supplementary materials


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Acta Cryst. (2013). E69, o777    [ doi:10.1107/S1600536813010465 ]

Methyl 3,5-bis[(3-chloropyrazin-2-yl)oxy]benzoate

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

Abstract top

In the title compound, C16H10Cl2N4O4, the pyrazine rings make dihedral angles of 67.82 (9) and 75.91 (9)° with the benzene ring, while the dihedral angle between the pyrazine rings is 44.69 (10)°. The methoxycarbonyl group makes a dihedral angle of 16.82 (8)° with the benzene ring to which it is attached. In the crystal, C-H...O hydrogen bonds link the molecules, forming chains running along the ab plane.

Comment top

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 title compound, the pyrazine ring (N1/N2/C1-C4) makes a dihedral angle of 67.82 (9)° with the benzene ring (C5-C10). The other pyrazine ring (N3/N4/C11-C14) makes a dihedral angle of 75.91 (9)° with the bezene ring. The dihedral angle between the two pyrazine rings is 44.69 (10)°. Moreover, the acteyl group (C15/03/04/C16) attached with the benzene ring makes a dihedral angle of 16.82 (8)° with the aryl ring. The chlorine atoms Cl1 and Cl2 attached with the pyrazine rings deviate by 0.0136 (6)Å and 0.0590 (7)Å. The crystal packing is stabilised by intermolecular C4–H4···O2 hydrogen bonds (Tab. 1 & Fig. 2).

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 a related structure, see: Nasir et al. (2010).

Experimental top

To a stirred solution of Cs2CO3/K2CO3 (22 mmol) in CH3CN (50 mL), methyl-3,5-dihydroxybenzoate (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 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 with C—H = 0.93 and 0.96 Å, for aryl and methyl type H-atoms, respectively, and refined in the riding model with fixed isotropic displacement parameters: Uiso(H) = 1.5Ueq(C) for methyl and Uiso(H) = 1.2Ueq(C) for aryl H-atoms.

