3-溴-2-氟苯甲酸的合成

Synthesis of 3-Bromo-2-fluorobenzoic Acid

以2-氨基-6-氟苯腈为原料,经溴化、水解和重氮化脱氨基反应合成3-溴-2-氟苯甲酸,产物的含量为99.20%(HPLC),总摩尔产率约38%。产物结构通过MS和1 H NMR验证。其中溴化反应的最佳条件为n(2-氨基-6-氟苯腈)∶n(NBS)=1∶1.05,n(2-氨基-6-氟苯腈)∶n(DMF)=1∶6,反应温度为5℃;水解反应的最佳反应条件为n(2-氨基-5-溴-6氟苯腈)∶n(NaOH)=1∶1.5,水解时间为8h,温度控制在回流状态下。该法具有生产成本低、反应条件温和、易于工业化生产的优点。

3-Bromo-2-fluorobenzoic acid with an overall yield of 38% and purity of 99.202%（HPLC）.was synthesized from 2-amino-6-fluorobenzonitrile by bromination,hydrolysis,diazotization and deamination.The structure of the product was confirmed by MS and 1H NMR.The optimized conditions of bromination were： n（2-amino-6-fluorobenzonitrile）∶n（NBS）=1∶1.05,n（2-amino-6-fluorobenzonitrile）∶n（DMF）=1∶6,temperature at 5℃.The optimized conditions of hydrolysis were： n（2-amino-5-bromo-6-fluorobenzonitrile）∶n（NaOH）=1∶1.5,8 h,under reflax.This method has the advantages of low cost and mild reaction conditions,and it is suitable for production in industrial scale.