4-Chloro-3',4'-di­hydroxy­bi­phenyl

The crystal structure of a metabolite of 4-chloro­bi­phenyl (PCB 3), 4-chloro-3',4'-di­hydroxybi­phenyl (C₁₂H₉ClO₂), is described. The dihedral angle of the title compound is 43.1 (3)°, which is in reasonable agreement with the calculated value of 37.2°.

Key indicators

• Single-crystal X-ray study
• T = 144 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.036
• wR factor = 0.075
• Data-to-parameter ratio = 15.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



STRVAL_01
         From the CIF: _refine_ls_abs_structure_Flack    0.510
         From the CIF: _refine_ls_abs_structure_Flack_su    0.060
           Alert C Flack test results are ambiguous.

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           27.40
         From the CIF: _reflns_number_total               2175
         Count of symmetry unique reflns         1235
         Completeness (_total/calc)            176.11%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured       940
         Fraction of Friedel pairs measured     0.761
         Are heavy atom types Z>Si present          yes
          Please check that the estimate of the number of Friedel pairs is
          correct. If it is not, please give the correct count in the
          _publ_section_exptl_refinement section of the submitted CIF.


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 1 Alert Level C = Please check

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S1. Comment

Polychlorinated biphenyls (PCBs) were commercially manufactured and available as complex mixtures for use in transformers, capacitors and hydraulic fluids where they impart chemical stability and fire retardency (Robertson & Hansen, 2001; Hansen, 1999). Their stability, lipophilic character and resistance to physical and biological decomposition contribute to the tendency of PCBs to accumulate in the food chain, where they persist and have become an environmental and human health hazard (Hansen, 1999). The varied mechanisms of PCB toxicity are still poorly understood, in part because the technical PCB products consist of many of the 209 possible PCB congeners.

PCBs are metabolized in vivo to hydroxy- and sulfur-containing metabolites. Hydroxylation proceeds primarily at the meta and para position either via an arene oxide or by direct insertion of a hydroxyl group (Letcher et al., 2000). One of the many unanswered questions is how the three dimensional structure of these important PCB metabolites determines their biological and toxic effects. Few crystal structures of PCB metabolites have been published, and improved knowledge about the three dimensional structure of PCB metabolites is urgently needed. 4-Chloro-3',4'-dihydroxybiphenyl, (I), is a major metabolite of 4-chlorobiphenyl (PCB 3) both in vivo and in vitro (McLean et al., 1996). We report here the crystal structure of this important metabolite.

The solid-state dihedral angle between the two phenyl rings of PCBs and their metabolites appears to depend on the degree of chlorination in the ortho position. According to published data, mono-ortho, di-ortho and tetra-ortho substituted PCBs show a dihedral-angle range of 49–58, 58–67 and 86–87°, respectively (summarized by Miao et al., 1997; see also Lehmler et al., 2001; Mannila & Rissanen, 1994; Singh et al., 1986). To the best of our knowledge, no crystal structures of metabolites of lower chlorinated PCBs such as 4-chlorobiphenyl have been published. The title compound shows a solid-state dihedral angle of 43.1 (3), which, as expected, is smaller than the dihedral angle of any ortho substituted PCB derivatives. The dihedral angle in aqueous solution was calculated to be 37.2°, which is close to the value observed in the solid state. The differences in the solid-state dihedral angle and the calculated angle are probably due to crystal packing effects.

S2. Experimental

4-Chloro-3',4'-dihydroxybiphenyl was synthesized in as described by McLean et al. (1996). Pale-yellow irregular crystals were obtained from n-hexanes/chloroform; m.p. = 415–416 K. The dihedral angle of the title compound was calculated with MM2* using GB/SA water solvent continuum as implemented by MacroModel 5.0 (Still et al., 1990).

S3. Refinement

Initial space group assignment as Pna2₁ was based upon systematic absences and intensity statistics. Space group Pnma was rejected because of the lack of a suitable solution and later by analysis of the structure. The assignment was confirmed by satisfactory solution and refinement in Pna2₁. There were no correlation coefficient matrix elements greater than 0.5. Nevertheless, the crystals are racemic twins, and this was accounted for using the SHELXL TWIN instruction. The hydroxyl H atoms were found in difference maps and refined using a riding model with U values set to 1.5Uiso of their corresponding O atoms.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in Siemens SHELXTL (Sheldrick, 1994); software used to prepare material for publication: SHELX97 and local programs.

Figures

Fig. 1. A view of 4-chloro-3',4'-dihydroxybiphenyl. Displacement ellipsoids are drawn at the 50% probability level.

