organic compounds
1,5-Dibromo-2,4-dimethoxybenzene
aGITAM University, Department of Engineering Chemistry, GIT, Rushikonda, Visakhapatnam, A.P. 530 045, India, bNational Institute of Technology-Karnataka, Department of Chemistry, Medicinal Chemistry Laboratory, Surathkal, Mangalore 575 025, India, and cNelson Mandela Metropolitan University, Summerstrand Campus, Department of Chemistry, University Way, Summerstrand, PO Box 77000, Port Elizabeth, 6031, South Africa
*Correspondence e-mail: richard.betz@webmail.co.za
In the title compound, C8H8Br2O2, all non-H atoms lie essentially in a common plane (r.m.s deviation of all fitted non-H atoms = 0.0330 Å). In the crystal, weak C—H⋯O hydrogen bonds connect the molecules, forming chains which extend along the b-axis direction.
Related literature
For background to the pharmacological importance of the title compound, see: Pahari & Rohr (2009). For the synthesis of the title compound, see: Yang et al. (2009). For a report listing the of 1-bromo-5-chloro-2,4-dimethoxybenzene but entered incorrectly as the title compound in the CSD (TASBAR), see: Yang et al. (2005). For graph-set analysis of hydrogen bonds, see: Bernstein et al. (1995).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2010); cell SAINT (Bruker, 2010); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009).
Supporting information
10.1107/S1600536812047848/zs2243sup1.cif
contains datablocks I, global. DOI:Supporting information file. DOI: 10.1107/S1600536812047848/zs2243Isup2.cdx
Structure factors: contains datablock I. DOI: 10.1107/S1600536812047848/zs2243Isup3.hkl
Supporting information file. DOI: 10.1107/S1600536812047848/zs2243Isup4.cml
1,5-Dibromo-2,4-dimethoxybenzene was synthesized according to a published procedure (Yang et al., 2009). The crude product was recrystallized from hot ethanol.
Carbon-bound H atoms were placed in calculated positions [C—H(aromatic) = 0.95 Å and C—H(methyl) = 0.98 Å] and with Uiso(H) = 1.2Ueq(C) (aromatic) and allowed to ride in the
The H atoms of the methyl groups were allowed to rotate with a fixed angle around the C—C bond to best fit the experimental electron density, with Uiso(H) = 1.5Ueq(C).Data collection: APEX2 (Bruker, 2010); cell
SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).C8H8Br2O2 | F(000) = 568 |
Mr = 295.96 | Dx = 2.086 Mg m−3 |
Monoclinic, P21/c | Melting point = 414–413 K |
Hall symbol: -P 2ybc | Mo Kα radiation, λ = 0.71073 Å |
a = 7.7944 (2) Å | Cell parameters from 9980 reflections |
b = 8.5884 (4) Å | θ = 2.7–28.3° |
c = 14.7877 (4) Å | µ = 8.56 mm−1 |
β = 107.838 (1)° | T = 200 K |
V = 942.32 (6) Å3 | Block, white |
Z = 4 | 0.47 × 0.46 × 0.34 mm |
Bruker APEXII CCD diffractometer | 2350 independent reflections |
Radiation source: fine-focus sealed tube | 2094 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.032 |
