.689666	0.446218	0.538081	0.020*
C5	0.5060 (3)	0.38841 (10)	0.65118 (16)	0.0162 (4)
C6	0.4880 (3)	0.36663 (9)	0.77716 (16)	0.0154 (4)
H6	0.363533	0.338240	0.792445	0.018*
C1'	0.6450 (3)	0.36330 (9)	1.01653 (16)	0.0146 (3)
C2'	0.8112 (3)	0.31794 (9)	1.08832 (16)	0.0140 (3)
C3'	0.8095 (3)	0.29685 (9)	1.21704 (16)	0.0145 (4)
C4'	0.6384 (3)	0.32091 (10)	1.27509 (16)	0.0171 (4)
H4'	0.636353	0.307008	1.362959	0.020*
C5'	0.4694 (3)	0.36558 (10)	1.20385 (17)	0.0193 (4)
H5'	0.351157	0.382046	1.243162	0.023*
C6'	0.4723 (3)	0.38623 (10)	1.07594 (17)	0.0190 (4)
H6'	0.355134	0.416388	1.028058	0.023*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0179 (2)	0.0205 (2)	0.0225 (2)	−0.00488 (18)	0.00431 (17)	0.00181 (18)
Cl2	0.0210 (2)	0.0269 (2)	0.0137 (2)	−0.00667 (18)	−0.00082 (17)	−0.00019 (17)
O1	0.0150 (6)	0.0252 (7)	0.0139 (6)	0.0082 (5)	0.0030 (5)	0.0026 (5)
O2	0.0195 (6)	0.0251 (7)	0.0123 (6)	0.0048 (5)	0.0041 (5)	0.0055 (5)
C1	0.0169 (8)	0.0130 (8)	0.0150 (8)	0.0045 (7)	0.0022 (7)	−0.0008 (7)
C2	0.0149 (8)	0.0138 (8)	0.0170 (8)	0.0020 (7)	0.0000 (7)	−0.0026 (7)
C3	0.0151 (8)	0.0113 (8)	0.0211 (9)	0.0004 (7)	0.0045 (7)	−0.0002 (7)
C4	0.0193 (9)	0.0152 (8)	0.0152 (8)	0.0022 (7)	0.0039 (7)	0.0018 (7)
C5	0.0145 (8)	0.0158 (8)	0.0164 (8)	0.0014 (7)	−0.0018 (7)	−0.0021 (7)
C6	0.0143 (8)	0.0140 (8)	0.0183 (9)	0.0003 (7)	0.0041 (7)	−0.0001 (7)
C1'	0.0157 (8)	0.0138 (8)	0.0135 (8)	−0.0017 (7)	0.0008 (7)	−0.0011 (7)
C2'	0.0139 (8)	0.0154 (8)	0.0134 (8)	−0.0024 (7)	0.0045 (7)	−0.0047 (7)
C3'	0.0156 (8)	0.0116 (8)	0.0153 (8)	−0.0019 (7)	0.0006 (7)	−0.0002 (7)
C4'	0.0201 (9)	0.0176 (8)	0.0142 (8)	−0.0041 (7)	0.0052 (7)	−0.0006 (7)
C5'	0.0182 (9)	0.0215 (9)	0.0198 (9)	0.0010 (8)	0.0079 (7)	−0.0029 (7)
C6'	0.0171 (9)	0.0201 (9)	0.0199 (9)	0.0030 (7)	0.0040 (7)	0.0005 (7)

Geometric parameters (Å, º) top

Cl1—C3	1.7386 (17)	C4—H4	0.9500
Cl2—C5	1.7445 (16)	C5—C6	1.392 (2)
O1—C2'	1.3842 (18)	C6—H6	0.9500
O1—H1O	0.79 (2)	C1'—C2'	1.387 (2)
O2—C3'	1.3704 (19)	C1'—C6'	1.395 (2)
O2—H2O	0.77 (2)	C2'—C3'	1.393 (2)
C1—C6	1.390 (2)	C3'—C4'	1.383 (2)
C1—C2	1.392 (2)	C4'—C5'	1.390 (2)
C1—C1'	1.493 (2)	C4'—H4'	0.9500
C2—C3	1.386 (2)	C5'—C6'	1.385 (2)
C2—H2	0.9500	C5'—H5'	0.9500
C3—C4	1.389 (2)	C6'—H6'	0.9500
C4—C5	1.381 (2)

