Synthesis
Step A. Preparation of 2-Chloro-6-nitroaniline
1-Chloro-3-nitrobenzene (3.1 g, 0.0197 mol) and o-methoxyamine hydrochloride (2.02 g, 0.0236 mol) were dissolved in N,N-dimethylformamide (15 mL). The solution was added dropwise over 15 minutes to a suspension of cuprous chloride and potassium tert-butoxide (11.07 g, 0.965 mol) in N,N-dimethylformamide (15 mL), which was cooled in a bath at 15°C. The cold bath was removed; the mixture was allowed to reach room temperature and stirred for 1 hour.
The reaction was quenched with an aqueous solution of ammonium chloride and extracted with ethyl acetate (4 × 100 mL). The combined organic layers were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, concentrated under vacuum, and purified by silica gel column chromatography to give the title compound 2-chloro-6-nitroaniline.
Step B. Preparation of 1-chloro-2-iodo-3-nitrobenzene
2-chloro-6-nitroaniline (1.0 g, 0.0058 mol) was dissolved in hydrochloric acid (10 mL) and cooled in an ice bath. Then, a solution of sodium nitrite (0.68 g, 0.0098 mol) in water (10 mL) was added very slowly with stirring. After 15 minutes, the reaction mixture was filtered through glass wool into a solution of potassium iodide (4.1 g, 0.024 mol) in water (10 mL). The resulting orange mixture was stirred overnight at room temperature. It was then extracted with ethyl acetate and washed with a 10% aqueous solution of sodium hydroxide (50 mL). The organic layer was washed with a saturated aqueous sodium chloride solution and concentrated under vacuum to give the title compound 1-chloro-2-iodo-3-nitrobenzene.
Step C. Preparation of 3-chloro-2-iodoaniline
At 0°C, stannous chloride dihydrate (5.5 g, 0.0245 mol) was added in portions to a stirred solution of 1-chloro-2-iodo-3-nitrobenzene (1.4 g, 0.00490 mol) in ethanol (20 mL). The reaction mixture was stirred at 70°C for 30 min. The reaction mixture was concentrated and diluted with ice-cold water (150 mL), and the pH was slightly alkaline by adding a saturated aqueous sodium carbonate solution, followed by extraction with ethyl acetate (4×100 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, and concentrated under vacuum to give the title compound 3-chloro-2-iodoaniline.
