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Acta Crystallogr Sect E Struct Rep Online. 2010 March 1; 66(Pt 3): o532.
Published online 2010 February 6. doi:  10.1107/S1600536810004137
PMCID: PMC2983628

3-Chloro-6-{4-[3-(trifluoro­meth­yl)phen­yl]piperazin-1-yl}pyridazine

Abstract

The title compound, C15H14ClF3N4, was synthesized from 3,6-dichloro­pyridazine and 1-[3-(trifluoro­meth­yl)phen­yl]piper­azine. The piperazine ring is flanked by 3-chloro­pyridazine and 3-trifluoro­methyl­phenyl rings and adopts a chair conformation, whereas the 3-chloro­pyridazine and 3-trifluoro­methyl­phenyl rings are planar, with maximum deviations of 0.0069 (13) and 0.0133 (14) Å, respectively. The crystal structure is stabilized by weak inter­molecular C—H(...)N hydrogen-bond inter­actions.

Related literature

For the synthesis and analgesic and anti-inflammatory activity of pyridazinone and pyridazine derivatives, see: Arslan et al. (2010 [triangle]); Giri & Mukhopadhyay (1998 [triangle]); Boissier et al. (1963 [triangle]); Gokce et al. (2001 [triangle], 2004 [triangle], 2005 [triangle], 2009 [triangle]); Sahin et al. (2004 [triangle]); Dundar et al. (2007 [triangle]). For general background to pyrazolone derivatives, see: Amir et al. (2008 [triangle]); Banoglu et al. (2004 [triangle]). For puckering parameters, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o532-scheme1.jpg

Experimental

Crystal data

  • C15H14ClF3N4
  • M r = 342.75
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o532-efi1.jpg
  • a = 9.461 (6) Å
  • b = 6.557 (4) Å
  • c = 24.123 (16) Å
  • β = 99.890 (9)°
  • V = 1474.1 (16) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.30 mm−1
  • T = 173 K
  • 0.41 × 0.25 × 0.24 mm

Data collection

  • Bruker APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2008 [triangle]) T min = 0.888, T max = 0.932
  • 19935 measured reflections
  • 3385 independent reflections
  • 2781 reflections with I > 2σ(I)
  • R int = 0.065

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.101
  • S = 1.06
  • 3385 reflections
  • 208 parameters
  • H-atom parameters constrained
  • Δρmax = 0.32 e Å−3
  • Δρmin = −0.23 e Å−3

Data collection: APEX2 (Bruker, 2008 [triangle]); cell refinement: SAINT (Bruker, 2008 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810004137/hg2643sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810004137/hg2643Isup2.hkl

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

supplementary crystallographic information

Comment

It is known that some pyrazolone derivatives like oxyphenbutazone, dipyrone, antipyrine and phenylbutazone are used primarily for their anti-inflammatory, antipyretic and analgesic activities, but several side effects have limited the clinical use of these drugs such as some of pyrazolone derivatives are toxic and carcinogenicin animals, clastogenic in somatic and germ cells of male mice, and also weakly mutagenic in Salmonella strain TA100 in presence of rat liver homogenate. In addition, some of pyrazolone derivatives induce peptic ulcer, hypersensitivity reaction, hepatitis, nephritis and bone marrow suppression (Giri & Mukhopadhyay, 1998).

Pyridazinone derivatives are structurally related to pyrazolone derivatives (Gokce et al., 2009). Many pyridazinone derivatives have been reported as analgesic and anti-inflammatory agents without gastrointestinal side effect (Amir et al., 2008, Banoglu et al., 2004, Gokce et al., 2009). This is agreement with in our experience in the pyridazinone field. (Dundar et al., 2007; Gokce et al., 2001, 2004, 2005, 2009; Sahin et al., 2004).

Recently, our research has focussed on the chemical, physical and biologycal properties of pyridazinone derivatives (Gokce et al., 2009, Arslan et al., 2010). The title compound, 3-chloro-6-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}pyridazine, I, Scheme 1, is an 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 3-trifluoromethylphenyl arms connected to a piperazine ring. The 3-chloropyridazine and 3-trifluoromethylphenyl rings are planar with a maximum deviation of -0.0069 (13) Å for atom C7 and -0.0133 (14) Å for atom C3. The dihedral angle between these two rings is 18.77 (6) °. The piperazine ring adopts a chair conformation. This is confirmed by the puckering parameters q2 = 0.0107 (14) Å, q3= 0.5479 (13) Å, QT = 0.5480 (13) Å, θ = 1.05 (15) ° and [var phi]= 85 (7) ° (Cremer & Pople, 1975).

