Preparation background and overview of 2-bromo-5-fluoropyridine
2-Bromo-5-fluoropyridine is a chemical substance with the molecular formula C5H3BrFN. It is a light yellow crystal and is often stored in a cold state. 2-Bromo-5-fluoropyridine is a starting material for the synthesis of many drugs, especially an important intermediate for many pyridine compounds. Currently, there is no reported synthesis method of this compound in China.
2-Bromo-5-fluoropyridine solution
Preparation and application of 2-bromo-5-fluoropyridine
2-Bromo-5-fluoropyridine is an important fine chemical intermediate and is widely used in the fields of medicine and pesticides. Fluorine-containing 2-bromo-5-fluoropyridine is widely used in pesticides, medicines, functional materials and other fields due to the particularity of fluorine atoms.
Preparation of 2-bromo-5-fluoropyridineMagnesium carbonate
Synthesis of 2-bromo-5-aminopyridine (bromination reaction): Add the solvent ml of carbon tetrachloride, 47.05g of 5-aminopyridine (0.5mol), and azobisisobutyl into a 1000ml three-neck flask. 0.41g of nitrile (AIBN), 195.78g (1.1mol) of N-bromosuccinimide (NBS) was added in batches at 20°C, and then the temperature was raised to 50°C and reacted for 4 hours. The raw material aminopyridine and The intermediate 2-bromo-5-aminoaminopyridine is converted into the target product 2-bromo-5-aminopyridine, and the reaction is stopped. Post-reaction treatment: The reaction solution was cooled to room temperature with stirring, filtered, the filter cake was fully washed with carbon tetrachloride several times, the filtrate was washed once with sodium bicarbonate aqueous solution and once with saturated brine, and the solvent carbon tetrachloride was removed by rotary evaporation. , the obtained crude product 120.60g of 2-bromo-5-aminoaminopyridine was directly used in the next step of reaction.
Synthesis of 2-bromo-5-fluoropyridine (diazotization reaction): Add 375ml concentrated hydrochloric acid and 375ml water to a 2000ml three-neck flask, and add the 2-bromo prepared in the previous step in batches at 25°C. -120.60g of 5-aminoaminopyridine, stir thoroughly to dissolve, cool the reaction bottle to 0°C in an ice-salt bath, slowly add a solution containing 38.5g (0.56mol) sodium nitrite and 150g of water, and control the temperature during the dropwise addition. 0~3℃, after the dropwise addition, stir for 30 minutes, then dropwise add 48% fluoroboric acid solution 164.6g mica (0.75mol) into the reaction system, control the temperature during the dropwise addition to 0~5℃, and maintain this temperature after the dropwise addition. temperature, stir for 1 hour, remove the ice-salt bath, raise the temperature to 50°C and react for 2 hours. Post-reaction treatment: After the reaction solution is cooled, pour it into ice water, stir thoroughly, and precipitate a light yellow crude 2-bromo-5-fluoropyridine. Filter the filtrate and neutralize it with 10% sodium hydroxide aqueous solution to pH=5.8, and use trichloride to neutralize it. Extract with methane, separate the liquids, neutralize the organic phase with 5% sodium hydroxide aqueous solution to pH=7.5, separate the liquids, wash the organic phase once with saturated brine, separate the liquids, dry the obtained organic layer with anhydrous sodium sulfate, and filter. The solvent chloroform was removed by rotary evaporation to obtain crude yellow 2-bromo-5-fluoropyridine. Filter the obtained filter cake, dry the water, combine the two solid parts, and recrystallize with n-hexane to obtain 104.0 grams of pure white 2-bromo-5-fluoropyridine, with a content of 98.8% and a yield of 81.6%.
