Pharmaceutical Intermediates-Synthesis Of2-cyano-4’-Methylbipheny

In recent years, hypertension disease as a high prevalence rate, a very commondisease into our lives, become an important threat to the life and health of the people.At present, for the treatment of high blood pressure is used in drug treatment, sartandrug because of its excellent therapeutic effect and side effects and other advantagesand become the important antihypertensive drugs, the market prospect is very wide,and the2-cyano-4’-methyl diphenyl (2-cyano the-4’-methyl diphenyl) is animportant intermediate for the sartan drug, most of the statin drugs have to beprepared by further reaction from it.This paper try one step reaction, Grignard reagent method and sodium method topreparate2-cyano-4’-methyl diphenyl, results show that when using p-chlorotolu-ene and o-chlorobenzonitrile as raw material, one step reaction can not synthesizetarget product; product of sodium method synthesis only have4of4’-, two methyldiphenyl without target product; Grignard reagent method can synthesize targetproducts, and higher yield.Grignard reagent preparation of2-cyano-4’-methyl diphenyl mainly dividedinto the preparation of Grignard reagent and the cross-coupling reaction of the twostep, the condition of the two step reaction were studied, the optimum reactionconditions.The p-tolyl magnesium chloride in the preparation process, the effects ofsolvent, raw material, influence of initiator on the yield of the product caused by. Intetrahydrofuran as solvent, magnesium scraps as raw material, using iodine vapor asinitiator, ensure the environment dry conditions, p-tolyl magnesium chloride yield canreach93.8%.In the cross coupling reaction of magnesium chloride in toluene ando-chlorobenzonitrile is best,5mol%MnCl2and1mol%copper complexes3by thecomposition of the mixed catalyst of catalytic effect; comprehensive consideration of various factors, the cross coupling reaction, V (toluene): V (THF)=1:1as solvent,reaction temperature was-10℃was optimumSeparation of the reaction has been studied the purification, ultimately byvacuum distillation, recrystallization steps of purification, The yield of the productcan reach70.1%，the purity of the product can be greater than95%.The2-cyano ’-4-methyl diphenyl samples by infrared spectroscopy (IR),nuclear magnetic resonance spectroscopy (1HNMR), mass spectrometry (MS)analysis methods were used to characterize the structure, the product is proved2-cyano-4’-methyl diphenyl.