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); 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.
[Figure 2] Fig. 2. The crystal packing of the title compound viewed down a axis. H-atoms not involved in H-bonds have been excluded for clarity.
Methyl 3,5-bis[(3-chloropyrazin-2-yl)oxy]benzoate top
Crystal data top
C16H10Cl2N4O4Z = 2
Mr = 393.18F(000) = 400
Triclinic, P1Dx = 1.542 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.5437 (15) ÅCell parameters from 3453 reflections
b = 9.2984 (18) Åθ = 1.8–26.6°
c = 11.545 (2) ŵ = 0.41 mm1
α = 88.592 (10)°T = 293 K
β = 74.974 (9)°Block, colourless
γ = 73.231 (9)°0.30 × 0.25 × 0.20 mm
V = 846.9 (3) Å3
Data collection top
Bruker SMART APEXII area-detector
diffractometer
3453 independent reflections
Radiation source: fine-focus sealed tube3076 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
ω and φ scansθmax = 26.6°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1010
Tmin = 0.886, Tmax = 0.922k = 1111
12425 measured reflectionsl = 1414
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)] = 0.039Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.124H-atom parameters constrained
S = 1.04 w = 1/[σ2(Fo2) + (0.0678P)2 + 0.3652P]
where P = (Fo2 + 2Fc2)/3
3453 reflections(Δ/σ)max < 0.001
236 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = 0.46 e Å3
Crystal data top
C16H10Cl2N4O4γ = 73.231 (9)°
Mr = 393.18V = 846.9 (3) Å3
Triclinic, P1Z = 2
a = 8.5437 (15) ÅMo Kα radiation
b = 9.2984 (18) ŵ = 0.41 mm1
c = 11.545 (2) ÅT = 293 K
α = 88.592 (10)°0.30 × 0.25 × 0.20 mm
β = 74.974 (9)°
Data collection top
Bruker SMART APEXII area-detector
diffractometer
3453 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
3076 reflections with I > 2σ(I)
Tmin = 0.886, Tmax = 0.922Rint = 0.024
12425 measured reflectionsθmax = 26.6°
Refinement top
R[F2 > 2σ(F2)] = 0.039H-atom parameters constrained
wR(F2) = 0.124Δρmax = 0.30 e Å3
S = 1.04Δρmin = 0.46 e Å3
3453 reflectionsAbsolute structure: ?
236 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
C11.2164 (2)0.13661 (19)0.56898 (15)0.0357 (4)
C21.3326 (2)0.2435 (2)0.48010 (16)0.0392 (4)
C31.2200 (3)0.4217 (2)0.5674 (2)0.0512 (5)
H31.21820.52120.57140.061*
C41.1050 (3)0.3171 (2)0.65286 (19)0.0486 (4)
H41.02650.34760.71250.058*
C51.1396 (2)0.10665 (18)0.66279 (15)0.0364 (4)
C61.1808 (2)0.07829 (19)0.77108 (16)0.0377 (4)
H61.25380.01360.78230.045*
C71.1100 (2)0.19087 (19)0.86279 (16)0.0376 (4)
C80.9977 (2)0.32842 (19)0.84678 (16)0.0394 (4)
H80.95320.40460.90730.047*
C90.9551 (2)0.34790 (19)0.73925 (17)0.0376 (4)
C101.0255 (2)0.23987 (19)0.64574 (16)0.0383 (4)
H100.99700.25620.57310.046*
C110.6780 (2)0.5146 (2)0.76707 (15)0.0376 (4)
C120.5715 (2)0.6516 (2)0.74204 (17)0.0443 (4)
C130.3460 (3)0.5899 (3)0.8520 (2)0.0683 (7)
H130.22940.61210.88380.082*
