8-Hydroxyjulolidine-9-aldehyde

Uses

8-Hydroxyjulolidine-9-carboxaldehyde is a reactant in the development of iminocoumarin-based zinc sensor suitable for ratiometric fluorescence imaging of neuronal zinc.

Synthesis

The general procedure for the synthesis of 8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline-8-ol and N,N-dimethylformamide (DMF) to synthesize 8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline-9-carboxaldehyde was carried out in the following manner: at 4 °C, a flask containing 10 mL DMF was slowly charged dropwise with chlorine phosphorus oxide (2.7 mL, 4.4 g, 29 mmol), and the dropwise addition process lasted for 15 min. Subsequently, a solution of 8-hydroxy-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolin-8-ol (5.15 g, 26.9 mmol) in DMF (5 mL) was added dropwise to the above mixture over 10 minutes. After dropwise addition, the reaction mixture was stirred at room temperature for 30 min, then warmed up to 100 °C and continued stirring for 30 min. Upon completion of the reaction, the mixture was cooled to room temperature and 30 mL of water was added to the stirring dark solution. The aqueous mixture was stirred for 1.5 hours until a blue-green precipitate formed. The precipitate was separated by filtration, washed with water and dried. The crude product was purified by silica gel column chromatography with an eluent of toluene/ethyl acetate (2:1 v/v). The final product yield was 94% and the melting point was 205°C (literature value 73-74°C).

References

[1] Chemical Communications, 2014, vol. 50, # 69, p. 9947 - 9950
[2] Journal of the American Chemical Society, 2003, vol. 125, # 16, p. 4708 - 4709
[3] Journal of Fluorescence, 2015, vol. 25, # 6, p. 1615 - 1628
[4] Organic Preparations and Procedures International, 2001, vol. 33, # 6, p. 603 - 613
[5] Journal of Organic Chemistry, 1987, vol. 52, # 8, p. 1465 - 1468