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Acta Crystallogr Sect E Struct Rep Online. 2009 September 1; 65(Pt 9): o2157–o2158.
Published online 2009 August 15. doi:  10.1107/S1600536809031870
PMCID: PMC2969917

n-Butyl 2-(3-chloro-1,2-dihydro­pyrazin-2-yl­idene)-2-cyano­acetate

Abstract

The title compound, C11H12ClN3O2, is essentially planar except for the n-but­oxy group [r.m.s. deviation from the least-squares plane = 0.0131 (1) Å for 11 non-H atoms]. An intra­molecular N—H(...)O inter­action results in the formation of an S(6) ring. The n-butoxy chain in the molecule is disordered over two sets of sites of equal occupancy.

Related literature

For applications of this class of compounds, see: Matter et al. (2005); Kaliszan et al. (1985 [triangle]); Petrusewicz et al. (1992 [triangle], 1993 [triangle], 1995 [triangle]). For pyrazin­yl–pyrazyl­idene tautomerism, see: Pilarski et al. (1984 [triangle]). For related structures, see: Vishweshwar et al. (2000 [triangle]); Wardell et al. (2006 [triangle]). For the synthesis, see: Pilarski & Foks (1981 [triangle], 1982 [triangle]).

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Object name is e-65-o2157-scheme1.jpg

Experimental

Crystal data

  • C11H12ClN3O2
  • M r = 253.69
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2157-efi1.jpg
  • a = 4.918 (3) Å
  • b = 25.642 (7) Å
  • c = 10.573 (4) Å
  • β = 95.80 (3)°
  • V = 1326.7 (9) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.28 mm−1
  • T = 120 K
  • 0.57 × 0.11 × 0.07 mm

Data collection

  • Oxford Diffraction KM-4/Xcalibur diffractometer with a Sapphire2 (large Be window) detector
  • Absorption correction: Gaussian (CrysAlis Pro; Oxford Diffraction, 2007 [triangle]) T min = 0.923, T max = 0.987
  • 4629 measured reflections
  • 1687 independent reflections
  • 1219 reflections with I > 2σ(I)
  • R int = 0.034

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.156
  • S = 1.04
  • 1687 reflections
  • 154 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.23 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 466 Friedel pairs
  • Flack parameter: 0.05 (18)

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 [triangle]); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 [triangle]); data reduction: CrysAlis RED (Oxford Diffraction, 2006 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809031870/ng2612sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809031870/ng2612Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank Drs Katarzyna Baranowska and Antoni Konitz for helpful discussions during the preparation of the manuscript. The work has been supported by the Fund for Science in the Year 2009 as a research project (DS/8410–4-0139–9).

supplementary crystallographic information

Comment

Heterocyclic compounds with active methylene moiety are known to have antiinflamatory (Petrusewicz et al., 1995), analgesic (Kaliszan et al., 1985) and large number of other pharmacological activities (Petrusewicz et al., 1992). Numerous scientific publications confirm that pyrazine derivatives, obtained by nucleophilic substitution of chlorine atom in the pyrazine ring system with active methylene compound, posses above mentioned activity. Some of pyrazine C—H and N—H acids also demonstrated antithrombotic and antiplatelet activity (Petrusewicz et al., 1993).

Such pharmacological activity (in group CH– andNH– acids) is possibly the result of acid character of particle and their structure, as in case of well known inhibitors of cyclooxygenase (Petrusewicz et al., 1993). Structural analysis of pyrazine-acetonitrile derivatives shows pyrazinyl-pyrazylidene tautomerism (Pilarski et al., 1984) but crystal of 2-butyl 2-(3-chloropyrazin- (1H)-ylidene)-2-cyanoacetateappears as NH-acid.

In the molecule of the title compound (Fig. 1) the bond lengths and angles characterizing the geometry of the pyrazines skeleton are typical for this group compounds (Vishweshwar et al. 2000; Wardell et al. 2006). The compound is essentially planar except for the n-butoxy group (r.m.s. deviation from the least-squares plane - 0.0131 (1) Å for 11 non-H atoms. An intramolecular N2—H2B···O1 contact generates a S(6) ring motif which stabilizes the molecular conformation. The n-butoxy chain in the molecule is disordered over two sets of sites in a 0.50 (1):0.50 (1) ratio.

