Synthesis of Quinolines by Electrophilic Cyclization of N-(2-Alkynyl)Anilines: 3-Iodo-4-Phenylquinoline

摘要

A. N-(2-Propynyl)aniline (3). An oven-dried 500-mL, three-necked, round-bottomed flask equipped with a 25-mm egg-shaped magnetic stirring bar, a thermometer, a pressure-equalizing dropping funnel, and a rubber septum is charged with aniline (1, 22.35 g, 240.0 mmol, 4.0 equiv) (Notes 1 and 2), potassium carbonate (16.58 g, 120.0 mmol, 2.0 equiv) (Note 3), and N,N-dimethylformamide (DMF, 300 mL) (Note 4). The mixture is stirred for 5 min at room temperature. A solution of propargyl bromide (2, 7.14 g, 80% solution in toluene, 6.68 mL, 60.0 mmol, 1.0 equiv) (Note 5) in N,N-dimethylformamide (DMF, 25 mL) is added to the flask dropwise (Note 6). The reaction mixture is stirred at room temperature for 6 h (Note 7). The reaction mixture is filtered under reduced pressure (Note 8). The original three-necked round-bottomed flask and the Buchner funnel are rinsed with 150 mL of diethyl ether. The combined filtrate is transferred to a 1-L separatory funnel and washed with brine (300 mL). The aqueous phase is extracted twice with diethyl ether (2 x 150 mL). The combined organic phases are washed with water (100 mL) and dried over anhydrous maenesium sulfate (MgSO4) (Note 9), filtered through a fritted glass funnel, rinsed with diethyl ether (50 mL), and concentrated by rotary evaporation (25 °C, 40 mmHg) to give a dark brown oil. The-residue is purified by flash column chromatography on silica gel (Note 10) to afford 6.52-6.85 g (83-87%) of N-(2-propynyl)aniline (3) as a light yellow oil (Note 11).