4-[2-(4-Fluoro­phen­yl)-1H-pyrrol-3-yl]pyridine

Abu Thaher, B.; Koch, P.; Schollmeyer, D.; Laufer, S.

doi:10.1107/S160053680900364X

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 65| Part 3| March 2009| Page o457

doi:10.1107/S160053680900364X

Open

access

4-[2-(4-Fluorophenyl)-1H-pyrrol-3-yl]pyridine

Bassam Abu Thaher,^a Pierre Koch,^b Dieter Schollmeyer ^c and Stefan Laufer ^b ^*

^aFaculty of Science, Chemistry Department, Islamic University of Gaza, Gaza Strip, Palestinian Territories, ^bInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and ^cDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 23 January 2009; accepted 29 January 2009; online 4 February 2009)

In the crystal structure of the title compound, C₁₅H₁₁FN₂, the pyrrole ring makes dihedral angles of 33.19 (9) and 36.33 (10)° with the pyridine and 4-fluorophenyl rings, respectively. The pyridine ring makes a dihedral angle of 46.59 (9)° with the 4-fluorophenyl ring. In the crystal structure, an N—H⋯N hydrogen bond joins the molecules into chains.

Related literature

Many 1-(4-fluorophenyl)-2-(pyridin-4-yl)pyrrol derivatives have been prepared and their biological activities studied; see: de Laszlo et al. (1998 ); Revesz et al. (2000 , 2002 ); Qian et al. (2006 ). For the synthesis of the title compound, see: Qian et al. (2006).

Experimental

Crystal data

C₁₅H₁₁FN₂
M_r = 238.26
Orthorhombic, P b c a
a = 9.2966 (7) Å
b = 8.1966 (5) Å
c = 30.5738 (19) Å
V = 2329.7 (3) Å³
Z = 8
Cu Kα radiation
μ = 0.76 mm⁻¹
T = 193 (2) K
0.25 × 0.20 × 0.18 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2175 measured reflections
2175 independent reflections
1744 reflections with I > 2σ(I)
3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

R[F² > 2σ(F²)] = 0.042
wR(F²) = 0.120
S = 1.03
2175 reflections
164 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N16ⁱ	0.93	1.97	2.8696 (19)	161
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, 2003 ); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680900364X/bt2858sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680900364X/bt2858Isup2.hkl

checkCIF report

Comment top

Functionalized 1-(4-fluorophenyl)-2-(pyridin-4-yl)pyrrols can be used as anticoccidial agents (Qian et al. 2006) or as p38 MAP kinase inhibitors (de Laszlo et al. 1998; Revesz et al. 2000, 2002).

The analysis of the crystal structure of the title compound is shown in Fig. 1. The pyrrole ring makes dihedral angles of 33.19 (9)° and 36.33 (10)° to the pyridine ring and the 4-fluorophenyl ring, respectively. The pyridine ring makes a dihedral angle of 46.59 (9)° to the 4-fluorophenyl ring.

The crystal packing (Fig. 2) shows that N1—H1 of the pyrrole ring forms an intermolecular N—H···N hydrogen bond to the pyridine ring (N16) resulting in a chain parallel to the a axis.

Related literature top

Many 1-(4-fluorophenyl)-2-(pyridin-4-yl)pyrrol derivatives have been prepared and their biological activities studied; see: de Laszlo et al. (1998); Revesz et al. (2000, 2002); Qian et al. (2006). For the synthesis of the title compound, see: Qian et al. (2006).

Experimental top

Ammonium acetate (2.20 g, 34.9 mmol) was added to a solution of 4-(4-fluorophenyl)-4-oxo-3-(pyridin-4-yl)butanal (0.50 g) in glacial acetic acid (10 ml). The resulting mixture was heated to 388–393 K for 2 h. The solvent was removed under reduced pressure and the residue was diluted with ethyl acetate and aq. NaHCO₃ solution. Solid Na₂CO₃ was added until effervescence ceased. The organic phase was washed with aq. NaHCO₃ solution and brine, dried over Na₂SO₄ and the solvent was evaporated under reduced pressure to give crude I. The residue was dissolved in ethyl acetate (7 ml) and filtered, then purified by flash chromatography (SiO₂, petroleum ether/ethyl acetate 1:1 to 1:4). Yield 135 mg. For X-ray suitable crystals of compound I were obtained by slow evaporation at 298 K of a solution of n-hexane–ethyl acetate.

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, 2003); software used to prepare material for publication: PLATON (Spek, 2003).

Figures top

	Fig. 1. View of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
	Fig. 2. Crystal packing of the title compound. The hydrogen bond is shown with dashed lines. View along the b axis.