Experimental

2-butyl 2-(3-chloropyrazin-2(1H)-ylidene)-2-cyanoacetate was obtained bygeneral method described in papers (Pilarski et al., 1981; Pilarski et al., 1982). Crystallization of this compound from methanol forms a crystal.

Refinement

Atoms O2, C8 (H8A, H8B), C9 (H9A, H9B), C10 (H10A, H10B), C11 (H11A, H11B, H11C) were disordered over two positions. During the refinement process the disordered atoms were refined with occupancies of 0.50 and 0.50. H atoms bonded to C were included in calculated positions and refined as riding on their parent C atom with C—H = 0.95 Å Uiso(H) = 1.2 Ueq(C) for aromatic, C—H = 0.99 Å Uiso(H) = 1.2 Ueq(C) for methylene and C—H = 0.98 Å Uiso(H) = 1.5 Ueq(C) for methyl H atoms. The H2B atom was located from difference Fourier map and refined isotropically resulting in N—H abond length 0.87 (2) Å Uiso(H) = 0.10 (2) Å2. The carbon atoms C8, C9, C10, C11 and C8A, C9A, C10A, C11A were located from a difference map, fixed at 1.50 for C—C distance and refined with the DFIX restraint. The Flack (1983) parameter was refined explicity, with both TWIN and BASF parameters.

Figures

Fig. 1.
The moleculare structure of the title compound showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C11H12ClN3O2F(000) = 528
Mr = 253.69Dx = 1.27 Mg m3
Monoclinic, CcMo Kα radiation, λ = 0.71073 Å
Hall symbol: C -2ycCell parameters from 1500 reflections
a = 4.918 (3) Åθ = 2.5–32.3°
b = 25.642 (7) ŵ = 0.28 mm1
c = 10.573 (4) ÅT = 120 K
β = 95.80 (3)°Block, yellow
V = 1326.7 (9) Å30.57 × 0.11 × 0.07 mm
Z = 4

Data collection

Oxford Diffraction KM-4/Xcalibur diffractometer with a Sapphire2 (large Be window) detector1687 independent reflections
graphite1219 reflections with I > 2σ(I)
Detector resolution: 8.1883 pixels mm-1Rint = 0.034
0.75° wide ω scansθmax = 25.5°, θmin = 2.5°
Absorption correction: gaussian (CrysAlis PRO; Oxford Diffraction, 2007)h = −3→5
Tmin = 0.923, Tmax = 0.987k = −31→31
4629 measured reflectionsl = −12→12

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.047H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.156w = 1/[σ2(Fo2) + (0.1833P)2] where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max < 0.001
1687 reflectionsΔρmax = 0.24 e Å3
154 parametersΔρmin = −0.23 e Å3
1 restraintAbsolute structure: Flack (1983), 466 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.05 (18)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 > σ(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)

xyzUiso*/UeqOcc. (<1)
Cl10.7083 (3)0.42260 (5)0.30244 (15)0.0753 (4)
O10.0928 (8)0.54438 (16)0.6099 (3)0.0731 (12)
N10.4291 (11)0.36488 (18)0.4525 (5)0.0827 (13)
N20.1819 (9)0.4445 (2)0.5738 (4)0.0612 (12)
N30.7225 (16)0.55178 (17)0.2917 (6)0.0874 (12)
C10.2496 (17)0.3549 (3)0.5468 (7)0.0905 (19)
H1A0.21020.31990.56810.109*
C20.1303 (11)0.3956 (3)0.6086 (5)0.0695 (16)
H2A0.01530.38890.67370.083*
C30.3572 (10)0.4596 (2)0.4816 (4)0.0548 (12)
C40.4796 (11)0.4144 (2)0.4225 (4)0.0649 (13)
C50.4002 (10)0.5136 (2)0.4565 (4)0.0569 (10)
C60.5828 (11)0.5330 (2)0.3632 (5)0.0617 (11)
C70.2549 (12)0.5528 (2)0.5259 (5)0.0626 (15)
O20.3471 (16)0.6051 (3)0.5012 (7)0.050 (2)*0.5
C80.202 (2)0.6474 (4)0.5635 (11)0.056 (3)*0.5
H8A0.25040.6470.65660.067*0.5
H8B0.00140.64340.54580.067*0.5
C90.296 (2)0.6977 (4)0.5064 (9)0.070 (3)*0.5
H9A0.49390.70170.53310.084*0.5
H9B0.20140.72690.54440.084*0.5
C100.253 (3)0.7037 (4)0.3607 (9)0.072 (3)*0.5
H10A0.36550.67690.32310.086*0.5
H10B0.05940.69550.33310.086*0.5
C110.316 (3)0.7546 (5)0.3052 (16)0.095 (4)*0.5
H11A0.15910.76640.2480.143*0.5
H11B0.47580.7510.25730.143*0.5
H11C0.35580.78020.37340.143*0.5
O2A0.268 (2)0.6013 (4)0.4705 (9)0.071 (3)*0.5
C8A0.111 (3)0.6434 (5)0.5272 (13)0.080 (4)*0.5
H8AA0.18280.64930.61690.095*0.5
H8AB−0.08430.63360.52460.095*0.5
C9A0.142 (3)0.6924 (5)0.4496 (14)0.102 (4)*0.5
H9A10.01020.68920.37280.122*0.5
H9A20.07750.72170.49980.122*0.5
C10A0.402 (3)0.7092 (5)0.4057 (13)0.092 (3)*0.5
H10C0.46680.67980.35590.11*0.5
H10D0.53350.71240.48270.11*0.5
C11A0.433 (4)0.7571 (5)0.3292 (13)0.089 (4)*0.5
H11D0.62270.76910.34210.133*0.5
H11E0.31160.78430.35610.133*0.5
H11F0.38450.74930.2390.133*0.5
H2B0.150 (14)0.4691 (19)0.627 (5)0.10 (2)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0730 (7)0.0881 (7)0.0692 (6)0.0104 (9)0.0279 (5)−0.0026 (8)
O10.085 (3)0.067 (2)0.073 (2)0.003 (2)0.035 (2)0.0011 (18)
N10.098 (3)0.070 (3)0.085 (3)0.007 (2)0.036 (2)0.001 (2)
N20.063 (3)0.067 (3)0.055 (2)0.006 (2)0.013 (2)−0.003 (2)
N30.087 (3)0.098 (3)0.082 (3)−0.002 (3)0.034 (2)0.021 (3)
C10.119 (5)0.063 (3)0.097 (4)0.004 (3)0.049 (4)−0.001 (3)
C20.075 (4)0.071 (4)0.067 (3)−0.004 (3)0.028 (3)0.002 (3)
C30.049 (3)0.073 (3)0.042 (2)0.003 (2)0.0044 (19)−0.007 (2)
C40.063 (3)0.080 (4)0.053 (2)0.009 (2)0.014 (2)−0.002 (2)
C50.055 (2)0.065 (3)0.052 (2)−0.002 (2)0.0109 (18)0.0014 (17)
C60.058 (2)0.073 (3)0.056 (2)0.002 (2)0.014 (2)0.002 (2)
C70.069 (3)0.060 (4)0.062 (3)−0.007 (3)0.018 (3)0.004 (3)

Geometric parameters (Å, °)

