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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o2886–o2887.
Published online 2010 October 23. doi:  10.1107/S1600536810041656
PMCID: PMC3009184

N-(2-Chloro­eth­yl)pyrazine-2-carboxamide

Abstract

In the title mol­ecule, C7H8ClN3O, the pyrazine and amide groups are almost co-planar [N—C—C—N torsion angle = −2.4 (2) °], a conformation stabilized by an intra­molecular N—H(...)N hydrogen bond. The chloro­ethyl group lies out of the plane [N—C—C—Cl = −65.06 (17) °]. In the crystal, the presence of N—H(...)N hydrogen bonds leads to the formation of a C(6) supra­molecular chain along the b axis. The carbonyl-O atom accepts two C—H(...)O inter­actions. These, plus Cl(...)Cl short contacts [3.3653 (6) Å], consolidate the packing of the chains in the crystal.

Related literature

For the anti­mycobacterial activity of pyrazinamide, see: Chaisson et al. (2002 [triangle]); Gordin et al. (2000 [triangle]); de Souza (2006 [triangle]). For structural studies on pyrazinamide derivatives; see: Wardell et al. (2008 [triangle]); Baddeley et al. (2009 [triangle]); Howie et al. (2010a [triangle],b [triangle],c [triangle],d [triangle]).

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Object name is e-66-o2886-scheme1.jpg

Experimental

Crystal data

  • C7H8ClN3O
  • M r = 185.61
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2886-efi1.jpg
  • a = 4.4639 (2) Å
  • b = 10.6865 (6) Å
  • c = 17.3583 (9) Å
  • β = 93.028 (3)°
  • V = 826.89 (7) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.41 mm−1
  • T = 120 K
  • 0.28 × 0.18 × 0.03 mm

Data collection

  • Nonius KappaCCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2007 [triangle]) T min = 0.631, T max = 0.746
  • 16245 measured reflections
  • 1867 independent reflections
  • 1628 reflections with I > 2σ(I)
  • R int = 0.044

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.110
  • S = 1.15
  • 1867 reflections
  • 112 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.23 e Å−3
  • Δρmin = −0.37 e Å−3

Data collection: COLLECT (Hooft, 1998 [triangle]); cell refinement: DENZO (Otwinowski & Minor, 1997 [triangle]) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 (Farrugia, 1997 [triangle]) and DIAMOND (Brandenburg, 2006 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2010 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks general, I. DOI: 10.1107/S1600536810041656/hb5682sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810041656/hb5682Isup2.hkl

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

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES (Brazil).

supplementary crystallographic information

Comment

Pyrazinamide has well known anti-mycobacterial activity and is the one of the most important drugs used in tuberculosis treatment (Chaisson et al., 2002; Gordin et al., 2000; de Souza, 2006). In continuation of our studies on pyrazinamide derivatives (Wardell et al., 2008; Baddeley et al., 2009; Howie et al., 2010a, 2010b, 2010c, 2010d), we report the structure of title compound, (I).

The pyrazine and amide groups are co-planar as seen in the value of the N1—C1—C2—N2 torsion angle of -2.4 (2) °, a conformation stabilized by an intramolecular N1—H···N2 hydrogen bond, Table 1. The ethyl group lies out of the plane through the rest of the molecule as seen in the N1—C6—C7—Cl1 torsion angle of -65.06 (17) °. The carbonyl-O1 lies to the opposite side of the molecule occupied by the amide and chlorido atoms.

In the crystal packing, the most prominent interactions are hydrogen bonding interactions of the type N—H···N, Table 1, which lead to a supramolecular chain along the screw axis, Fig. 2. The chains are connected into the 3-D structure by C—H···O interactions, involving the bifurcated carbonyl-O atom interacting with two methylene-H atoms, Table 1, and Cl···Cl contacts [Cl1···Cl1i = 3.3653 (6) Å for i: 1 - x, 1 - y, 1 - z], Fig. 3.

Experimental

The title compound was prepared by refluxing a mixture of thionyl chloride (1 ml) and N-(2-chloroethyl)pyrazine-2-carboxamide (0.2 g), obtained from methyl 2-pyrazinecarboxylate, ethanolamine and triethylamine. After 6 h, the excess thionyl chloride was removed under reduced pressure, the residue extracted into ethyl acetate (20 ml) and washed with saturated sodium bicarbonate solution (60 ml). The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford title compound, yield: 70%; m. pt.: 384–386 K. The crystals used in the structure determination were grown from EtOH solution.