C2'—O1—H1O	109.5	C5—C6—H6	120.6
C3'—O2—H2O	109.5	C2'—C1'—C6'	118.12 (15)
C6—C1—C2	119.67 (15)	C2'—C1'—C1	120.19 (15)
C6—C1—C1'	120.70 (15)	C6'—C1'—C1	121.69 (15)
C2—C1—C1'	119.64 (15)	O1—C2'—C1'	119.45 (14)
C3—C2—C1	119.85 (15)	O1—C2'—C3'	119.12 (14)
C3—C2—H2	120.1	C1'—C2'—C3'	121.42 (15)
C1—C2—H2	120.1	O2—C3'—C4'	125.29 (15)
C2—C3—C4	121.61 (15)	O2—C3'—C2'	114.97 (14)
C2—C3—Cl1	118.58 (13)	C4'—C3'—C2'	119.73 (15)
C4—C3—Cl1	119.81 (13)	C3'—C4'—C5'	119.48 (15)
C5—C4—C3	117.39 (15)	C3'—C4'—H4'	120.3
C5—C4—H4	121.3	C5'—C4'—H4'	120.3
C3—C4—H4	121.3	C6'—C5'—C4'	120.41 (16)
C4—C5—C6	122.57 (15)	C6'—C5'—H5'	119.8
C4—C5—Cl2	118.82 (13)	C4'—C5'—H5'	119.8
C6—C5—Cl2	118.61 (13)	C5'—C6'—C1'	120.82 (16)
C1—C6—C5	118.87 (15)	C5'—C6'—H6'	119.6
C1—C6—H6	120.6	C1'—C6'—H6'	119.6

C6—C1—C2—C3	0.1 (2)	C2—C1—C1'—C6'	121.12 (18)
C1'—C1—C2—C3	−179.80 (15)	C6'—C1'—C2'—O1	178.10 (14)
C1—C2—C3—C4	−1.6 (2)	C1—C1'—C2'—O1	−2.6 (2)
C1—C2—C3—Cl1	177.41 (12)	C6'—C1'—C2'—C3'	−1.3 (2)
C2—C3—C4—C5	1.3 (2)	C1—C1'—C2'—C3'	178.05 (15)
Cl1—C3—C4—C5	−177.66 (12)	O1—C2'—C3'—O2	1.7 (2)
C3—C4—C5—C6	0.4 (2)	C1'—C2'—C3'—O2	−178.96 (14)
C3—C4—C5—Cl2	−178.77 (12)	O1—C2'—C3'—C4'	−178.90 (14)
C2—C1—C6—C5	1.6 (2)	C1'—C2'—C3'—C4'	0.5 (2)
C1'—C1—C6—C5	−178.52 (15)	O2—C3'—C4'—C5'	179.68 (15)
C4—C5—C6—C1	−1.9 (2)	C2'—C3'—C4'—C5'	0.3 (2)
Cl2—C5—C6—C1	177.29 (12)	C3'—C4'—C5'—C6'	−0.3 (3)
C6—C1—C1'—C2'	121.97 (18)	C4'—C5'—C6'—C1'	−0.5 (3)
C2—C1—C1'—C2'	−58.2 (2)	C2'—C1'—C6'—C5'	1.3 (3)
C6—C1—C1'—C6'	−58.8 (2)	C1—C1'—C6'—C5'	−178.00 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···Cl2ⁱ	0.79	2.73	3.2538 (12)	126
O1—H1O···O2	0.79	2.20	2.6459 (16)	117
O2—H2O···O1ⁱⁱ	0.77	2.02	2.7708 (16)	169

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

Acknowledgements

The Nonius 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 No. P42 ES013661; grant No. P30 ES005605; grant No. R21 ES027169).

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