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Acta Cryst. (2009). E65, o573    [ doi:10.1107/S1600536809005650 ]

4-[5-(4-Fluorophenyl)-1H-imidazol-4-yl]pyridine

P. Koch, D. Schollmeyer and S. Laufer

Abstract top

In the title compound, C14H10FN3, the imidazole ring makes dihedral angles of 28.2 (1) and 36.60 (9)° with the pyridine ring and the 4-fluorophenyl ring, respectively. The pyridine ring forms a dihedral angle of 44.68 (9)° with the 4-fluorophenyl ring. Intermolecular N-H...N hydrogen bonds are observed in the crystal structure.

Comment top

5(4)-(4-Fluorophenyl)-4(5)-(pyridin-4-yl)imidazole derivatives with various substitution patterns have been considered to be potential p38 MAP kinase inhibitors (Liverton et al. 1999, Koch et al. 2008, Peifer et al. 2006).

The molecular structure of compound I is shown in Figure 1. The imidazole ring realises dihedral angles of 28.2 (1)° and 36.60 (9)° with the pyridine ring and the 4-fluorophenyl ring, respectively. The pyridine ring encloses a dihedral angle of 44.68 (9)° with the 4-fluorophenyl ring.

The crystal packing (Figure 2) shows N1—H1 of the imidazole ring to form an intermolecular N–H···N hydrogen bond towards pyridine (N15) resulting in a infinite chain parallel to the a axis. The hydrogen bond measures 1.94 Å.

Related literature top

For biological activity of the title compound, see: Liverton et al. (1999). For applications of functionalized 5(4)-(4-fluorophenyl)-4(5)-(pyridin-4-yl)imidazoles, see: Koch et al. (2008), Peifer et al. (2006).

Experimental top

1-(4-Fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dione (46 mg, 0.2 mmol), formaldehyde (15 µL, 0.2 mmol, 37% aq. solution), ammonium acetate (154 mg, 2.0 mmol) and 1 ml glacial acetic acid were combined in a reaction vial. The reaction vessel was heated in a CEM microwave reactor for 5 min at 453 K (initial power 200 W), after which a stream of compressed air cooled the reaction vessel. The reaction mixture was added dropwise to a concentrated NH4OH solution at 0 °C. The formed colorless precipitate was collected by filtration, washed with water and dried (yield: 43 mg, 90%). Crystals of compound I suitable for X-ray diffraction were obtained by slow evaporation at 298 K of a solution of n-hexane - diethyl ether (3:2).

