[Synthesis]
The general procedure for the synthesis of 3,4-dichloro-2-iodoaniline from 3,4-dichloroaniline was as follows: to a stirred suspension of 3,4-dichloroaniline (20 g, 123 mmol), hydriodic acid (48%, 15.7 g, 123 mmol), and hydrogen peroxide (30%, 8.3 g, 246 mmol) in water (62 mL) at 37 °C. The reaction mixture was stirred overnight at room temperature protected from light. Upon completion of the reaction, the supernatant was discarded, the reaction mixture was diluted with ethyl acetate:hexane (1:10), quenched with saturated sodium bisulfite solution, stirred at ambient temperature for 1 h. The solid was collected by filtration. The filtrate was washed sequentially with water and saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered and concentrated to give a mixture of 1:4 regional isomers of the iodo derivative (the primary target being the secondary isomer). The mixture was recrystallized from cyclohexane to give a 1:1 mixture of regional isomers enriched in the filtrate. The mixture was further purified by silica gel fast column chromatography using ethyl acetate:hexane (0-2%) gradient elution to afford the target compound 3,4-dichloro-2-iodoaniline as a cream-colored solid (5.2 g, ~15% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.22 (d, J=8.6 Hz, 1H), 6.60 (d, J=8.6 Hz, 1H), 4.32 (br, 2H). |