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

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1,3-Bis[(3-chloro­pyrazin-2-yl)­­oxy]benzene

aCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India, and bDepartment of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
*Correspondence e-mail: shirai2011@gmail.com

(Received 6 April 2013; accepted 25 April 2013; online 30 April 2013)

The asymmetric unit of the title compound, C14H8Cl2N4O2, contains one half-mol­ecule, the complete mol­ecule being generated by the operation of a twofold rotation axis. The Cl atom deviates significantly from the plane of the pyrazine ring [0.0215 (4) Å]. The central benzene ring makes a dihedral angle of 72.82 (7)° with the plane of the pyrazine ring.

Related literature

For applications of the pyrazine ring system in drug development, see: Du et al. (2009[Du, X. H., Gustin, D. J., Chen, X. Q., Duquette, J., McGee, L. R., Wang, Z. L., Ebsworth, K., Henne, K., Lemon, B., Ma, J., Miao, S. C., Sabalan, E., Sullivan, T. J., Tonn, G., Collins, T. L. & Medina, J. C. (2009). Bioorg. Med. Chem. Lett. 19, 5200-5204.]); Dubinina et al. (2006[Dubinina, G. G., Platonov, M. O., Golovach, S. M., Borysko, P. O., Tolmachov, A. O. & Volovenko, Y. M. (2006). Eur. J. Med. Chem. 41, 727-737.]); Ellsworth et al. (2007[Ellsworth, B. A., Wang, Y., Zhu, Y. H., Pendri, A., Gerritz, S. W., Sun, C. Q., Carlson, K. E., Kang, L. Y., Baska, R. A., Yang, Y. F., Huang, Q., Burford, N. T., Cullen, M. J., Johnghar, S., Behnia, K., Pelleymounter, M. A., Washburn, W. N. & Ewing, W. R. (2007). Bioorg. Med. Chem. Lett. 17, 3978-3982.]); Mukaiyama et al. (2007[Mukaiyama, H., Nishimura, T., Kobayashi, S., Ozawa, T., Kamada, N., Komatsu, Y., Kikuchi, S., Oonota, H. & Kusama, H. (2007). Bioorg. Med. Chem. Lett. 15, 868-885.]). For background to the fluorescence properties of compounds related to the title compound, see: Kawai et al. (2001[Kawai, M., Lee, M. J., Evans, K. O. & Norlund, T. (2001). J. Fluoresc. 11, 23-32.]); Abdullah (2005[Abdullah, Z. (2005). Intl J. Chem. Sci. 3 , 9-15.]). For a related structure, see: Nasir et al. (2010[Nasir, S. B., Abdullah, Z., Fairuz, Z. A., Ng, S. W. & Tiekink, E. R. T. (2010). Acta Cryst. E66, o2187.]).

[Scheme 1]

Experimental

Crystal data
  • C14H8Cl2N4O2

  • Mr = 335.14

  • Monoclinic, C 2/c

  • a = 9.9618 (3) Å

  • b = 10.2196 (4) Å

  • c = 14.6010 (6) Å

  • β = 106.231 (2)°

  • V = 1427.22 (9) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.47 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[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.873, Tmax = 0.912

  • 6736 measured reflections

  • 1781 independent reflections

  • 1552 reflections with I > 2σ(I)

  • Rint = 0.026

Refinement
  • R[F2 > 2σ(F2)] = 0.036

  • wR(F2) = 0.113

  • S = 1.00

  • 1781 reflections

  • 101 parameters

  • H-atom parameters constrained

  • Δρmax = 0.25 e Å−3

  • Δρmin = −0.31 e Å−3

Data collection: APEX2 (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2008[Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; 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: ORTEP-3 for Windows (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]) and Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]); software used to prepare material for publication: SHELXL97and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information


Comment top

The pyrazine ring system is a useful structural element in medicinal chemistry and has found broad applications in drug development which can be used as antiproliferative agent (Dubinina et al., 2006), potent CXCR3 antagonists (Du et al., 2009), CB1 antagonists (Ellsworth et al., 2007), and c-Src inhibitory (Mukaiyama et al., 2007). On-going structural studies of heterocyclic N-containing derivatives (Nasir et al., 2010) are motivated by an investigation of their fluorescence properties (Kawai et al., 2001; Abdullah, 2005). In view of different applications of this class of compounds, we have undertaken the single crystal structure determination of the title compound.

