2-氯-6,7-二氢-5H-环戊并[b]吡啶的合成  

SYNTHESIS OF 2-CHLORO-6,7-DIHYDRO-5H-CYCLOPENTANO[b]PYRIDINE

作　　者：周尽花[1] 高海丽[1] 孙汉洲[1] 吴宇雄[1] 

机构地区：[1]中南林业科技大学理学院,湖南长沙410004

出　　处：《精细石油化工》2012年第5期1-4,共4页Speciality Petrochemicals

摘　　要：实验以环戊酮与苄胺为起始原料,经亲核加成、乙酰化、Vilsmeier反应关环合成了第四代抗生素头孢匹罗的重要中间体2-氯-6,7-二氢-5 H-环戊并[b]吡啶,经3步反应制备了2-氯-6,7-二氢-5 H-环戊并[b]吡啶。合成中间产物N-亚环戊基苄胺的较佳条件为:反应温度为117～121℃,n(苄胺)∶n(环戊酮)=1∶1.02,回流反应时间为40min;合成中间产物N-环戊烯基-N-苄基乙酰胺的较佳条件为:加料温度0～5℃,反应温度25℃,n(苄胺)∶n(乙酸酐)=1∶1.1,反应时间14h;合成2-氯-6,7-二氢-5 H-环戊并[b]吡啶的条件为:三氯氧磷加料温度0～5℃,回流反应时间15h,水解温度为40～45℃。三步反应的总收率为45.9%,产品结构经1 H NMR和LC-MS确证。The important intermediate of the fourth-generation antibiotics cefpirome,2-chloro-6,7-dihydro-5H-cyclopentano[b]pyridine,was synthesized from cyclopentanone and benzylamine via nucleophilic addition,acetylization and Vilsmeier cyclization.The main synthetic conditions were found.For the intermediate N-cyclopentylidene（phenyl） methanamine,the reaction temperature were 117-121 ℃ with material molar ratio n（benzylamine）∶n（cyclopentanone）=1∶1.02 and refluxing reaction time of 40 min.For the intermediate N-benzyl-N-cyclopentenylacetamide,the feed temperature was 0-5 ℃,reaction temperature 20-25 ℃,n（benzylamine） ： n（acetic anhydride）=1∶1.1,reaction time 14 h.The optimal synthetic conditions for the product 2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridine were detailed as follows： phosphorus oxychloride feed temperature 0-5 ℃,refluxing reaction time 15 h,hydrolysis temperature 40-45 ℃.The overall yield after the three-step reactions was 45.9% and the target product structure was confirmed by LC-MS and 1H NMR.

关 键 词：2-氯-6 7-二氢-5H-环戊并[b]吡啶 2 3-环戊烯并[b]吡啶 头孢匹罗 Vilsmeier反应 

分 类 号：TQ253.2[化学工程—有机化工]