ϕ and ω scans | θmax = 28.4°, θmin = 2.8° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −10→10 |
Tmin = 0.674, Tmax = 1.000 | k = −11→11 |
15097 measured reflections | l = −18→19 |
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)] = 0.021 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.049 | H-atom parameters constrained |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0199P)2 + 0.5315P] where P = (Fo2 + 2Fc2)/3 |
2350 reflections | (Δ/σ)max = 0.001 |
111 parameters | Δρmax = 0.55 e Å−3 |
0 restraints | Δρmin = −0.52 e Å−3 |
C8H8Br2O2 | V = 942.32 (6) Å3 |
Mr = 295.96 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 7.7944 (2) Å | µ = 8.56 mm−1 |
b = 8.5884 (4) Å | T = 200 K |
c = 14.7877 (4) Å | 0.47 × 0.46 × 0.34 mm |
β = 107.838 (1)° |
Bruker APEXII CCD diffractometer | 2350 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 2094 reflections with I > 2σ(I) |
Tmin = 0.674, Tmax = 1.000 | Rint = 0.032 |
15097 measured reflections |
R[F2 > 2σ(F2)] = 0.021 | 0 restraints |
wR(F2) = 0.049 | H-atom parameters constrained |
S = 1.08 | Δρmax = 0.55 e Å−3 |
2350 reflections | Δρmin = −0.52 e Å−3 |
111 parameters |
x | y | z | Uiso*/Ueq | ||
Br1 | 0.43964 (3) | 0.63810 (3) | 0.268745 (16) | 0.04029 (7) | |
Br2 | 0.29505 (3) | 0.26527 (3) | −0.060701 (15) | 0.03453 (7) | |
O1 | 0.07656 (18) | 0.52208 (17) | 0.26640 (10) | 0.0321 (3) | |
O2 | −0.04398 (17) | 0.19995 (17) | −0.01445 (10) | 0.0323 (3) | |
C1 | 0.2839 (2) | 0.5013 (2) | 0.18080 (13) | 0.0256 (4) | |
C2 | 0.3359 (2) | 0.4436 (2) | 0.10619 (13) | 0.0265 (4) | |
H2 | 0.4487 | 0.4729 | 0.0992 | 0.032* | |
C3 | 0.2236 (2) | 0.3432 (2) | 0.04159 (13) | 0.0243 (4) | |
C4 | 0.0576 (2) | 0.2998 (2) | 0.05093 (13) | 0.0235 (4) | |
C5 | 0.0069 (2) | 0.3587 (2) | 0.12664 (13) | 0.0250 (4) | |
H5 | −0.1056 | 0.3292 | 0.1339 | 0.030* | |
C6 | 0.1190 (2) | 0.4601 (2) | 0.19174 (13) | 0.0244 (4) | |
C7 | −0.2196 (3) | 0.1625 (3) | −0.00979 (15) | 0.0338 (4) | |
H7A | −0.2815 | 0.0957 | −0.0636 | 0.051* | |
H7B | −0.2888 | 0.2585 | −0.0123 | 0.051* | |
H7C | −0.2089 | 0.1075 | 0.0498 | 0.051* | |
C8 | −0.0860 (3) | 0.4691 (3) | 0.28213 (15) | 0.0340 (4) | |
H8A | −0.0983 | 0.5179 | 0.3397 | 0.051* | |
H8B | −0.0816 | 0.3557 | 0.2898 | 0.051* | |
H8C | −0.1894 | 0.4976 | 0.2277 | 0.051* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.02623 (10) | 0.04018 (13) | 0.05077 (14) | −0.00833 (8) | 0.00632 (9) | −0.01578 (9) |
Br2 | 0.02932 (11) | 0.04093 (12) | 0.03863 (12) | −0.00448 (8) | 0.01823 (9) | −0.00465 (8) |
O1 | 0.0301 (7) | 0.0358 (8) | 0.0333 (7) | −0.0062 (6) | 0.0138 (6) | −0.0083 (6) |
O2 | 0.0238 (7) | 0.0400 (8) | 0.0353 (7) | −0.0105 (6) | 0.0123 (6) | −0.0101 (6) |
C1 | 0.0209 (8) | 0.0209 (8) | 0.0314 (9) | −0.0031 (6) | 0.0026 (7) | −0.0002 (7) |
C2 | 0.0195 (8) | 0.0241 (9) | 0.0356 (10) | −0.0015 (7) | 0.0082 (7) | 0.0049 (7) |