The title compound C14 H8 Cl2 N4 O2, contains a half of the molecule in an asymmetric unit; the complete molecule is generated by two the fold rotation axis along the direction [0 1 0] with the symmetry code: -x, y, -z+1/2. X-ray analysis confirms the molecular structure and atom connectivity of the compound (Fig. 1). The deviation of the atom Cl1 from the pyrazine ring (C1/N1/C2/C3/N2/C4) is -0.0215 (4) Å.

The central phenyl ring (C5/C6/C7/C8/C5i/C7i) forms the dihedral angle of 72.82 (7) ° with the pyrazine ring (C1/N1/C2/C3/N2/C4). The dihedral angle between the pyrazine rings (C1/N1/C2/C3/N2/C4) and (C1i/N1i/C2i/C3i/N2i/C4i) is 68.38 (3) ° (Macrae et al., 2008). The crystal packing is via van der Waals interactions, only.

Related literature top

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 background to the fluorescence properties of compounds related to the title compound, see: Kawai et al. (2001); Abdullah (2005). For a related structure, see: Nasir et al. (2010).

Experimental top

To a stirred solution of Cs2CO3/K2CO3 (22 mmol) in CH3CN (50 mL), resorcinol (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 allowed for stirring 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.

Refinement top

The hydrogen atoms were placed in calculated positions with C—H = 0.93 Å, refined in the riding model with fixed isotropic displacement parameters:Uiso(H) = 1.2Ueq(C).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); 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) and Mercury (Macrae, et al.,2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radius. The related atoms have the symmetry code: (a) -x, y, -z+1/2.
1,3-Bis[(3-chloropyrazin-2-yl)oxy]benzene top
Crystal data top
C14H8Cl2N4O2F(000) = 680
Mr = 335.14Dx = 1.560 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 1781 reflections
a = 9.9618 (3) Åθ = 2.9–28.4°
b = 10.2196 (4) ŵ = 0.47 mm1
c = 14.6010 (6) ÅT = 293 K
β = 106.231 (2)°Block, colourless
V = 1427.22 (9) Å30.30 × 0.25 × 0.20 mm
Z = 4
Data collection top
Bruker SMART APEXII area-detector
diffractometer
1781 independent reflections
Radiation source: fine-focus sealed tube1552 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
ω and ϕ scansθmax = 28.4°, θmin = 2.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1313
Tmin = 0.873, Tmax = 0.912k = 1312
6736 measured reflectionsl = 1914
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.113H-atom parameters constrained
S = 1.00 w = 1/[σ2(Fo2) + (0.0685P)2 + 0.5533P]
where P = (Fo2 + 2Fc2)/3
1781 reflections(Δ/σ)max < 0.001
101 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = 0.31 e Å3
Crystal data top
C14H8Cl2N4O2V = 1427.22 (9) Å3
Mr = 335.14Z = 4
Monoclinic, C2/cMo Kα radiation
a = 9.9618 (3) ŵ = 0.47 mm1
b = 10.2196 (4) ÅT = 293 K
c = 14.6010 (6) Å0.30 × 0.25 × 0.20 mm
β = 106.231 (2)°
Data collection top
Bruker SMART APEXII area-detector
diffractometer
1781 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
1552 reflections with I > 2σ(I)
Tmin = 0.873, Tmax = 0.912Rint = 0.026
