1-Benzofuran-5-carbaldehyde

Chemical Properties

Colorless to light yellow liqui

Uses

1-Benzofuran-5-carbaldehyde is a building block used as a reactant in the synthetic preparation of benzofuranyl oxadiazoles as inhibitors of glycogen synthase kinase-3β with good brain permeability. It is also used in the synthesis of pyrroloquinolone PDE5 inhibitors used for clinical studies on erectile dysfunction.

Synthesis

General procedure for the synthesis of benzofuran-5-carbaldehyde from 2,3-dihydrobenzofuran-5-carbaldehyde: N-bromosuccinimide (NBS, 0.656 g, 3.69 mmol) and azobisisobutyronitrile (AIBN, 8.10 mg, 49.2 μmol) were added to a solution of chlorobenzene (7.3 mL) at room temperature and under argon protection to 2,3-dihydrobenzofuran-5-carbaldehyde (0.364 g, 2.46 mmol) in a solution of chlorobenzene (7.3 mL). The reaction mixture was stirred at 80 °C for 1 h before being cooled to room temperature and diluted with ethyl acetate (EtOAc). The organic layer was washed sequentially with saturated aqueous sodium bicarbonate (NaHCO3) and brine, dried over anhydrous sodium sulfate (Na2SO4) and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane, 3:97) to afford benzofuran-5-carbaldehyde (0.268 g, 1.84 mmol, 75% yield) as a colorless oil. Its 1H-NMR (CDCl3, 400 MHz) data were as follows: δ 6.82 (d, J = 2.0 Hz, 1H, furan-H), 7.54 (d, J = 8.8 Hz, 1H, Ar-H), 7.65 (d, J = 2.0 Hz, 1H, furan-H), 7.79 (d, J = 8.8 Hz, 1H, Ar-H), 8.07 (s 1H, Ar-H), 9.99 (s, 1H, -CHO). The spectral data of the obtained compounds are in agreement with literature reports (van Otterlo et al., 2005).

References

[1] Journal of Medicinal Chemistry, 2009, vol. 52, # 20, p. 6270 - 6286
[2] Phytochemistry, 2013, vol. 96, p. 132 - 147
[3] Patent: US2014/309427, 2014, A1. Location in patent: Paragraph 0074; 0075; 0076; 0077
[4] Patent: WO2018/64135, 2018, A1. Location in patent: Paragraph 0174-0177