2-氨基-5-氟吡啶的制备工艺研究.pdf

天津大学硕士学位论文 2-氨基-5-氟吡啶的制备工艺研究姓名:王昭申请学位级别:硕士专业:应用化学指导教师:张天永 20090501 摘要 ,主要用于合成多种酶、激素的抑制剂、拮抗剂等医药中间体。,经硝化、重排、酰胺基保护、还原、重氮化、热分解及水解共七步反应,。主要结果如下: 、混酸组成对2一硝酰氨基吡啶收率的影响;重排过程研究了重排温度对异构体比例的影响及水蒸汽蒸馏后处理条件优化。()%,熔点187~190。C, %。 。较佳工艺条件::,回流反应lh,%, 熔点202~206℃,%(HPLC)。还原反应条件的研究中,。。研究了铁粉用量、电解质冰乙酸用量对反应的影响。较佳的还原条件为:、、 ,%。,研究了氟硼酸用量、亚硝酸钠用量对重氮盐收率的影响。还原、%(. 硝基吡啶计)。 、分散介质、氢氧化钠溶液浓度、后处理方式等因素。较好的条件为:~140。C下加热分解2h,加入40%的氢氧化钠溶液34mL,回流,%,熔点98~101 ℃,%(HPLC)。关键词: ;硝化;;铁粉还原;重氮化; ABSTRACT 2-Amino·-5·-fluoropyridine is an important medicinal intermediate anic synthesis ofthe inhibitor of enzyme and hormone,the antagonists of 5-HTlA receptor(WAY-100635).And it was prepared from 2-aminopyridine by aseven—step way including nitration,rearrangement,acetylation,reduction,diazotization,thermal position andhydrolysis. Inthe process ofnitration,nitrationtemperature and position ofmixed acidsinfluencing the yield of 2-nitraminopyridine were studied;while in the rearrangement process,effect ofrearrangement temperature on isomer ratioand optimization ontheafiertreatment ofsteam distillationwere yield(purity) of2-amino-5一nitropyridine prepared from 2-aminopyridine was %(%),mp: 187~190℃. The effectofaceticanhydride on theyield ofthereaction inthe acetylation process of2-amino一5一nitropyridine was theprocess ofaftertreatment was optimized acetylation conditions were as follows:l mol 2-amino-5-nitropyridine and acetic anhydride was refluxed in h,and the product Was %yield and99