Synthesis
General procedure for the synthesis of 4-chloro-8-nitroquinoline (6a) and 4-chloro-5-nitroquinoline (6d) from 4-chloroquinoline:
1. 4-Chloroquinoline (10.0 g, 61.3 mmol) was added in batches to sulfuric acid (45 mL) at a controlled temperature not exceeding 15°C.
2. cool the reaction solution to -5°C and maintain that temperature.
3. Slowly add fuming nitric acid (9 mL).
4. Gradually warm the reaction mixture to room temperature and continue stirring for 3 hours.
5. Pour the reaction mixture into ice water and adjust the pH to 9 with NH4OH.
6. The precipitate was collected by filtration, washed well with water, dried and recrystallized from methanol to give 7.5 g (59%) of 4-chloro-8-nitroquinoline (6a) as golden-brown acicular crystals with a melting point of 128-129 °C (literature value 129-130 °C).
1H NMR (CDCl3) δ: 7.67 (d, 1H, J=4.5 Hz), 7.75 (dd, 1H, J=8.6 Hz, J=7.6 Hz), 8.10 (dd, 1H, J=7.6 Hz, J=1.3 Hz), 8.48 (dd, 1H, J=8.6 Hz, J=1.3 Hz), 8.94 (d, 1H, J= 4.5 Hz); 13C NMR (CDCl
13C NMR (CDCl3) δ: 123.0, 124.4, 126.5, 127.5, 128.3, 140.6, 143.2, 148.7, 152.1.
7. The mother liquor was concentrated and separated by silica gel column chromatography (eluent: hexane-ethyl acetate = 19:1) to afford 2.05 g (16%) of 4-chloro-5-nitroquinoline (6d) as a very pale yellow solid with a melting point of 144-146 °C (literature value 150 °C).
1H NMR (CDCl3) δ: 7.65 (d, 1H, J=4.7 Hz), 7.82 (m, 2H), 8.35 (dd, 1H, J=2.5 Hz, J=7.3 Hz), 8.90 (d, 1H, J=4.7 Hz).
13C NMR (CDCl3) δ: 118.2, 123.4, 125.1, 128.8, 134.2, 135.6, 139.1, 149.7, 151.2.
References
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 13, p. 3731 - 3742
[2] Patent: WO2004/14906, 2004, A2. Location in patent: Page 31
[3] Journal of the American Chemical Society, 1946, vol. 68, p. 1532,1534
[4] Journal of the Chemical Society, 1948, p. 1707
[5] Journal of the American Chemical Society, 1947, vol. 69, p. 303,306
