Toluene → 4-Chloro-6-iodoquinazoline

Participants

Reaction Steps

In a 500 mL-volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 50.0 g (184 mmol) of 6-iodoquinazolin-4-one, 33.8 g (221 mmol) of phosphorus oxychloride, and 300 mL of toluene in a nitrogen atmosphere. While the mixture was stirred at room temperature, 22.3 g (221 mmol) of triethylamine was slowly added. The resulting mixture was heated at 60° C. for 30 minutes and then heated at 75° C. for 2 hours, for carrying out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature, and 50 mL of acetone was added. The mixture was then cooled to 0° C. and stirred for 30 minutes. Thus precipitated pale yellow crystalline product of 6-iodo-4-chloroquinazoline was collected by filtration. Subsequently, the crystalline product was placed in 200 mL of water, and 9 mL of aqueous sodium hydroxide (1 mol/L) was added. The aqueous mixture (pH 10-11) was stirred for 30 minutes at room temperature. The crystalline product was collected by filtration, washed successively with 100 mL of acetone, 200 mL of water and 100 mL of acetone, and dried at 60° C. under reduced pressure, to give 47.4 g (isolated yield: 89%, purity 99% in terms of area percentage determined by high performance liquid chromatography) of 6-iodo-4-chloroquinazoline as a yellowish crystalline product.

Provenance & Evidence