C140.4482 (3)0.4569 (3)0.8760 (2)0.0594 (6)
H140.39930.39080.92350.071*
C151.1546 (2)0.1705 (2)0.98024 (17)0.0458 (4)
C161.2714 (4)0.0079 (3)1.1083 (2)0.0749 (8)
H16A1.35820.03661.11280.112*
H16B1.31250.11501.11230.112*
H16C1.17330.03181.17420.112*
N11.3349 (2)0.38465 (18)0.47831 (15)0.0479 (4)
N21.10203 (19)0.17218 (18)0.65331 (14)0.0427 (3)
N30.4081 (2)0.6891 (2)0.78443 (18)0.0618 (5)
N40.6181 (2)0.41812 (19)0.83301 (15)0.0462 (4)
O11.22265 (18)0.00741 (14)0.56204 (11)0.0460 (3)
O20.84699 (15)0.48570 (14)0.71782 (13)0.0445 (3)
O31.1276 (3)0.27208 (19)1.05207 (15)0.0702 (5)
O41.2263 (2)0.02685 (17)0.99597 (13)0.0623 (4)
Cl11.47807 (7)0.18931 (7)0.36871 (5)0.06146 (19)
Cl20.65455 (7)0.77453 (6)0.65015 (6)0.06183 (19)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0370 (8)0.0322 (8)0.0376 (8)0.0068 (6)0.0133 (7)0.0005 (7)
C20.0381 (8)0.0391 (9)0.0390 (9)0.0076 (7)0.0117 (7)0.0023 (7)
C30.0665 (13)0.0348 (10)0.0563 (12)0.0176 (9)0.0197 (10)0.0023 (8)
C40.0532 (11)0.0477 (11)0.0505 (11)0.0232 (9)0.0137 (9)0.0039 (9)
C50.0381 (8)0.0292 (8)0.0387 (9)0.0092 (6)0.0052 (7)0.0010 (7)
C60.0351 (8)0.0289 (8)0.0434 (9)0.0028 (6)0.0078 (7)0.0018 (7)
C70.0357 (8)0.0336 (8)0.0402 (9)0.0070 (7)0.0082 (7)0.0030 (7)
C80.0371 (8)0.0315 (8)0.0433 (9)0.0049 (7)0.0050 (7)0.0018 (7)
C90.0310 (8)0.0283 (8)0.0498 (10)0.0052 (6)0.0087 (7)0.0068 (7)
C100.0391 (9)0.0361 (9)0.0410 (9)0.0112 (7)0.0128 (7)0.0059 (7)
C110.0367 (8)0.0358 (9)0.0377 (9)0.0049 (7)0.0113 (7)0.0021 (7)
C120.0453 (10)0.0402 (10)0.0426 (9)0.0009 (8)0.0161 (8)0.0015 (8)
C130.0368 (10)0.0936 (19)0.0598 (13)0.0022 (11)0.0063 (9)0.0058 (13)
C140.0465 (11)0.0787 (16)0.0515 (12)0.0204 (11)0.0089 (9)0.0103 (11)
C150.0447 (10)0.0449 (10)0.0424 (10)0.0061 (8)0.0100 (8)0.0018 (8)
C160.0865 (18)0.0765 (17)0.0503 (13)0.0020 (14)0.0283 (12)0.0137 (12)
N10.0530 (9)0.0366 (8)0.0518 (9)0.0062 (7)0.0168 (7)0.0036 (7)
N20.0406 (8)0.0419 (8)0.0449 (8)0.0126 (6)0.0093 (6)0.0002 (6)
N30.0438 (9)0.0655 (12)0.0591 (11)0.0096 (8)0.0132 (8)0.0027 (9)
N40.0418 (8)0.0467 (9)0.0483 (9)0.0107 (7)0.0114 (7)0.0056 (7)
O10.0592 (8)0.0332 (6)0.0397 (7)0.0130 (6)0.0035 (6)0.0006 (5)
O20.0352 (6)0.0316 (6)0.0607 (8)0.0030 (5)0.0107 (6)0.0111 (6)
O30.1037 (14)0.0530 (9)0.0501 (9)0.0085 (9)0.0293 (9)0.0063 (7)
O40.0801 (11)0.0483 (8)0.0498 (8)0.0040 (7)0.0279 (8)0.0045 (7)
Cl10.0616 (3)0.0610 (3)0.0520 (3)0.0218 (3)0.0069 (2)0.0066 (2)
Cl20.0665 (3)0.0411 (3)0.0743 (4)0.0066 (2)0.0239 (3)0.0175 (2)
Geometric parameters (Å, º) top
C1—N21.300 (2)C9—C101.380 (3)
C1—O11.355 (2)C9—O21.4057 (19)
C1—C21.407 (2)C10—H100.9300
C2—N11.308 (2)C11—N41.294 (2)
C2—Cl11.7185 (19)C11—O21.356 (2)
C3—N11.340 (3)C11—C121.409 (2)
C3—C41.370 (3)C12—N31.297 (3)
C3—H30.9300C12—Cl21.718 (2)
C4—N21.340 (3)C13—N31.332 (3)
C4—H40.9300C13—C141.362 (4)