C3 | 0.0215 (8) | 0.0235 (9) | 0.0288 (9) | 0.0008 (6) | 0.0093 (7) | 0.0039 (7) |
C4 | 0.0197 (8) | 0.0222 (8) | 0.0272 (9) | −0.0012 (7) | 0.0053 (7) | 0.0030 (7) |
C5 | 0.0195 (8) | 0.0257 (9) | 0.0309 (9) | −0.0025 (7) | 0.0094 (7) | 0.0026 (7) |
C6 | 0.0248 (8) | 0.0218 (8) | 0.0263 (9) | 0.0015 (7) | 0.0071 (7) | 0.0034 (7) |
C7 | 0.0227 (9) | 0.0418 (11) | 0.0371 (11) | −0.0098 (8) | 0.0093 (8) | −0.0034 (9) |
C8 | 0.0336 (10) | 0.0397 (11) | 0.0328 (10) | −0.0050 (8) | 0.0165 (8) | −0.0030 (9) |
Br1—C1 | 1.8918 (18) | C3—C4 | 1.393 (2) |
Br2—C3 | 1.8873 (19) | C4—C5 | 1.392 (3) |
O1—C6 | 1.355 (2) | C5—C6 | 1.391 (3) |
O1—C8 | 1.431 (2) | C5—H5 | 0.9500 |
O2—C4 | 1.352 (2) | C7—H7A | 0.9800 |
O2—C7 | 1.428 (2) | C7—H7B | 0.9800 |
C1—C2 | 1.379 (3) | C7—H7C | 0.9800 |
C1—C6 | 1.389 (2) | C8—H8A | 0.9800 |
C2—C3 | 1.382 (3) | C8—H8B | 0.9800 |
C2—H2 | 0.9500 | C8—H8C | 0.9800 |
C6—O1—C8 | 117.21 (15) | C4—C5—H5 | 119.6 |
C4—O2—C7 | 117.93 (15) | O1—C6—C1 | 117.41 (16) |
C2—C1—C6 | 120.73 (17) | O1—C6—C5 | 123.47 (16) |
C2—C1—Br1 | 119.28 (13) | C1—C6—C5 | 119.12 (17) |
C6—C1—Br1 | 119.99 (14) | O2—C7—H7A | 109.5 |
C1—C2—C3 | 119.87 (17) | O2—C7—H7B | 109.5 |
C1—C2—H2 | 120.1 | H7A—C7—H7B | 109.5 |
C3—C2—H2 | 120.1 | O2—C7—H7C | 109.5 |
C2—C3—C4 | 120.59 (17) | H7A—C7—H7C | 109.5 |
C2—C3—Br2 | 119.71 (13) | H7B—C7—H7C | 109.5 |
C4—C3—Br2 | 119.70 (14) | O1—C8—H8A | 109.5 |
O2—C4—C5 | 123.84 (16) | O1—C8—H8B | 109.5 |
O2—C4—C3 | 117.20 (16) | H8A—C8—H8B | 109.5 |
C5—C4—C3 | 118.96 (16) | O1—C8—H8C | 109.5 |
C6—C5—C4 | 120.72 (16) | H8A—C8—H8C | 109.5 |
C6—C5—H5 | 119.6 | H8B—C8—H8C | 109.5 |
C6—C1—C2—C3 | −0.3 (3) | O2—C4—C5—C6 | 179.44 (17) |
Br1—C1—C2—C3 | 179.81 (14) | C3—C4—C5—C6 | 0.5 (3) |
C1—C2—C3—C4 | 0.2 (3) | C8—O1—C6—C1 | −174.78 (17) |
C1—C2—C3—Br2 | 179.77 (14) | C8—O1—C6—C5 | 5.2 (3) |
C7—O2—C4—C5 | 5.2 (3) | C2—C1—C6—O1 | −179.57 (17) |
C7—O2—C4—C3 | −175.84 (17) | Br1—C1—C6—O1 | 0.3 (2) |
C2—C3—C4—O2 | −179.34 (16) | C2—C1—C6—C5 | 0.5 (3) |
Br2—C3—C4—O2 | 1.1 (2) | Br1—C1—C6—C5 | −179.65 (13) |
C2—C3—C4—C5 | −0.3 (3) | C4—C5—C6—O1 | 179.48 (17) |
Br2—C3—C4—C5 | −179.86 (13) | C4—C5—C6—C1 | −0.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C7—H7C···O1i | 0.98 | 2.70 | 3.632 (3) | 160 |
C1—Br1···Cgii | 1.89 (1) | 3.75 (1) | 5.5701 (19) | 161 (1) |
Symmetry codes: (i) −x, y−1/2, −z+1/2; (ii) −x+1, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H8Br2O2 |
Mr | 295.96 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 200 |
a, b, c (Å) | 7.7944 (2), 8.5884 (4), 14.7877 (4) |
β (°) | 107.838 (1) |
V (Å3) | 942.32 (6) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 8.56 |
Crystal size (mm) | 0.47 × 0.46 × 0.34 |
Data collection | |
Diffractometer | Bruker APEXII CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Bruker, 2008) |
