Preparation of 5-bromo-2-iodoaniline_Kain Industrial Additive

Background and overview^[1][2]

5-Bromo-2-iodoaniline can be used as a pharmaceutical and chemical synthesis intermediate. If 5-bromo-2-iodoaniline is inhaled, move the patient to fresh air; if the skin comes into contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if the eyes are clear In case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[4]

The preparation of 5-bromo-2-iodoaniline is as follows:

Step 1: Add a solution of 4-bromo-2-nitroaniline (50g, 0.23mol) in THF (750mL) to BF3/Et2O (125mL, 0.97mol) solution, and then incubate in THF (750mL) at -50°C. 750 mL), add tert-butyl nitrite (102 mL, 0.86 mmol), cool the reaction to -5°C, add diethyl ether (1.5L), and stir the reaction mixture at -5°C for 15 minutes until a light yellow solid precipitates. The yellow solid was collected and dissolved in acetonitrile (750 mL), and then potassium iodide (55 g, 0.33 mmol) and iodine (42 g, 0.16 mmol) were added to the above mixture. The resulting mixture was stirred at room temperature for 15 minutes. The mixture was partitioned between aqueous sodium sulfite solution (saturated, 1 L) and dichloromethane (1 L). The organic layer was separated, dried over sodium sulfate, and concentrated under reduced pressure to give 4-bromo-1-iodo-2-nitrobenzene (66 g, 88%) as a crude yellow solid.

Step 2: Add stannous chloride (226g, 1mol) to a solution of 4-bromo-1-iodo-2-nitrobenzene (66g, 0.2mol) in MeOH (700mL) at 0°C, and The mixture was heated to reflux (80°C) for 4 hours, the solvent was removed under reduced pressure, and the residue was diluted with ethyl acetate (1L), washed with H2O (1L), dried over sodium sulfate, and concentrated to give a residue that was passed to column chromatography. Purification (eluent: petroleum) diethyl ether: ethyl acetate = 20:1) gave 5-bromo-2-iodoaniline (39 g, 65%) as a white solid.

Main reference materials

[1] Chemical & Pharmaceutical Bulletin, , vol. 35, # 5 p. 1823 - 1828