organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

1-Bromo-4-chloro-2,5-di­meth­oxy­benzene

aCollege of Pharmaceutical Sciences, Southwest University, Chong Qing 400716, People's Republic of China, bDepartment of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA, and cDepartment of Occupational and Environmental Health, The University of Iowa, 100 Oakdale Campus, 124 IREH, Iowa City, IA 52242-5000, USA
*Correspondence e-mail: hans-joachim-lehmler@uiowa.edu

(Received 15 December 2009; accepted 5 January 2010; online 13 January 2010)

The mol­ecule of the title compound, C8H8BrClO2, sits on a crystallographic inversion centre, which ensures that the halogen sites are disordered, with exactly 50% Br and 50% Cl at each halogen site. The inversion renders the two meth­oxy groups equivalent. These groups lie almost in the plane of the aromatic ring system, making dihedral angles of 8.8 (4)° to the ring.

Related literature

For the synthesis of PCBs and PCB metabolites using the Suzuki coupling reaction, see: Lehmler & Robertson (2001[Lehmler, H.-J. & Robertson, L. W. (2001). Chemosphere, 45, 1119-1127.]); Song et al. (2008[Song, Y., Buettner, G. R., Parkin, S., Wagner, B. A., Robertson, L. W. & Lehmler, H.-J. (2008). J. Org. Chem. 73, 8296-8304.]). For similar structures of halogenated meth­oxy-benzenes, see: Rissanen et al. (1988[Rissanen, K., Valkonen, J. & Mannila, B. (1988). Acta Cryst. C44, 682-684.]); Telu et al. (2008[Telu, S., Parkin, S., Robertson, L. W. & Lehmler, H.-J. (2008). Acta Cryst. E64, o424.]) and literature cited therein. For general background about PCBs, see: Hansen (1999[Hansen, L. G. (1999). The ortho side of PCBs: Occurrence and disposition. Boston: Kluwer Academic Publishers.]); Robertson & Hansen (2001[Robertson, L. W. & Hansen, L. G. (2001). Recent advances in the environmental toxicology and health effects of PCBs. University Press of Kentucky, Lexington.]).

[Scheme 1]

Experimental

Crystal data
  • C8H8BrClO2

  • Mr = 251.50

  • Monoclinic, P 21 /n

  • a = 6.3804 (7) Å

  • b = 8.2586 (10) Å

  • c = 8.6337 (11) Å

  • β = 90.853 (6)°

  • V = 454.89 (9) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 4.77 mm−1

  • T = 90 K

  • 0.25 × 0.22 × 0.22 mm

Data collection
  • Nonius KappaCCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996[Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.]) Tmin = 0.310, Tmax = 0.350

  • 1938 measured reflections

  • 1021 independent reflections

  • 824 reflections with I > 2σ(I)

  • Rint = 0.032

Refinement
  • R[F2 > 2σ(F2)] = 0.030

  • wR(F2) = 0.069

  • S = 1.04

  • 1021 reflections

  • 61 parameters

  • 2 restraints

  • H-atom parameters constrained

  • Δρmax = 0.57 e Å−3

  • Δρmin = −0.49 e Å−3

Data collection: COLLECT (Nonius, 1998[Nonius (1998). COLLECT. Nonius BV, Delft,The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by Carter, C. W. Jr & Sweet, R. M. pp. 307-326. New York: Academic Press.]); data reduction: DENZO-SMN (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by Carter, C. W. Jr & Sweet, R. M. pp. 307-326. New York: Academic Press.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: XP in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELX97 and local procedures.

Supporting information


Comment top

The title compound is a precursor for the synthesis of hydroxylated metabolites of polychlorinated biphenyls (PCBs) (Lehmler & Robertson, 2001; Song et al., 2008), a class of abundant, persistent organic pollutants in the global ecosystem (Hansen, 1999; Robertson & Hansen, 2001). The molecule of the title compound sits on a crystallographic inversion centre, which ensures that the Br/Cl sites are disordered exactly 50:50 in very nearly the same position. Furthermore, the inversion renders the two methoxy groups equivalent. The chlorine, bromine and the two methoxy groups essentially lie within the plane of the benzene ring, with the dihedral angles between the plane of the benzene ring (C1 through C3 and C1A through C3A) and the methoxy group being 8.8 (4)° (for both methoxy groups). This is comparable to the solid state conformation of the methoxy group of other methoxybenzenes with none or only one ortho substituent (Rissanen et al., 1988). Overall, these structural characteristics make the title compound a perfect precurusor for the synthesis of PCB derivatives using the Suzuki coupling reaction (Song et al., 2008).

