3,5-Di­chloro-3′,4′-di­meth­oxy­biphen­yl

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

doi:10.1107/S2414314619005182

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 4| Part 4| April 2019| x190518

https://doi.org/10.1107/S2414314619005182

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3,5-Dichloro-3′,4′-dimethoxybiphenyl

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, Lexington, KY 40506, USA
^*Correspondence e-mail: hans-joachim-lehmler@uiowa.edu

Edited by J. Simpson, University of Otago, New Zealand (Received 12 April 2019; accepted 15 April 2019; online 25 April 2019)

The title compound, C₁₄H₁₂Cl₂O₂, is a dimethoxylated derivative of 3,4-dichlorobiphenyl (PCB 14). The dihedral angle between the benzene rings is 42.49 (6)°. The methoxy groups on the non-chlorinated ring lie essentially in the plane of the benzene ring, with C—C—O—C torsion angles of 4.0 (2) and −2.07 (19)°. In the crystal, the compound displays π–π stacking interactions between inversion-related chlorinated benzene rings, with an interplanar stacking distance of 3.3695 (17) Å.

Keywords: crystal structure; polychlorinated biphenyls; metabolite.

CCDC reference: 1910304

Structure description

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that can be metabolized to mono- and di-hydroxylated PCB metabolites (Grimm et al., 2015 ; Kania-Korwel & Lehmler, 2016 ). The interaction of PCB metabolites with biological macromolecules, such as proteins, depends on their three-dimensional structure. For example, non-ortho-substituted PCB congeners bind to the aryl hydrocarbon receptor (AhR) (Bandiera et al., 1982 ), whereas PCB congeners with multiple ortho-chlorine substituents are potent sensitizers of ryanodine receptors (RyR) (Holland et al., 2017 ; Pessah et al., 2006 ). The three-dimensional structure of PCB derivatives depends on their substitution pattern and the dihedral angle between the two benzene rings of the biphenyl moiety. However, only limited information about the structure of PCBs and their metabolites is currently available. Here we report the crystal structure of the title compound, 3,5-dichloro-3′,4′-dimethoxybiphenyl, a precursor for the synthesis of 3,5-dichloro-3′,4′-dihydroxybiphenyl, a putative dihydroxylated PCB metabolite of PCB 12.

The title compound (Fig. 1) crystallizes in the monoclinic space group P2₁/c and shows π–π stacking interactions between inversion-related C1–C6 rings, with an interplanar stacking distance of 3.3695 (17) Å. The dihedral angle between the least-squares mean planes of the two benzene rings is 42.49 (6)°. Similarly, the solid-state dihedral angles of other non-ortho-chlorine-substituted PCB derivatives range from 4.9 to 43.94° (e.g., see: Li et al., 2010 ; Shaikh et al., 2008 ). Larger dihedral angles are typically reported for PCB derivatives with one or more ortho-chlorine substituents (e.g., see: Lehmler et al., 2001 ; Vyas et al., 2006 ). Both methoxy groups are almost coplanar with the benzene ring, with torsion angles of 4.0 (2)° and −2.09 (19)° for the methoxy groups at C3′ and C4′, respectively. This orientation of the methoxy groups relative to the plane of the benzene ring is typical for methoxylated benzene derivatives that do not have substituents ortho to the respective methoxy group (Lehmler et al., 2013 ).

Figure 1
View of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

Synthesis and crystallization

The title compound was prepared via a Suzuki cross-coupling reaction of 3-bromo-1,2-dimethoxybenzene with 3,5-dichlorophenylboronic acid in the presence of Pd(PPh₃)₄ and a 2M aqueous solution of Na₂CO₃ (Bauer et al., 1995 ). Crystals suitable for structure analysis were obtained by recrystallization of the title compound 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 1. Refinement progress was checked using PLATON (Spek, 2009 ) and by an R-tensor (Parkin, 2000 ).

