Fluconazole NEW

About:

Fluconazole is a new triazole anti-fungal infection drug, which was first developed by Pfizer in the United States. It has a broad spectrum anti-fungal effect and belongs to the whole body anti-fungal product. It is highly selective to the inhibition of fungal cytochrome P-450-dependent enzymes, and is also a powerful and specific fungal alcohol synthesis inhibitor.

Production method:

Method 1:1H-1, 2, 4-triazole was obtained from formamide, hydrazine hydrate and 85% formic acid. M-difluorobenzene is obtained from m-phenylenediamine, which is then brominated to 2, 4-difluorobromobenzene. Magnesium was dissolved in anhydrous ether, and an ether solution of 2, 4-difluorobromobenzene was added under ultrasonic radiation, and then an ether solution of 1, 3-dichloroacetone was added under ice bath cooling, and stirred at room temperature overnight. Add glacial acetic acid and water. The separated organic layer concentrates after drying. The concentrated solution, triazole, potassium carbonate and PEG600 were dissolved in dry ethyl acetate and refluxed. Strain, rinse until neutral and dry. Fluconazole was obtained by recrystallization of ethyl acetate monohexane (1:1) with a total yield of 33.6% and melting point of 138.5-140℃. The last step can also be performed in propionitrile. Fluconazole was obtained by reflux of 1, 3-dihalide (x=Br or Cl)-2-(2, 4-difluorophenyl) -2-propanol and 1h-1, 2, 4-triazole in propionitrile, catalyzed by sodium hydroxide and catalyzed by PEG600 phase transfer. The crude product is dissolved in fat alcohol (such as propyl alcohol, isopropyl alcohol or butanol, etc.), heated to dissolve, decolorized with a small amount of activated carbon, cooled to crystallize, that is, fluconazole fine, melting point 139 ~ 140℃.

Method 2:2, 4-difluorobenzoate methyl ester and 1-chloromethyl-1, 2, 4-triazole Grignard reagent reaction and hydrolysis to obtain fluconazole. Method 3: Difluorobenzene is brominated to produce 1-bromo-2, 4-difluorobenzene, and then converted into its Grignard reagent. The Grignard reagent obtained above is reacted with 1, 3-bis (1H-1,2, 4-triazolidyl) acetone and then hydrolyzed to obtain fluconazole.