Related literature top

For the synthesis of PCBs and PCB metabolites using the Suzuki coupling reaction, see: Lehmler & Robertson (2001); Song et al. (2008). For similar structures of halogenated methoxy-benzenes, see: Rissanen et al. (1988); Telu et al. (2008) and literature cited therein. For general background, see: Hansen (1999); Robertson & Hansen (2001).

Experimental top

The title compound was synthesized by chlorination of 1-bromo-2,5-dimethoxy-benzene with HCl/H2O2 as chlorination reagent as described previously (Song et al., 2008). Crystals suitable for X-ray diffraction were grown by slow evaporation of a saturated solution of the title compound in CHCl3.

Refinement top

H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained C—H distances of 0.98 Å (CMeH) and 0.95 Å (CArH) with Uiso(H) values set to either 1.5Ueq or 1.2Ueq of the attached C atom respectively. For the disordered halogen sites, the distances were refined subject to a condition whereby the C—Cl distance was restrained (using DFIX in SHELXL97) to be 0.916 times the C—Br length (International Tables, vol C). The halogen displacement parameters were constrained to be equal (EADP in SHELXL97).

Computing details top

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, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELX97 (Sheldrick, 2008) and local procedures.

Figures top
[Figure 1] Fig. 1. View of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. Atoms labelled A are inversion related, symmetry code A: 1 - x, 1 - y, 1 - z. The disordered atoms ClB and BrB have been omitted for clarity.
1-Bromo-4-chloro-2,5-dimethoxybenzene top
Crystal data top
C8H8BrClO2F(000) = 248
Mr = 251.50Dx = 1.836 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 1051 reflections
a = 6.3804 (7) Åθ = 1.0–27.5°
b = 8.2586 (10) ŵ = 4.77 mm1
c = 8.6337 (11) ÅT = 90 K
β = 90.853 (6)°Block, colourless
V = 454.89 (9) Å30.25 × 0.22 × 0.22 mm
Z = 2
Data collection top
Nonius KappaCCD
diffractometer
1021 independent reflections
Radiation source: fine-focus sealed tube824 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.032
Detector resolution: 18 pixels mm-1θmax = 27.3°, θmin = 3.4°
ω scans at fixed χ = 55°h = 88
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
k = 1010
Tmin = 0.310, Tmax = 0.350l = 1111
1938 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030H-atom parameters constrained
wR(F2) = 0.069 w = 1/[σ2(Fo2) + (0.0274P)2 + 0.2316P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
1021 reflectionsΔρmax = 0.57 e Å3
61 parametersΔρmin = 0.49 e Å3
2 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.010 (2)
Crystal data top
C8H8BrClO2V = 454.89 (9) Å3
Mr = 251.50Z = 2
Monoclinic, P21/nMo Kα radiation
a = 6.3804 (7) ŵ = 4.77 mm1
b = 8.2586 (10) ÅT = 90 K
c = 8.6337 (11) Å0.25 × 0.22 × 0.22 mm
β = 90.853 (6)°
Data collection top
Nonius KappaCCD
diffractometer
1021 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
824 reflections with I > 2σ(I)
Tmin = 0.310, Tmax = 0.350Rint = 0.032
1938 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0302 restraints
wR(F2) = 0.069H-atom parameters constrained
S = 1.04Δρmax = 0.57 e Å3
1021 reflectionsΔρmin = 0.49 e Å3
61 parameters
Special details top

Experimental. The crystals were of surprisingly poor quality, with diffraction spots around 3° wide. Nevertheless, because the cell is quite small there were no problems with reflection overlap.

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 > 2σ(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.

