4-甲硫基苯乙酸的合成研究

Synthesis of 4-(Methylthio)benzeneacetic Acid

以茴香硫醚(Ⅰ)为原料,经Friedel-Crafts酰基化、Willgerodt-Kindler反应合成了COX-2抑制剂的中间体4-甲硫基苯乙酸(Ⅳ)。确定了较理想的工艺条件为:n(Ⅰ)n(乙酰氯)/n(AlCl3)=1∶1.1∶1.3,CS2为溶剂,在0°C下反应6 h得到4-甲硫基苯乙酮(Ⅱ),收率为75.9%(以Ⅰ计),Ⅱ与吗啉和硫回流5 h得到硫代吗啉化合物(Ⅲ),再在10%的NaOH溶液中回流10 h得到Ⅳ,总收率为63.5%,纯度99.0%,结构经IR与1H NMR证实。

As an intermediate for COX-2 inhibiters, 4-（methylthio） benzeneacetic acid（ Ⅳ ） was prepared via Friedel-Crafts and Willgerodt-Kindler reaction from thioanisole（ Ⅰ ）. When the molar ratio of Ⅰ to acetyl chloride and AlCl3 was 1 ： 1.1： 1.3 and CS2 was used as solvent, after reacting at 0℃ for 6 h the yield of 4-（methyhhio） acetophenone（ Ⅱ ） was 75.9%. Ⅱ was refluxed 5 h with morpholine and sulfur to give thioacetmorpholide（ Ⅲ ）, then Ⅲ was refluxed in 10% NaOH for 10 h to give Ⅳ with an overall yield of 63.5% and purity of 99.0% （by HPLC）. The structure was confirmed by IR and ^1H NMR.