C5—C61.384 (2)C13—H130.9300
C5—C101.383 (2)C14—N41.348 (3)
C5—O11.398 (2)C14—H140.9300
C6—C71.393 (2)C15—O31.203 (3)
C6—H60.9300C15—O41.329 (2)
C7—C81.401 (2)C16—O41.450 (3)
C7—C151.495 (3)C16—H16A0.9600
C8—C91.375 (3)C16—H16B0.9600
C8—H80.9300C16—H16C0.9600
N2—C1—O1120.32 (16)C5—C10—H10120.8
N2—C1—C2121.66 (16)N4—C11—O2120.75 (16)
O1—C1—C2117.98 (15)N4—C11—C12121.81 (17)
N1—C2—C1122.44 (17)O2—C11—C12117.44 (16)
N1—C2—Cl1117.86 (14)N3—C12—C11122.06 (19)
C1—C2—Cl1119.69 (14)N3—C12—Cl2117.28 (15)
N1—C3—C4121.89 (18)C11—C12—Cl2120.64 (15)
N1—C3—H3119.1N3—C13—C14121.9 (2)
C4—C3—H3119.1N3—C13—H13119.0
N2—C4—C3122.12 (18)C14—C13—H13119.0
N2—C4—H4118.9N4—C14—C13122.0 (2)
C3—C4—H4118.9N4—C14—H14119.0
C6—C5—C10121.86 (16)C13—C14—H14119.0
C6—C5—O1121.32 (15)O3—C15—O4124.21 (19)
C10—C5—O1116.59 (15)O3—C15—C7123.90 (18)
C5—C6—C7118.28 (15)O4—C15—C7111.88 (17)
C5—C6—H6120.9O4—C16—H16A109.5
C7—C6—H6120.9O4—C16—H16B109.5
C6—C7—C8120.99 (16)H16A—C16—H16B109.5
C6—C7—C15121.16 (15)O4—C16—H16C109.5
C8—C7—C15117.83 (16)H16A—C16—H16C109.5
C9—C8—C7118.26 (16)H16B—C16—H16C109.5
C9—C8—H8120.9C2—N1—C3115.66 (17)
C7—C8—H8120.9C1—N2—C4116.18 (17)
C8—C9—C10122.16 (15)C12—N3—C13116.28 (19)
C8—C9—O2120.22 (16)C11—N4—C14115.96 (18)
C10—C9—O2117.42 (16)C1—O1—C5118.77 (13)
C9—C10—C5118.35 (16)C11—O2—C9118.32 (13)
C9—C10—H10120.8C15—O4—C16117.08 (18)
N2—C1—C2—N11.4 (3)C6—C7—C15—O417.0 (3)
O1—C1—C2—N1179.07 (16)C8—C7—C15—O4164.56 (17)
N2—C1—C2—Cl1178.52 (14)C1—C2—N1—C30.5 (3)
O1—C1—C2—Cl10.9 (2)Cl1—C2—N1—C3179.52 (14)
N1—C3—C4—N20.9 (3)C4—C3—N1—C21.6 (3)
C10—C5—C6—C72.9 (3)O1—C1—N2—C4179.72 (16)
O1—C5—C6—C7171.39 (15)C2—C1—N2—C42.1 (3)
C5—C6—C7—C81.1 (3)C3—C4—N2—C11.0 (3)
C5—C6—C7—C15177.37 (16)C11—C12—N3—C130.8 (3)
C6—C7—C8—C91.9 (3)Cl2—C12—N3—C13177.75 (19)
C15—C7—C8—C9179.61 (16)C14—C13—N3—C120.4 (4)
C7—C8—C9—C103.3 (3)O2—C11—N4—C14179.00 (18)
C7—C8—C9—O2178.05 (15)C12—C11—N4—C140.0 (3)
C8—C9—C10—C51.5 (3)C13—C14—N4—C110.4 (3)
O2—C9—C10—C5176.47 (15)N2—C1—O1—C517.9 (2)
C6—C5—C10—C91.6 (3)C2—C1—O1—C5164.46 (15)
O1—C5—C10—C9172.90 (15)C6—C5—O1—C159.1 (2)
N4—C11—C12—N30.6 (3)C10—C5—O1—C1126.30 (17)
O2—C11—C12—N3179.63 (18)N4—C11—O2—C90.6 (3)
N4—C11—C12—Cl2177.87 (15)C12—C11—O2—C9178.44 (16)
O2—C11—C12—Cl21.2 (2)C8—C9—O2—C1178.8 (2)
N3—C13—C14—N40.2 (4)C10—C9—O2—C11106.15 (18)
C6—C7—C15—O3163.5 (2)O3—C15—O4—C161.1 (3)
C8—C7—C15—O315.0 (3)C7—C15—O4—C16178.4 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···O2i0.932.473.192 (3)135
Symmetry code: (i) x, y1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···O2i0.932.473.192 (3)135
Symmetry code: (i) x, y1, z.
Acknowledgements top

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 thanks the DST for an Inspire fellowship.

references
References top

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