5-METHOXYQUINOLINE

Brown Oil

4.2 5-Hydroxyquinoline (4.0 g, 27.6 mmol) was dissolved in N, N-dimethylformamide (60 mL) under argon atmosphere and sodium hydride (1.3 g, 33.1 mmol) was slowly added at 0 °C. After stirring for 30 minutes, Iodomethane (4.7 g, 33.1 mmol) was slowly added to the reaction solution, stirred at room temperature for 30 minutes, The completion of the reaction was confirmed by TLC (hexane: ethyl acetate = 2: 1). The reaction mixture was poured into water (300 mL) And extracted with diethyl ether (6 X 100 mL). The organic solvent layer was washed with saturated sodium chloride solution (600 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent to give the desired compound (4.0 g, 92percent yield).To a solution of 5-quinolinol (164 mg, 1.13 mmol) in MeOH (7 mL) cooled to 0 °C was slowly added trimethylsilyldiazomethane (6 mL, 0.5 M in EtGeneral procedure: To a solution of 5-quinolinol 5 (164 mg, 1.13 mmol) in MeOH (7 mL) cooled to 0 °C was slowly added trimethylsilyldiazomethane (6 mL, 0.5 M in Et2O). The reaction mixture was allowed to warm to room temperature and stirred for 26 h. After addition of water, the reaction mixture was extracted with ethyl acetate (3 × 15mL). The combined organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The crude oil was purified by column chromatography on silica gel (EtOAc/CH2Cl2/hexane = 1:2:4) to give 5-methoxyquinoline 6a (76 mg, 42percent) as a white solid: 4.3 5-Methoxyquinoline-N-oxide (2) [30, 31] 5-Methoxyquinoline (1) (4.03 g, 25.3 mmol) was dissolved in dichloromethane (DCM, 40 mL) under nitrogen and treated with mCPBA (70%; 6.56 g, 38.0 mmol) at 0 C. The reaction mixture was stirred at rt for 6 h, then water (100 mL) was added and the aqueous phase was adjusted to alkaline pH upon addition of saturated aqueous sodium carbonate solution. The aqueous phase was extracted with DCM (3 * 150 mL) and the combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure and stored in refrigerator overnight to afford the desired product; yellow solid; yield: 4.085 g (92%); 1H NMR (400 MHz, CDCl3) delta 8.60 (dd, J = 6.0, 0.8 Hz, 1H), 8.34 (d, J = 9.2 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.70 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 4.8 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3) delta 155.60, 142.14, 136.48, 130.89, 123.31, 121.92, 119.74, 111.40, 106.59, 56.12; LC/MS (ESI+) m/z = 175 (M+).Under an argon atmosphere, the To solution of General procedure: To solution of 4.2 5-Methoxyquinoline (1) A solution of 5-hydroxyquinoline (4.0 g, 27.6 mmol) in anhydrous DMF (60 mL) was cooled and then added slowly to NaH (1.33 g, 33.12 mmol, 60% dispersion in mineral oil) at 0 C under argon atmosphere. The resulting mixture was stirred at the same temperature for 30 min. Methyl iodide (4.7 g, 33.12 mmol) was added dropwise to the suspension and the reaction mixture was allowed to warm to room temperature (rt) while stirring for additional 30 min. The reaction mixture was quenched with water (300 mL) and then extracted with diethyl ether (6 * 100 mL). The combined organic layers were washed with water and then brine, dried over anhydrous Na2SO4, filtered and the solvent was removed under reduced pressure to afford the title product as brown oil; yield: 4.03 g (92%); 1H NMR (400 MHz, CDCl3) delta 8.95 (dd, J = 4.2, 2.0 Hz, 1H), 8.62 (dd, J = 8.4, 1.2 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.4 Hz, 1H), 7.42 (dd, J = 8.4, 4.4 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 4.05 (s, 3H); 13C NMR (100 MHz, CDCl3) delta 155.17, 150.66, 148.70, 130.81, 129.37, 121.58, 120.85, 120.19, 104.22, 55.76.5-Hydroxyquinoline (4.0 g, 27.6 mmol) was dissolved in N, N-dimethylformamide (60 mL) under argon atmosphere and sodium hydride (1.3 g, 33.1 mmol) was slowly added at 0 C. After stirring for 30 minutes, Iodomethane (4.7 g, 33.1 mmol) was slowly added to the reaction solution, stirred at room temperature for 30 minutes, The completion of the reaction was confirmed by TLC (hexane: ethyl acetate = 2: 1). The reaction mixture was poured into water (300 mL) And extracted with diethyl ether (6 X 100 mL). The organic solvent layer was washed with saturated sodium chloride solution (600 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent to give the desired compound (4.0 g, 92% yield).General procedure: Experimental Procedure: A dried 25 mL Schlenk tube equipped with a magnetic stir bar was charged with Togni's Reagent 2 (0.25 mmol, 1.0 equiv), free anilines 1 (0.75 mmol, 3.0 equiv), K2CO3 (0.375 mmol, 1.5 equiv) and CH3CN (1.5 mL). The reaction mixture was then stirred at 75 C for 6 h under an argon atmosphere. The reaction progress was monitored by TLC. After cooling to room temperature, the mixture was washed with water and extracted with CH2Cl2 three times, then washed with saturated NaCl solution. The combined organic layer was dried with anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (Elutent: petroleum ether-EtOAc) to give the pure product. The products were characterized by 1H NMR, 13C NMR, 19F NMR, GC -MS.

Molecular Weight:159.18
XLogP3:2.6
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:159.068413911
Monoisotopic Mass:159.068413911
Topological Polar Surface Area:22.1
Heavy Atom Count:12
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes