8,15-Dioxa-10,13-di­aza­tetra­cyclo­[14.4.0.0^2,7.0^9,14]icosa-1(16),2,4,6,9(14),10,12,17,19-nona­ene

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); 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

Crystal data

• C₁₆H₁₀N₂O₂

• M_r = 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) ų

• 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) T_min = 0.972, T_max = 0.981

• 6082 measured reflections

• 1502 independent reflections

• 1226 reflections with I > 2σ(I)

• R_int = 0.029

Refinement

• R[F² > 2σ(F²)] = 0.033

• wR(F²) = 0.106

• S = 1.03

• 1502 reflections

• 92 parameters

• H-atom parameters constrained

• Δρ_max = 0.22 e Å⁻³

• Δρ_min = −0.13 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) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009).

Supporting information

S1. Comment

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

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).

S2. Experimental

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.

S3. Refinement

The hydrogen atoms were placed in calculated positions and refined in the riding model approximation: C—H = 0.93 Å with U_iso(H) = 1.2U_eq(C).

Computing details

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

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[14.4.0.0^2,7.0^9,14]icosa-1(16),2,4,6,9(14),10,12,17,19-nonaene

Crystal data

C16H10N2O2	F(000) = 544
Mr = 262.26	Dx = 1.426 Mg m^−3
Orthorhombic, Pbcn	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2n 2ab	Cell parameters from 1502 reflections
a = 14.429 (3) Å	θ = 2.5–28.3°
b = 10.162 (2) Å	µ = 0.10 mm^−1
c = 8.3313 (18) Å	T = 293 K
V = 1221.6 (4) Å^3	Block, colourless
Z = 4	0.30 × 0.25 × 0.20 mm

Data collection

Bruker SMART APEXII area-detector diffractometer	1502 independent reflections
Radiation source: fine-focus sealed tube	1226 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
ω and φ scans	θmax = 28.3°, θmin = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −18→19
Tmin = 0.972, Tmax = 0.981	k = −5→13
6082 measured reflections	l = −7→10

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.033	H-atom parameters constrained
wR(F^2) = 0.106	w = 1/[σ^2(Fo^2) + (0.0544P)^2 + 0.1721P] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
1502 reflections	Δρmax = 0.22 e Å^−3
92 parameters	Δρmin = −0.13 e Å^−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.012 (3)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.53624 (10)	1.14890 (12)	0.19682 (18)	0.0623 (4)
H1	0.5600	1.2289	0.1616	0.075*
C2	0.53746 (8)	0.92738 (11)	0.19677 (13)	0.0426 (3)
C3	0.60493 (7)	0.71770 (11)	0.24296 (13)	0.0395 (3)
C4	0.54878 (7)	0.61036 (10)	0.27797 (12)	0.0390 (3)
C5	0.58736 (8)	0.50933 (12)	0.36919 (14)	0.0480 (3)
H5	0.5523	0.4349	0.3922	0.058*
C6	0.67748 (9)	0.51846 (14)	0.42609 (16)	0.0568 (4)
H6	0.7020	0.4509	0.4883	0.068*
C7	0.73073 (8)	0.62674 (15)	0.39094 (15)	0.0594 (4)
H7	0.7908	0.6328	0.4305	0.071*
C8	0.69529 (8)	0.72654 (12)	0.29713 (15)	0.0505 (3)
H8	0.7317	0.7989	0.2706	0.061*
N1	0.57395 (7)	1.03683 (10)	0.14200 (14)	0.0546 (3)
O1	0.57275 (5)	0.81298 (8)	0.13462 (9)	0.0446 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0751 (9)	0.0430 (6)	0.0688 (9)	−0.0077 (6)	−0.0246 (6)	0.0065 (6)
C2	0.0464 (6)	0.0431 (6)	0.0383 (6)	−0.0018 (4)	−0.0088 (4)	0.0017 (4)
C3	0.0383 (5)	0.0458 (5)	0.0344 (5)	0.0021 (4)	0.0021 (4)	−0.0019 (4)
C4	0.0382 (5)	0.0429 (5)	0.0357 (5)	0.0033 (4)	0.0052 (4)	−0.0026 (4)
C5	0.0498 (6)	0.0476 (6)	0.0467 (6)	0.0092 (5)	0.0103 (5)	0.0029 (5)
C6	0.0547 (7)	0.0697 (8)	0.0461 (6)	0.0241 (6)	0.0024 (5)	0.0049 (6)
C7	0.0417 (6)	0.0870 (10)	0.0496 (7)	0.0130 (6)	−0.0066 (5)	−0.0073 (7)
C8	0.0394 (6)	0.0623 (7)	0.0497 (7)	−0.0040 (5)	−0.0005 (5)	−0.0078 (6)
N1	0.0593 (6)	0.0495 (6)	0.0548 (6)	−0.0094 (5)	−0.0118 (5)	0.0090 (5)
O1	0.0486 (5)	0.0467 (4)	0.0384 (4)	−0.0009 (3)	0.0040 (3)	0.0041 (3)