Tmin, Tmax | 0.674, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 15097, 2350, 2094 |
Rint | 0.032 |
(sin θ/λ)max (Å−1) | 0.668 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.021, 0.049, 1.08 |
No. of reflections | 2350 |
No. of parameters | 111 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.55, −0.52 |
Computer programs: APEX2 (Bruker, 2010), SAINT (Bruker, 2010), SHELXS97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 2012) and Mercury (Macrae et al., 2008), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
C7—H7C···O1i | 0.98 | 2.70 | 3.632 (3) | 159.7 |
Symmetry code: (i) −x, y−1/2, −z+1/2. |
Acknowledgements
AMI is thankful to the Department of Atomic Energy, Board for Research in Nuclear Sciences, Government of India, for a Young Scientist award.
References
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The title compound 1,5-dibromo-2,4-dimethoxybenzene is an important intermediate for the synthesis of the anti-HIV drug Elvitegravir and the anticancer drug Psoralidin (Pahari et al., 2009). The crystal structure of 1-bromo-5-chloro-2,4-dimethoxybenzene has been determined (Yang et al., 2005), but the compound was in fact reported erroneously as 1,5-dibromo-2,4-dimethoxybenzene in the CSD (CCDC 271922, ref-code: TASBAR). The error is the result of 50% rotational disorder between the two halogen atoms in the molecule and this fact is also mentioned among the deposited experimental details in the CSD entry. Furthermore, the cell constants reported in this entry [a = 7.722 (4) Å, b = 7.949 (3) Å, c = 7.405 (3) Å, β = 91.78 (1) °, V = 454.315 Å3, Z = 2, space group P 2/c] differed significantly from those of the title compound. In view of the importance of the title compound in synthetic as well as medicinal chemistry, and to rectify the anomaly in the deposited crystallographic data, it was resynthesized and the crystal structure is reported herein.
The title compound is essentially planar (r.m.s. of all fitted non-hydrogen atoms = 0.0330 Å), with one of the methyl carbon atoms deviating most from this common plane by -0.073 (2) Å (Fig. 1). Intracyclic C–C–C angles cover a range from 118.96 (16) ° to 120.73 (17)° with the smallest angle found at one of the carbon atoms bearing a methoxy substituent (C4) and the largest angle at the bromo-substituted carbon atom (C1) in the para position to C4.
In the crystal, a weak intermolecular methyl C—H···O contact (Table 1) whose value falls slightly below the sum of van-der-Waals radii of the atoms participating, is observed, connecting the molecules into chains which extend along b (Fig. 2). A C1–Br1···Cgii contact is also present. According to a graph-set analysis (Bernstein et al., 1995), the descriptor for the C–H···O contacts is C(7). The shortest intercentroid distance between two aromatic ring systems is 4.0267 (10) Å (Fig. 3).