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

Koch, P.; Schollmeyer, D.; Laufer, S.

doi:10.1107/S1600536809005650

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 3| March 2009| Page o573

doi:10.1107/S1600536809005650

Open

access

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

Pierre Koch,^a Dieter Schollmeyer ^b and Stefan Laufer ^a ^*

^aInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and ^bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 26 January 2009; accepted 17 February 2009; online 21 February 2009)

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.

Related literature

For the 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

Crystal data

C₁₄H₁₀FN₃
M_r = 239.25
Orthorhombic, P b c a
a = 9.217 (2) Å
b = 8.1064 (5) Å
c = 30.665 (5) Å
V = 2291.1 (6) Å³
Z = 8
Cu Kα radiation
μ = 0.80 mm⁻¹
T = 193 K
0.54 × 0.20 × 0.13 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2121 measured reflections
2121 independent reflections
1707 reflections with I > 2σ(I)
3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

R[F² > 2σ(F²)] = 0.076
wR(F²) = 0.201
S = 1.09
2121 reflections
163 parameters
H-atom parameters constrained
Δρ_max = 0.58 e Å⁻³
Δρ_min = −0.54 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N15ⁱ	0.89	1.94	2.815 (3)	164
Symmetry code: (i) x-1, y, z.

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809005650/im2099sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809005650/im2099Isup2.hkl

checkCIF report

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).

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

	Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
	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

C₁₄H₁₀FN₃	D_x = 1.387 Mg m⁻³
M_r = 239.25	Melting point: 285.5 K
Orthorhombic, Pbca	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 9.217 (2) Å	θ = 31–53°
b = 8.1064 (5) Å	µ = 0.80 mm⁻¹
c = 30.665 (5) Å	T = 193 K
V = 2291.1 (6) Å³	Needle, colourless
Z = 8	0.54 × 0.20 × 0.13 mm
F(000) = 992

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.000
Radiation source: rotating anode	θ_max = 69.6°, θ_min = 2.9°
Graphite monochromator	h = 0→11
ω/2θ scans	k = 0→9
2121 measured reflections	l = −36→0
2121 independent reflections	3 standard reflections every 60 min
1707 reflections with I > 2σ(I)	intensity decay: 2%

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.076	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.201	H-atom parameters constrained
S = 1.09	w = 1/[σ²(F_o²) + (0.1422P)² + 0.0554P] where P = (F_o² + 2F_c²)/3
2121 reflections	(Δ/σ)_max < 0.001
163 parameters	Δρ_max = 0.58 e Å⁻³
0 restraints	Δρ_min = −0.54 e Å⁻³

Crystal data top

C₁₄H₁₀FN₃	V = 2291.1 (6) Å³
M_r = 239.25	Z = 8
Orthorhombic, Pbca	Cu Kα radiation
a = 9.217 (2) Å	µ = 0.80 mm⁻¹
b = 8.1064 (5) Å	T = 193 K
c = 30.665 (5) Å	0.54 × 0.20 × 0.13 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.000
2121 measured reflections	3 standard reflections every 60 min
2121 independent reflections	intensity decay: 2%
1707 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.076	0 restraints
wR(F²) = 0.201	H-atom parameters constrained
S = 1.09	Δρ_max = 0.58 e Å⁻³
2121 reflections	Δρ_min = −0.54 e Å⁻³
163 parameters

