Synthesis
Step 1: 5 g of 4-hydroxyquinoline (34.48 mmol, purchased from Jiuding Chemical) was dissolved in 40 mL of propionic acid (purity ≥99.5%) and heated to 120 °C. Subsequently, 3.5 mL of concentrated nitric acid (41.38 mmol, concentration 65-68%) was diluted with propionic acid and slowly added dropwise to the reaction system over 1.5 hours. After about 15 minutes of dropwise addition, a yellow precipitate appeared in the reaction solution. 20 mL of propionic acid was added and the reaction was continued at reflux for 1 hour. The progress of the reaction was monitored by thin layer chromatography (TLC) to confirm that the 4-hydroxyquinoline was completely consumed. The heating was stopped and the reaction solution was cooled to room temperature. The reaction mixture was filtered, the filter cake was washed with petroleum ether and dried under vacuum to give 4-hydroxy-3-nitroquinoline as a yellow solid (5.28 g, 80.7% yield).
References
[1] Patent: US5367076, 1994, A
[2] Patent: US5175296, 1992, A
[3] Journal of Medicinal Chemistry, 2005, vol. 48, # 10, p. 3481 - 3491
[4] Patent: CN108003153, 2018, A. Location in patent: Paragraph 0063; 0068
[5] Patent: US2011/136801, 2011, A1. Location in patent: Page/Page column 21
