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

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