4-[(7-Fluoro­quinazolin-4-yl)­oxy]aniline

Jing Jia; Guibin Wang; Dingqiang Lu

doi:10.1107/S1600536810053286

. 2010 Dec 24;67(Pt 1):o229. doi: 10.1107/S1600536810053286

4-[(7-Fluoroquinazolin-4-yl)oxy]aniline

Jing Jia ^a,^b, Guibin Wang ^c, Dingqiang Lu ^a,^b,^*

PMCID: PMC3050189 PMID: 21522728

Abstract

In the molecule of the title compound, C₁₄H₁₀FN₃O, the bicyclic quinazoline system is effectively planar, with a mean deviation from planarity of 0.0140 (3) Å. The quinazoline heterocyclic system and the adjacent benzene ring make a dihedral angle of 85.73 (9)°. Two intermolecular N—H⋯N hydrogen bonds contribute to the stability of the crystal structure. In addition, a weak π–π stacking interaction [centroid–centroid distance = 3.902 (2) Å] is observed.

Related literature

For general background to quinazolines, see: Labuda et al. (2009 ▶). Graves et al. (2002 ▶); For the preparation of the title compound, see: Zhang et al. (2010 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₄H₁₀FN₃O
M _r = 255.25
Orthorhombic,
a = 8.0210 (16) Å
b = 8.3370 (17) Å
c = 17.562 (4) Å
V = 1174.4 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.969, T _max = 0.990
2351 measured reflections
1256 independent reflections
883 reflections with I > 2σ(I)
R _int = 0.082
3 standard reflections every 200 reflections intensity decay: 1%

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.110
S = 1.02
1256 reflections
172 parameters
H-atom parameters constrained
Δρ_max = 0.12 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810053286/zl2317sup1.cif

e-67-0o229-sup1.cif^{(17.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810053286/zl2317Isup2.hkl

e-67-0o229-Isup2.hkl^{(62.1KB, 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
N1—H1A⋯N2ⁱ	0.89	2.67	3.408 (4)	142
N1—H1B⋯N3ⁱⁱ	0.89	2.38	3.205 (4)	154

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors thank the Center of Testing and Analysis, Nanjing University, for the data collection.

supplementary crystallographic information

Comment

Quinazoline and its derivatives have been a research hotspot for a long time, owing to their significant role in the synthesis of some tyrosine protein kinase inhibitors and their potential anti-cancer activities (Labuda et al., 2009; Graves et al., 2002). As part of our studies into the synthesis of quinazoline derivatives, the title compound 4-[(4-benzenamine)yloxy]-7-fluoroquinazoline, which may be used as an intermediate towards some quinazoline derivatives, was synthesised. We report herein the crystal structure of the title compound.

In the molecule of the title compound, (Fig. 1), the bond lengths (Allen et al., 1987) and angles are within normal ranges. The bicyclic quinazoline system is effectively planar with a mean deviation of only 0.0140 (3)Å. The dihedral angle between the benzene ring C1-C6 and the quinazoline ring system is 85.73 (9)°.

Two intermolecular N-H···N hydrogen bonds contribute to the stability of the molecular configuration and the packing of the molecules (Fig. 2 and Table 1). The crystal structure (Fig. 2) is also stabilized by a weak π–π stacking interaction with centroid–centroid separation of 3.902 (2) Å for Cg1···Cg2ⁱ , where Cg1, Cg2 are the centroids of the rings N2/C7/C14/C9/N3/C8 and C1–C6, respectively [symmetry code: (i) -1/2+x, 1/2-y, 1-z].

Experimental

The title compound was prepared by following a reported procedure (Zhang et al., 2010). 4-Chloro-7-fluoroquinazoline (10 g, 54.77 mmol) was added to a mixture of dimethylformamide (100 ml), potassium tert-butoxide (6.15 g, 54.77 mmol) and 4-aminophenol (5.98 g, 54.77 mmol), and then heated to 343 K for 8 h. After cooling to room temperature, the reaction mixture was added to water (250 ml) and ethyl acetate (250 ml). The organic phase was collected and the water phase was extracted with ethyl acetate (250 ml). All the organic phases were combined and washed with brine (2× 250 ml). The organic phase was dried with anhydrous sodium sulfate for 6 h and then distilled (b.p. 313 K at 0.1 Mpa) and recrystallized from ethyl acetate, to give a total yield of 4-[(4-benzenamine)yloxy]-7-fluoroquinazoline of 81.0 % (11.32 g, 44.35 mmol). M.p. 353-355 K. ESI-MS(m/z): 256.1[M+H]⁺, 278.1[M+Na]⁺. ¹H NMR (500 MHz, DMSO-d₆) δ: 8.72 (s, 1 H, 8-H), 8.40 (dd, J_H-F = 6.0 Hz, J = 9.0 Hz, 1 H, 13-H), 7.7 (dd, J = 2.5 Hz, J_H-F = 10.0 Hz, 1 H, 10-H), 7.61 (td, J = 2.5, 9.0 Hz, J_H-F = 9.0 Hz, 1H, 12-H), 7.00 (d, J = 9.0 Hz, 1H, C1-H), 7.00 (d, J = 9.0 Hz, 1H, C5-H), 6.71 (d, J = 8.5 Hz, 1H, C2-H), 6.71 (d, J = 8.5 Hz, 1H, C4-H), 5.10(s, 2H, N1-H). ¹³C NMR(500 MHz, DMSO-d₆) δ: 166.58 (C-7), 165.12 (d, J_C-F = 251.3 Hz, C-11), 155.17 (C-8), 152.64 (d, J_C-F = 13.8 Hz, C-9), 146.47 (C-6), 142.05 (C-3), 126.55 (d, J_C-F = 11.3 Hz, C-13), 121.89 (C-1), 121.89 (C-5), 117.38 (d, J_C-F = 25.0 Hz, C-12), 114.18 (C-2), 114.18 (C-4), 112.82 (C-14), 111.38 (d, J_C-F = 21.3 Hz, C-10). IR(KBr)(cm^-1): ν_N-H (3420.80, 3327.69), ν_C_═_C-H (3077.53), ν_C_═_N (1628.11), δ_C_═_C-H (1609.25, 1575.87, 1509.07, 1459.02), ν_C-N (1286.23), ν_Ar-O (1248.06). UV-vis: λ_max(CH₃OH) nm (ε): 217.5 (40174), λ_max (0.1M HCl) nm (ε): 230.2 (30173), λ_max(0.1M NaOH) nm (ε): 216.4 (16773).

Crystals of the title compound suitable for X-ray diffraction were grown from ethyl acetate.