1,5-Dibromo-2,4-dimeth­oxy­benzene

Vijesh, A.M.; Isloor, A.M.; Gerber, T.; Brecht, B. van; Betz, R.

doi:10.1107/S1600536812047848

organic compounds

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ISSN: 2056-9890

Volume 68| Part 12| December 2012| Page o3479

doi:10.1107/S1600536812047848

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1,5-Dibromo-2,4-dimethoxybenzene

A. M. Vijesh,^a Arun M. Isloor,^b Thomas Gerber,^c Benjamin van Brecht ^c and Richard Betz ^c ^*

^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

(Received 2 November 2012; accepted 21 November 2012; online 30 November 2012)

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 crystal structure 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

C₈H₈Br₂O₂
M_r = 295.96
Monoclinic, P 2₁ /c
a = 7.7944 (2) Å
b = 8.5884 (4) Å
c = 14.7877 (4) Å
β = 107.838 (1)°
V = 942.32 (6) Å³
Z = 4
Mo Kα radiation
μ = 8.56 mm⁻¹
T = 200 K
0.47 × 0.46 × 0.34 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ) T_min = 0.674, T_max = 1.000
15097 measured reflections
2350 independent reflections
2094 reflections with I > 2σ(I)
R_int = 0.032

Refinement

R[F² > 2σ(F²)] = 0.021
wR(F²) = 0.049
S = 1.08
2350 reflections
111 parameters
H-atom parameters constrained
Δρ_max = 0.55 e Å⁻³
Δρ_min = −0.52 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7C⋯O1ⁱ	0.98	2.70	3.632 (3)	160
Symmetry code: (i) $[-x, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: APEX2 (Bruker, 2010 ); cell refinement: 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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812047848/zs2243sup1.cif

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

checkCIF report

Comment top

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).

Related literature top

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 crystal structure of 1-bromo-5-chloro-2,4-dimethoxybenzene but entered incorrectly as the title compound in the CSD (CCDC 271922), see: Yang et al. (2005). For graph-set analysis of hydrogen bonds, see: Bernstein et al. (1995).

Experimental top

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.

Computing details top

Data collection: APEX2 (Bruker, 2010); cell refinement: 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).

Figures top

	Fig. 1. The molecular structure of the title compound showing atom labels, with anisotropic displacement ellipsoids drawn at the 50% probability level.
	Fig. 2. Intermolecular contacts, viewed along [-1 0 0], with hydrogen bonds shown as dashed lines. For symmetry codes, see Table 1.
	Fig. 3. Molecular packing of the title compound, viewed down [0 1 0] (anisotropic displacement ellipsoids drawn at 50% probability level).

1,5-Dibromo-2,4-dimethoxybenzene top

Crystal data top

C₈H₈Br₂O₂	F(000) = 568
M_r = 295.96	D_x = 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

Data collection top

Bruker APEXII CCD diffractometer	2350 independent reflections
Radiation source: fine-focus sealed tube	2094 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.032
ϕ and ω scans	θ_max = 28.4°, θ_min = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −10→10
T_min = 0.674, T_max = 1.000	k = −11→11
15097 measured reflections	l = −18→19

Refinement top

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(F_o²) + (0.0199P)² + 0.5315P] where P = (F_o² + 2F_c²)/3
2350 reflections	(Δ/σ)_max = 0.001
111 parameters	Δρ_max = 0.55 e Å⁻³
0 restraints	Δρ_min = −0.52 e Å⁻³

Crystal data top

C₈H₈Br₂O₂	V = 942.32 (6) Å³
M_r = 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)°

Data collection top

Bruker APEXII CCD diffractometer	2350 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2008)	2094 reflections with I > 2σ(I)
T_min = 0.674, T_max = 1.000	R_int = 0.032
15097 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.021	0 restraints
wR(F²) = 0.049	H-atom parameters constrained
S = 1.08	Δρ_max = 0.55 e Å⁻³
2350 reflections	Δρ_min = −0.52 e Å⁻³
111 parameters

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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···C_gⁱⁱ	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
M_r	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)
T_min, T_max	0.674, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	15097, 2350, 2094
R_int	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
Δρ_max, Δρ_min (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).

Hydrogen-bond geometry (Å, º) top

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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