广东化工2023年第6期·4·www.gdchem.com第50卷总第488期溴代沙坦联苯的合成工艺研究何星1，刘跃龙1,2*(1．江西科技师范大学化学化工学院，江西南昌330013；2．江西省水性涂料工程实验室，江西南昌330013)[摘要]沙坦类药物目前是临床上备受关注的新型高血压药物，4’-溴甲基-2-氰基联苯(溴代沙坦联苯)是大部分沙坦类药物合成的关键中间体。以4’-甲基-2-氰基联苯(OTBN)为起始原料，通过对溴代试剂、反应溶剂的比例、重结晶阶段条件的探究，开发了一条以二氯甲烷和甲基叔丁基醚(MTBE)混合溶剂作反应体系合成高纯度溴代沙坦联苯的工艺，此工艺以偶氮二异丁腈(AIBN)为引发剂，以二氯甲烷和MTBE混合溶剂作为反应体系，采用同时滴加的方式滴加氢溴酸和过氧化氢，50℃回流反应，反应结束后经精制得到高纯度溴代沙坦联苯。制备得溴代沙坦联苯为白色粉末状，收率为78.1%，使用HPLC检测纯度达到99.7%。适用于工业化生产。[关键词]溴代沙坦联苯；溴代试剂；混合溶剂；重结晶；高纯度[中图分类号]TQ[文献标识码]A[文章编号]1007-1865(2023)06-0004-04StudyontheSynthesisProcessofBromosartanBiphenylHeXing1,LiuYuelong1,2*(1.SchoolofChemistryandChemicalEngineering,JiangxiUniversityofScienceandTechnology,Nanchang330013；2.EngineeringLaboratoryofWaterborneCoatingsinJiangxiProvince,Nanchang330013,China)Abstract:Sartansarenownovelhypertensivedrugsofgreatclinicalinterest,and4'-bromomethyl-2-cyanobiphenyl(bromosartanbiphenyl)isakeyintermediateinthesynthesisofmostsartans.Aprocessforthesynthesisofhighpuritybromosartanbiphenylusingdichloromethaneandmethyltert-butylether(MTBE)asthereactionsystemwasdevelopedbyinvestigatingthebrominatedreagents,theratioofreactionsolvents,andtheconditionsofrecrystallizationstageusing4'-methyl-2-cyanobiphenyl(OTBN)asthestartingmaterial,andusingazodiisobutyronitrile(AIBN)astheinitiatoranddichloromethaneandMTBEasthereactionsystem.ThisprocessusesAIBNastheinitiator,dichloromethaneandMTBEasthereactionsystem,andhydrobromicacidandhydrogenperoxideareaddeddropwiseat50℃.Thereactionisrefinedtoobtainhigh-puritybromosartanbiphenyl.Thepreparedbromosartanbiphenylwasintheformofwhitepowderwith78.1%yieldand99.7%puritybyHPLC.Itissuitableforindustrialproduc...
