Thieno[2,3-b]pyridine-2-carbaldehyde

Synthesis

Thieno[2,3-b]pyridine-2-carbaldehyde was synthesized as follows: 1.3 mL (2.08 mmol) of a hexane solution of 0.8 M n-butyllithium was mixed with 0.3 mL (3.3 mmol) of N,N,N',N'-tetramethylethylenediamine under the protection of argon gas and was stirred magnetically for 30 min at room temperature. Subsequently, the reaction mixture was diluted with 5 mL of hexane and cooled in a dry ice-ethanol bath. Under vigorous stirring, 0.23 g (1.7 mmol) of thieno[2,3-b]pyridine was added dropwise (using a small needle syringe). The reaction mixture was stirred in a cooling bath for 7 hours, then slowly warmed to room temperature and continued stirring for 12 hours. After completion of the reaction, the mixture was cooled in an ice bath, 0.15 g (2.1 mmol) of dimethylformamide was added and stirred for 1 hour. Subsequently, 1 mL of ethanol, 3 mL of saturated aqueous ammonium chloride solution and 4 mL of water were added sequentially. The organic layer was separated and the aqueous layer was extracted with chloroform. The organic layers were combined, dried with magnesium sulfate and the solvent was evaporated. The residue was ground with hexane to give 0.18 g (66% yield) of a brown solid with a melting point of 131.5-132.5°C. Recrystallization by ethanol (with the addition of activated charcoal to decolorize the product once) yielded white needle-like crystals. The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.41 (dd, J = 4.5 Hz, 8.1 Hz, 1H), 7.99 (s, 1H), 8.24 (dd, J = 1.8 Hz, 8.1 Hz, 1H), 8.73 (dd, J = 1.8 Hz, 4.5 Hz, 1H), 10.12 (s, 1H).13C NMR (75 MHz, CDCl3) showed: δ 120.7, 131.8, 132.3, 134.0, 143.2, 150.5, 163.8, 185.0. a carbonyl absorption peak at 1682 cm-1 was observed in the IR spectrum (CHCl3, cm-1). The mass spectrum (EI, 70 eV) showed: m/z [%] = 162 [M]+ (100), 134 [M-CO]+ (26). High-resolution mass spectrum (FAB+) calculated value C8H6NOS [M+1] 164.0170, measured value 164.0167.

References

[1] Tetrahedron Letters, 2017, vol. 58, # 20, p. 1952 - 1956
[2] Tetrahedron Letters, 1994, vol. 35, # 7, p. 1011 - 1014
[3] Journal of Heterocyclic Chemistry, 1974, vol. 11, p. 355 - 361