通过靛红(isatin)合成多取代邻氨基苯甲酸

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Synthesis of lanthranilic acid via oxidative opening of isatin

通过靛红(isatin)合成多取代邻氨基苯甲酸  第1张

通过靛红(isatin)合成多取代邻氨基苯甲酸  第2张

Chloral hydrate (90 g, 0.54 mol) and anhydrous Na2SO4 (453 g, 3.2 mol) were added to water (1.5 L) with rapid stirring. A slurry of hydroxylamine sulfate (410 g, 2.5 mol) and 2,3-dimethylaniline (58.1 g, 0.48 mol) in water (500 mL) containing concentrated HC1 (50 mL) was then added, and the stirred mixture was heated slowly to 45 °C over 90 min,to 52 °C over 45 min, and finally to 75 °C for 60 min. After cooling, the precipitate was collected, washed with water followed by petroleum ether, and dried to give the crude isonitroso compound (80.2 g, 87%).


Crude, powdered, isonitroso compound (60.0 g, 0.31 mol) was added in portions to stirred CH3SO3H (240 mL) at 70-80 °C. The cooled mixture was poured onto ice and diluted with water, and the precipitate was collected and dissolved in excess 1 N aqueous NaOH. Neutralization with AcOH precipitated impurities which were removed by filtration, and acidification (HCl) of the clarified solution gave isatin as an orange-red solid (35.8 g, 65%).


A solution of 6,7-dimethylisatin (37.8 g, 0.22 mol) in water (400 mL) containing NaOH (14.0 g) and KCl (35 g) was vigorously stirred and treated dropwise at 8-10 °C with 35% H2O2 (ca. 45 g) over 45 min. The reaction mixture was then stirred at 20 °C until TLC analysis indicated complete reaction. Addition of AcOH precipitated the crude anthranilic acid, which was washed with water and dried (23.2g, 65%).


J. Med. Chem. 1991, 34, 217-222

标签: isatin

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