The conformations of the 3-chloropyridazine and 3-trifluoromethylphenyl rings are best described by the torsion angles of 159.40 (11) ° and -165.62 (11) ° for C7—N2—C6—C5 and C4—N1—C12—C11, respectively; thus they adopt + antiperiplanar and - antiperiplanar conformations, respectively.

The crystal packing is dominated by weak intermolecular C11—H11B···N4 (x, y-1, z) hydrogen bonds, with H···N = 2.69 Å and a C—H···N angle of 150 ° (Figure 2).

Experimental

A mixture of 3,6-dichloropyridazine, II, (1.7 mol) and 1-[3-(trifluoromethyl)phenyl]piperazine, III, (2.0 mol) in ethanol (10 ml) was heated under reflux for 4 hours 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 ml) to give the compound, 3-chloro-6-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}pyridazine, I, as white crystals. Yields: 0.485 g, 83%. M.p.: 167 °C. 1H-NMR (DMSO-d6) δ: 7.56-7.54 (d, 1H, pyridazin), 7.46-7.40 (m, 2H, phenyl), 7.28-7.21 (m, 1H, phenyl), 7.14-7.12 (d, 1H, phenyl), 7.09-7.07 (d, 1H, pyridazin), 3.74-3.71 (t, 2H, piperazine), 3.45-3.43 (t, 2H, piperazine), 3.19-3.17 (t, 4H, piperazine). MS (EI) m/z: 343 (M+). Anal. Calc. for C15H14N4ClF3: C, 52.56; H, 4.12; N, 16.35%. Found: C, 52.61; H, 4.09; N, 16.40%.

Refinement

The H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H distances of 0.95 Å (CH) or 0.99 Å (CH2), and with Uiso(H) = 1.2Ueq of the parent atoms.

Figures

Fig. 1.
The molecular structure of (I), showing ellipsoids at the 50% probability level.
Fig. 2.
The molecular packing of (I). The hydrogen bonds are shown as dashed lines.
Fig. 3.
Synthesis of the title compound.

Crystal data

C15H14ClF3N4F(000) = 704
Mr = 342.75Dx = 1.544 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 7857 reflections
a = 9.461 (6) Åθ = 2.2–29.7°
b = 6.557 (4) ŵ = 0.30 mm1
c = 24.123 (16) ÅT = 173 K
β = 99.890 (9)°Block, colourless
V = 1474.1 (16) Å30.41 × 0.25 × 0.24 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer3385 independent reflections
Radiation source: fine-focus sealed tube2781 reflections with I > 2σ(I)
graphiteRint = 0.065
[var phi] and ω scansθmax = 27.5°, θmin = 1.7°
Absorption correction: multi-scan (SADABS; Bruker, 2008)h = −12→12
Tmin = 0.888, Tmax = 0.932k = −8→8
19935 measured reflectionsl = −31→31

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) = 0.101H-atom parameters constrained
S = 1.06w = 1/[σ2(Fo2) + (0.0589P)2 + 0.1216P] where P = (Fo2 + 2Fc2)/3
3385 reflections(Δ/σ)max = 0.005
208 parametersΔρmax = 0.32 e Å3
0 restraintsΔρmin = −0.23 e Å3

