3.1. General Information
Melting point was determined on a Büchi melting point B-450 apparatus (Instrumart, South Bulington, VT, USA). IR spectra were recorded on a Shimadzu FTIR 8400 spectrophotometer (Scientific Instruments Inc., Seattle, WA, USA) using KBr disks. NMR spectra were recorded on a Bruker Avance 400 spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) operating at 400.13 MHz for 1H and 100.61 MHz for 13C, and using tetramethylsilane as an internal standard. NMR spectroscopic data were recorded in CDCl3 using as internal standards the residual non-deuteriated signal for 1H-NMR and the deuteriated solvent signal for 13C-NMR spectroscopy. Chemical shifts (δ) are in ppm, coupling constants (J) are in Hertz (Hz) and the classical abbreviations are used to describe the signal multiplicities. The mass spectrum was obtained on a SHIMADZU-GCMS 2010-DI-2010 spectrometer (Scientific Instruments Inc., Columbia, NC, USA) equipped with a direct inlet probe operating at 70 eV. High resolution mass spectra (HRMS) were recorded on an Agilent Technologies Q-TOF 6520 spectrometer (Agilent Technologies, Waldbronn, Germany) via an electrospray ionization (ESI). Silica gel aluminum plates (Merck 60 F254, Darmstadt, Germany) were used for analytical TLC. The starting fluorobenzoyl chloride 1, 5-chloro-8-hydroxyquinoline 2, and triethylamine were purchased from Sigma-Aldrich (San Luis, MO, USA); they were analytical grade reagents, and were used without further purification.
3.2. Synthesis of (5-Chloroquinolin-8-yl)-2-fluorobenzoate (3)
2-Fluorobenzoyl chloride 1 (119 μL, 1.0 mmol) was added dropwise to a solution of 5-chloro-8-hydroxyquinoline 2 (179 mg, 1.0 mmol) and triethylamine (167 μL, 1.2 mmol) in dichloromethane (5.0 mL). The mixture was stirred at room temperature for 1 h until the starting materials were no longer detected by thin-layer chromatography. After solvent was removed under reduced pressure, water (5.0 mL) was added, and the aqueous solution was extracted with ethyl acetate (2 × 5.0 mL). The combined organic layers were dried with anhydrous magnesium sulfate, and the pure product 3 was obtained as a white solid (277 mg, 92%) after purification by column chromatography on silica gel using dichloromethane as eluent. Recrystallization of 3 from acetone afforded crystalline white prisms suitable for single-crystal X-ray diffraction analysis. M.P. 129 °C. FTIR (KBr): ν = 3072, 2942, 1741 (C=O), 1608, 1587, 1213, 1153, 1126, 1066, 1029 (C–O) cm−1. 1H-NMR (400 MHz, CDCl3): δ = 7.21–7.27 (m, 1H), 7.31 (td, J = 1.1, 7.6 Hz, 1H), 7.50–7.56 (m, 2H), 7.60–7.64 (m, 1H), 7.66 (d, J = 8.0 Hz, 1H), 8.28 (td, J = 1.8, 7.6 Hz, 1H), 8.59 (dd, J = 1.6, 8.8 Hz, 1H), 8.94 (dd, J = 1.6, 4.2 Hz, 1H) ppm. 13C-NMR (100 MHz, CDCl3): δ = 117.3 (CH, d, JC-F = 22.0 Hz), 117.9 (C, d, JC-F = 9.5 Hz), 121.6 (CH), 122.6 (CH), 124.3 (CH, d, JC-F = 4.4 Hz), 126.2 (CH), 127.5 (C), 129.1 (C), 133.1 (CH), 133.2 (CH), 135.4 (CH, d, JC-F = 8.8 Hz), 141.8 (C), 146.6 (C), 151.2 (CH), 162.7 (C, d, JC-F = 261.8 Hz), 162.8 (C, d, JC-F = 3.6 Hz) ppm. MS (EI, 70 eV) m/z (%): 303/301 (3/9) [M+], 123 (100), 95 (21), 75 (8). HRMS (ESI+): calcd. for C16H10ClFNO2+ 302.0384 [M+H]+; found: 302.0378.
Crystal Data: C16H9ClFNO2 (M = 301.69 g/mol): monoclinic, space group P 21/c (No. 14), a = 7.5003(6) Å, b = 22.0264(16) Å, c = 8.5046(7) Å, α = 90.0, β = 105.547(7), γ = 90.0, V = 1353.59(19) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.297 mm−1, Dcalc = 1.480 Mg/m3, 14033 reflections measured (3.372° ≤ θ ≤ 27.664°), 3079 unique (Rint = 0.0274, Rsigma = 0.0181) which were used in all calculations. The final R1 was 0.0524 (I > 2_(I)) and wR2 was 0.0635 (all data).
Data Collection and Refinement Details:
Diffraction data were collected on a Rigaku XTABLAB P-200 DS diffractometer using CrystalClear [21
]; using graphite monochromated MoKα
radiation (0.71073 Å). The corrected data were solved by direct methods with SHELXS-2014
] and refined by full-matrix methods on F2
]. All H-atoms, were positioned at geometrically idealized positions, C—H= 0.9300 Å, and were refined using a riding model approximation with Uiso(H) = 1.2 Ueq(parent atom). Correctness of the model was confirmed by low residual peaks (0.418) and holes (−0.342 e.Å3
) in the final difference map. (CCDC 1522239 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44 1223 336033; E-mail: [email protected]