5-Nitroquinoline

Chemical Properties

white to light yellow crystal powder

Uses

5-Nitroquinoline serves as a substrate for aldehyde oxidase to study oxidative and reductive transformations, including the monitoring of product formation and relative percent activity in the presence of inhibitors such as hydralazine[6].

Safety Profile

Mutation data reported. Whenheated to decomposition it emits toxic fumes of NOx. Seealso other nitroquinoline entries.

Synthesis

General procedure for the synthesis of 8-nitroquinoline and 5-nitroquinoline from quinoline: Pure sulfuric acid (H2SO4) was slowly added to 1 equivalent of quinoline at 0 °C. Subsequently, 3 equivalents of 65% nitric acid (HNO3) were added dropwise and the reaction mixture was stirred at room temperature for 1 hour. Upon completion of the reaction, the mixture was poured sequentially into ice water, neutralized with sodium carbonate (Na2CO3) to pH neutral, and then extracted twice with dichloromethane (DCM). The organic layers were combined, washed with water, dried over anhydrous sodium sulfate (Na2SO4) and finally the solvent was evaporated under vacuum. 8-Nitroquinoline (compound 35) was obtained as a light yellow solid in 34% yield; melting point 90 °C, literature value: 89-90 °C [43].1H NMR (200 MHz, CDCl3) δ: 7.53-7.66 (m, 2H), 8.04 (d, J = 8.0 Hz, 2H), 8.27 (dd, J = 1.6 and 8.4 Hz, 1H). 9.70 (dd, J = 1.7 and 4.2 Hz, 1H). 13C NMR (50 MHz, CDCl3) δ: 122.8 (CH), 123.8 (CH), 125.3 (CH), 129.0 (C), 132.0 (CH), 136.1 (CH), 139.5 (C), 148.2 (C), 152.6 (CH ). Recrystallization by isopropanol afforded 5-nitroquinoline (compound 36) as a light yellow solid in 38% yield; melting point 71 °C, literature value: 71-72 °C [41].1H NMR (200 MHz, CDCl3) δ: 7.61-7.68 (m, 1H), 7.76-7.85 (m, 1H), 8.36-8.45 (m, 2H). 8.98-9.04 (m, 2H).13C NMR (50MHz, CDCl3) δ: 121.2 (C), 123.9 (CH), 124.6 (CH), 127.5 (CH), 131.9 (CH), 136.6 (CH), 145.5 (C), 148.2 (C), 151.6 (C).

Purification Methods

Crystallise 5-nitroquinoline from pentane, then from *benzene. The hydrochloride has m 224o and the picrate has m 206o, 214o(from MeOH). [Beilstein 20 H 371, 20 II 235, 20 III/IV 3397.]

References

[1] European Journal of Medicinal Chemistry,  2012,  vol. 54,  p. 75 - 86
[2] European Journal of Medicinal Chemistry,  2018,  vol. 155,  p. 135 - 152
[3] Journal of the Chemical Society,  1892,  vol. 61,  p. 788
[4] Chemische Berichte,  1885,  vol. 18,  p. 1243
[5] Journal fuer Praktische Chemie (Leipzig),  1896,  vol.<2>53,  p. 392
[6] Paragas, E. M., Humphreys, S. C., Min, J., Joswig-Jones, C. A., & Jones, J. P. (2017). The two faces of aldehyde oxidase: Oxidative and reductive transformations of 5-nitroquinoline. Biochemical Pharmacology, 145, 210–217. https://doi.org/10.1016/j.bcp.2017.09.002