4-[2-(4-Fluorophenyl)-1H-pyrrol-3-yl]pyridine top

Crystal data top

C₁₅H₁₁FN₂	F(000) = 992
M_r = 238.26	D_x = 1.359 Mg m⁻³
Orthorhombic, Pbca	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 9.2966 (7) Å	θ = 30–51.7°
b = 8.1966 (5) Å	µ = 0.76 mm⁻¹
c = 30.5738 (19) Å	T = 193 K
V = 2329.7 (3) Å³	Plate, light brown
Z = 8	0.25 × 0.20 × 0.18 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.000
Radiation source: rotating anode	θ_max = 69.5°, θ_min = 2.9°
Graphite monochromator	h = 0→11
ω/2θ scans	k = −9→0
2175 measured reflections	l = −36→0
2175 independent reflections	3 standard reflections every 60 min
1744 reflections with I > 2σ(I)	intensity decay: 2%

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.042	H-atom parameters constrained
wR(F²) = 0.120	w = 1/[σ²(F_o²) + (0.0641P)² + 0.5148P] where P = (F_o² + 2F_c²)/3
S = 1.03	(Δ/σ)_max < 0.001
2175 reflections	Δρ_max = 0.26 e Å⁻³
164 parameters	Δρ_min = −0.17 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00086 (16)

Crystal data top

C₁₅H₁₁FN₂	V = 2329.7 (3) Å³
M_r = 238.26	Z = 8
Orthorhombic, Pbca	Cu Kα radiation
a = 9.2966 (7) Å	µ = 0.76 mm⁻¹
b = 8.1966 (5) Å	T = 193 K
c = 30.5738 (19) Å	0.25 × 0.20 × 0.18 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.000
2175 measured reflections	3 standard reflections every 60 min
2175 independent reflections	intensity decay: 2%
1744 reflections with I > 2σ(I)

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.120	H-atom parameters constrained
S = 1.03	Δρ_max = 0.26 e Å⁻³
2175 reflections	Δρ_min = −0.17 e Å⁻³
164 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
N1	0.51524 (14)	0.21406 (17)	0.41905 (5)	0.0278 (3)
H1	0.6083	0.2266	0.4081	0.033*
C2	0.39066 (16)	0.2347 (2)	0.39570 (6)	0.0249 (4)
C3	0.27690 (16)	0.2008 (2)	0.42407 (5)	0.0255 (4)
C4	0.33869 (18)	0.1586 (2)	0.46491 (6)	0.0311 (4)
H4	0.2876	0.1288	0.4906	0.037*
C5	0.48474 (18)	0.1684 (2)	0.46075 (6)	0.0317 (4)
H5	0.5531	0.1470	0.4831	0.038*
C6	0.39610 (16)	0.2800 (2)	0.34938 (5)	0.0264 (4)
C7	0.50091 (18)	0.3890 (2)	0.33407 (6)	0.0331 (4)
H7	0.5698	0.4322	0.3539	0.040*
C8	0.5055 (2)	0.4345 (3)	0.29053 (6)	0.0421 (5)
H8	0.5773	0.5075	0.2802	0.051*
C9	0.4047 (2)	0.3721 (3)	0.26266 (6)	0.0429 (5)
C10	0.3009 (2)	0.2630 (3)	0.27593 (6)	0.0395 (5)
H10	0.2329	0.2207	0.2557	0.047*
C11	0.29785 (18)	0.2163 (2)	0.31936 (6)	0.0311 (4)
H11	0.2279	0.1397	0.3289	0.037*
F12	0.40632 (16)	0.4201 (2)	0.22006 (4)	0.0706 (5)
C13	0.12145 (16)	0.20955 (19)	0.41599 (5)	0.0244 (4)
C14	0.05747 (18)	0.3235 (2)	0.38834 (6)	0.0292 (4)
H14	0.1155	0.3991	0.3727	0.035*
C15	−0.09026 (18)	0.3267 (2)	0.38362 (6)	0.0318 (4)
H15	−0.1307	0.4053	0.3644	0.038*
N16	−0.17994 (14)	0.2253 (2)	0.40458 (5)	0.0329 (4)
C17	−0.11823 (18)	0.1169 (2)	0.43157 (6)	0.0320 (4)
H17	−0.1791	0.0442	0.4472	0.038*
C18	0.02834 (17)	0.1046 (2)	0.43807 (5)	0.0286 (4)
H18	0.0657	0.0248	0.4575	0.034*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0166 (6)	0.0319 (8)	0.0348 (8)	−0.0002 (6)	−0.0004 (5)	0.0008 (6)
C2	0.0176 (7)	0.0249 (8)	0.0322 (9)	0.0008 (6)	0.0008 (6)	−0.0021 (6)
C3	0.0207 (8)	0.0253 (8)	0.0304 (8)	−0.0006 (6)	0.0015 (6)	−0.0009 (7)
C4	0.0258 (8)	0.0379 (10)	0.0297 (9)	0.0005 (7)	0.0018 (7)	0.0050 (7)
C5	0.0266 (8)	0.0359 (10)	0.0327 (9)	0.0011 (7)	−0.0036 (7)	0.0037 (7)
C6	0.0199 (7)	0.0276 (8)	0.0316 (9)	0.0044 (6)	0.0034 (6)	−0.0020 (6)
C7	0.0267 (8)	0.0374 (10)	0.0353 (9)	−0.0029 (7)	0.0064 (7)	−0.0013 (7)
C8	0.0413 (10)	0.0452 (11)	0.0399 (10)	−0.0017 (9)	0.0160 (9)	0.0048 (8)
C9	0.0483 (11)	0.0538 (12)	0.0266 (9)	0.0098 (10)	0.0091 (8)	0.0025 (8)
C10	0.0377 (10)	0.0475 (11)	0.0332 (10)	0.0072 (9)	−0.0022 (8)	−0.0071 (8)
C11	0.0253 (8)	0.0342 (9)	0.0339 (9)	0.0030 (7)	0.0007 (7)	−0.0027 (7)
F12	0.0869 (11)	0.0956 (11)	0.0292 (6)	−0.0015 (9)	0.0080 (6)	0.0113 (7)
C13	0.0204 (8)	0.0262 (8)	0.0264 (8)	−0.0003 (6)	0.0028 (6)	−0.0052 (6)
C14	0.0226 (8)	0.0289 (9)	0.0361 (9)	0.0001 (7)	0.0041 (7)	0.0013 (7)
C15	0.0232 (8)	0.0343 (9)	0.0380 (10)	0.0042 (7)	0.0013 (7)	0.0012 (8)
N16	0.0197 (7)	0.0426 (9)	0.0362 (8)	0.0000 (6)	0.0031 (6)	−0.0027 (7)
C17	0.0237 (8)	0.0384 (10)	0.0339 (9)	−0.0049 (7)	0.0065 (7)	0.0000 (7)
C18	0.0244 (8)	0.0326 (9)	0.0286 (8)	−0.0009 (7)	0.0025 (6)	0.0005 (7)

