2-Bromo-6-fluorophenol

Synthesis

Synthesis of 2-fluoro-6-bromophenol:

1) Synthesis of sodium 3-fluoro-4-hydroxybenzenesulfonate (B) (steps a and b, sulfonation reaction):

a: Add 112g (1.0mol) of A to the reaction vessel, raise the temperature to about 120℃, and slowly add 80ml (1.5mol) of 98% sulfuric acid dropwise over 30 minutes with stirring. After the addition is complete, continue the reaction at 120℃ for 5 hours. After the reaction is complete, cool to below 100℃.

b: Add 400 ml of saturated sodium chloride solution to the above reaction mixture. A large amount of sodium salt precipitates out. After complete cooling, filter and wash twice with 10% sodium chloride solution to obtain 192.6 g of product B, with a yield of 90%.

2) Synthesis of sodium 3-fluoro-6-bromo-4-hydroxybenzenesulfonate (C) (step c, halogenation reaction):

c: Before the reaction, all raw materials and equipment are anhydrous. Bromine is washed twice with concentrated sulfuric acid to remove water. A 250 ml three-necked flask is equipped with a mechanical stirrer, thermometer, separatory funnel, and reflux condenser. Add 171.2 g (0.8 mol) of B, 11.2 g of iron powder, and 120 ml of carbon tetrachloride to the flask. Stir and heat in a water bath to 55 °C. Control the temperature at 50-60 °C and add 134.4 g (0.84 mol) of bromine dropwise over 4 hours. After the addition is complete, keep warm and stir for 2 hours.

3) Synthesis of 2-fluoro-6-bromophenol (D) (step d, deprotection reaction):

d: 146.5g (0.5mol) of C and 200ml of 70% sulfuric acid solution were added to a 250ml reaction vessel. After reacting at 180℃ for 5 hours, the mixture was cooled to room temperature, and 200ml of dichloromethane was added for extraction. The extract was washed, dried, and the solvent was evaporated to obtain 76.4g of oily product D, with a yield of 80%.

Application

2-Bromo-6-fluorophenol is an organic synthesis intermediate and a pharmaceutical intermediate that can be used in laboratory research and development processes as well as in biochemical production processes.

Chemical Properties

Pale yellow liquid