Synthesis
General procedure for the synthesis of quinoline-6-carbaldehyde from 6-hydroxymethylquinoline: method adapted from Meyers et al. (Meyers, A. G.; Zhong, B.; Movassaghi, M.; Kung, D. W.; Lanman, B. A.; Kwon, S. Tetrahedron Lett. 2000, 41, 1359-1362). Dess-Martin periodinane (2.57 g, 6.05 mmol) was added to a 0.28 M solution of 6-hydroxymethylquinoline (0.459 g, 2.88 mmol) in water-saturated dichloromethane (10 mL). The reaction mixture was stirred for 10 min and then dichloromethane (3 x 1 mL) was added in batches over 15 min. Subsequently, the reaction mixture was diluted with ether (10 mL) and 80% saturated aqueous sodium bicarbonate solution (10 mL) of sodium thiosulfate (7.87 g, 31.7 mmol) was added. The mixture was stirred rapidly for 45 minutes. The organic and aqueous layers were separated and the aqueous layer was extracted with ether (2 x 20 mL). The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution (30 mL), water (2 x 30 mL) and saturated sodium chloride solution (2 x 30 mL). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (30-60% ethyl acetate/hexane) to give 0.383 g (85%) of quinoline-6-carbaldehyde (S4a) as a white solid with a melting point of 76.2-76.5 °C. 1H NMR (400 MHz, CDCl3): δ 7.53 (dd, 1H, J = 4.4, 8.4 Hz), 8.18-8.23 (m, 2H ), 8.33 (dd, 1H, J = 2.0, 8.4 Hz), 8.36 (s, 1H), 9.05 (dd, 1H, J = 2.0, 4.4 Hz), 10.20 (s, 1H).13C NMR (100 MHz, CDCl3): δ 122.4, 126.8, 127.8, 130.9, 133.8, 134.4 , 137.6, 151.0, 153.3, 191.6. HRMS-FAB (m/z): calculated value of 157.0528 for [MH]+ C10H7NO; measured value of 157.0521.
References
[1] Patent: WO2004/7491, 2004, A1. Location in patent: Page 56
[2] Journal of the American Chemical Society, 2008, vol. 130, # 20, p. 6404 - 6410
[3] Patent: WO2009/75778, 2009, A2. Location in patent: Page/Page column 49; 50-51
[4] Patent: US2005/54670, 2005, A1. Location in patent: Page/Page column 27
[5]
Tsotinis, A., Vlachou, M., Zouroudis, S., Jeney, A., Timar, F., Thurston, D., Roussakis, C. (2005). A Facile Synthesis of C2-Substituted Pyrrolo[2,3-f]quinolines with Cytotoxic Activity. Letters in Drug Design & Discovery, 2(3), 189–192.
https://doi.org/10.2174/1570180053765075 [6]
Arachchige, D. L., Dwivedi, S. K., Agyemang, P., Lanquaye, H., Peters, J., Rickauer, G., Beatty, A. C., Plansinis, M., Zhang, Y., Ata, A., Werner, T., Liu, H. (2025). Deep-Red Cyanine-Based Fluorescent Probes with 6-Quinolinium Acceptors for Mitochondrial NAD(P)H Imaging in Live Cells and Human Diseased Kidney Tissues. ACS Applied Bio Materials, 8(4), 3205–3217.
https://doi.org/10.1021/acsabm.5c00015
