6-Nitroquinoline

Chemical Properties

beige to light brown powder

Uses

6-Nitroquinoline serves as a precursor for synthesizing 6-hydroxylaminoquinoline via reduction with hydrazine hydrate in the presence of Raney nickel. It acts as a pro-fluorescent substrate that is converted to the fluorophore 6-aminoquinoline by xanthine/xanthine oxidase under hypoxic conditions, or to 6-nitroquinolin-2(1H)-one by xanthine oxidase under aerobic conditions. The compound is also employed for the quantitative determination and removal of palladium from solution using hot saturated aqueous conditions, and its electrochemical behavior allows for detection via polarographic and voltammetric methods[3][4][5].

Safety Profile

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

Synthesis

GENERAL STEPS: 6-bromoquinoline (0.5 mmol), copper(II) trifluoromethanesulfonate (45 mg, 0.125 mmol), potassium nitrite (KNO2, 128 mg, 1.5 mmol), and anhydrous dimethylsulfoxide (DMSO, 0.6 mL) were sequentially added to a pre-dried oven-dried pressure tube under nitrogen protection. The pressure tube was sealed with a PTFE screw cap with a micro-valve and purged by nitrogen for 5 min to remove air. Subsequently, the reaction mixture was stirred at room temperature for 10 minutes and then gradually warmed up to 130°C and the reaction was continued at this temperature for 48 hours. Upon completion of the reaction, the mixture was cooled to room temperature, washed with excess ice water and extracted with ethyl acetate (3 x 10 mL). The organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography on silica gel (for entries 1-18 in Table 2) or basic alumina (for entries 19-23 in Table 2), using a solvent mixture of ethyl acetate and hexane as eluent, and the target product, 6-nitroquinoline, was finally obtained in good yield.

References

[1] Tetrahedron Letters,  2012,  vol. 53,  # 12,  p. 1511 - 1513
[2] Tetrahedron,  2013,  vol. 69,  # 31,  p. 6409 - 6414
[3] Rajapakse, A., Linder, C., Morrison, R. D., Sarkar, U., Leigh, N. D., Barnes, C. L., Daniels, J. S., Gates, K. S. (2013). Enzymatic Conversion of 6-Nitroquinoline to the Fluorophore 6-Aminoquinoline Selectively under Hypoxic Conditions. Chemical Research in Toxicology, 26(4), 555–563. https://doi.org/10.1021/tx300483z
[4] Vyskočil, V., Jiránek, I., Daňhel, A., Zima, J., Barek, J., Wang, J., Pecková, K. (2011). Polarographic and voltammetric determination of genotoxic nitro derivatives of quinoline using mercury electrodes. Collection of Czechoslovak Chemical Communications, 76(12), 1991–2004. https://doi.org/10.1135/cccc2011173
[5] Ogburn, S. C., Riesmeyer, A. H. (1928). THE QUANTITATIVE DETERMINATION OF PALLADIUM BY MEANS OF 6-NITROQUINOLINE. Journal of the American Chemical Society, 50(11), 3018–3022. https://doi.org/10.1021/ja01398a023