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

Abstract

The title structure [systematic name: 4-(3,5-dichlorophenyl)benzene-1,2-diol], 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.

Structure description

Humans are exposed to polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, via the 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 organism, it is important to characterize the three-dimensional structure of these PCB metabolites (Lehmler et al., 2002; Shaikh et al., 2008).

4-(3,5-Dichlorophenyl)benzene-1,2-diol (Figure 1) is a putative metabolite of PCB 14 (3,5-dichlorobiphenyl). The dihedral angle between the least-square planes of the two benzene rings of the title compound 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 et al., 2001; Perrin et al., 1987). Dihedral angles of PCB derivatives without any ortho chlorine substituents are 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 (Figure 2, Table 2) and intermolecular O— H···Cl interactions (Figure 3, Table 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 2.

Figure 2.

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

Table 2.

Hydrogen-bond geometry (Å, °) for (k02114)

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.

Figure 3.

A packing plot viewed approximately along the b-axis. Intermolecular hydrogen···chlorine interactions are drawn as solid dashed lines. For information regarding the hydrogen bond geometry, see Table 2.

Synthesis and crystallization

The title compound was synthesized via Suzuki cross coupling reaction of 1-bromo-3,5-dichlorobenzene with 2,3-di-methoxyphenyl boronic acid in the presence of Pd(PPh₃)₄, and 2M aqueous solution of Na₂CO₃ followed by demethylation with BBr₃ (Bauer et al., 1995). Crystals suitable for crystal structure analysis were obtained by recrystallization of the title compound from diethyl ether : hexanes (approximately 1:3, v/v) as described (Bauer et al., 1995).

Refinement

H atoms were found in difference Fourier maps, but subsequently included in the refinement using riding models, with constrained distances set to 0.95 Å (C_sp2H). U_iso(H) parameters were set to values of either 1.2U_eq or 1.5U_eq (RCH₃ only) of the attached atom.

Table 1.

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)
Tmin, Tmax	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
Δρmax, Δρmin (e Å−3)	0.31, −0.28

Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 2006), DENZO-SMN (Otwinowski & Minor, 2006), SHELXT (Sheldrick, 2015a), SHELXL-2018/1 (Sheldrick, 2015b), XP in SHELXTL (Sheldrick, 2008), SHELX(Sheldrick, 2008) and CIFFIX(Parkin, 2013).