3-(4-Fluoro­phen­yl)-6-meth­oxy-2-(4-pyrid­yl)quinoxaline

Hartmut Jahns; Pierre Koch; Dieter Schollmeyer; Stefan Laufer

doi:10.1107/S1600536809022119

. 2009 Jun 20;65(Pt 7):o1626. doi: 10.1107/S1600536809022119

3-(4-Fluorophenyl)-6-methoxy-2-(4-pyridyl)quinoxaline

Hartmut Jahns ^a, Pierre Koch ^a, Dieter Schollmeyer ^b, Stefan Laufer ^a,^*

PMCID: PMC2969274 PMID: 21582893

Abstract

In the title compound, C₂₀H₁₄FN₃O, the quinoxaline system makes dihedral angles of 32.38 (7) and 48.04 (7)° with the 4-fluorophenyl and pyridine rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 57.77 (9)° with the pyridine ring. In the crystal, the molecules form dimeric C—H⋯N hydrogen-bonded R ₂ ²(20) ring motifs lying about crystallographic inversion centers. The dimeric units stack via π–π interactions between methoxyphenyl rings and pyridine–fluorophenyl rings with centroid–centroid distances of 3.720 (1) and 3.823 (1) Å, respectively. The respective average perpendicular distances are 3.421 and 3.378 Å, with dihedral angles between the rings of 1.31 (9) and 11.64 (9)°.

Related literature

Many chinoxaline derivatives have been prepared and their biological activity have been studied, see: He et al. (2003 ▶); Kim et al. (2004 ▶). For intermolecular C—H⋯N hydrogen bonds, see: Taylor & Kennard (1982 ▶). For distinct ring motifs formed via O—H⋯N hydrogen bonds, see: Habib & Janiak (2008 ▶); Friščič & MacGillivray (2003 ▶). For graph-set notation, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₂₀H₁₄FN₃O
M _r = 331.34
Orthorhombic,
a = 7.3886 (4) Å
b = 12.2071 (8) Å
c = 34.562 (6) Å
V = 3117.3 (6) Å³
Z = 8
Cu Kα radiation
μ = 0.80 mm⁻¹
T = 193 K
0.45 × 0.22 × 0.13 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: none
2950 measured reflections
2950 independent reflections
2542 reflections with I > 2σ(I)
3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.124
S = 1.05
2950 reflections
228 parameters
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.24 e Å⁻³

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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809022119/si2176sup1.cif

e-65-o1626-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809022119/si2176Isup2.hkl

e-65-o1626-Isup2.hkl^{(144.9KB, 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
C15—H15⋯N21ⁱ	0.95	2.44	3.368 (3)	165

Open in a new tab

Symmetry code: (i) Inline graphic .

supplementary crystallographic information

Comment

Functionalized quinoxaline derivatives are well known in pharmaceutical industry. They have been shown to possess antibacterial activity (Kim et al. 2004) and as PDGF-R tyrosine kinase inhibitors (He et al. 2003).

The title compound, (I), was prepared in the course of our studies on 2-(2-alkylaminopyridin-4-yl)-3-(4-fluorophenyl)quinoxalines as potent p38 mitogen-activated protein (MAP) kinase inhibitors. The two molecules of I are connected into a centrosymmetric dimer by intermolecular C15–H15···N21 hydrogen bonds [graph set R₂²(20) (Bernstein et al. 1995)] (Fig.1 and Table 1). By searching the CCDC a similar O—H···N hydrogen bond pattern could be found in the structure EHOTUQ (Friščič & MacGillivray 2003), with a R₄⁴(46) ring system. A variety of distinct ring motifs formed via hydrogen bonded donors and acceptors (O—H···O, O—H···N) has been described for the 4/1/2 adduct of benzene-1,3,5-tricarboxylic acid, 1,2-bis(1,2,4-triazol-4-yl)ethane and water by Habib & Janiak (2008). The C—H···N hydrogen bond of the title compound (Table 1) confirms the hydrogen-bond geometry values reviewed by Taylor & Kennard (1982), where the C—H···N distances vary between 2.523 Å and 2.721 Å, and the angles around the H atom range between 124.6° and 157.3°. The quinoxaline ring makes dihedral angles of 32.38 (7)° and 48.04 (7)° to the 4-fluorophenyl ring and the pyridine ring, respectively. The 4-fluorophenyl ring makes dihedral angles of 57.77 (9)° with the pyridine ring.

π—π interactions between the pyridin rings and the 4-fluorophenyl rings along the b axis have Cg2···Cg4ⁱⁱ distances of 3.823 (1) Å, and the distances between Cg3···Cg3ⁱⁱⁱ of the methoxyphenyl rings are 3.720 (1) Å along the a axis (Fig. 2). The respective average perpendicular stacking distances are 3.378 Å and 3.421 Å, with dihedral angles between the rings 1.31° and 11.64°. Symmetry codes ii = 1/2 - x, 1/2 + y, z; iii = -1/2 + xy, 3/2 - z. Cg2, Cg3 and Cg4 are the centroids of rings N21, C20, C19, C18, C23, C22; C4 - C9; and C11 - C16.

Experimental

The title compound I was prepared by irradiating 1-(4-fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dion (137 mg, 0.6 mmol), o-phenylendiamine (82 mg, 0.6 mmol) and methanol-acetic acid (9:1, 6 ml) in a sealed tube at 433 K for 5 min by moderating the initial microwave power (250 W). After the mixture was cooled to room temperature in a stream of compressed air, the solvent was removed under reduced pressure and the residue was purified by flash chromatography (silica gel, from petroleum ether/ ethyl acetate 2:1 to 1:2) to yield 82 mg of I. Crystals suitable for X-ray analysis were obtained by slow crystallization from diethylether/n-hexane.