Table 1
Experimental details

Crystal data
Chemical formula	C₁₄H₁₂Cl₂O₂
M_r	283.14
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	90
a, b, c (Å)	10.8596 (10), 15.1262 (10), 7.9040 (3)
β (°)	103.749 (10)
V (Å³)	1261.14 (16)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.50
Crystal size (mm)	0.35 × 0.35 × 0.30

Data collection
Diffractometer	Nonius KappaCCD diffractometer
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 2006 )
T_min, T_max	0.843, 0.863
No. of measured, independent and observed [I > 2σ(I)] reflections	11657, 2899, 2521
R_int	0.036
(sin θ/λ)_max (Å⁻¹)	0.649

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.030, 0.072, 1.09
No. of reflections	2899
No. of parameters	166
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.24
Computer programs: COLLECT (Nonius, 1998 ), SCALEPACK (Otwinowski & Minor, 2006), DENZO-SMN (Otwinowski & Minor, 2006), SHELXS (Sheldrick, 2008 ), SHELXL2018 (Sheldrick, 2015 ), XP in SHELXTL (Sheldrick, 2008), SHELX (Sheldrick, 2008) and CIFFIX (Parkin, 2013 ).

Structural data

CCDC reference: 1910304

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314619005182/sj4203sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314619005182/sj4203Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314619005182/sj4203Isup3.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 (Sheldrick, 2015); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX (Sheldrick, 2008) and CIFFIX (Parkin, 2013).

3,5-Dichloro-3',4'-dimethoxybiphenyl top

Crystal data top

C₁₄H₁₂Cl₂O₂	F(000) = 584
M_r = 283.14	D_x = 1.491 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.8596 (10) Å	Cell parameters from 6723 reflections
b = 15.1262 (10) Å	θ = 1.0–27.5°
c = 7.9040 (3) Å	µ = 0.50 mm⁻¹
β = 103.749 (10)°	T = 90 K
V = 1261.14 (16) Å³	Block, colourless
Z = 4	0.35 × 0.35 × 0.30 mm

Data collection top

Nonius KappaCCD diffractometer	2899 independent reflections
Radiation source: fine-focus sealed-tube	2521 reflections with I > 2σ(I)
Detector resolution: 9.1 pixels mm^-1	R_int = 0.036
φ and ω scans at fixed χ = 55°	θ_max = 27.5°, θ_min = 1.9°
Absorption correction: multi-scan (Scalepack; Otwinowski & Minor, 2006)	h = −14→13
T_min = 0.843, T_max = 0.863	k = −19→19
11657 measured reflections	l = −10→10

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F² > 2σ(F²)] = 0.030	H-atom parameters constrained
wR(F²) = 0.072	w = 1/[σ²(F_o²) + (0.0274P)² + 0.5814P] where P = (F_o² + 2F_c²)/3
S = 1.09	(Δ/σ)_max < 0.001
2899 reflections	Δρ_max = 0.29 e Å⁻³
166 parameters	Δρ_min = −0.24 e Å⁻³
0 restraints	Extinction correction: SHELXL2018 (Sheldrick, 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0036 (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.

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. Refinement progress was checked using PLATON (Spek, 2009) 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
Cl1	0.60753 (3)	0.14404 (3)	0.24758 (5)	0.02195 (11)
Cl2	0.68140 (3)	0.00465 (2)	0.89050 (4)	0.01849 (11)
C1	0.38939 (13)	0.13567 (9)	0.59009 (18)	0.0143 (3)
C2	0.43570 (13)	0.15454 (9)	0.44322 (18)	0.0158 (3)
H2	0.384740	0.185934	0.347780	0.019*
C3	0.55644 (14)	0.12705 (10)	0.43819 (18)	0.0161 (3)
C4	0.63554 (13)	0.08233 (9)	0.57460 (18)	0.0162 (3)
H4	0.718627	0.064728	0.569857	0.019*
C5	0.58725 (13)	0.06454 (9)	0.71870 (18)	0.0147 (3)
C6	0.46684 (13)	0.09022 (9)	0.72952 (18)	0.0153 (3)
H6	0.437275	0.077075	0.830574	0.018*
C1'	0.25668 (13)	0.15968 (9)	0.59000 (17)	0.0144 (3)
C2'	0.17925 (13)	0.09856 (9)	0.65066 (17)	0.0141 (3)
H2'	0.213997	0.044236	0.700603	0.017*
C3'	0.05248 (13)	0.11749 (9)	0.63765 (17)	0.0138 (3)
C4'	0.00084 (13)	0.19851 (9)	0.56645 (17)	0.0142 (3)
C5'	0.07794 (14)	0.25948 (9)	0.51099 (18)	0.0155 (3)
H5'	0.044267	0.314924	0.465840	0.019*
C6'	0.20519 (14)	0.23956 (10)	0.52135 (18)	0.0166 (3)
H6'	0.257030	0.281250	0.480869	0.020*
O1	−0.03319 (9)	0.06153 (6)	0.68480 (13)	0.0172 (2)
C7	0.01422 (14)	−0.02040 (9)	0.76311 (19)	0.0174 (3)
H7A	0.057591	−0.052147	0.685996	0.026*
H7B	−0.056387	−0.056294	0.782171	0.026*
H7C	0.074053	−0.009068	0.874989	0.026*
O2	−0.12548 (9)	0.20904 (6)	0.55654 (13)	0.0171 (2)
C8	−0.18099 (14)	0.29114 (9)	0.4881 (2)	0.0177 (3)
H8A	−0.140273	0.339681	0.562957	0.027*
H8B	−0.271851	0.290436	0.484248	0.027*
H8C	−0.168898	0.299578	0.370183	0.027*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0224 (2)	0.0305 (2)	0.01586 (18)	−0.00474 (15)	0.01035 (14)	−0.00050 (15)
Cl2	0.01430 (18)	0.0238 (2)	0.01618 (18)	0.00001 (13)	0.00128 (13)	0.00173 (14)
C1	0.0154 (7)	0.0134 (7)	0.0142 (6)	−0.0019 (5)	0.0035 (5)	−0.0031 (5)
C2	0.0172 (7)	0.0156 (7)	0.0146 (7)	−0.0014 (5)	0.0036 (5)	−0.0002 (5)
C3	0.0185 (7)	0.0180 (7)	0.0136 (7)	−0.0060 (6)	0.0072 (6)	−0.0027 (5)
C4	0.0128 (7)	0.0177 (7)	0.0188 (7)	−0.0034 (5)	0.0051 (5)	−0.0042 (6)
C5	0.0153 (7)	0.0144 (7)	0.0131 (6)	−0.0020 (5)	0.0006 (5)	−0.0013 (5)
C6	0.0160 (7)	0.0169 (7)	0.0141 (6)	−0.0038 (5)	0.0059 (5)	−0.0009 (6)
C1'	0.0154 (7)	0.0170 (7)	0.0109 (6)	−0.0005 (5)	0.0033 (5)	−0.0023 (5)
C2'	0.0166 (7)	0.0136 (6)	0.0113 (6)	0.0008 (5)	0.0019 (5)	0.0002 (5)
C3'	0.0155 (7)	0.0150 (7)	0.0111 (6)	−0.0027 (5)	0.0034 (5)	−0.0007 (5)
C4'	0.0140 (7)	0.0169 (7)	0.0114 (6)	0.0006 (5)	0.0025 (5)	−0.0026 (5)
C5'	0.0203 (7)	0.0129 (7)	0.0133 (6)	0.0014 (5)	0.0040 (6)	0.0006 (5)
C6'	0.0193 (7)	0.0172 (7)	0.0150 (7)	−0.0022 (6)	0.0071 (6)	0.0012 (6)
O1	0.0141 (5)	0.0150 (5)	0.0228 (5)	0.0000 (4)	0.0049 (4)	0.0057 (4)
C7	0.0175 (7)	0.0158 (7)	0.0183 (7)	−0.0001 (5)	0.0029 (6)	0.0040 (6)
O2	0.0137 (5)	0.0164 (5)	0.0213 (5)	0.0033 (4)	0.0042 (4)	0.0033 (4)
C8	0.0176 (7)	0.0144 (7)	0.0212 (7)	0.0047 (5)	0.0049 (6)	0.0007 (6)

Geometric parameters (Å, º) top

Cl1—C3	1.7439 (14)	C3'—O1	1.3732 (16)
Cl2—C5	1.7464 (14)	C3'—C4'	1.4082 (19)
C1—C6	1.398 (2)	C4'—O2	1.3646 (16)
C1—C2	1.3998 (19)	C4'—C5'	1.385 (2)
C1—C1'	1.4861 (19)	C5'—C6'	1.398 (2)
C2—C3	1.385 (2)	C5'—H5'	0.9500
C2—H2	0.9500	C6'—H6'	0.9500
C3—C4	1.385 (2)	O1—C7	1.4256 (17)
C4—C5	1.389 (2)	C7—H7A	0.9800
C4—H4	0.9500	C7—H7B	0.9800
C5—C6	1.386 (2)	C7—H7C	0.9800
C6—H6	0.9500	O2—C8	1.4293 (16)
C1'—C6'	1.387 (2)	C8—H8A	0.9800
C1'—C2'	1.408 (2)	C8—H8B	0.9800
C2'—C3'	1.3858 (19)	C8—H8C	0.9800
C2'—H2'	0.9500