Special details

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 > 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*/Ueq
C11.35124 (16)0.4693 (2)0.76675 (6)0.0301 (3)
C21.23214 (15)0.35744 (19)0.78778 (5)0.0228 (3)
C31.15571 (14)0.45817 (19)0.82401 (5)0.0212 (3)
H31.18110.59390.83540.025*
C41.04104 (14)0.36134 (18)0.84400 (5)0.0194 (3)
C51.01095 (15)0.65546 (17)0.90409 (6)0.0235 (3)
H5A1.05630.73740.87750.028*
H5B1.08560.62190.93680.028*
C60.89367 (15)0.78043 (18)0.92372 (6)0.0241 (3)
H6A0.93640.90310.94390.029*
H6B0.82400.82620.89060.029*
C70.74380 (13)0.76537 (18)0.99646 (5)0.0186 (3)
C80.62135 (14)0.9883 (2)1.06758 (5)0.0220 (3)
C90.60062 (14)0.7770 (2)1.06879 (5)0.0236 (3)
H60.54580.71631.09390.028*
C100.66253 (14)0.66193 (19)1.03229 (5)0.0221 (3)
H100.65170.51791.03090.027*
C110.76124 (14)0.47012 (18)0.93414 (6)0.0223 (3)
H11A0.68460.50220.90190.027*
H11B0.71830.38810.96140.027*
C120.87797 (15)0.34660 (18)0.91356 (6)0.0226 (3)
H12A0.94760.29870.94640.027*
H12B0.83440.22500.89300.027*
C131.01216 (15)0.15733 (18)0.82706 (5)0.0238 (3)
H130.93650.08620.83990.029*
C141.09205 (16)0.05852 (19)0.79199 (5)0.0277 (3)
H141.0708−0.07960.78190.033*
C151.20215 (16)0.1564 (2)0.77128 (6)0.0268 (3)
H151.25520.08860.74670.032*
Cl10.54631 (4)1.14481 (6)1.113190 (14)0.03333 (13)
F11.47712 (10)0.45600 (17)0.80245 (4)0.0510 (3)
F21.37526 (11)0.39838 (16)0.71726 (4)0.0517 (3)
F31.32478 (10)0.66983 (13)0.75974 (4)0.0438 (3)
N10.95396 (11)0.46588 (15)0.87639 (4)0.0201 (2)
N20.81888 (12)0.66056 (15)0.96101 (4)0.0201 (2)
N30.75776 (12)0.96974 (15)0.99729 (4)0.0233 (3)
N40.69511 (12)1.08204 (16)1.03382 (5)0.0248 (3)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0290 (8)0.0347 (7)0.0294 (7)−0.0006 (6)0.0132 (6)−0.0075 (6)
C20.0230 (7)0.0259 (6)0.0203 (6)0.0020 (5)0.0054 (5)−0.0013 (5)
C30.0239 (7)0.0189 (6)0.0219 (6)−0.0001 (5)0.0065 (5)−0.0028 (5)
C40.0236 (7)0.0184 (6)0.0163 (6)0.0026 (5)0.0040 (5)0.0014 (4)
C50.0269 (7)0.0156 (6)0.0314 (7)−0.0049 (5)0.0147 (6)−0.0026 (5)
C60.0318 (8)0.0149 (5)0.0298 (7)−0.0027 (5)0.0175 (6)0.0001 (5)
C70.0176 (7)0.0194 (6)0.0189 (6)−0.0007 (5)0.0032 (5)0.0011 (4)
C80.0196 (7)0.0285 (6)0.0181 (6)0.0016 (5)0.0038 (5)−0.0036 (5)
C90.0201 (7)0.0307 (7)0.0211 (6)−0.0022 (5)0.0063 (5)0.0041 (5)
C100.0225 (7)0.0202 (6)0.0244 (6)−0.0025 (5)0.0063 (5)0.0031 (5)
C110.0231 (7)0.0182 (6)0.0274 (7)−0.0055 (5)0.0094 (5)−0.0023 (5)
C120.0281 (8)0.0144 (5)0.0278 (7)−0.0037 (5)0.0118 (6)−0.0007 (5)
C130.0314 (8)0.0186 (6)0.0226 (6)−0.0027 (5)0.0081 (6)0.0012 (5)
C140.0415 (9)0.0184 (6)0.0237 (6)0.0011 (6)0.0073 (6)−0.0026 (5)
C150.0324 (8)0.0258 (7)0.0237 (7)0.0055 (5)0.0089 (6)−0.0042 (5)
Cl10.0347 (2)0.0404 (2)0.0277 (2)0.00403 (15)0.01307 (16)−0.00988 (14)
F10.0271 (6)0.0704 (7)0.0556 (6)−0.0063 (5)0.0077 (5)0.0012 (5)
F20.0615 (7)0.0616 (6)0.0419 (6)−0.0158 (5)0.0369 (5)−0.0197 (5)
F30.0458 (6)0.0321 (5)0.0617 (6)−0.0037 (4)0.0324 (5)0.0035 (4)
N10.0250 (6)0.0148 (5)0.0228 (5)−0.0022 (4)0.0107 (5)−0.0010 (4)
N20.0239 (6)0.0144 (5)0.0246 (6)−0.0032 (4)0.0115 (5)0.0001 (4)
N30.0279 (7)0.0186 (5)0.0261 (6)−0.0026 (4)0.0121 (5)−0.0027 (4)
N40.0279 (7)0.0225 (5)0.0258 (6)−0.0017 (5)0.0096 (5)−0.0057 (4)

