Iodine → 2-Fluoro-3-iodo-4-methylbenzonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 2,2,6,6,-tetramethylpiperidine (45 mL, 267 mmol) in THF (400 mL) was cooled below −80° C. under N2-atmosphere. n-Butyl lithium (2.5M in hexane, 110 mL, 275 mmol) was added slowly maintaining the temperature of the mixture below −70° C. After complete addition, the reaction mixture was warmed to −50° C. and stirred at this temperature for 30 minutes. The clear solution became turbid indicating the salt formation. It was cooled to −80° C. again and a solution of 2-fluoro-4-methylbenzonitrile (32.4 g, 240 mmol) in THF (150 mL) was slowly added taking care that the temperature of the reaction mixture remained below −70° C. It was then warmed up to −50° C. and stirred for 30 minutes. The mixture was then cooled to −70° C. and a saturated solution of I2 (67 g, 264 mmol) in THF was added slowly maintaining the temperature at −70° C. After complete addition, the mixture was warmed to ambient temperature. It was added to a solution of Na2S2O3 (160 g in 1.5 L of water) and stirred for an hour. The organic part was separated and the aqueous layer was extracted with EtOAc. The organic layers were combined and washed with brine. The organic layer was then dried over Na2SO4 and filtered. The volatiles were evaporated under reduced pressure. The crude product was subjected to vacuum distillation; at about 60° C., excess TMP was removed, at about 100° C., the starting compound 2-fluoro-4-methylbenzonitrile and a small amount of product was removed and, finally at 115° C., pure 2-fluoro-3-iodo-4-methylbenzonitrile was obtained (30 g, 48% yield). MS (M+H)+ 262.

Provenance & Evidence