C6—C1—C2	119.12 (13)	O1—C3'—C4'	114.44 (12)
C6—C1—C1'	121.49 (12)	C2'—C3'—C4'	120.25 (13)
C2—C1—C1'	119.29 (12)	O2—C4'—C5'	125.39 (13)
C3—C2—C1	119.46 (13)	O2—C4'—C3'	115.09 (12)
C3—C2—H2	120.3	C5'—C4'—C3'	119.52 (13)
C1—C2—H2	120.3	C4'—C5'—C6'	120.11 (13)
C4—C3—C2	122.72 (13)	C4'—C5'—H5'	119.9
C4—C3—Cl1	118.61 (11)	C6'—C5'—H5'	119.9
C2—C3—Cl1	118.57 (11)	C1'—C6'—C5'	120.78 (13)
C3—C4—C5	116.61 (13)	C1'—C6'—H6'	119.6
C3—C4—H4	121.7	C5'—C6'—H6'	119.6
C5—C4—H4	121.7	C3'—O1—C7	117.10 (11)
C6—C5—C4	122.82 (13)	O1—C7—H7A	109.5
C6—C5—Cl2	118.94 (11)	O1—C7—H7B	109.5
C4—C5—Cl2	118.22 (11)	H7A—C7—H7B	109.5
C5—C6—C1	119.27 (13)	O1—C7—H7C	109.5
C5—C6—H6	120.4	H7A—C7—H7C	109.5
C1—C6—H6	120.4	H7B—C7—H7C	109.5
C6'—C1'—C2'	119.18 (13)	C4'—O2—C8	116.80 (11)
C6'—C1'—C1	120.93 (13)	O2—C8—H8A	109.5
C2'—C1'—C1	119.79 (12)	O2—C8—H8B	109.5
C3'—C2'—C1'	120.13 (13)	H8A—C8—H8B	109.5
C3'—C2'—H2'	119.9	O2—C8—H8C	109.5
C1'—C2'—H2'	119.9	H8A—C8—H8C	109.5
O1—C3'—C2'	125.28 (13)	H8B—C8—H8C	109.5

C6—C1—C2—C3	0.7 (2)	C1—C1'—C2'—C3'	−174.65 (12)
C1'—C1—C2—C3	−175.75 (13)	C1'—C2'—C3'—O1	176.85 (12)
C1—C2—C3—C4	−1.1 (2)	C1'—C2'—C3'—C4'	−1.1 (2)
C1—C2—C3—Cl1	175.29 (11)	O1—C3'—C4'—O2	0.44 (17)
C2—C3—C4—C5	1.0 (2)	C2'—C3'—C4'—O2	178.57 (12)
Cl1—C3—C4—C5	−175.35 (11)	O1—C3'—C4'—C5'	−178.72 (12)
C3—C4—C5—C6	−0.6 (2)	C2'—C3'—C4'—C5'	−0.6 (2)
C3—C4—C5—Cl2	177.65 (10)	O2—C4'—C5'—C6'	−177.32 (13)
C4—C5—C6—C1	0.3 (2)	C3'—C4'—C5'—C6'	1.8 (2)
Cl2—C5—C6—C1	−177.94 (10)	C2'—C1'—C6'—C5'	−0.4 (2)
C2—C1—C6—C5	−0.3 (2)	C1—C1'—C6'—C5'	175.76 (13)
C1'—C1—C6—C5	176.03 (13)	C4'—C5'—C6'—C1'	−1.3 (2)
C6—C1—C1'—C6'	142.42 (14)	C2'—C3'—O1—C7	4.0 (2)
C2—C1—C1'—C6'	−41.23 (19)	C4'—C3'—O1—C7	−177.97 (12)
C6—C1—C1'—C2'	−41.44 (19)	C5'—C4'—O2—C8	−2.07 (19)
C2—C1—C1'—C2'	134.91 (14)	C3'—C4'—O2—C8	178.82 (12)
C6'—C1'—C2'—C3'	1.6 (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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