2-氟-4-甲基苯甲酸的合成

Synthesis of 2-fluoro-4-methylbenzoic acid

以2-溴-5-甲基苯胺为原料,经重氮化、氰化和水解3步合成标题化合物,产物的含量为99.185%(HPLC),总收率约35%,产物结构通过1HNMR和MS验证。其中氰化反应的最佳条件为n(4-溴-3-氟甲苯)∶n(氰化亚铜)=1∶1.25,反应温度为150℃,保温时间为6 h;水解反应的最佳反应条件为n(2-氟-4-甲基苯甲腈)∶n(硫酸)=1∶4,温度控制在回流温度130℃,反应时间为3 h。该法具有原料来源丰富、反应条件温和易操作、生产成本低和有利于工业化生产等特点。

2-Fluoro-4-methylbenzoie acid was synthesized by using 2-hromo-5-methylaniline, which subjected to diazoti- zation, cyanidation and hydrolysis with an overall yield of 35% and purity of 99. 185% （HPLC）. The structure of the product was confirmed by 1HNMR and MS. The optimized conditions by cyanidation were ： n （ 4-bromo-3-fluorotouIene ） ： n （ CuCN ） = 1 ： 1.25, temperature, 150 ℃ , insulation time, 6 h; the optimized conditions by hydrolytic reaction were： n（2-fluoro-4-methylbenzonitrile） ： n （ sulfuric acid ） = 1 ： 4, reflux temperature, 130 ℃, reaction time, 3 h. This method has such advantages as rich raw material, mild condition, low cost. The process is easy and suitable for industrial produc- tion.