1H NMR (200 MHz, DMSO-d6) δ: 9.19 (1H, s, H3), 9.12 (1H, s, NH), 8.88 (1H, s, H6), 8.74 (1H, s, H5), 3.76–3.63 (4H, m, CH2CH2Cl). 13C NMR (50 MHz, DMSO-d6) δ: 153.8, 138.4, 135.2, 134.3, 134.1, 33.6, 31.6 p.p.m.. MS/ESI: [M—H]: 184.

Refinement

The C-bound H atoms were geometrically placed (C–H = 0.95–0.99 Å) and refined as riding with Uiso(H) = 1.2Ueq(C). The N-bound H atom was located from a difference map and refined with the distance restraint N–H = 0.88±0.01 Å, and with Uiso(H) = 1.2Ueq(N).

Figures

Fig. 1.
The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.
Fig. 2.
Supramolecular chain in (I) aligned along the b axis. The N—H···N hydrogen bonds are shown as blue dashed lines.
Fig. 3.
A view in projection down the a axis of the crystal packing in (I). The N—H···N hydrogen bonds, and C—H···O and Cl···Cl contacts are shown as blue, orange and green ...

Crystal data

C7H8ClN3OF(000) = 384
Mr = 185.61Dx = 1.491 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 25954 reflections
a = 4.4639 (2) Åθ = 2.9–27.5°
b = 10.6865 (6) ŵ = 0.41 mm1
c = 17.3583 (9) ÅT = 120 K
β = 93.028 (3)°Prism, colourless
V = 826.89 (7) Å30.28 × 0.18 × 0.03 mm
Z = 4

Data collection

Nonius KappaCCD diffractometer1867 independent reflections
Radiation source: Enraf Nonius FR591 rotating anode1628 reflections with I > 2σ(I)
10 cm confocal mirrorsRint = 0.044
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.0°
[var phi] and ω scansh = −5→5
Absorption correction: multi-scan (SADABS; Sheldrick, 2007)k = −13→13
Tmin = 0.631, Tmax = 0.746l = −22→22
16245 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.110H atoms treated by a mixture of independent and constrained refinement
S = 1.15w = 1/[σ2(Fo2) + (0.0577P)2 + 0.3276P] where P = (Fo2 + 2Fc2)/3
1867 reflections(Δ/σ)max < 0.001
112 parametersΔρmax = 0.23 e Å3
1 restraintΔρmin = −0.37 e Å3

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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*/Ueq
Cl10.65306 (10)0.64380 (4)0.49830 (2)0.02780 (17)
O10.7056 (3)1.04630 (12)0.60138 (7)0.0247 (3)
N10.8112 (3)0.84349 (13)0.63161 (8)0.0195 (3)
H1n0.785 (5)0.7824 (15)0.6637 (10)0.028*
N20.4415 (3)0.85341 (14)0.75082 (8)0.0222 (3)
N30.1647 (4)1.07915 (15)0.78848 (9)0.0275 (4)
C10.6754 (4)0.95343 (16)0.64249 (9)0.0182 (3)
C20.4763 (4)0.95775 (15)0.70976 (9)0.0180 (3)
C30.2635 (4)0.86226 (18)0.80989 (10)0.0249 (4)
H30.22730.78970.83960.030*
C40.1292 (4)0.97467 (19)0.82923 (10)0.0264 (4)
H40.00870.97720.87270.032*
C50.3352 (4)1.06922 (17)0.72769 (10)0.0229 (4)
H50.36071.14030.69590.028*
C61.0072 (4)0.82477 (17)0.56832 (9)0.0212 (4)
H6A1.14990.75650.58210.025*
H6B1.12520.90200.56130.025*
C70.8395 (4)0.79260 (17)0.49280 (10)0.0232 (4)
H7A0.98230.79000.45110.028*
H7B0.68940.85860.47990.028*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0327 (3)0.0252 (3)0.0255 (3)−0.00579 (17)0.00184 (18)−0.00416 (17)
O10.0294 (7)0.0222 (7)0.0229 (6)−0.0018 (5)0.0045 (5)0.0058 (5)
N10.0221 (7)0.0200 (8)0.0164 (7)−0.0010 (6)0.0025 (5)0.0017 (5)
N20.0248 (8)0.0230 (8)0.0190 (7)−0.0010 (6)0.0023 (6)0.0019 (6)
N30.0312 (8)0.0271 (9)0.0245 (8)−0.0003 (6)0.0048 (6)−0.0055 (6)
C10.0173 (7)0.0210 (8)0.0163 (7)−0.0040 (6)−0.0011 (6)−0.0017 (6)
C20.0190 (8)0.0194 (8)0.0152 (7)−0.0036 (6)−0.0014 (6)−0.0013 (6)
C30.0293 (9)0.0279 (10)0.0179 (8)−0.0026 (7)0.0042 (7)0.0026 (7)
C40.0282 (9)0.0333 (10)0.0181 (8)−0.0029 (8)0.0047 (7)−0.0031 (7)
C50.0272 (9)0.0211 (9)0.0206 (8)−0.0024 (7)0.0028 (7)−0.0015 (7)
C60.0189 (8)0.0253 (9)0.0199 (8)−0.0018 (7)0.0046 (6)−0.0006 (7)
C70.0273 (9)0.0237 (9)0.0190 (8)−0.0025 (7)0.0044 (7)0.0011 (7)

Geometric parameters (Å, °)

Cl1—C71.7997 (19)C2—C51.390 (2)
O1—C11.234 (2)C3—C41.391 (3)
N1—C11.340 (2)C3—H30.9500
N1—C61.454 (2)C4—H40.9500
N1—H1n0.870 (10)C5—H50.9500
N2—C31.334 (2)C6—C71.514 (2)
N2—C21.337 (2)C6—H6A0.9900
N3—C41.336 (3)C6—H6B0.9900
N3—C51.338 (2)C7—H7A0.9900
C1—C21.505 (2)C7—H7B0.9900
C1—N1—C6121.46 (14)C3—C4—H4119.0
C1—N1—H1N119.4 (14)N3—C5—C2121.86 (17)
C6—N1—H1N119.1 (14)N3—C5—H5119.1
C3—N2—C2116.20 (15)C2—C5—H5119.1
C4—N3—C5116.09 (16)N1—C6—C7113.30 (14)
O1—C1—N1124.03 (15)N1—C6—H6A108.9
O1—C1—C2120.73 (15)C7—C6—H6A108.9
N1—C1—C2115.24 (14)N1—C6—H6B108.9
N2—C2—C5121.91 (15)C7—C6—H6B108.9
N2—C2—C1118.55 (15)H6A—C6—H6B107.7
C5—C2—C1119.53 (15)C6—C7—Cl1111.32 (12)
N2—C3—C4121.91 (17)C6—C7—H7A109.4
N2—C3—H3119.0Cl1—C7—H7A109.4
C4—C3—H3119.0C6—C7—H7B109.4
N3—C4—C3121.95 (16)Cl1—C7—H7B109.4
N3—C4—H4119.0H7A—C7—H7B108.0
C6—N1—C1—O1−0.6 (2)C2—N2—C3—C4−2.0 (3)
C6—N1—C1—C2179.20 (13)C5—N3—C4—C30.4 (3)
C3—N2—C2—C50.1 (2)N2—C3—C4—N31.8 (3)
C3—N2—C2—C1179.85 (15)C4—N3—C5—C2−2.3 (3)
O1—C1—C2—N2177.44 (15)N2—C2—C5—N32.2 (3)
N1—C1—C2—N2−2.4 (2)C1—C2—C5—N3−177.58 (15)
O1—C1—C2—C5−2.8 (2)C1—N1—C6—C7−83.3 (2)
N1—C1—C2—C5177.37 (15)N1—C6—C7—Cl1−65.06 (17)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1n···N20.87 (2)2.34 (2)2.7162 (19)107 (1)
N1—H1n···N3i0.87 (2)2.33 (2)3.146 (2)156 (2)
C5—H5···N2ii0.952.603.212 (2)123
C7—H7A···O1iii0.992.443.180 (2)131
C7—H7B···O1iv0.992.423.337 (2)153

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) −x+1, y+1/2, −z+3/2; (iii) −x+2, −y+2, −z+1; (iv) −x+1, −y+2, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5682).

References

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