Application
In basic organic chemistry research, 3-hydroxypyridine-4-aldehyde can be used as a synthetic raw material for organic ligands for the structural modification and synthesis of pyridine ligands. By modifying the compound with different functional groups, its electronic properties, stereochemical properties, etc. can be changed, thus modulating the properties of the synthesized organic ligands. In addition, 3-hydroxypyridine-4-aldehyde can be used as a pyridine-like substrate for evaluating the applicability of newly developed synthetic methods and optimization of reaction conditions.
Synthesis
To a stirred solution of 3-methoxymethoxypyridine-4-carboxaldehyde (11.0 g, 65.83 mmol) in tetrahydrofuran (THF, 50 mL) was added 3 N hydrochloric acid (HCl, 100 mL) and the reaction mixture was stirred for 1 h at 60 °C. The reaction was carried out in an ice bath. Upon completion of the reaction, the mixture was cooled in an ice bath and the pH was adjusted with solid potassium carbonate (K2CO3) to 7. Subsequently, the mixture was extracted with ethyl acetate (EtOAc, 5 × 250 mL). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (100-200 mesh) with 23% ethyl acetate/hexane as eluent to give 3-hydroxypyridine-4-carboxaldehyde (4.0 g, 32.496 mmol, 49.4% yield) as a light yellow solid. The product was analyzed by GC-MS showing a molecular ion peak of 123 (m/z), and the 1H-NMR (DMSO-d6, 400 MHz) data were as follows: δ 11.04 (broad single peak, 1H), 10.37 (single peak, 1H), 8.46 (single peak, 1H), 8.20 (double peak, 1H, J = 4.88 Hz), and 7.46 (double peak, 1H, J = 4.88 Hz).The purity of GC-FID analysis was 99.51%.
References
[1] Patent: WO2016/27241, 2016, A1. Location in patent: Page/Page column 30; 43
[2] Patent: WO2014/186035, 2014, A1. Location in patent: Page/Page column 146
