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

Srinivasan, T.; Kalpana, V.; Rajakumar, P.; Velmurugan, D.

doi:10.1107/S160053681301129X

organic compounds

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ISSN: 2056-9890

Volume 69| Part 5| May 2013| Page o815

https://doi.org/10.1107/S160053681301129X

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

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

^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 ); 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

Crystal data

C₁₄H₈Cl₂N₄O₂
M_r = 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 ) T_min = 0.873, T_max = 0.912
6736 measured reflections
1781 independent reflections
1552 reflections with I > 2σ(I)
R_int = 0.026

Refinement

R[F² > 2σ(F²)] = 0.036
wR(F²) = 0.113
S = 1.00
1781 reflections
101 parameters
H-atom parameters constrained
Δρ_max = 0.25 e Å⁻³
Δρ_min = −0.31 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: SHELXL97and PLATON (Spek, 2009 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S160053681301129X/kp2450sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S160053681301129X/kp2450Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S160053681301129X/kp2450Isup3.cml

checkCIF report

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.

Structure description 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).

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

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

C₁₄H₈Cl₂N₄O₂	F(000) = 680
M_r = 335.14	D_x = 1.560 Mg m⁻³
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2yc	Cell parameters from 1781 reflections
a = 9.9618 (3) Å	θ = 2.9–28.4°
b = 10.2196 (4) Å	µ = 0.47 mm⁻¹
c = 14.6010 (6) Å	T = 293 K
β = 106.231 (2)°	Block, colourless
V = 1427.22 (9) Å³	0.30 × 0.25 × 0.20 mm
Z = 4

Data collection top

Bruker SMART APEXII area-detector diffractometer	1781 independent reflections
Radiation source: fine-focus sealed tube	1552 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.026
ω and φ scans	θ_max = 28.4°, θ_min = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −13→13
T_min = 0.873, T_max = 0.912	k = −13→12
6736 measured reflections	l = −19→14

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)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.113	H-atom parameters constrained
S = 1.00	w = 1/[σ²(F_o²) + (0.0685P)² + 0.5533P] where P = (F_o² + 2F_c²)/3
1781 reflections	(Δ/σ)_max < 0.001
101 parameters	Δρ_max = 0.25 e Å⁻³
0 restraints	Δρ_min = −0.31 e Å⁻³

Crystal data top

C₁₄H₈Cl₂N₄O₂	V = 1427.22 (9) Å³
M_r = 335.14	Z = 4
Monoclinic, C2/c	Mo Kα radiation
a = 9.9618 (3) Å	µ = 0.47 mm⁻¹
b = 10.2196 (4) Å	T = 293 K
c = 14.6010 (6) Å	0.30 × 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)
T_min = 0.873, T_max = 0.912	R_int = 0.026
6736 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.036	0 restraints
wR(F²) = 0.113	H-atom parameters constrained
S = 1.00	Δρ_max = 0.25 e Å⁻³
1781 reflections	Δρ_min = −0.31 e Å⁻³
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

	x	y	z	U_iso*/U_eq
C1	0.10770 (15)	0.37514 (13)	−0.02670 (10)	0.0461 (3)
C2	−0.07466 (18)	0.3213 (2)	−0.15100 (11)	0.0644 (4)
H2	−0.1203	0.3246	−0.2159	0.077*
C3	−0.13428 (17)	0.25363 (19)	−0.09216 (11)	0.0618 (4)
H3	−0.2196	0.2121	−0.1178	0.074*
C4	0.04654 (14)	0.30517 (13)	0.03426 (9)	0.0417 (3)
C5	0.05477 (14)	0.23121 (15)	0.18814 (9)	0.0454 (3)
C6	0.0000	0.3013 (2)	0.2500	0.0436 (4)
H6	0.0000	0.3923	0.2500	0.052*
C7	0.05777 (19)	0.09686 (17)	0.18801 (10)	0.0597 (4)
H7	0.0979	0.0516	0.1470	0.072*
C8	0.0000	0.0305 (2)	0.2500	0.0694 (7)
H8	0.0000	−0.0605	0.2500	0.083*
N1	0.04795 (16)	0.38337 (13)	−0.11809 (9)	0.0580 (3)
N2	−0.07257 (13)	0.24545 (13)	0.00221 (8)	0.0515 (3)
O1	0.11655 (11)	0.30189 (12)	0.12853 (7)	0.0537 (3)
Cl1	0.26460 (5)	0.45456 (4)	0.01959 (4)	0.06883 (19)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0581 (7)	0.0383 (6)	0.0511 (8)	0.0030 (5)	0.0308 (6)	−0.0006 (5)
C2	0.0681 (10)	0.0875 (12)	0.0390 (7)	0.0107 (9)	0.0175 (7)	0.0107 (7)
C3	0.0527 (8)	0.0885 (12)	0.0432 (8)	−0.0002 (8)	0.0121 (6)	0.0067 (7)
C4	0.0491 (6)	0.0447 (7)	0.0363 (6)	0.0042 (5)	0.0201 (5)	0.0004 (5)
C5	0.0493 (7)	0.0565 (8)	0.0298 (6)	−0.0035 (5)	0.0104 (5)	0.0000 (5)
C6	0.0461 (9)	0.0492 (10)	0.0340 (8)	0.000	0.0085 (7)	0.000
C7	0.0861 (11)	0.0587 (9)	0.0385 (7)	0.0055 (8)	0.0240 (7)	−0.0053 (6)
C8	0.119 (2)	0.0472 (12)	0.0468 (12)	0.000	0.0308 (13)	0.000
N1	0.0756 (8)	0.0596 (8)	0.0484 (7)	0.0084 (6)	0.0332 (6)	0.0117 (6)
N2	0.0489 (6)	0.0689 (8)	0.0387 (6)	−0.0036 (5)	0.0157 (5)	0.0063 (5)
O1	0.0553 (6)	0.0703 (7)	0.0374 (5)	−0.0130 (5)	0.0162 (4)	−0.0022 (4)
Cl1	0.0778 (3)	0.0608 (3)	0.0815 (4)	−0.02286 (19)	0.0447 (2)	−0.01437 (19)