Cl1—C41.791 (5)C9—H9A0.99
O1—C71.271 (7)C9—H9B0.99
N1—C41.338 (7)C10—C111.478 (14)
N1—C11.421 (8)C10—H10A0.99
N2—C21.338 (9)C10—H10B0.99
N2—C31.419 (8)C11—H11A0.98
N2—H2B0.87 (2)C11—H11B0.98
N3—C61.175 (8)C11—H11C0.98
C1—C21.392 (10)O2A—C8A1.489 (17)
C1—H1A0.95C8A—C9A1.516 (14)
C2—H2A0.95C8A—H8AA0.99
C3—C51.428 (7)C8A—H8AB0.99
C3—C41.475 (7)C9A—C10A1.469 (14)
C5—C71.472 (8)C9A—H9A10.99
C5—C61.486 (7)C9A—H9A20.99
C7—O2A1.379 (11)C10A—C11A1.487 (14)
C7—O21.448 (10)C10A—H10C0.99
O2—C81.489 (13)C10A—H10D0.99
C8—C91.514 (12)C11A—H11D0.98
C8—H8A0.99C11A—H11E0.98
C8—H8B0.99C11A—H11F0.98
C9—C101.541 (12)
C4—N1—C1118.8 (5)C10—C9—H9A107.8
C2—N2—C3126.2 (5)C8—C9—H9B107.8
C2—N2—H2B117 (5)C10—C9—H9B107.8
C3—N2—H2B114 (5)H9A—C9—H9B107.2
C2—C1—N1121.0 (6)C11—C10—C9118.2 (10)
C2—C1—H1A119.5C11—C10—H10A107.8
N1—C1—H1A119.5C9—C10—H10A107.8
N2—C2—C1118.3 (5)C11—C10—H10B107.8
N2—C2—H2A120.9C9—C10—H10B107.8
C1—C2—H2A120.9H10A—C10—H10B107.1
N2—C3—C5120.3 (5)C7—O2A—C8A115.7 (8)
N2—C3—C4112.3 (5)O2A—C8A—C9A107.3 (11)
C5—C3—C4127.5 (5)O2A—C8A—H8AA110.2
N1—C4—C3123.5 (4)C9A—C8A—H8AA110.2
N1—C4—Cl1115.1 (4)O2A—C8A—H8AB110.2
C3—C4—Cl1121.4 (4)C9A—C8A—H8AB110.2
C3—C5—C7118.7 (4)H8AA—C8A—H8AB108.5
C3—C5—C6124.0 (4)C10A—C9A—C8A123.5 (13)
C7—C5—C6117.3 (5)C10A—C9A—H9A1106.5
N3—C6—C5175.5 (5)C8A—C9A—H9A1106.5
O1—C7—O2A120.7 (6)C10A—C9A—H9A2106.5
O1—C7—O2120.9 (5)C8A—C9A—H9A2106.5
O2A—C7—O219.8 (5)H9A1—C9A—H9A2106.5
O1—C7—C5127.1 (5)C9A—C10A—C11A123.6 (13)
O2A—C7—C5111.0 (6)C9A—C10A—H10C106.4
O2—C7—C5111.5 (5)C11A—C10A—H10C106.4
C7—O2—C8115.0 (7)C9A—C10A—H10D106.4
O2—C8—C9105.3 (8)C11A—C10A—H10D106.4
O2—C8—H8A110.7H10C—C10A—H10D106.5
C9—C8—H8A110.7C10A—C11A—H11D109.5
O2—C8—H8B110.7C10A—C11A—H11E109.5
C9—C8—H8B110.7H11D—C11A—H11E109.5
H8A—C8—H8B108.8C10A—C11A—H11F109.5
C8—C9—C10117.8 (9)H11D—C11A—H11F109.5
C8—C9—H9A107.8H11E—C11A—H11F109.5
C4—N1—C1—C2−0.9 (10)C6—C5—C7—O1−179.2 (5)
C3—N2—C2—C1−2.4 (9)C3—C5—C7—O2A−166.0 (6)
N1—C1—C2—N22.2 (11)C6—C5—C7—O2A13.6 (8)
C2—N2—C3—C5−178.1 (5)C3—C5—C7—O2172.8 (5)
C2—N2—C3—C41.2 (7)C6—C5—C7—O2−7.6 (8)
C1—N1—C4—C3−0.4 (8)O1—C7—O2—C8−10.3 (11)
C1—N1—C4—Cl1−179.9 (5)O2A—C7—O2—C885.0 (19)
N2—C3—C4—N10.3 (7)C5—C7—O2—C8177.5 (7)
C5—C3—C4—N1179.5 (5)C7—O2—C8—C9−170.4 (8)
N2—C3—C4—Cl1179.8 (3)O2—C8—C9—C1056.8 (12)
C5—C3—C4—Cl1−1.0 (7)C8—C9—C10—C11173.4 (12)
N2—C3—C5—C7−1.4 (6)O1—C7—O2A—C8A7.6 (13)
C4—C3—C5—C7179.5 (5)O2—C7—O2A—C8A−89.0 (19)
N2—C3—C5—C6179.1 (5)C5—C7—O2A—C8A175.8 (9)
C4—C3—C5—C6−0.1 (8)C7—O2A—C8A—C9A−177.5 (10)
C3—C5—C6—N318E1(10)O2A—C8A—C9A—C10A−42.8 (19)
C7—C5—C6—N30(8)C8A—C9A—C10A—C11A179.8 (14)
C3—C5—C7—O11.2 (8)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2B···O10.87 (2)1.96 (5)2.632 (6)133 (6)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: NG2612).

References

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