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

	x	y	z	U_iso*/U_eq
F1	0.0873 (2)	0.0708 (3)	0.21998 (6)	0.0596 (6)
N1	−0.0150 (2)	0.2988 (2)	0.42177 (7)	0.0243 (5)
H1	−0.1070	0.2883	0.4130	0.029*
C2	0.1085 (2)	0.2755 (3)	0.39720 (8)	0.0224 (5)
C3	0.2212 (3)	0.3123 (3)	0.42585 (8)	0.0227 (5)
N4	0.1672 (2)	0.3595 (3)	0.46674 (7)	0.0285 (5)
C5	0.0257 (3)	0.3479 (3)	0.46279 (9)	0.0279 (6)
H5	−0.0408	0.3708	0.4857	0.033*
C6	0.1015 (2)	0.2250 (3)	0.35030 (8)	0.0228 (5)
C7	0.1984 (3)	0.2872 (3)	0.31898 (9)	0.0286 (6)
H7	0.2682	0.3669	0.3277	0.034*
C8	0.1955 (3)	0.2353 (3)	0.27519 (9)	0.0338 (6)
H8	0.2639	0.2764	0.2547	0.041*
C9	0.0907 (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	−0.0131	0.2828	0.042*
C11	−0.0043 (3)	0.1128 (3)	0.33599 (8)	0.0274 (6)
H11	−0.0731	0.0705	0.3562	0.033*
C12	0.3785 (3)	0.3036 (3)	0.41935 (8)	0.0216 (5)
C13	0.4700 (3)	0.4057 (3)	0.44398 (8)	0.0246 (5)
H13	0.4299	0.4814	0.4643	0.030*
C14	0.6182 (3)	0.3961 (3)	0.43855 (8)	0.0282 (6)
H14	0.6783	0.4650	0.4559	0.034*
N15	0.6824 (2)	0.2927 (3)	0.40951 (7)	0.0287 (5)
C16	0.5937 (3)	0.1937 (3)	0.38606 (9)	0.0290 (6)
H16	0.6367	0.1193	0.3659	0.035*
C17	0.4456 (3)	0.1942 (3)	0.38966 (8)	0.0264 (6)
H17	0.3885	0.1218	0.3724	0.032*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0846 (15)	0.0588 (13)	0.0354 (10)	−0.0016 (11)	−0.0071 (9)	−0.0100 (9)
N1	0.0210 (10)	0.0106 (9)	0.0414 (12)	−0.0012 (7)	0.0000 (8)	−0.0015 (8)
C2	0.0225 (11)	0.0050 (10)	0.0398 (14)	0.0003 (7)	0.0019 (9)	0.0031 (9)
C3	0.0277 (13)	0.0048 (10)	0.0355 (12)	−0.0005 (8)	0.0005 (9)	0.0007 (8)
N4	0.0293 (11)	0.0182 (10)	0.0379 (12)	−0.0021 (8)	0.0020 (9)	−0.0029 (8)
C5	0.0273 (12)	0.0166 (11)	0.0399 (14)	−0.0008 (9)	0.0058 (10)	−0.0027 (10)
C6	0.0234 (11)	0.0078 (10)	0.0371 (13)	0.0037 (8)	−0.0022 (9)	0.0011 (9)
C7	0.0308 (12)	0.0139 (11)	0.0410 (15)	0.0016 (9)	−0.0012 (10)	0.0027 (10)
C8	0.0379 (14)	0.0257 (13)	0.0377 (15)	0.0053 (10)	0.0035 (11)	0.0069 (11)
C9	0.0499 (17)	0.0278 (14)	0.0319 (14)	0.0083 (11)	−0.0085 (12)	−0.0012 (11)
C10	0.0383 (14)	0.0215 (12)	0.0460 (16)	−0.0033 (11)	−0.0113 (12)	−0.0041 (11)
C11	0.0277 (12)	0.0139 (11)	0.0407 (14)	−0.0017 (9)	−0.0044 (10)	0.0020 (9)
C12	0.0239 (12)	0.0070 (10)	0.0337 (13)	−0.0007 (8)	−0.0014 (9)	0.0044 (8)
C13	0.0282 (12)	0.0151 (11)	0.0306 (12)	−0.0020 (9)	−0.0004 (9)	−0.0006 (9)
C14	0.0294 (13)	0.0194 (12)	0.0357 (13)	−0.0036 (9)	−0.0039 (10)	−0.0016 (10)
N15	0.0231 (10)	0.0223 (11)	0.0408 (12)	0.0008 (8)	−0.0016 (9)	0.0022 (9)
C16	0.0286 (13)	0.0156 (12)	0.0429 (15)	0.0050 (9)	−0.0006 (10)	−0.0024 (10)
C17	0.0273 (12)	0.0091 (10)	0.0427 (15)	−0.0001 (9)	−0.0044 (10)	−0.0017 (9)

Geometric parameters (Å, º) top

F1—C9	1.380 (3)	C8—H8	0.9500
N1—C5	1.372 (3)	C9—C10	1.382 (4)
N1—C2	1.378 (3)	C10—C11	1.406 (4)
N1—H1	0.8936	C10—H10	0.9500
C2—C3	1.393 (3)	C11—H11	0.9500
C2—C6	1.496 (3)	C12—C13	1.402 (3)
C3—N4	1.402 (3)	C12—C17	1.414 (3)
C3—C12	1.465 (3)	C13—C14	1.379 (3)
N4—C5	1.313 (3)	C13—H13	0.9500
C5—H5	0.9500	C14—N15	1.359 (3)
C6—C11	1.403 (3)	C14—H14	0.9500
C6—C7	1.405 (3)	N15—C16	1.353 (3)
C7—C8	1.407 (4)	C16—C17	1.370 (3)
C7—H7	0.9500	C16—H16	0.9500
C8—C9	1.379 (4)	C17—H17	0.9500