Geometric parameters (Å, º)

C1—N1	1.3423 (17)	C4—C5	1.3935 (16)
C1—C1^i	1.371 (3)	C4—C4^i	1.483 (2)
C1—H1	0.9300	C5—C6	1.3871 (17)
C2—N1	1.3124 (15)	C5—H5	0.9300
C2—O1	1.3707 (14)	C6—C7	1.374 (2)
C2—C2^i	1.398 (2)	C6—H6	0.9300
C3—C8	1.3826 (15)	C7—C8	1.3787 (18)
C3—C4	1.3897 (15)	C7—H7	0.9300
C3—O1	1.4029 (13)	C8—H8	0.9300
N1—C1—C1^i	121.95 (8)	C6—C5—H5	119.6
N1—C1—H1	119.0	C4—C5—H5	119.6
C1^i—C1—H1	119.0	C7—C6—C5	120.33 (12)
N1—C2—O1	116.01 (10)	C7—C6—H6	119.8
N1—C2—C2^i	122.05 (7)	C5—C6—H6	119.8
O1—C2—C2^i	121.79 (6)	C6—C7—C8	120.18 (11)
C8—C3—C4	122.16 (11)	C6—C7—H7	119.9
C8—C3—O1	118.51 (10)	C8—C7—H7	119.9
C4—C3—O1	118.93 (9)	C7—C8—C3	119.14 (11)
C3—C4—C5	117.38 (10)	C7—C8—H8	120.4
C3—C4—C4^i	119.18 (8)	C3—C8—H8	120.4
C5—C4—C4^i	123.41 (8)	C2—N1—C1	115.99 (12)
C6—C5—C4	120.77 (12)	C2—O1—C3	117.73 (8)
C8—C3—C4—C5	−0.82 (16)	C4—C3—C8—C7	−0.97 (17)
O1—C3—C4—C5	171.84 (9)	O1—C3—C8—C7	−173.66 (10)
C8—C3—C4—C4^i	177.25 (11)	O1—C2—N1—C1	176.77 (10)
O1—C3—C4—C4^i	−10.09 (16)	C2^i—C2—N1—C1	1.3 (2)
C3—C4—C5—C6	1.84 (16)	C1^i—C1—N1—C2	−0.2 (2)
C4^i—C4—C5—C6	−176.15 (12)	N1—C2—O1—C3	126.38 (10)
C4—C5—C6—C7	−1.07 (18)	C2^i—C2—O1—C3	−58.13 (16)
C5—C6—C7—C8	−0.78 (19)	C8—C3—O1—C2	−86.29 (12)
C6—C7—C8—C3	1.78 (18)	C4—C3—O1—C2	100.77 (11)

Symmetry code: (i) −x+1, y, −z+1/2.