Preparation of 1,5-Disubstituted 1,2,3-Triazoles via Ruthenium-catalyzed Azide Alkyne Cycloaddition

摘要

1-Benzyl-5-phenyl-1H-1,2,3-triazole. Benzyl azide (10.0 g, 75 mmol, 1.0 equiv) (Note 1) is placed in a 500-mL, three-necked round-bottomed flask and equipped with an 8 × 30 mm, octagon-shaped Teflon coated-magnetic stirring bar. The center neck is equipped with a three-way stopcock connected to argon line and bubbler. The other two necks are equipped with a rubber septum. The reaction vessel is purged with argon supplied by an argon filled balloon, after which the three-way stopcock is reconnected. 1,2-Dichlorethane (150 mL) (Note 2) and phenylacetylene (Note 3) (8.06 g, 8.66 mL, 79 mmol, 1.05 equiv) are added sequentially to the flask and the stirred solution is placed in a 45 °C oil bath. After five min, a solution of chloro(1,5-cyclooctadiene)(pentamethylcyclopentadiene)-ruthenium (285 mg, 0.75 mmol, 1 mol %) (Note 4) in DCE (3 mL) is added to the reaction vessel via syringe. The orange solution becomes dark brown (Notes 5 and 6). After 30 min the solution is cooled to room temperature and silica gel (35 g) (Note 7) is added. The solvent is removed by rotary evaporation (35 °C, 40 mmHg). The resulting light brown powder is placed in a 5 cm diameter column and flushed with ethyl acetate (2 × 200 mL). The dark brown solution is concentrated again by rotary evaporation (35 °C, 40 mmHg) to give a dark brown solid. The solid material is transferred to a 250-mL one-necked round-bottomed flask, hexanes (200 mL) are added and the heterogeneous solution is triturated (Note 8) for 15 h. The mixture is filtered using a Buchner funnel, rinsed with hexanes (4 × 25 mL) and dried in vacuo (rt, 18 mmHg) to afford 15.9-16.2 g (90-92%) of the titled compound as a beige powder (Note 9).