Uses
Imidazole-2-carboxaldehyde is a novel protein tyrosine phosphatase 1B (PTP1B) inhibitor with an important application to treat type-2 diabetes. It is used in the preparation of tridentate Schiff-base carboxylate-containing ligands by undergoing condensation reaction with amino acids beta-alanine and 2-aminobenzoic acid. It is also involved in the study of the imidazole-directed allylation of aldimines.
Synthesis Reference(s)
Organic Syntheses, Coll. Vol. 7, p. 287, 1990
The Journal of Organic Chemistry, 60, p. 1090, 1995
DOI: 10.1021/jo00109a052
Synthesis
To a solution of 2-bromo-1H-imidazole (0.65 g, 4.4 mmol, 1.0 eq.) in anhydrous THF (20 mL) was slowly added a solution of 2 M i-PrMgCl in THF (2.2 mL, 4.4 mmol, 1.0 eq.) over 5 min at 0 °C. The reaction mixture was continued to be stirred at this temperature for 5 min. Subsequently, a hexane solution of 2.5 M n-BuLi (3.5 mL, 8.8 mmol, 2.0 eq.) was added dropwise over 5 min while the reaction temperature was controlled below 20 °C. After dropwise addition, the reaction mixture was stirred at this temperature for 30 min. Then, dry N,N-dimethylformamide (DMF, 0.32 g, 4.4 mmol, 1.0 eq.) was added and the reaction mixture was slowly warmed up to 20 °C over 0.5 h. The reaction was completed with the addition of 6 mL of N,N-dimethylformamide. Upon completion of the reaction, the reaction was quenched with 6 mL of water, kept below 20 °C and stirred for 10 min. The organic and aqueous phases were separated and the aqueous phase was extracted once with ethyl acetate (10 mL). The organic phases were combined, and the resulting suspension was returned to room temperature, filtered through a silica gel pad (0.5 cm × 1 cm), and eluted with 10 mL of ethyl acetate. The filtrate was concentrated and the residue was purified by rapid chromatography on silica gel (eluent: petroleum ether/ethyl acetate = 10:1) to afford 2-imidazolecarboxaldehyde (3k) as a light yellow solid with a yield of 0.38 g (91% yield) and a melting point of 205-206 °C. 1H-NMR (600 MHz, DMSO-d6) δ 13.60 (s, 1H), 9.64 (s, 1H) , 7.42 (s, 2H).13C-NMR (151 MHz, DMSO-d6) δ 181.66, 146.09.
References
[1] Molecules, 2017, vol. 22, # 11,
