Preparation background and overview of 2,6-dichloro-4-hydroxypyridine
2,6-Dichloro-4-hydroxypyridine can be used as a pharmaceutical synthesis intermediate. It can be prepared from dimethyl sulfoxide using 2,6-dichloropyridine as the reaction raw material, and can prepare pharmaceutical active substances with cardiovascular activity. .
Preparation of 2,6-dichloro-4-hydroxypyridine
2,6-Dichloro-4-hydroxypyridine is prepared as follows:
In a drying oven, combine 2,6-dichloropyridine (148mg, 1.0mmol), HBPin (1.5-2.5mmoles), (Ind)Ir(COD) (8.3mg, 0.02mmol, 2mol%) and dmpe ( 3.0 mg, 0.02 mmol, 2 mol%) or dppe (8.0 mg, 0.02 mmol, 2 mol%) into an airless flask equipped with a stir bar (in the case of using cyclohexane as solvent, dissolve the reagent in 1 mL of cyclohexane in hexanes and transfer to an air-free flask). Seal the flask and remove from the drying oven and place in an oil bath heated to 150°C (dmpe) or 100°C (dppe) until the reaction is judged to be complete by GC-FID. The reaction was allowed to cool to room temperature and the solvent was removed under reduced pressure. Add 3.2 mL of acetone to the crude material (usually a dark orange or brown gel-like liquid or solid). After stirring to produce a homogeneous solution, add Oxone aqueous solution (6.15 g, 1.0 mmol in 3.2 mL) dropwise over 2-4 minutes. After the addition was completed, the reaction mixture was stirred vigorously for 7 minutes, and the reaction was quenched with NaHSO3 lithium tetraborate aqueous solution. A layer of dark orange oil was observed. The reaction mixture was extracted three times with diethyl ether or CH2Cl2. The combined organics were washed with brine, then water, and concentrated in vacuo. The crude material was then dissolved in diethyl ether and passed through a silica plug (pentane/ether 2:1), the solvent was evaporated and sublimed at 110°C and 0.1mmHg to obtain analytically pure 2,6-dichloro-4-hydroxypyridine , as a white solid. Melting point: 201-202℃. 1HNMR (300MHz, acetone-d6): δ10.48 (brs, 1H), 6.88 (s, 2H); m/z. 13CNMR (75MHz, acetone-d6): δ168.3, 151.5, 111.5; measured values. Infrared (KBr): 3200~2500 (br), 1597, 1576, 1554, 1427, 1294, 1211, 1157, 1092, 993, 966, 847cm-1.
References
[1] Maleczka R E , Shi F , Holmes D , et al. C-H activation/borylation/oxidation: a one-pot unified route to meta-substituted phenols bearing ortho-/para-directing groups.[J]. Journal of the American Chemical Society, 2003, 125(44):7792-3.
