Uses
6-Nitro-1H-benzo[d][1,3]oxazine-2,4-dione is a useful research chemical for organic synthesis/bioactive molecule design. 6-Nitro-1H-benzo[d][1,3]oxazine-2,4-dione is also used in the RNA structure probing studies.
Preparation
5-Nitroisatoic anhydride is prepared from 5-nitro indole (9g) by stirring in a 4:1 mixture of CH3CN/H2O for 1 h at 40℃. 1 H NMR (DMSO-d6): δ12.34 (s, Br., 1H), 8.59 (s Hz, 1H), 8.51 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 8.7 Hz, 1H).
Synthesis
Concentrated sulfuric acid (100 mL) was added to a 250 mL three-necked flask, the reaction system was cooled to 0-10 °C and indigo anhydride 1 (30.0 g, 0.18 mol) was added slowly under mechanical stirring. After complete dissolution of indirubic anhydride, 65% concentrated nitric acid (21.4 g, 0.22 mol) was slowly added dropwise, and the rate of dropwise acceleration was controlled to maintain the reaction temperature in the range of 0-10°C. The reaction was completed in about 1 h. The reaction system was cooled to 0-10°C with mechanical stirring. The dropwise addition process was completed in about 1 hour, after which the reaction was continued with stirring at the same temperature for 1 hour. Upon completion of the reaction, stirring was stopped and the reaction mixture was slowly poured into 300 mL of ice-water mixture and stirred for 20 min to fully precipitate the product. The precipitated solid was collected by filtration, washed with water several times and dried to give 5-nitroisatoic anhydride 2 (37.5 g, yield: 97.9%).
References
[1] Patent: CN103613549, 2016, B. Location in patent: Paragraph 0033-0035
[2] Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 23, p. 8032 - 8042
[3] Chemical Communications, 2013, vol. 49, # 2, p. 190 - 192
[4] Synthetic Communications, 2011, vol. 41, # 22, p. 3265 - 3279
[5] Journal fuer Praktische Chemie (Leipzig), 1884, vol. <2> 30, p. 474