Refinement top

Hydrogen atoms attached to carbons were placed at calculated positions with C—H = 0.95 Å (aromatic C-atoms). The position of H1 was determined from the difference Fourier map. All H atoms were refined in the riding-model approximation with isotropic displacement parameters (set at 1.2 times of the Ueq of the parent atom).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
[Figure 2] Fig. 2. Part of the crystal packing of compound I. The hydrogen bonds are represented by dashed lines. View along b axis.
4-[5-(4-Fluorophenyl)-1H-imidazol-4-yl]pyridine top
Crystal data top
C14H10FN3Dx = 1.387 Mg m−3
Mr = 239.25Melting point: 285.5 K
Orthorhombic, PbcaCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2abCell parameters from 25 reflections
a = 9.217 (2) Åθ = 31–53°
b = 8.1064 (5) ŵ = 0.80 mm−1
c = 30.665 (5) ÅT = 193 K
V = 2291.1 (6) Å3Needle, colourless
Z = 80.54 × 0.20 × 0.13 mm
F(000) = 992
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.0000
Radiation source: rotating anodeθmax = 69.6°, θmin = 2.9°
graphiteh = 0→11
ω/2θ scansk = 0→9
2121 measured reflectionsl = −36→0
2121 independent reflections3 standard reflections every 60 min
1707 reflections with I > 2σ(I) intensity decay: 2%
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.076Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.201H-atom parameters constrained
S = 1.09 w = 1/[σ2(Fo2) + (0.1422P)2 + 0.0554P]
where P = (Fo2 + 2Fc2)/3
2121 reflections(Δ/σ)max < 0.001
163 parametersΔρmax = 0.58 e Å−3
0 restraintsΔρmin = −0.54 e Å−3
Crystal data top
C14H10FN3V = 2291.1 (6) Å3
Mr = 239.25Z = 8
Orthorhombic, PbcaCu Kα radiation
a = 9.217 (2) ŵ = 0.80 mm−1
b = 8.1064 (5) ÅT = 193 K
c = 30.665 (5) Å0.54 × 0.20 × 0.13 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.0000
2121 measured reflectionsθmax = 69.6°
2121 independent reflections3 standard reflections every 60 min
1707 reflections with I > 2σ(I) intensity decay: 2%
Refinement top
R[F2 > 2σ(F2)] = 0.076H-atom parameters constrained
wR(F2) = 0.201Δρmax = 0.58 e Å−3
S = 1.09Δρmin = −0.54 e Å−3
2121 reflectionsAbsolute structure: ?
163 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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) top
xyzUiso*/Ueq
F10.0873 (2)0.0708 (3)0.21998 (6)0.0596 (6)
N1−0.0150 (2)0.2988 (2)0.42177 (7)0.0243 (5)
H1−0.10700.28830.41300.029*
C20.1085 (2)0.2755 (3)0.39720 (8)0.0224 (5)
C30.2212 (3)0.3123 (3)0.42585 (8)0.0227 (5)
N40.1672 (2)0.3595 (3)0.46674 (7)0.0285 (5)
C50.0257 (3)0.3479 (3)0.46279 (9)0.0279 (6)
H5−0.04080.37080.48570.033*
C60.1015 (2)0.2250 (3)0.35030 (8)0.0228 (5)
C70.1984 (3)0.2872 (3)0.31898 (9)0.0286 (6)
H70.26820.36690.32770.034*
C80.1955 (3)0.2353 (3)0.27519 (9)0.0338 (6)
H80.26390.27640.25470.041*
C90.0907 (3)0.1233 (3)0.26276 (9)0.0365 (7)
C10−0.0096 (3)0.0625 (3)0.29215 (9)0.0353 (6)
H10−0.0819−0.01310.28280.042*
C11−0.0043 (3)0.1128 (3)0.33599 (8)0.0274 (6)
H11−0.07310.07050.35620.033*
C120.3785 (3)0.3036 (3)0.41935 (8)0.0216 (5)
C130.4700 (3)0.4057 (3)0.44398 (8)0.0246 (5)
H130.42990.48140.46430.030*
C140.6182 (3)0.3961 (3)0.43855 (8)0.0282 (6)
H140.67830.46500.45590.034*
N150.6824 (2)0.2927 (3)0.40951 (7)0.0287 (5)
C160.5937 (3)0.1937 (3)0.38606 (9)0.0290 (6)
H160.63670.11930.36590.035*
C170.4456 (3)0.1942 (3)0.38966 (8)0.0264 (6)
H170.38850.12180.37240.032*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0846 (15)0.0588 (13)0.0354 (10)−0.0016 (11)−0.0071 (9)−0.0100 (9)
N10.0210 (10)0.0106 (9)0.0414 (12)−0.0012 (7)0.0000 (8)−0.0015 (8)
