C2 amination of pyridine with primary amines mediated by sodium hydride in the presence of lithium iodide

Abstract

N-Butylpyridin-2-amine (3). An oven-dried, 250 mL three-necked roundbottomed flask fitted with a 25 x 15 mm Teflon-coated oval magnetic stir bar, a thermometer, rubber septum and a Liebig reflux condenser, is connected to a Schlenk line (Note 2). Sodium hydride (NaH) (3.00 g, 75.0 mmol, 3.0 equiv) (Note 3) is charged to the reaction vessel, after which it is evacuated and backfilled with argon three times. Anhydrous THF (Note 4) (35 mL) is added via a syringe. The reaction flask is suspended in a 22 °C water bath, and lithium iodide (LiI) (6.69 g, 50.0 mmol, 2.0 equiv) (Note 5) is introduced through the top of the reflux condenser, after which the Ar line is reintroduced with an out needle in place for 5 min to exchange the atmosphere.