Background and overview[1]
2-Fluorophenylhydrazine is an important intermediate, especially a pharmaceutical intermediate. The existing technology uses 2-fluorophenylhydrazine as raw material, and prepares 2-fluorophenylhydrazine through diazotization reaction, sodium sulfite reduction and hydrolysis. -The synthesis method of fluphenylhydrazine requires a long reaction time, generally requires a yield of only 63-72%, and has high production costs.
Structure
Preparation method[1-2]
Method 1: A method for preparing 2-fluorophenylhydrazine, using 2-fluorophenylamine as the starting material, through diazotization reaction, reduction reaction, and hydrolysis to prepare 2-fluorophenylhydrazine. The reduction The reaction was carried out using sodium metabisulfite as the reducing agent at 10-35°C and pH 7-9.
The specific steps are as follows: Add 200ml of water to a 1000ml beaker, stir, add 115ml of 10N hydrochloric acid, and cool to 0℃. Slowly add 44.4 g of 2-fluoroaniline to obtain a light brown solution. Cool the solution to below 0 degrees, slowly add sodium nitrite solution (made of 30 grams of sodium nitrite and 60 grams of water), react for 20 minutes, filter and retain the filtrate. Add 250 ml of water to a 2000 ml beaker, add 128 grams of sodium metabisulfite and 130 grams of sodium hydroxide while stirring. At this time, the pH of the solution is 7 and the temperature of the solution is 35°C. Wait until the solution cools to 15 After -18℃, slowly add the above filtrate. When the addition is completed, the solution temperature is 20-22℃ and the pH is 7. After 30 minutes of reaction, add 230ml of 10N hydrochloric acid and raise the temperature to 97-100℃, and after reacting at this temperature for 30 minutes, add 17 grams of activated carbon, decolorize at 90℃ for 10 minutes, and then filter to obtain a colorless solution. At 55℃, add 255g of salt and cool to 5℃. When the material precipitates, filter and drain to obtain 78g of filter cake, and dry the product to obtain 48.8g. The purity measured by high performance liquid chromatography was 98.5%.
Method 2: A method for preparing 2-fluorophenylhydrazine hydrochloride. The steps are as follows:
1) Diazotization: Mix 2-fluoroaniline and 37% concentrated hydrochloric acid and cool to 0~5℃, add 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 0 The reaction time is 1 to 1.5 hours at ~5℃.
2) Reduction: Add 37% concentrated hydrochloric acid, water and zinc powder to the reaction solution, keep the temperature between 15 and 20°C until the reaction is complete and the reaction solution turns off-white, then Add 20 to 30% sodium hydroxide solution until the pH of the reaction solution is 10, incubate at 5°C for 1 to 2 hours, precipitate crystals, and filter to obtain crude 2-fluorophenylhydrazine.
3) Purification: Dissolve the crude 2-fluorophenylhydrazine in water, heat to 60℃ to completely dissolve it, then add an appropriate amount of activated carbon for decolorization for 20 minutes, and hot filter to obtain a colorless filtrate. 5℃Incubate for 1 to 2 hours, crystals will precipitate, and filter to obtain pure 2-fluorophenylhydrazine.
Main reference materials
[1] CN200710134933.X A kind of preparation method of 2-fluorophenylhydrazine
[2] CN201510578057.4 A preparation method of 2-fluorophenylhydrazine hydrochloride
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