Synthesis
General procedure for the synthesis of 5-amino-2-chlorobenzoic acid from 2-chloro-5-nitrobenzoic acid: 75 g of 2-chloro-5-nitrobenzoic acid, 59 g of iron powder, 800 mL of ethanol, 150 mL of water, and 115 g of ammonium chloride were added to a reaction flask equipped with a stirrer. The mixture was heated to 78-80°C and the reaction was refluxed for 5 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent was petroleum ether/ethyl acetate=1:3) during the reaction. Upon completion of the reaction, the reaction mixture was filtered while hot and the solids were washed with 150 mL of hot ethanol. The filtrate was dried at 60°C to obtain the crude product. Subsequently, the crude product was dissolved in 400 mL of ethyl acetate and heated to reflux pulping for 2 hours. The mixture was cooled to 0~5°C in a salt bath and then naturally reduced to room temperature and crystallized for more than 30 minutes. The crystals were separated by centrifugation and washed with 50 mL of ethyl acetate. Finally, it was dried under reduced pressure at 50°C to give 60.7 g of yellow solid 5-amino-2-chlorobenzoic acid with 99.1% purity and 95.1% yield.
References
[1] Arzneimittel-Forschung/Drug Research, 1982, vol. 32, # 3, p. 183 - 186
[2] Chemical and Pharmaceutical Bulletin, 1988, vol. 36, # 9, p. 3462 - 3467
[3] Patent: CN106748721, 2017, A. Location in patent: Paragraph 0029; 0030
[4] Angewandte Chemie - International Edition, 1999, vol. 38, # 18, p. 2777 - 2779
[5] Justus Liebigs Annalen der Chemie, 1868, vol. 147, p. 258