(I)

Crystal data

C12H9ClO2	Dx = 1.443 Mg m^−3
Mr = 220.64	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pna21	Cell parameters from 4573 reflections
a = 18.358 (1) Å	θ = 1.0–27.5°
b = 6.621 (2) Å	µ = 0.35 mm^−1
c = 8.356 (3) Å	T = 144 K
V = 1015.7 (5) Å^3	Irregular fragment from large slab, pale yellow
Z = 4	0.32 × 0.18 × 0.18 mm
F(000) = 456

Data collection

Nonius KappaCCD diffractometer	1886 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.038
Graphite monochromator	θmax = 27.4°, θmin = 2.2°
Detector resolution: 18 pixels mm^-1	h = −23→23
ω scans at fixed χ = 55°	k = −8→8
8374 measured reflections	l = −10→10
2175 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.036	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.075	w = 1/[σ^2(Fo^2) + (0.0296P)^2 + 0.0647P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max = 0.006
2175 reflections	Δρmax = 0.23 e Å^−3
137 parameters	Δρmin = −0.22 e Å^−3
41 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.51 (6)

Special details

Experimental. Space group assignment as non-centrosymmetric was based upon several factors including intensity distribution, E statistics, easy structure solution and refinement. Attempts at assignment of a centrosymmetric space group (Pnma) were unsuccessful. Nevertheless, the crystals are racemic twins, and this was accounted for using the SHELXL 'TWIN' instruction. There were no correlation coefficient matrix elements greater than 0.5.

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.25796 (7)	0.7503 (2)	0.31412 (17)	0.0277 (3)
H1O	0.2274	0.8655	0.2930	0.042*
O2	0.24006 (6)	0.9810 (2)	0.05802 (16)	0.0297 (3)
H2O	0.2394	1.0492	−0.0267	0.045*
Cl1	0.61061 (2)	−0.15826 (7)	0.06978 (7)	0.03645 (16)
C1	0.43988 (9)	0.3339 (3)	0.0469 (3)	0.0231 (4)
C2	0.50969 (10)	0.3637 (3)	−0.0166 (3)	0.0277 (5)
H2	0.5211	0.4882	−0.0674	0.033*
C3	0.56216 (11)	0.2151 (3)	−0.0066 (3)	0.0297 (5)
H3	0.6097	0.2384	−0.0474	0.036*
C4	0.54492 (9)	0.0323 (3)	0.0633 (2)	0.0267 (4)
C5	0.47682 (10)	−0.0032 (3)	0.1256 (3)	0.0310 (5)
H5	0.4654	−0.1302	0.1723	0.037*
C6	0.42516 (10)	0.1492 (3)	0.1193 (2)	0.0294 (5)
H6	0.3786	0.1269	0.1655	0.035*
C1'	0.38429 (10)	0.4973 (3)	0.0410 (2)	0.0248 (5)
C2'	0.34265 (10)	0.5393 (3)	0.1762 (2)	0.0226 (4)
H2'	0.3469	0.4567	0.2687	0.027*
C3'	0.29505 (10)	0.7018 (3)	0.1756 (2)	0.0226 (4)
C4'	0.28663 (10)	0.8211 (3)	0.0406 (2)	0.0236 (5)
C5'	0.32558 (11)	0.7759 (3)	−0.0965 (3)	0.0293 (5)
H5'	0.3188	0.8543	−0.1906	0.035*
C6'	0.37483 (11)	0.6151 (3)	−0.0966 (3)	0.0284 (5)
H6'	0.4020	0.5856	−0.1904	0.034*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0313 (7)	0.0276 (7)	0.0242 (8)	0.0077 (7)	0.0049 (6)	0.0072 (7)
O2	0.0329 (7)	0.0302 (7)	0.0261 (7)	0.0061 (5)	−0.0011 (7)	0.0121 (7)
Cl1	0.0342 (3)	0.0339 (3)	0.0413 (3)	0.0088 (2)	−0.0030 (3)	−0.0040 (3)
C1	0.0253 (9)	0.0224 (9)	0.0217 (11)	−0.0039 (7)	0.0010 (9)	−0.0003 (9)
C2	0.0311 (11)	0.0249 (11)	0.0272 (11)	−0.0055 (9)	0.0040 (9)	0.0010 (10)
C3	0.0276 (10)	0.0302 (12)	0.0314 (12)	−0.0027 (8)	0.0080 (9)	−0.0003 (10)
C4	0.0266 (9)	0.0282 (10)	0.0252 (11)	0.0019 (7)	−0.0035 (10)	−0.0055 (11)
C5	0.0337 (12)	0.0241 (11)	0.0353 (13)	−0.0019 (9)	0.0040 (9)	0.0030 (10)
C6	0.0248 (10)	0.0300 (12)	0.0333 (14)	−0.0049 (8)	0.0037 (9)	0.0002 (10)
C1'	0.0256 (9)	0.0246 (10)	0.0243 (12)	−0.0045 (7)	−0.0026 (8)	−0.0012 (9)
C2'	0.0263 (10)	0.0213 (10)	0.0202 (10)	−0.0034 (8)	0.0009 (8)	0.0048 (9)
C3'	0.0210 (10)	0.0267 (10)	0.0202 (10)	−0.0035 (8)	−0.0011 (8)	0.0021 (9)
C4'	0.0228 (9)	0.0241 (10)	0.0238 (12)	−0.0017 (8)	−0.0019 (8)	0.0060 (9)
C5'	0.0354 (11)	0.0312 (11)	0.0211 (10)	−0.0013 (9)	−0.0012 (9)	0.0062 (10)
C6'	0.0342 (11)	0.0312 (12)	0.0197 (10)	−0.0018 (9)	0.0031 (9)	0.0046 (10)

