2-Fluorobenzene-1,4-diol

Uses

Reactant for:• ;Regioselective propanoylation mediated by Candida lipase B in organic solvents1

Uses

Reactant for:

• Regioselective propanoylation mediated by Candida lipase B in organic solvents

Synthesis

367-12-4

55660-73-6

General procedure for the synthesis of 2-fluoro-1,4-benzenediol from 2-fluorophenol: 2-fluorophenol (5.6 g, 50.0 mmol) was dissolved in 6% aqueous NaOH (200 mL), and solid potassium persulfate (13.5 g, 50.0 mmol) was added in batches over a 10-minute period with stirring, and the reaction solution changed to a dark color. The reaction mixture was stirred overnight at room temperature and subsequently concentrated under reduced pressure to about 100 mL. after cooling to 0 °C, it was neutralized with concentrated HCl to pH 6.5 and extracted once with ether (100 mL). The organic phase was dried over MgSO4 and concentrated under reduced pressure, and the unreacted 2.0 g of 2-fluorophenol was isolated by fast silica gel column chromatography using hexane/ethyl acetate (V/V 6:1) as eluent.The aqueous phase was acidified with concentrated HCl (50 mL), refluxed for 1 hr, and then concentrated under reduced pressure to ca. 50 mL.The inorganic salts were precipitated by the addition of acetone (100 mL), and removed by filtration. The filtrate was dried by rotary evaporator and the dark residue dissolved in acetone was adsorbed onto silica gel (10 g). After drying, column chromatography (hexane/ethyl acetate 3:1) was carried out to give the product 2.2 g as a white solid, melting point 120-121 °C, yield 52%, Rf 0.30 (hexane solution of 20% EtOAc).1H NMR (300 MHz, CDCl3): δ 6.51-6.56 (m, 1H), 6.64-6.69 (m, 1H). 6.85-6.92 (m, 1H), 4.77 (brs, 2H, 2×OH).EI-MS calculated value C6H5FO2 128 (M+), measured value 129 (M+1)+, 128 (M+).

References

[1] European Journal of Medicinal Chemistry, 2012, vol. 58, p. 72 - 83
[2] Journal of the Chemical Society. Perkin Transactions 1, 2002, # 23, p. 2719 - 2728
[3] Tetrahedron, 2014, vol. 71, # 23, p. 3915 - 3923