Geometric parameters (Å, °)

C1—F21.3364 (16)C8—N41.3129 (17)
C1—F31.3439 (18)C8—C91.400 (2)
C1—F11.3472 (18)C8—Cl11.7425 (14)
C1—C21.504 (2)C9—C101.3654 (18)
C2—C151.3920 (19)C9—H60.9500
C2—C31.3928 (18)C10—H100.9500
C3—C41.4114 (18)C11—N21.4681 (17)
C3—H30.9500C11—C121.5199 (18)
C4—N11.4073 (16)C11—H11A0.9900
C4—C131.4115 (18)C11—H11B0.9900
C5—N11.4691 (17)C12—N11.4676 (16)
C5—C61.5190 (18)C12—H12A0.9900
C5—H5A0.9900C12—H12B0.9900
C5—H5B0.9900C13—C141.3878 (19)
C6—N21.4650 (16)C13—H130.9500
C6—H6A0.9900C14—C151.388 (2)
C6—H6B0.9900C14—H140.9500
C7—N31.3462 (17)C15—H150.9500
C7—N21.3845 (16)N3—N41.3600 (15)
C7—C101.4236 (17)
F2—C1—F3106.53 (12)C10—C9—H6121.4
F2—C1—F1106.34 (12)C8—C9—H6121.4
F3—C1—F1105.59 (12)C9—C10—C7117.68 (12)
F2—C1—C2112.59 (12)C9—C10—H10121.2
F3—C1—C2112.66 (11)C7—C10—H10121.2
F1—C1—C2112.60 (13)N2—C11—C12111.21 (11)
C15—C2—C3121.75 (12)N2—C11—H11A109.4
C15—C2—C1119.53 (12)C12—C11—H11A109.4
C3—C2—C1118.72 (12)N2—C11—H11B109.4
C2—C3—C4120.89 (12)C12—C11—H11B109.4
C2—C3—H3119.6H11A—C11—H11B108.0
C4—C3—H3119.6N1—C12—C11112.04 (11)
N1—C4—C13121.30 (11)N1—C12—H12A109.2
N1—C4—C3121.89 (11)C11—C12—H12A109.2
C13—C4—C3116.70 (11)N1—C12—H12B109.2
N1—C5—C6111.56 (11)C11—C12—H12B109.2
N1—C5—H5A109.3H12A—C12—H12B107.9
C6—C5—H5A109.3C14—C13—C4121.34 (12)
N1—C5—H5B109.3C14—C13—H13119.3
C6—C5—H5B109.3C4—C13—H13119.3
H5A—C5—H5B108.0C15—C14—C13121.65 (12)
N2—C6—C5110.97 (11)C15—C14—H14119.2
N2—C6—H6A109.4C13—C14—H14119.2
C5—C6—H6A109.4C14—C15—C2117.62 (12)
N2—C6—H6B109.4C14—C15—H15121.2
C5—C6—H6B109.4C2—C15—H15121.2
H6A—C6—H6B108.0C4—N1—C12118.34 (10)
N3—C7—N2116.34 (10)C4—N1—C5117.42 (11)
N3—C7—C10121.81 (11)C12—N1—C5110.68 (10)
N2—C7—C10121.77 (12)C7—N2—C6117.79 (10)
N4—C8—C9124.58 (11)C7—N2—C11120.25 (11)
N4—C8—Cl1115.68 (10)C6—N2—C11111.53 (10)
C9—C8—Cl1119.73 (10)C7—N3—N4119.73 (10)
C10—C9—C8117.13 (12)C8—N4—N3119.05 (11)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C11—H11B···N4i0.992.693.628 (2)158

Symmetry codes: (i) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2643).

References

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