Geometric parameters (Å, º) top

C1—N1	1.303 (2)	C5—C7	1.373 (2)
C1—C4	1.4064 (18)	C5—C6	1.3789 (17)
C1—Cl1	1.7229 (15)	C5—O1	1.3991 (17)
C2—N1	1.340 (2)	C6—C5ⁱ	1.3789 (17)
C2—C3	1.362 (2)	C6—H6	0.9300
C2—H2	0.9300	C7—C8	1.379 (2)
C3—N2	1.345 (2)	C7—H7	0.9300
C3—H3	0.9300	C8—C7ⁱ	1.379 (2)
C4—N2	1.2996 (18)	C8—H8	0.9300
C4—O1	1.3584 (16)

N1—C1—C4	121.76 (14)	C6—C5—O1	117.57 (14)
N1—C1—Cl1	118.42 (11)	C5—C6—C5ⁱ	117.45 (19)
C4—C1—Cl1	119.81 (11)	C5—C6—H6	121.3
N1—C2—C3	121.90 (14)	C5ⁱ—C6—H6	121.3
N1—C2—H2	119.0	C5—C7—C8	118.51 (15)
C3—C2—H2	119.0	C5—C7—H7	120.7
N2—C3—C2	121.51 (15)	C8—C7—H7	120.7
N2—C3—H3	119.2	C7ⁱ—C8—C7	121.1 (2)
C2—C3—H3	119.2	C7ⁱ—C8—H8	119.4
N2—C4—O1	120.78 (11)	C7—C8—H8	119.4
N2—C4—C1	121.62 (12)	C1—N1—C2	116.50 (13)
O1—C4—C1	117.60 (12)	C4—N2—C3	116.71 (13)
C7—C5—C6	122.18 (14)	C4—O1—C5	116.90 (10)
C7—C5—O1	120.12 (13)

N1—C2—C3—N2	−0.1 (3)	C4—C1—N1—C2	−0.2 (2)
N1—C1—C4—N2	0.0 (2)	Cl1—C1—N1—C2	−179.30 (12)
Cl1—C1—C4—N2	179.08 (11)	C3—C2—N1—C1	0.3 (3)
N1—C1—C4—O1	179.94 (13)	O1—C4—N2—C3	−179.81 (14)
Cl1—C1—C4—O1	−0.95 (17)	C1—C4—N2—C3	0.2 (2)
C7—C5—C6—C5ⁱ	−1.04 (11)	C2—C3—N2—C4	−0.1 (3)
O1—C5—C6—C5ⁱ	−176.94 (13)	N2—C4—O1—C5	0.4 (2)
C6—C5—C7—C8	2.0 (2)	C1—C4—O1—C5	−179.61 (12)
O1—C5—C7—C8	177.84 (11)	C7—C5—O1—C4	75.09 (18)
C5—C7—C8—C7ⁱ	−0.99 (11)	C6—C5—O1—C4	−108.92 (13)

Symmetry code: (i) −x, y, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₄H₈Cl₂N₄O₂
M_r	335.14
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	293
a, b, c (Å)	9.9618 (3), 10.2196 (4), 14.6010 (6)
β (°)	106.231 (2)
V (Å³)	1427.22 (9)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.47
Crystal size (mm)	0.30 × 0.25 × 0.20

Data collection
Diffractometer	Bruker SMART APEXII area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2008)
T_min, T_max	0.873, 0.912
No. of measured, independent and observed [I > 2σ(I)] reflections	6736, 1781, 1552
R_int	0.026
(sin θ/λ)_max (Å⁻¹)	0.668

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.113, 1.00
No. of reflections	1781
No. of parameters	101
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	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.

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