Geometric parameters (Å, º) top

N1—C5	1.358 (2)	C9—F12	1.360 (2)
N1—C2	1.371 (2)	C9—C10	1.377 (3)
N1—H1	0.9339	C10—C11	1.382 (3)
C2—C3	1.396 (2)	C10—H10	0.9500
C2—C6	1.465 (2)	C11—H11	0.9500
C3—C4	1.417 (2)	C13—C14	1.393 (2)
C3—C13	1.468 (2)	C13—C18	1.395 (2)
C4—C5	1.366 (2)	C14—C15	1.381 (2)
C4—H4	0.9500	C14—H14	0.9500
C5—H5	0.9500	C15—N16	1.340 (2)
C6—C11	1.396 (2)	C15—H15	0.9500
C6—C7	1.402 (2)	N16—C17	1.341 (2)
C7—C8	1.383 (3)	C17—C18	1.381 (2)
C7—H7	0.9500	C17—H17	0.9500
C8—C9	1.366 (3)	C18—H18	0.9500
C8—H8	0.9500

C5—N1—C2	110.27 (14)	F12—C9—C10	118.54 (19)
C5—N1—H1	124.1	C8—C9—C10	122.70 (18)
C2—N1—H1	125.6	C9—C10—C11	118.50 (18)
N1—C2—C3	106.96 (15)	C9—C10—H10	120.8
N1—C2—C6	120.37 (14)	C11—C10—H10	120.8
C3—C2—C6	132.65 (15)	C10—C11—C6	120.97 (17)
C2—C3—C4	106.80 (14)	C10—C11—H11	119.5
C2—C3—C13	129.17 (15)	C6—C11—H11	119.5
C4—C3—C13	124.00 (15)	C14—C13—C18	116.25 (15)
C5—C4—C3	107.84 (15)	C14—C13—C3	123.73 (15)
C5—C4—H4	126.1	C18—C13—C3	119.96 (15)
C3—C4—H4	126.1	C15—C14—C13	120.04 (16)
N1—C5—C4	108.13 (15)	C15—C14—H14	120.0
N1—C5—H5	125.9	C13—C14—H14	120.0
C4—C5—H5	125.9	N16—C15—C14	123.85 (17)
C11—C6—C7	118.26 (16)	N16—C15—H15	118.1
C11—C6—C2	121.19 (15)	C14—C15—H15	118.1
C7—C6—C2	120.55 (15)	C15—N16—C17	116.02 (14)
C8—C7—C6	120.96 (18)	N16—C17—C18	123.98 (16)
C8—C7—H7	119.5	N16—C17—H17	118.0
C6—C7—H7	119.5	C18—C17—H17	118.0
C9—C8—C7	118.57 (18)	C17—C18—C13	119.86 (16)
C9—C8—H8	120.7	C17—C18—H18	120.1
C7—C8—H8	120.7	C13—C18—H18	120.1
F12—C9—C8	118.76 (19)

