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

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ISSN: 2056-9890
Volume 69| Part 5| May 2013| Pages o813-o814

8,15-Dioxa-10,13-di­aza­tetra­cyclo­[14.4.0.02,7.09,14]icosa-1(16),2,4,6,9(14),10,12,17,19-nona­ene

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 10 April 2013; accepted 25 April 2013; online 30 April 2013)

The asymmetric unit of the title compound, C16H10N2O2, contains one half-mol­ecule, the complete mol­ecule being generated by twofold rotation symmetry. The plane of the pyrazine ring forms a dihedral angle of 64.87 (6)° with that of the benzene ring, and the planes of the two benzene rings are inclined to one another by 54.20 (6)°. The O atom deviates from the plane of the benzene ring by 0.1549 (8) Å. There are no significant inter­molecular inter­actions in the crystal.

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 related compounds, 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.]) and for their biological activity, see: Seitz et al. (2002[Seitz, L. E., Suling, W. J. & Reynolds, R. C. (2002). J. Med. Chem. 45, 5604-5606.]); Temple et al. (1970[Temple, C. Jr, Rose, J. D. & Montgomery, J. A. (1970). J. Med. Chem. 13, 1234-1235.]). 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
  • C16H10N2O2

  • Mr = 262.26

  • Orthorhombic, P b c n

  • a = 14.429 (3) Å

  • b = 10.162 (2) Å

  • c = 8.3313 (18) Å

  • V = 1221.6 (4) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.10 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 = 0.972, Tmax = 0.981

  • 6082 measured reflections

  • 1502 independent reflections

  • 1226 reflections with I > 2σ(I)

  • Rint = 0.029

Refinement
  • R[F2 > 2σ(F2)] = 0.033

  • wR(F2) = 0.106

  • S = 1.03

  • 1502 reflections

  • 92 parameters

  • H-atom parameters constrained

  • Δρmax = 0.22 e Å−3

  • Δρmin = −0.13 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: SHELXL97 and 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). Pyrazine derivatives were shown to display antimycobacterial (Seitz et al., 2002) and potential antimalarial (Temple et al., 1970) activities. In view of different applications of this class of compounds, we have undertaken the crystal structure determination of the title compound.

The title compound, Fig. 1, contains one half molecule in the asymmetric unit; the complete molecule is generated by a two-fold rotation axis, about [010]; symmetry code:(i) -x+1, y, -z+1/2.

The central pyrazine ring (C1/N1/C2/C1i/N1i/C2i) forms a dihedral angle of 64.87 (6) ° with the phenyl ring (C3-C8). The dihedral angle between the symmetry related phenyl rings (C3-C8) and (C3i-C8i) is 54.20 (6) °. The deviation of the atom O1 from the phenyl ring (C3-C8) is 0.1549 (8) Å.

In the crystal, there are no significant intermolecular interactions present.

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 related compounds, see: Kawai et al. (2001); Abdullah (2005) and for their biological activity, see: Seitz et al.(2002); Temple et al. (1970). For a related structure, see: Nasir et al. (2010).

Experimental top

To a stirred solution of Cs2CO3(15 mmol) in CH3CN (5 mL), was added dropwise independently a solution of corresponding diol (10 mmol) in CH3CN (25 mL) and a solution of 2,3-dichloropyrazine (10 mmol) in CH3CN (25 mL). The reaction mixture was stirred at reflux for 12 h. The reaction mixture was allowed to cool to room temperature and then poured into water (200 mL), and extracted with CH2Cl2 (2X100 mL). The combined organic layers were washed with water (100 mL), brine (50 mL) and dried over Na2SO4. The solvent was evaporated and the crude product was purified by column chromatography with CHCl3 as an eluent to give the title 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 and refined in the riding model approximation: C—H = 0.93 Å with 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 molecule, with atom labelling (symmetry code: (a) -x+1, y, -z+1/2). Displacement ellipsoids are drawn at the 30% probability level.
8,15-Dioxa-10,13-diazatetracyclo[14.4.0.02,7.09,14]icosa-1(16),2,4,6,9(14),10,12,17,19-nonaene top
Crystal data top
C16H10N2O2F(000) = 544
Mr = 262.26Dx = 1.426 Mg m3
Orthorhombic, PbcnMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2n 2abCell parameters from 1502 reflections
a = 14.429 (3) Åθ = 2.5–28.3°
b = 10.162 (2) ŵ = 0.10 mm1
c = 8.3313 (18) ÅT = 293 K
V = 1221.6 (4) Å3Block, colourless
Z = 40.30 × 0.25 × 0.20 mm
Data collection top
Bruker SMART APEXII area-detector
diffractometer
1502 independent reflections
Radiation source: fine-focus sealed tube1226 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.029
ω and ϕ scansθmax = 28.3°, θmin = 2.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1819
Tmin = 0.972, Tmax = 0.981k = 513
6082 measured reflectionsl = 710
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)] = 0.033H-atom parameters constrained
wR(F2) = 0.106 w = 1/[σ2(Fo2) + (0.0544P)2 + 0.1721P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
1502 reflectionsΔρmax = 0.22 e Å3
92 parametersΔρmin = 0.13 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.012 (3)
Crystal data top
C16H10N2O2V = 1221.6 (4) Å3
Mr = 262.26Z = 4
Orthorhombic, PbcnMo Kα radiation
a = 14.429 (3) ŵ = 0.10 mm1
b = 10.162 (2) ÅT = 293 K
c = 8.3313 (18) Å0.30 × 0.25 × 0.20 mm
Data collection top
Bruker SMART APEXII area-detector
diffractometer
1502 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
1226 reflections with I > 2σ(I)
Tmin = 0.972, Tmax = 0.981Rint = 0.029
6082 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0330 restraints
wR(F2) = 0.106H-atom parameters constrained
S = 1.03Δρmax = 0.22 e Å3
1502 reflectionsΔρmin = 0.13 e Å3
92 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
C10.53624 (10)1.14890 (12)0.19682 (18)0.0623 (4)
H10.56001.22890.16160.075*
C20.53746 (8)0.92738 (11)0.19677 (13)0.0426 (3)
C30.60493 (7)0.71770 (11)0.24296 (13)0.0395 (3)
C40.54878 (7)0.61036 (10)0.27797 (12)0.0390 (3)
C50.58736 (8)0.50933 (12)0.36919 (14)0.0480 (3)
H50.55230.43490.39220.058*
C60.67748 (9)0.51846 (14)0.42609 (16)0.0568 (4)
H60.70200.45090.48830.068*
C70.73073 (8)0.62674 (15)0.39094 (15)0.0594 (4)
H70.79080.63280.43050.071*
C80.69529 (8)0.72654 (12)0.29713 (15)0.0505 (3)
H80.73170.79890.27060.061*
N10.57395 (7)1.03683 (10)0.14200 (14)0.0546 (3)
O10.57275 (5)0.81298 (8)0.13462 (9)0.0446 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0751 (9)0.0430 (6)0.0688 (9)0.0077 (6)0.0246 (6)0.0065 (6)
C20.0464 (6)0.0431 (6)0.0383 (6)0.0018 (4)0.0088 (4)0.0017 (4)
C30.0383 (5)0.0458 (5)0.0344 (5)0.0021 (4)0.0021 (4)0.0019 (4)
C40.0382 (5)0.0429 (5)0.0357 (5)0.0033 (4)0.0052 (4)0.0026 (4)
C50.0498 (6)0.0476 (6)0.0467 (6)0.0092 (5)0.0103 (5)0.0029 (5)
C60.0547 (7)0.0697 (8)0.0461 (6)0.0241 (6)0.0024 (5)0.0049 (6)
C70.0417 (6)0.0870 (10)0.0496 (7)0.0130 (6)0.0066 (5)0.0073 (7)
C80.0394 (6)0.0623 (7)0.0497 (7)0.0040 (5)0.0005 (5)0.0078 (6)
N10.0593 (6)0.0495 (6)0.0548 (6)0.0094 (5)0.0118 (5)0.0090 (5)
O10.0486 (5)0.0467 (4)0.0384 (4)0.0009 (3)0.0040 (3)0.0041 (3)
Geometric parameters (Å, º) top
C1—N11.3423 (17)C4—C51.3935 (16)
C1—C1i1.371 (3)C4—C4i1.483 (2)
C1—H10.9300C5—C61.3871 (17)
C2—N11.3124 (15)C5—H50.9300
C2—O11.3707 (14)C6—C71.374 (2)
C2—C2i1.398 (2)C6—H60.9300
C3—C81.3826 (15)C7—C81.3787 (18)
C3—C41.3897 (15)C7—H70.9300
C3—O11.4029 (13)C8—H80.9300
N1—C1—C1i121.95 (8)C6—C5—H5119.6
N1—C1—H1119.0C4—C5—H5119.6
C1i—C1—H1119.0C7—C6—C5120.33 (12)
N1—C2—O1116.01 (10)C7—C6—H6119.8
N1—C2—C2i122.05 (7)C5—C6—H6119.8
O1—C2—C2i121.79 (6)C6—C7—C8120.18 (11)
C8—C3—C4122.16 (11)C6—C7—H7119.9
C8—C3—O1118.51 (10)C8—C7—H7119.9
C4—C3—O1118.93 (9)C7—C8—C3119.14 (11)
C3—C4—C5117.38 (10)C7—C8—H8120.4
C3—C4—C4i119.18 (8)C3—C8—H8120.4
C5—C4—C4i123.41 (8)C2—N1—C1115.99 (12)
C6—C5—C4120.77 (12)C2—O1—C3117.73 (8)
C8—C3—C4—C50.82 (16)C4—C3—C8—C70.97 (17)
O1—C3—C4—C5171.84 (9)O1—C3—C8—C7173.66 (10)
C8—C3—C4—C4i177.25 (11)O1—C2—N1—C1176.77 (10)
O1—C3—C4—C4i10.09 (16)C2i—C2—N1—C11.3 (2)
C3—C4—C5—C61.84 (16)C1i—C1—N1—C20.2 (2)
C4i—C4—C5—C6176.15 (12)N1—C2—O1—C3126.38 (10)
C4—C5—C6—C71.07 (18)C2i—C2—O1—C358.13 (16)
C5—C6—C7—C80.78 (19)C8—C3—O1—C286.29 (12)
C6—C7—C8—C31.78 (18)C4—C3—O1—C2100.77 (11)
Symmetry code: (i) x+1, y, z+1/2.

Experimental details

Crystal data
Chemical formulaC16H10N2O2
Mr262.26
Crystal system, space groupOrthorhombic, Pbcn
Temperature (K)293
a, b, c (Å)14.429 (3), 10.162 (2), 8.3313 (18)
V3)1221.6 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.30 × 0.25 × 0.20
Data collection
DiffractometerBruker SMART APEXII area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2008)
Tmin, Tmax0.972, 0.981
No. of measured, independent and
observed [I > 2σ(I)] reflections
6082, 1502, 1226
Rint0.029
(sin θ/λ)max1)0.666
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.033, 0.106, 1.03
No. of reflections1502
No. of parameters92
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.22, 0.13

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 citationSeitz, L. E., Suling, W. J. & Reynolds, R. C. (2002). J. Med. Chem. 45, 5604–5606.  Web of Science CrossRef PubMed CAS
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
First citationTemple, C. Jr, Rose, J. D. & Montgomery, J. A. (1970). J. Med. Chem. 13, 1234–1235.  CrossRef CAS PubMed Web of Science

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ISSN: 2056-9890
Volume 69| Part 5| May 2013| Pages o813-o814
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