Background and Overview
2-Amino-3-bromobenzoic acid is an organic intermediate, white to light yellow crystal powder, density 1.793 g/cm3, melting point 173-175ºC, boiling point 343.5ºC at 760 mmHg, lightning 161.5ºC, vapor Pressure 2.68E-05mmHg at 25°C.
Preparation[1]
Step 1. Preparation of N-(2-bromo-phenyl)-2-hydroxyimino-acetamide
Add chloral hydrate (11.6g, 70mmol) to a 150ml aqueous solution of sodium sulfate (18g, 127mmol). (6 mL) was added to a suspension of 2-bromoaniline (10 g, 58 mmol) in 50 mL of water. Add a small amount of DMSO until the solution is clear. This mixture was then added to the previous solution, followed by a solution of hydroxylamine hydrochloride (15 g, 216 mmol) in 70 mL of water. The mixture was slowly heated to reflux (over 90 minutes). The reflux was then held for 10 minutes. The reaction was then cooled to room temperature and filtered. The light brown solid was washed thoroughly with water and dried under vacuum. Obtained 7.95 g solids (56%).
Step 2, 7 bromoindigo
Add N-(2-bromo-phenyl)-2-hydroxyimino-acetamide (7.8g, 32mmol) in small portions to 41mL sulfuric acid at 60°C to keep the reaction temperature at 80° C below. After the addition was complete, the temperature was raised to 80°C and the reaction was stirred at this temperature for 1 hour. The mixture is then cooled to room temperature and poured over crushed ice. The red solid formed was isolated by filtration, rinsed thoroughly with water and dried under vacuum. Obtained 6.36 g solid (88%).
Step 3, synthesis of 2-amino-3-bromobenzoic acid
H2O2 (30%, 141 mL) was added dropwise to a mixture of 7-bromoisatin (6.3 g, 28.1 mmol) and sodium hydroxide (5% aqueous solution, 141 mL). After the addition was complete, the reaction was stirred at 50°C for 30 minutes. After this time, 30 mL HCl 1N was added to pH 4. A white solid precipitated. Collect by filtration and dry under vacuum. 2.66 g of solid 2-amino-3-bromobenzoic acid were obtained (44%).
Main reference materials
[1] WO2006002474 (A1)