The structure straddles an inversion centre but the molecule itself does not possess inversion point symmetry, thus it is forced to be disordered in the crystal. This disorder places Cl and Br atoms at 50% occupancy in essentially the same position. For refinement, the C—Cl distance was restrained to be 0.916 times that of the C—Br distance. The ratio used was taken from the International Tables volume C. Further, anisotropic displacement parameters for the Br and Cl atoms were made equal.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
Br10.7756 (12)0.2627 (9)0.7207 (9)0.0235 (3)0.50
Cl10.760 (3)0.271 (2)0.711 (2)0.0235 (3)0.50
O10.6036 (3)0.5566 (2)0.19443 (19)0.0247 (4)
C10.6144 (4)0.3987 (3)0.5927 (3)0.0212 (6)
C20.6749 (4)0.4217 (3)0.4409 (3)0.0213 (6)
H20.79450.36730.40230.026*
C30.5597 (4)0.5244 (3)0.3457 (3)0.0208 (6)
C40.7634 (4)0.4604 (3)0.1242 (3)0.0281 (6)
H4A0.89900.48390.17400.042*
H4B0.77010.48610.01360.042*
H4C0.73020.34540.13710.042*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0261 (12)0.0218 (8)0.0226 (10)0.0081 (6)0.0047 (6)0.0023 (5)
Cl10.0261 (12)0.0218 (8)0.0226 (10)0.0081 (6)0.0047 (6)0.0023 (5)
O10.0299 (11)0.0221 (10)0.0222 (10)0.0029 (8)0.0045 (8)0.0016 (7)
C10.0221 (14)0.0181 (13)0.0232 (14)0.0004 (10)0.0038 (10)0.0013 (10)
C20.0214 (14)0.0165 (13)0.0259 (14)0.0000 (10)0.0005 (10)0.0043 (10)
C30.0230 (14)0.0162 (12)0.0232 (13)0.0037 (10)0.0012 (10)0.0016 (10)
C40.0278 (16)0.0314 (15)0.0254 (15)0.0043 (12)0.0069 (12)0.0011 (12)
Geometric parameters (Å, º) top
Br1—C11.872 (4)C2—C31.385 (3)
Cl1—C11.727 (9)C2—H20.9500
O1—C31.366 (3)C3—C1i1.392 (3)
O1—C41.434 (3)C4—H4A0.9800
C1—C21.385 (3)C4—H4B0.9800
C1—C3i1.392 (3)C4—H4C0.9800
C3—O1—C4116.95 (19)O1—C3—C2124.9 (2)
C2—C1—C3i122.3 (2)O1—C3—C1i116.9 (2)
C2—C1—Cl1119.2 (8)C2—C3—C1i118.2 (2)
C3i—C1—Cl1118.5 (8)O1—C4—H4A109.5
C2—C1—Br1118.8 (3)O1—C4—H4B109.5
C3i—C1—Br1118.9 (3)H4A—C4—H4B109.5
C3—C2—C1119.5 (2)O1—C4—H4C109.5
C3—C2—H2120.2H4A—C4—H4C109.5
C1—C2—H2120.2H4B—C4—H4C109.5
C3i—C1—C2—C30.1 (4)C4—O1—C3—C1i171.2 (2)
Cl1—C1—C2—C3179.7 (8)C1—C2—C3—O1180.0 (2)
Br1—C1—C2—C3178.7 (3)C1—C2—C3—C1i0.1 (4)
C4—O1—C3—C28.7 (4)
Symmetry code: (i) x+1, y+1, z+1.

Experimental details

Crystal data
Chemical formulaC8H8BrClO2
Mr251.50
Crystal system, space groupMonoclinic, P21/n
Temperature (K)90
a, b, c (Å)6.3804 (7), 8.2586 (10), 8.6337 (11)
β (°) 90.853 (6)
V3)454.89 (9)
Z2
Radiation typeMo Kα
µ (mm1)4.77
Crystal size (mm)0.25 × 0.22 × 0.22
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.310, 0.350
No. of measured, independent and
observed [I > 2σ(I)] reflections
1938, 1021, 824
Rint0.032
(sin θ/λ)max1)0.645
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.030, 0.069, 1.04
No. of reflections1021
No. of parameters61
No. of restraints2
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.57, 0.49

Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), SHELX97 (Sheldrick, 2008) and local procedures.

 

Acknowledgements

This research was supported by grants ES05605, ES012475, ES013661 from the National Institute of Environmental Health Sciences, NIH, (HJL) and SWUB2008077 from the Science Foundation of Southwest University, China (YS).

References

First citationHansen, L. G. (1999). The ortho side of PCBs: Occurrence and disposition. Boston: Kluwer Academic Publishers.
First citationLehmler, H.-J. & Robertson, L. W. (2001). Chemosphere, 45, 1119–1127.  Web of Science CrossRef PubMed CAS
First citationNonius (1998). COLLECT. Nonius BV, Delft,The Netherlands.
First citationOtwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by Carter, C. W. Jr & Sweet, R. M. pp. 307–326. New York: Academic Press.
First citationRissanen, K., Valkonen, J. & Mannila, B. (1988). Acta Cryst. C44, 682–684.  CSD CrossRef CAS Web of Science IUCr Journals
First citationRobertson, L. W. & Hansen, L. G. (2001). Recent advances in the environmental toxicology and health effects of PCBs. University Press of Kentucky, Lexington.
First citationSheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSong, Y., Buettner, G. R., Parkin, S., Wagner, B. A., Robertson, L. W. & Lehmler, H.-J. (2008). J. Org. Chem. 73, 8296–8304.  Web of Science CSD CrossRef PubMed CAS
First citationTelu, S., Parkin, S., Robertson, L. W. & Lehmler, H.-J. (2008). Acta Cryst. E64, o424.  Web of Science CSD CrossRef IUCr Journals

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds