3-Chloro-6-[4-(2-pyrid­yl)piperazin-1-yl]pyridazine

Hakan Arslan; Semra Utku; Kenneth I Hardcastle; Mehtap Gökçe; Sheri Lense

doi:10.1107/S1600536809050727

. 2009 Dec 4;66(Pt 1):o35. doi: 10.1107/S1600536809050727

3-Chloro-6-[4-(2-pyridyl)piperazin-1-yl]pyridazine

Hakan Arslan ^a,^b,^*, Semra Utku ^c, Kenneth I Hardcastle ^a, Mehtap Gökçe ^d, Sheri Lense ^a

PMCID: PMC2980189 PMID: 21580140

Abstract

In the title compound, C₁₃H₁₄ClN₅, the piperazine ring adopts a chair conformation and the dihedral angle between the aromatic rings is 13.91 (7)°. The crystal structure is stabilized by weak intermolecular C—H⋯N hydrogen-bond interactions.

Related literature

For the synthesis, structures and analgesic and anti-inflammatory activity of substituted pyridazine derivatives, see: Boissier et al. (1963 ▶); Gokce et al. (2001 ▶, 2004 ▶, 2005 ▶, 2009 ▶); Sahin et al. (2004 ▶); Dundar et al. (2007 ▶). For general background to non-opioid analgesic derivatives, see: Sato et al. (1981 ▶); Banoglu et al. (2004 ▶); Giovannoni et al. (2003 ▶)·For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₃H₁₄ClN₅
M _r = 275.74
Triclinic,
a = 5.912 (3) Å
b = 8.088 (5) Å
c = 13.689 (8) Å
α = 83.359 (9)°
β = 83.019 (9)°
γ = 75.168 (9)°
V = 625.5 (6) Å³
Z = 2
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 296 K
0.16 × 0.15 × 0.14 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.954, T _max = 0.959
11395 measured reflections
3275 independent reflections
2264 reflections with I > 2σ(I)
R _int = 0.049

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.095
S = 0.95
3275 reflections
172 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.23 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: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809050727/hg2610sup1.cif

e-66-00o35-sup1.cif^{(17.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050727/hg2610Isup2.hkl

e-66-00o35-Isup2.hkl^{(160.6KB, 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
C3—H3⋯N1ⁱ	0.93	2.58	3.346 (3)	140

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Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

The opioid derivative analgesics have significant side effects, therefore, the current research is focused on non-opioid analgesics that do not have serious side effects but are as effective as the opioids. One of the non-opioid analgesic derivatives is emorfazone which has a substituted pyridazine (Sato et al., 1981). In addition, some pyridazinone derivatives bearing an alkylpiperazinyl alkyl moiety also show interesting antinociceptive activity (Banoglu et al., 2004; Giovannoni et al., 2003).

Recently, our team focused on the synthesis, characterization, and analgesics-anti-inflammatory activity of substituted pyridazine derivatives (Dundar et al., 2007; Gokce et al., 2001, 2004, 2005, 2009; Sahin et al., 2004). The compound, 3-chloro-6-(4-pyridin-2-ylpiperazin-1-yl)pyridazine, (I), Scheme 1, is one example and in this article we report on the crystal structure of the title compound, Figure 1.

The molecular structure of (I) consists of 3-chloropyridazine and pyridine arms connected to a piperazine ring. The 3-chloropyridazine and pyridine rings are planar with a maximum deviation of 0.006 (1) Å for atom C4 and -0.014 (2) Å for atom C12. The dihedral angle between these two rings is 13.91 (7) °. The piperazine ring adopts a chair conformation. This is confirmed by the puckering parameters q₂ = 0.0056 (13) Å, q₃ = -0.5388 (13) Å, Q_T = 0.5388 (13) Å, θ = 179.67 (14) ° and φ = 221 (14) ° (Cremer & Pople, 1975).

The conformations of the 3-chloropyridazine and pyridine rings are best described by the torsion angles of -155.41 (12) ° and 156.51 (12) ° for C4—N3—C5—C6 and C9—N4—C7—C8, respectively; thus they adopt - antiperiplanar and + antiperiplanar conformations, respectively.

The crystal packing is dominated by weak intermolecular C3—H3···N1 (1 + x, y, z) hydrogen bonds, with H···N = 2.58 Å and a C—H···N angle of 140 ° (Figure 2).

Experimental

A mixture of 3,6-dichloropyridazine, (II), (1.7 mol) and 1-(2-pyridyl)piperazine, (III), (2.0 mol) in ethanol (10 ml) was heated under reflux for 4 h after which the mixture was cooled to room temperature (Figure 3) (Boissier et al., 1963). The resulting crude precipitate was filtered off and purified by repeated washing with small portions of cold ethanol. The precipitate formed was crystallized from CH₂Cl₂:ethanol (5:10) to give the compound 3-chloro-6-(4-pyridin-2-ylpiperazin-1-yl) pyridazine, (I), as white crystals. Yields: 0.270 g, 58%. M.p.: 153 °C. ¹H NMR (DMSO-d₆) δ: 8.16–8.13 (d, 1H, pyridyl), 7.63–7.56 (m, 2H, pyridyl), 7.47–7.44 (d, 1H, pyridazin), 6.93–6.89 (d, 1H, pyridyl), 6.75–6.66 (d, 1H, pyridazin), 3.73–3.62(m, 4H, piperazine), 3.17–3.14 (m, 4H, piperazine). MS (EI) m/z: 276 (M⁺). Anal. Calc. for C₁₃H₁₄N₅Cl: C, 56.63; H, 5.12; N, 25.40%. Found: C, 56.60; H, 5.10; N, 24.42%.