Uses
Methyl 3-amino-4-iodobenzoate is an important raw material and intermediate used in organic synthesis, pharmaceuticals, agrochemicals and dyestuff fields.
Synthesis
1. Methyl 4-iodobenzoate (5.24 g, 20.0 mmol) was dissolved in sulfuric acid solution at 0 °C and 1.43 mL of concentrated nitric acid was added slowly and dropwise. The reaction mixture was stirred at room temperature for 5 hours and then warmed up to 40°C to continue the reaction for 1 hour. The resulting orange solution was poured into 100 g of ice, 200 mL of ethyl acetate was added, shaken for 30 min and filtered. The organic and aqueous phases were separated and the aqueous phase was extracted with 200 mL of ethyl acetate. The organic layers were combined, washed sequentially with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 100% ethyl acetate) to give 2.0 g of methyl 4-iodo-3-nitrobenzoate as a yellow solid in 33% yield.
2. Methyl 4-iodo-3-nitrobenzoate (2.0 g, 6.50 mmol) was dissolved in a mixed solution of 25 mL of anhydrous ethanol and 15 mL of glacial acetic acid, iron powder (3.6 g, 65.0 mmol) was added, and the reaction was heated for 1 hour. After completion of the reaction, the mixture was filtered through a silica pad, the filter cake was washed with ethanol and the filtrate was concentrated under reduced pressure. The residue was diluted with potassium carbonate solution and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate and filtered, concentrated under reduced pressure to give 1.6 g of methyl 3-amino-4-iodobenzoate as a white solid in 88% yield.
3. At room temperature, methyl 3-amino-4-iodobenzoate (1.59 g, 5.74 mmol) was dissolved in 40 mL of dichloromethane, trifluoroacetic anhydride (3 mL, 21 mmol) was added and the reaction was carried out for 30 min. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, the residue was dissolved in cold water, filtered and dried to give 2.1 g of the target product as an off-white solid in quantitative yield.
References
[1] Tetrahedron Letters, 2008, vol. 49, # 2, p. 363 - 366
[2] Patent: WO2005/40157, 2005, A2. Location in patent: Page/Page column 68
[3] Patent: WO2005/30213, 2005, A1. Location in patent: Page/Page column 189
[4] Tetrahedron Letters, 1997, vol. 38, # 46, p. 7963 - 7966