6736 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0360 restraints
wR(F2) = 0.113H-atom parameters constrained
S = 1.00Δρmax = 0.25 e Å3
1781 reflectionsΔρmin = 0.31 e Å3
101 parameters
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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 (Å2) top
xyzUiso*/Ueq
C10.10770 (15)0.37514 (13)0.02670 (10)0.0461 (3)
C20.07466 (18)0.3213 (2)0.15100 (11)0.0644 (4)
H20.12030.32460.21590.077*
C30.13428 (17)0.25363 (19)0.09216 (11)0.0618 (4)
H30.21960.21210.11780.074*
C40.04654 (14)0.30517 (13)0.03426 (9)0.0417 (3)
C50.05477 (14)0.23121 (15)0.18814 (9)0.0454 (3)
C60.00000.3013 (2)0.25000.0436 (4)
H60.00000.39230.25000.052*
C70.05777 (19)0.09686 (17)0.18801 (10)0.0597 (4)
H70.09790.05160.14700.072*
C80.00000.0305 (2)0.25000.0694 (7)
H80.00000.06050.25000.083*
N10.04795 (16)0.38337 (13)0.11809 (9)0.0580 (3)
N20.07257 (13)0.24545 (13)0.00221 (8)0.0515 (3)
O10.11655 (11)0.30189 (12)0.12853 (7)0.0537 (3)
Cl10.26460 (5)0.45456 (4)0.01959 (4)0.06883 (19)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0581 (7)0.0383 (6)0.0511 (8)0.0030 (5)0.0308 (6)0.0006 (5)
C20.0681 (10)0.0875 (12)0.0390 (7)0.0107 (9)0.0175 (7)0.0107 (7)
C30.0527 (8)0.0885 (12)0.0432 (8)0.0002 (8)0.0121 (6)0.0067 (7)
C40.0491 (6)0.0447 (7)0.0363 (6)0.0042 (5)0.0201 (5)0.0004 (5)
C50.0493 (7)0.0565 (8)0.0298 (6)0.0035 (5)0.0104 (5)0.0000 (5)
C60.0461 (9)0.0492 (10)0.0340 (8)0.0000.0085 (7)0.000
C70.0861 (11)0.0587 (9)0.0385 (7)0.0055 (8)0.0240 (7)0.0053 (6)
C80.119 (2)0.0472 (12)0.0468 (12)0.0000.0308 (13)0.000
N10.0756 (8)0.0596 (8)0.0484 (7)0.0084 (6)0.0332 (6)0.0117 (6)
N20.0489 (6)0.0689 (8)0.0387 (6)0.0036 (5)0.0157 (5)0.0063 (5)
O10.0553 (6)0.0703 (7)0.0374 (5)0.0130 (5)0.0162 (4)0.0022 (4)
Cl10.0778 (3)0.0608 (3)0.0815 (4)0.02286 (19)0.0447 (2)0.01437 (19)
Geometric parameters (Å, º) top
C1—N11.303 (2)C5—C71.373 (2)
C1—C41.4064 (18)C5—C61.3789 (17)
C1—Cl11.7229 (15)C5—O11.3991 (17)
C2—N11.340 (2)C6—C5i1.3789 (17)
C2—C31.362 (2)C6—H60.9300
C2—H20.9300C7—C81.379 (2)
C3—N21.345 (2)C7—H70.9300
C3—H30.9300C8—C7i1.379 (2)
C4—N21.2996 (18)C8—H80.9300
C4—O11.3584 (16)
N1—C1—C4121.76 (14)C6—C5—O1117.57 (14)
N1—C1—Cl1118.42 (11)C5—C6—C5i117.45 (19)
C4—C1—Cl1119.81 (11)C5—C6—H6121.3
N1—C2—C3121.90 (14)C5i—C6—H6121.3
N1—C2—H2119.0C5—C7—C8118.51 (15)
C3—C2—H2119.0C5—C7—H7120.7
N2—C3—C2121.51 (15)C8—C7—H7120.7
N2—C3—H3119.2C7i—C8—C7121.1 (2)
C2—C3—H3119.2C7i—C8—H8119.4
N2—C4—O1120.78 (11)C7—C8—H8119.4
N2—C4—C1121.62 (12)C1—N1—C2116.50 (13)
O1—C4—C1117.60 (12)C4—N2—C3116.71 (13)
C7—C5—C6122.18 (14)C4—O1—C5116.90 (10)
C7—C5—O1120.12 (13)
N1—C2—C3—N20.1 (3)C4—C1—N1—C20.2 (2)
N1—C1—C4—N20.0 (2)Cl1—C1—N1—C2179.30 (12)
Cl1—C1—C4—N2179.08 (11)C3—C2—N1—C10.3 (3)
N1—C1—C4—O1179.94 (13)O1—C4—N2—C3179.81 (14)
Cl1—C1—C4—O10.95 (17)C1—C4—N2—C30.2 (2)
C7—C5—C6—C5i1.04 (11)C2—C3—N2—C40.1 (3)
O1—C5—C6—C5i176.94 (13)N2—C4—O1—C50.4 (2)
C6—C5—C7—C82.0 (2)C1—C4—O1—C5179.61 (12)
O1—C5—C7—C8177.84 (11)C7—C5—O1—C475.09 (18)
C5—C7—C8—C7i0.99 (11)C6—C5—O1—C4108.92 (13)
Symmetry code: (i) x, y, z+1/2.