C5—N1—C2—C3	0.13 (19)	C7—C8—C9—C10	−1.6 (3)
C5—N1—C2—C6	−178.44 (15)	F12—C9—C10—C11	−178.99 (17)
N1—C2—C3—C4	−0.29 (18)	C8—C9—C10—C11	0.8 (3)
C6—C2—C3—C4	178.03 (17)	C9—C10—C11—C6	1.0 (3)
N1—C2—C3—C13	177.86 (16)	C7—C6—C11—C10	−1.9 (2)
C6—C2—C3—C13	−3.8 (3)	C2—C6—C11—C10	178.16 (16)
C2—C3—C4—C5	0.4 (2)	C2—C3—C13—C14	−33.5 (3)
C13—C3—C4—C5	−177.92 (16)	C4—C3—C13—C14	144.40 (18)
C2—N1—C5—C4	0.1 (2)	C2—C3—C13—C18	149.46 (17)
C3—C4—C5—N1	−0.3 (2)	C4—C3—C13—C18	−32.7 (2)
N1—C2—C6—C11	142.67 (16)	C18—C13—C14—C15	−0.8 (2)
C3—C2—C6—C11	−35.5 (3)	C3—C13—C14—C15	−177.95 (16)
N1—C2—C6—C7	−37.2 (2)	C13—C14—C15—N16	0.4 (3)
C3—C2—C6—C7	144.63 (19)	C14—C15—N16—C17	0.3 (3)
C11—C6—C7—C8	1.1 (3)	C15—N16—C17—C18	−0.7 (3)
C2—C6—C7—C8	−178.99 (17)	N16—C17—C18—C13	0.3 (3)
C6—C7—C8—C9	0.6 (3)	C14—C13—C18—C17	0.4 (2)
C7—C8—C9—F12	178.17 (18)	C3—C13—C18—C17	177.73 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N16ⁱ	0.93	1.97	2.8696 (19)	161

Symmetry code: (i) x+1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₅H₁₁FN₂
M_r	238.26
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	193
a, b, c (Å)	9.2966 (7), 8.1966 (5), 30.5738 (19)
V (Å³)	2329.7 (3)
Z	8
Radiation type	Cu Kα
µ (mm⁻¹)	0.76
Crystal size (mm)	0.25 × 0.20 × 0.18

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2175, 2175, 1744
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.607

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.120, 1.03
No. of reflections	2175
No. of parameters	164
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.17

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N16ⁱ	0.93	1.97	2.8696 (19)	160.8

Symmetry code: (i) x+1, y, z.

Acknowledgements

The authors thank the Alexander von Humbolt Foundation (AvH) for funding.

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
Laszlo, S. E. de, Visco, D., Agarwal, L., Chang, L., Chin, J., Croft, G., Forsyth, A., Fletcher, D., Frantz, B., Hacker, C., Hanlon, W., Harper, C., Kostura, M., Li, B., Luell, S., MacCoss, M., Mantlo, N., O'Neill, E. A., Orevillo, C., Pang, M., Parsons, J., Rolando, A., Sahly, Y., Sidler, K., Widmer, W. R. & O'Keefe, S. J. (1998). Bioorg. Med. Chem. Lett. 8, 2689–2694. Web of Science PubMed Google Scholar
Qian, X., Liang, G.-B., Feng, D., Fisher, M., Crumley, T., Rattray, S., Dulski, P. M., Gurnett, A., Leavitt, P. S., Liberator, P. A., Misura, A. S., Samaras, S., Tamas, T., Schmatz, D. M., Wyvratt, M. & Biftu, T. (2006). Bioorg. Med. Chem. Lett. 16, 2817–2821. Web of Science CrossRef PubMed CAS Google Scholar
Revesz, L., Di Padova, F. E., Buhl, T., Feifel, R., Gram, H., Hiestand, P., Manning, U., Wolf, R. & Zimmerlin, A. G. (2002). Bioorg. Med. Chem. Lett. 12, 2109–2112. Web of Science CrossRef PubMed CAS Google Scholar
Revesz, L., Di Padova, F. E., Buhl, T., Feifel, R., Gram, H., Hiestand, P., Manning, U. & Zimmerlin, A. G. (2000). Bioorg. Med. Chem. Lett. 10, 1261–1264. 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. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar