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

Camilo H da Silva Lima; Marcus V N de Souza; Solange M S V Wardell; James L Wardell; Edward R T Tiekink

doi:10.1107/S1600536810041656

. 2010 Oct 23;66(Pt 11):o2886–o2887. doi: 10.1107/S1600536810041656

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

Camilo H da Silva Lima ^a, Marcus V N de Souza ^a, Solange M S V Wardell ^b, James L Wardell ^c,^‡, Edward R T Tiekink ^d,^*

PMCID: PMC3009184 PMID: 21589067

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 ▶); Gordin et al. (2000 ▶); de Souza (2006 ▶). For structural studies on pyrazinamide derivatives; see: Wardell et al. (2008 ▶); Baddeley et al. (2009 ▶); Howie et al. (2010a ▶,b ▶,c ▶,d ▶).

Experimental

Crystal data

C₇H₈ClN₃O
M _r = 185.61
Monoclinic,
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 ▶) 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
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.37 e Å⁻³

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

Supplementary Material

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

e-66-o2886-sup1.cif^{(15.3KB, cif)}

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

e-66-o2886-Isup2.hkl^{(90KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1n⋯N2	0.87 (2)	2.34 (2)	2.7162 (19)	107 (1)
N1—H1n⋯N3ⁱ	0.87 (2)	2.33 (2)	3.146 (2)	156 (2)
C5—H5⋯N2ⁱⁱ	0.95	2.60	3.212 (2)	123
C7—H7A⋯O1ⁱⁱⁱ	0.99	2.44	3.180 (2)	131
C7—H7B⋯O1^iv	0.99	2.42	3.337 (2)	153

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) .

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.