Direct Synthesis of Azaheterocycles from N-Aryl/Vinyl Amides. Synthesis of 4-(Methylthio)-2-phenylquinazoline and 4-(4-Methoxyphenyl)-2-phenylquinoline

摘要

A. 4-(Methylthio)-2-phenylquinazoline (3). A flame-dried, 300-mL three-necked round-bottomed flask equipped with a 3.0 cm football-shaped stir bar, rubber septum, and low temperature thermometer is charged with benzanilide (1) (Note 1) (6.02 g, 30.5 mmol, 1 equiv), sealed under an argon atmosphere, and fitted with an argon inlet. Anhydrous dichloromethane (Note 2) (60 mL) followed by 2-chloropyridine (Note 3) (5.76 mL, 6.97 g, 61.4 mmol, 2.01 equiv) is added via syringe, and the heterogeneous mixture is vigorously stirred and cooled to <-70 °C (dry-ice-acetone bath, internal temperature). After 10 min, trifluoromethanesulfonic anhydride (Note 4) (Tf2O, 5.60 mL, 9.39 g, 33.3 mmol, 1.09 equiv) is added via syringe over 5 min at <-65 °C (internal temperature). After 15 min, the reaction flask is warmed to 0 °C (ice-water bath). After 5 min, the deep red solution becomes homogeneous and a solution of thiocyanic acid methyl ester (2) (Note 1) (2.52 mL, 2.67 g, 36.5 mmol, 1.20 equiv) in anhydrous dichloromethane (40 mL) is added via cannula over 5 min at 5-6 °C (Note