C2 Amination of Pyridine with Primary Amines Mediated by Sodium Hydride in the Presence of Lithium Iodide

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. The addition of LiI to the reaction mixture resulted in an exotherm which causes the internal temperature to rise to 35 °C. The reaction mixture is allowed to cool to 25 °C under Ar atmosphere while stirring (Note 6), at which time n-butylamine (2) (5.00 mL, 50.6 mmol, 2.0 equiv) (Note 7) is added to the grey suspension in one portion using a syringe. Pyridine (1) (1.985 g, 25.1 mmol, 1.0 equiv) (Note 8) is weighed into a dry N + H2N 2 (2 equiv) NaH (3 equiv) LiI (2 equiv)