摘要
研究了铜催化条件下,酮肟的衍生物与苄烯丙二腈的环化反应,考察不同的催化剂、溶剂、添加剂等对反应的影响,成功的构建了一系列的2-氨基吡啶骨架化合物.并对苯乙酮肟以及苄烯丙二腈芳环上不同位置具有不同性质取代基的底物进行了拓展,以31%~81%的收率分离得到相应的目标产物,反应具有较好的底物普适性.
The 2-aminopyridine is the core structure of many potential drug candidates for the treatment of a variety of disorders.It is widely used as building block for the synthesis of series nitrogen-containing heterocycles.However,the traditional synthesis of 2-aminopyridines relies on amination of 2-unsubstituted pyridines with sodium amide which is limited to low yield and narrow scope for the using of strongly basic conditions.Oximes and their derivatives are a class of powerful building blocks in organic synthesis.Recently,a series of reports are focus on copper-catalyzed cyclization of oxime esters,and various methods are developed for the construction of five-or six-membered heterocycles.Based on our sustained efforts to copper-catalyzed cyclization for access to heterocyles,we herein report a novel process of copper-catalyzed cyclization of oxime esters with 2-benzylidenemalononitrile for the construction of 2-aminopyridines.Various 2-aminopyridines were obtained in middle to good yields under the optimized reaction conditions.In this case,the N—O bond cleavage would occur for oxime esters reduced by copper(I) catalyst,followed by the formation of nucleophilic copper(II) enamide which serve as a precursor in heterocycle synthesis.A representative procedure for the copper-catalyzed construction of 2-aminopyridines by cyclization of oxime esters with 2-benzylidenemalononitrile is as following: The substrate acetophenone O-acetyl oxime(1a,0.5 mmol,0.0885 g),2-benzylidenemalononitrile(2a,0.5 mmol,0.0770 g),CuCl(0.1 mmol,0.0989 g,20 mol%),and NaHSO3(1.0 mmol,0.1041 g) were added to a 10 mL Schlenk tube,followed by addition of DMF(dried by calcium hydride and freshly distilled,3 mL).The mixture was stirred at 60 ℃ as monitored by TLC.The solution was then quenched by H2O and extracted with EtOAc(20 mL×3),the combined organic layers were dried over Na2SO4,filtered,and evaporated under vaccum.The residue was purified by column chromatography on silica gel(eluent: light petroleum ether∶ethyl acetate,V∶V=5∶1) t
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2014年第8期914-919,共6页
Acta Chimica Sinica
基金
国家自然科学基金(No.21172162)
国家青年自然科学基金(No.21202111)
江苏省青年自然科学基金(No.BK2012174)资助~~