C5—N1—C2	108.4 (2)	F1—C9—C10	119.7 (3)
C5—N1—H1	124.3	C9—C10—C11	119.8 (2)
C2—N1—H1	127.3	C9—C10—H10	120.1
N1—C2—C3	104.0 (2)	C11—C10—H10	120.1
N1—C2—C6	121.9 (2)	C6—C11—C10	120.7 (2)
C3—C2—C6	134.2 (2)	C6—C11—H11	119.6
C2—C3—N4	111.0 (2)	C10—C11—H11	119.6
C2—C3—C12	129.9 (2)	C13—C12—C17	117.0 (2)
N4—C3—C12	119.0 (2)	C13—C12—C3	119.6 (2)
C5—N4—C3	104.5 (2)	C17—C12—C3	123.4 (2)
N4—C5—N1	112.1 (2)	C14—C13—C12	119.8 (2)
N4—C5—H5	123.9	C14—C13—H13	120.1
N1—C5—H5	123.9	C12—C13—H13	120.1
C11—C6—C7	117.4 (2)	N15—C14—C13	123.1 (2)
C11—C6—C2	120.5 (2)	N15—C14—H14	118.5
C7—C6—C2	122.1 (2)	C13—C14—H14	118.5
C6—C7—C8	122.2 (2)	C16—N15—C14	116.8 (2)
C6—C7—H7	118.9	N15—C16—C17	123.9 (2)
C8—C7—H7	118.9	N15—C16—H16	118.0
C9—C8—C7	118.3 (3)	C17—C16—H16	118.0
C9—C8—H8	120.9	C16—C17—C12	119.3 (2)
C7—C8—H8	120.9	C16—C17—H17	120.3
C8—C9—F1	118.8 (3)	C12—C17—H17	120.3
C8—C9—C10	121.5 (3)

C5—N1—C2—C3	0.3 (2)	C7—C8—C9—C10	0.0 (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—C11	178.5 (2)
C6—C2—C3—N4	177.8 (2)	C7—C6—C11—C10	1.6 (3)
N1—C2—C3—C12	177.2 (2)	C2—C6—C11—C10	−178.8 (2)
C6—C2—C3—C12	−4.1 (4)	C9—C10—C11—C6	0.2 (4)
C2—C3—N4—C5	1.2 (2)	C2—C3—C12—C13	153.7 (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—N4	0.4 (3)	N4—C3—C12—C17	150.5 (2)
N1—C2—C6—C11	−37.4 (3)	C17—C12—C13—C14	0.0 (3)
C3—C2—C6—C11	144.1 (2)	C3—C12—C13—C14	178.9 (2)
N1—C2—C6—C7	142.3 (2)	C12—C13—C14—N15	1.1 (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—C17	0.9 (4)
C2—C6—C7—C8	177.6 (2)	N15—C16—C17—C12	0.1 (4)
C6—C7—C8—C9	2.0 (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, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N15ⁱ	0.89	1.94	2.815 (3)	164

Symmetry code: (i) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₀FN₃
M_r	239.25
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	193
a, b, c (Å)	9.217 (2), 8.1064 (5), 30.665 (5)
V (Å³)	2291.1 (6)
Z	8
Radiation type	Cu Kα
µ (mm⁻¹)	0.80
Crystal size (mm)	0.54 × 0.20 × 0.13

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2121, 2121, 1707
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.608

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.076, 0.201, 1.09
No. of reflections	2121
No. of parameters	163
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.58, −0.54

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N15ⁱ	0.89	1.94	2.815 (3)	164

Symmetry code: (i) x−1, y, z.

References

Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119. Web of Science CrossRef CAS IUCr Journals Google Scholar
Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761–762. Google Scholar
Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Koch, P., Bäuerlein, C., Jank, H. & Laufer, S. (2008). J. Med. Chem. 51, 5630–5640. Web of Science CrossRef PubMed CAS Google Scholar
Liverton, N. J., Butcher, J. W., Claiborne, C. F., Claremon, D. A., Libby, B. E., Nguyen, K. T., Pitzenberger, S. M., Selnick, H. G., Smith, G. R., Tebben, A., Vacca, J. P., Varga, S. L., Agarwal, L., Dancheck, K., Forsyth, A. J., Fletcher, D. S., Frantz, B., Hanlon, W. A., Harper, C. F., Hofsess, S. J., Kostura, M., Lin, J., Luell, S., O'Neill, E. A., Orevillo, C. J., Pang, M., Parsons, J., Rolando, A., Sahly, Y., Visco, D. M. & O'Keefe, S. J. (1999). J. Med. Chem. 42, 2180–2190. Web of Science CrossRef PubMed CAS Google Scholar
Peifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem. 6, 113–149. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 3| March 2009| Page o573

doi:10.1107/S1600536809005650

Open

access