C20.0225 (11)0.0050 (10)0.0398 (14)0.0003 (7)0.0019 (9)0.0031 (9)
C30.0277 (13)0.0048 (10)0.0355 (12)−0.0005 (8)0.0005 (9)0.0007 (8)
N40.0293 (11)0.0182 (10)0.0379 (12)−0.0021 (8)0.0020 (9)−0.0029 (8)
C50.0273 (12)0.0166 (11)0.0399 (14)−0.0008 (9)0.0058 (10)−0.0027 (10)
C60.0234 (11)0.0078 (10)0.0371 (13)0.0037 (8)−0.0022 (9)0.0011 (9)
C70.0308 (12)0.0139 (11)0.0410 (15)0.0016 (9)−0.0012 (10)0.0027 (10)
C80.0379 (14)0.0257 (13)0.0377 (15)0.0053 (10)0.0035 (11)0.0069 (11)
C90.0499 (17)0.0278 (14)0.0319 (14)0.0083 (11)−0.0085 (12)−0.0012 (11)
C100.0383 (14)0.0215 (12)0.0460 (16)−0.0033 (11)−0.0113 (12)−0.0041 (11)
C110.0277 (12)0.0139 (11)0.0407 (14)−0.0017 (9)−0.0044 (10)0.0020 (9)
C120.0239 (12)0.0070 (10)0.0337 (13)−0.0007 (8)−0.0014 (9)0.0044 (8)
C130.0282 (12)0.0151 (11)0.0306 (12)−0.0020 (9)−0.0004 (9)−0.0006 (9)
C140.0294 (13)0.0194 (12)0.0357 (13)−0.0036 (9)−0.0039 (10)−0.0016 (10)
N150.0231 (10)0.0223 (11)0.0408 (12)0.0008 (8)−0.0016 (9)0.0022 (9)
C160.0286 (13)0.0156 (12)0.0429 (15)0.0050 (9)−0.0006 (10)−0.0024 (10)
C170.0273 (12)0.0091 (10)0.0427 (15)−0.0001 (9)−0.0044 (10)−0.0017 (9)
Geometric parameters (Å, °) top
F1—C91.380 (3)C8—H80.9500
N1—C51.372 (3)C9—C101.382 (4)
N1—C21.378 (3)C10—C111.406 (4)
N1—H10.8936C10—H100.9500
C2—C31.393 (3)C11—H110.9500
C2—C61.496 (3)C12—C131.402 (3)
C3—N41.402 (3)C12—C171.414 (3)
C3—C121.465 (3)C13—C141.379 (3)
N4—C51.313 (3)C13—H130.9500
C5—H50.9500C14—N151.359 (3)
C6—C111.403 (3)C14—H140.9500
C6—C71.405 (3)N15—C161.353 (3)
C7—C81.407 (4)C16—C171.370 (3)
C7—H70.9500C16—H160.9500
C8—C91.379 (4)C17—H170.9500
C5—N1—C2108.4 (2)F1—C9—C10119.7 (3)
C5—N1—H1124.3C9—C10—C11119.8 (2)
C2—N1—H1127.3C9—C10—H10120.1
N1—C2—C3104.0 (2)C11—C10—H10120.1
N1—C2—C6121.9 (2)C6—C11—C10120.7 (2)
C3—C2—C6134.2 (2)C6—C11—H11119.6
C2—C3—N4111.0 (2)C10—C11—H11119.6
C2—C3—C12129.9 (2)C13—C12—C17117.0 (2)
N4—C3—C12119.0 (2)C13—C12—C3119.6 (2)
C5—N4—C3104.5 (2)C17—C12—C3123.4 (2)
N4—C5—N1112.1 (2)C14—C13—C12119.8 (2)
N4—C5—H5123.9C14—C13—H13120.1
N1—C5—H5123.9C12—C13—H13120.1
C11—C6—C7117.4 (2)N15—C14—C13123.1 (2)
C11—C6—C2120.5 (2)N15—C14—H14118.5
C7—C6—C2122.1 (2)C13—C14—H14118.5
C6—C7—C8122.2 (2)C16—N15—C14116.8 (2)
C6—C7—H7118.9N15—C16—C17123.9 (2)
C8—C7—H7118.9N15—C16—H16118.0
C9—C8—C7118.3 (3)C17—C16—H16118.0
C9—C8—H8120.9C16—C17—C12119.3 (2)
C7—C8—H8120.9C16—C17—H17120.3
C8—C9—F1118.8 (3)C12—C17—H17120.3
C8—C9—C10121.5 (3)
C5—N1—C2—C30.3 (2)C7—C8—C9—C100.0 (4)
C5—N1—C2—C6−178.6 (2)C8—C9—C10—C11−1.1 (4)
N1—C2—C3—N4−0.9 (2)F1—C9—C10—C11178.5 (2)
C6—C2—C3—N4177.8 (2)C7—C6—C11—C101.6 (3)
N1—C2—C3—C12177.2 (2)C2—C6—C11—C10−178.8 (2)
C6—C2—C3—C12−4.1 (4)C9—C10—C11—C60.2 (4)
C2—C3—N4—C51.2 (2)C2—C3—C12—C13153.7 (2)
C12—C3—N4—C5−177.14 (19)N4—C3—C12—C13−28.4 (3)
C3—N4—C5—N1−1.0 (3)C2—C3—C12—C17−27.5 (4)
C2—N1—C5—N40.4 (3)N4—C3—C12—C17150.5 (2)
N1—C2—C6—C11−37.4 (3)C17—C12—C13—C140.0 (3)
C3—C2—C6—C11144.1 (2)C3—C12—C13—C14178.9 (2)
N1—C2—C6—C7142.3 (2)C12—C13—C14—N151.1 (4)
C3—C2—C6—C7−36.3 (4)C13—C14—N15—C16−1.5 (4)
C11—C6—C7—C8−2.7 (3)C14—N15—C16—C170.9 (4)
C2—C6—C7—C8177.6 (2)N15—C16—C17—C120.1 (4)
C6—C7—C8—C92.0 (4)C13—C12—C17—C16−0.5 (3)
C7—C8—C9—F1−179.6 (2)C3—C12—C17—C16−179.4 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N15i0.891.942.815 (3)164
Symmetry codes: (i) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···N15i0.891.942.815 (3)164
Symmetry codes: (i) x−1, y, z.
references
References top

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