1,4-Bis(3-chloro­pyrazin-2-yl­oxy)benzene

Thothadri Srinivasan; Venkatesan Kalpana; Perumal Rajakumar; Devadasan Velmurugan

doi:10.1107/S1600536813007824

. 2013 Mar 28;69(Pt 4):o611. doi: 10.1107/S1600536813007824

1,4-Bis(3-chloropyrazin-2-yloxy)benzene

Thothadri Srinivasan ^a, Venkatesan Kalpana ^b, Perumal Rajakumar ^b, Devadasan Velmurugan ^a,^*

PMCID: PMC3629649 PMID: 23634136

Abstract

In the title compound, C₁₄H₈Cl₂N₄O₂, the pyrazine rings are orthogonal to the benzene ring, making dihedral angles of 88.42 (8) and 89.22 (8)°. The Cl atoms attached to the pyrazine rings deviate by −0.0597 (5) and 0.0009 (5) Å from the ring plane. The crystal structure features C—H⋯N hydrogen bonds.

Related literature

For applications of the pyrazine ring system in drug development, see: Du et al. (2009 ▶); Dubinina et al. (2006 ▶); Ellsworth et al. (2007 ▶); Mukaiyama et al. (2007 ▶). For a related structure, see: Nasir et al. (2010 ▶). graphic file with name e-69-0o611-scheme1.jpg

Experimental

Crystal data

C₁₄H₈Cl₂N₄O₂
M _r = 335.14
Monoclinic,
a = 11.083 (2) Å
b = 10.0452 (17) Å
c = 12.846 (2) Å
β = 105.681 (6)°
V = 1376.9 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.48 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.869, T _max = 0.909
12550 measured reflections
3461 independent reflections
2835 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.092
S = 1.04
3461 reflections
199 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); 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 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(22.8KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813007824/pv2624sup1.cif

e-69-0o611-sup1.cif^{(22.8KB, cif)}

Click here for additional data file.^{(166.3KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813007824/pv2624Isup2.hkl

e-69-0o611-Isup2.hkl^{(166.3KB, hkl)}

Click here for additional data file.^{(5.3KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813007824/pv2624Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C13—H13⋯N3ⁱ	0.93	2.60	3.480 (2)	159

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors thank the TBI X-ray facility and the UGC (SAP), CAS in Crystallography and Biophysics, University of Madras, India, for the data collection and other facilities. TS also thanks the DST for an Inspire fellowship.

supplementary crystallographic information

Comment

The pyrazine ring is a useful structural unit in medicinal chemistry and has found broad applications in drug development and can be used as antiproliferative agent (Dubinina et al., 2006), potent CXCR3 antagonist (Du et al., 2009), CB1 antagonist (Ellsworth et al., 2007) and c-Src inhibitor (Mukaiyama et al., 2007). In view of different applications of this class of compounds, we have undertaken the single-crystal structure determination of the title compound.

The bond distances and angles in the title compound (Fig. 1) agree very well with the corresponding bond distances and angles reported in a closely related compound (Nasir et al., 2010). In the titled compound, the pyrazine ring (N1/N2/C1-C4) makes a dihedral angle of 88.42 (8)° with the benzene ring (C5-C10), which shows that these are orthogonal to each other. The other pyrazine ring (N3/N4/C11-C14) makes a dihedral angle of 89.22 (8)° with the bezene ring, which also shows that these are also orthogonal to each other. The dihedral angle between the two pyrazine rings is 3.18 (7)°. The chlorine atoms Cl1 and Cl2 attached with the pyrazine rings deviate by -0.0597 (5) and 0.0009 (5)Å. The crystal packing is stabilised by intermolecular C–H···N hydrogen bonds (Tab. 1 & Fig. 2).

Experimental

To a stirred solution of Cs₂CO₃/K₂CO₃ (22 mmol) in CH₃CN (50 mL), dihydroxybenzenes (10 mmol) was added and stirred for 5 min. 2,3-Dichloropyrazine (20 mmol) in CH₃CN (100 mL) was added dropwise to the above reaction mixture and stirring was allowed at refluxing condition for 12 h. After the reaction was complete, the reaction mixture was allowed to attain room temperature and then evaporated to dryness. The residue obtained was extracted with CH₂Cl₂ (3 x 100 mL), washed with water (3 x 100 mL), brine and then dried over Na₂SO₄. Evaporation of the organic layer gave a residue, which on purification using column chromatography with hexane/CHCl₃ (1:1) as an eluent gave the corresponding compound. Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a solution of the title compound in hexane at room temperature.