化工进展

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对甲基苯基氯化镁的合成工艺改进

严生虎,康 琳,张 跃,刘建武,沈介发   

  1. 常州大学化工设计研究院,江苏 常州 213164
  • 出版日期:2013-12-05 发布日期:2013-12-04

Improvement of synthesizing p-tolylmagnesium chloride

YAN Shenghu,KANG Lin,ZHANG Yue,LIU Jianwu,SHEN Jiefa   

  1. Chemical Design & Research Institute,Changzhou University,Changzhou 213164,Jiangsu,China
  • Online:2013-12-05 Published:2013-12-04

摘要: 对甲基苯基卤化镁是合成2-氰基-4'-甲基联苯的重要原料,后者是最新一代沙坦类抗高血压药物的关键中间体。价廉的对氯甲苯原料在格氏反应中由于引发困难,影响了对甲基苯基氯化镁格氏试剂的应用。本文以镁粉、对氯甲苯为原料,在无水2-甲基四氢呋喃-四氢呋喃混合溶剂中制备格氏试剂,对影响反应的多种因素进行了研究,确定了最优工艺条件,合成收率达95.4%。与传统工艺方法相比,本文方法降低了装置无水性要求,操作简便,收率较高。该工艺为对甲基苯基卤化镁格氏试剂的生产提供了可行的技术路线,可显著降低2-氰基-4'-甲基联苯的合成成本。

关键词: 对甲基苯基氯化镁, 格氏试剂, 2-甲基四氢呋喃-四氢呋喃, 混合溶剂

Abstract: p-Tolylmagnesium halide is an important raw material for synthesizing 2-cyano-4’-methyl- biphenyl (OTBN),which is a key intermediate of the latest generation of anti-hypertensive drugs. Due to hard initiation,the cheaper chlorotoluene has not been used for synthesizing the above Grignard reagent of p-tolylmagnesium chloride. With magnesium and chlorotoluene as starting materials,p-tolylmagnesium chloride was synthesized via Grignard reaction using 2-methyltetrahydrofuran and tetrahydrofuran as mixed solvent. The synthesis process of the Grignard reagent was optimized with a 95.4% yield of target product. Comparing with the cases of traditional preparation process,the technique offered a new one with lower reactor anhydration,simplified operation and raised product yield. This new technique provides a feasible route for thesynthesis of p-tolylmagnesium halide,which can significantly reduce the cost of raw material for synthesizing OTBN.

Key words: p-tolylmagnesium chloride, Grignard reagent, 2-methyltetrahydrofuran-tetrahydrofuran, mixed solvent