Geometric parameters (Å, º)

O1—C3'	1.380 (2)	C5—C6	1.386 (3)
O1—H1O	0.9633	C5—H5	0.9500
O2—C4'	1.368 (2)	C6—H6	0.9500
O2—H2O	0.8400	C1'—C2'	1.392 (3)
Cl1—C4	1.7461 (18)	C1'—C6'	1.400 (3)
C1—C6	1.391 (3)	C2'—C3'	1.386 (3)
C1—C2	1.401 (3)	C2'—H2'	0.9500
C1—C1'	1.488 (2)	C3'—C4'	1.386 (3)
C2—C3	1.379 (3)	C4'—C5'	1.383 (3)
C2—H2	0.9500	C5'—C6'	1.397 (3)
C3—C4	1.381 (3)	C5'—H5'	0.9500
C3—H3	0.9500	C6'—H6'	0.9500
C4—C5	1.375 (3)
C3'—O1—H1O	108.5	C1—C6—H6	119.2
C4'—O2—H2O	109.5	C2'—C1'—C6'	119.12 (17)
C6—C1—C2	117.80 (16)	C2'—C1'—C1	119.66 (17)
C6—C1—C1'	121.37 (16)	C6'—C1'—C1	121.18 (17)
C2—C1—C1'	120.80 (16)	C3'—C2'—C1'	119.93 (17)
C3—C2—C1	121.01 (18)	C3'—C2'—H2'	120.0
C3—C2—H2	119.5	C1'—C2'—H2'	120.0
C1—C2—H2	119.5	O1—C3'—C2'	119.27 (16)
C2—C3—C4	119.40 (18)	O1—C3'—C4'	119.67 (16)
C2—C3—H3	120.3	C2'—C3'—C4'	121.01 (16)
C4—C3—H3	120.3	O2—C4'—C5'	125.32 (18)
C5—C4—C3	121.24 (17)	O2—C4'—C3'	115.08 (17)
C5—C4—Cl1	119.52 (15)	C5'—C4'—C3'	119.58 (17)
C3—C4—Cl1	119.23 (14)	C4'—C5'—C6'	119.97 (19)
C4—C5—C6	118.91 (18)	C4'—C5'—H5'	120.0
C4—C5—H5	120.5	C6'—C5'—H5'	120.0
C6—C5—H5	120.5	C5'—C6'—C1'	120.32 (19)
C5—C6—C1	121.59 (18)	C5'—C6'—H6'	119.8
C5—C6—H6	119.2	C1'—C6'—H6'	119.8
C6—C1—C2—C3	−0.5 (3)	C6'—C1'—C2'—C3'	−2.9 (3)
C1'—C1—C2—C3	177.8 (2)	C1—C1'—C2'—C3'	174.73 (16)
C1—C2—C3—C4	1.8 (3)	C1'—C2'—C3'—O1	−175.44 (16)
C2—C3—C4—C5	−1.2 (3)	C1'—C2'—C3'—C4'	1.7 (3)
C2—C3—C4—Cl1	177.91 (17)	O1—C3'—C4'—O2	−0.5 (2)
C3—C4—C5—C6	−0.7 (3)	C2'—C3'—C4'—O2	−177.64 (16)
Cl1—C4—C5—C6	−179.85 (15)	O1—C3'—C4'—C5'	177.99 (16)
C4—C5—C6—C1	2.1 (3)	C2'—C3'—C4'—C5'	0.9 (3)
C2—C1—C6—C5	−1.5 (3)	O2—C4'—C5'—C6'	176.17 (17)
C1'—C1—C6—C5	−179.78 (19)	C3'—C4'—C5'—C6'	−2.2 (3)
C6—C1—C1'—C2'	43.1 (3)	C4'—C5'—C6'—C1'	0.9 (3)
C2—C1—C1'—C2'	−135.0 (2)	C2'—C1'—C6'—C5'	1.6 (3)
C6—C1—C1'—C6'	−139.3 (2)	C1—C1'—C6'—C5'	−175.99 (17)
C2—C1—C1'—C6'	42.6 (3)