Experimental details

Crystal data
Chemical formulaC14H8Cl2N4O2
Mr335.14
Crystal system, space groupMonoclinic, C2/c
Temperature (K)293
a, b, c (Å)9.9618 (3), 10.2196 (4), 14.6010 (6)
β (°) 106.231 (2)
V3)1427.22 (9)
Z4
Radiation typeMo Kα
µ (mm1)0.47
Crystal size (mm)0.30 × 0.25 × 0.20
Data collection
DiffractometerBruker SMART APEXII area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2008)
Tmin, Tmax0.873, 0.912
No. of measured, independent and
observed [I > 2σ(I)] reflections
6736, 1781, 1552
Rint0.026
(sin θ/λ)max1)0.668
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.036, 0.113, 1.00
No. of reflections1781
No. of parameters101
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.25, 0.31

Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae, et al.,2008), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

 

Acknowledgements

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection. TS and DV thank the UGC (SAP–CAS) for the departmental facilties. TS also thanks the DST Inspire program for financial assistance.

References

First citationAbdullah, Z. (2005). Intl J. Chem. Sci. 3 , 9–15.  CAS
First citationBruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationDu, X. H., Gustin, D. J., Chen, X. Q., Duquette, J., McGee, L. R., Wang, Z. L., Ebsworth, K., Henne, K., Lemon, B., Ma, J., Miao, S. C., Sabalan, E., Sullivan, T. J., Tonn, G., Collins, T. L. & Medina, J. C. (2009). Bioorg. Med. Chem. Lett. 19, 5200–5204.  Web of Science CrossRef PubMed CAS
First citationDubinina, G. G., Platonov, M. O., Golovach, S. M., Borysko, P. O., Tolmachov, A. O. & Volovenko, Y. M. (2006). Eur. J. Med. Chem. 41, 727–737.  Web of Science CrossRef PubMed CAS
First citationEllsworth, B. A., Wang, Y., Zhu, Y. H., Pendri, A., Gerritz, S. W., Sun, C. Q., Carlson, K. E., Kang, L. Y., Baska, R. A., Yang, Y. F., Huang, Q., Burford, N. T., Cullen, M. J., Johnghar, S., Behnia, K., Pelleymounter, M. A., Washburn, W. N. & Ewing, W. R. (2007). Bioorg. Med. Chem. Lett. 17, 3978–3982.  Web of Science CrossRef PubMed CAS
First citationFarrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.  Web of Science CrossRef CAS IUCr Journals
First citationKawai, M., Lee, M. J., Evans, K. O. & Norlund, T. (2001). J. Fluoresc. 11, 23–32.  Web of Science CrossRef CAS
First citationMacrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.  Web of Science CrossRef CAS IUCr Journals
First citationMukaiyama, H., Nishimura, T., Kobayashi, S., Ozawa, T., Kamada, N., Komatsu, Y., Kikuchi, S., Oonota, H. & Kusama, H. (2007). Bioorg. Med. Chem. Lett. 15, 868–885.  CrossRef CAS
First citationNasir, S. B., Abdullah, Z., Fairuz, Z. A., Ng, S. W. & Tiekink, E. R. T. (2010). Acta Cryst. E66, o2187.  Web of Science CSD CrossRef IUCr Journals
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals

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