4-Iodo-2-methylaniline

583-75-5

13194-68-8

General procedure for the synthesis of 4-iodo-2-methylaniline from 2-methyl-4-bromoaniline: the aromatic Finkelstein reaction is used. Since copper(I) iodide is sensitive to moisture and oxygen, the reaction is carried out under argon protection using the standard Schlenk technique. The procedure is as follows: 2-methyl-4-bromoaniline, NaI (2 equiv., relative to bromine exchange) and CuI (5 mol%, relative to bromine exchange) are added to a two-necked pear-shaped flask equipped with a reflux condenser. N,N'-dimethylethylenediamine (L1) or N,N'-dimethyl-1,2-cyclohexanediamine (L2) (10 mol%, relative to bromine exchange) and anhydrous 1,4-dioxane (0.5 mL per 1 mmol NaI) were subsequently added. The resulting suspension was heated to 110°C and reacted for 18 hours. After completion of the reaction, it was cooled to room temperature and the mixture was poured into a 25% ammonia solution. The blue solution was diluted with deionized water until doubled in volume and extracted three times with dichloromethane. If 2,2'-bipyridine was used as the ligand, the combined organic phases were additionally washed with aqueous EDTA; otherwise, the combined organic phases were washed with saturated saline only and dried with anhydrous magnesium sulfate. The solvent is removed by concentration under reduced pressure to give pure 4-iodo-2-methylaniline. If necessary, the crude product can be further purified by column chromatography or recrystallization.