化学学报 ›› 2014, Vol. 72 ›› Issue (8): 914-919.DOI: 10.6023/A14040263 上一篇    下一篇

研究通讯

铜(I)催化条件下酮肟衍生物与苄烯丙二腈的环化反应构建2-氨基吡啶

蔡忠建, 陆新谋, 汪顺义, 纪顺俊   

  1. 苏州大学 材料与化学化工学部 苏州 215123
  • 收稿日期:2014-04-09 出版日期:2014-08-14 发布日期:2014-06-05
  • 通讯作者: 汪顺义, 纪顺俊 E-mail:shunyi@suda.edu.cn;shunjun@suda.edu.cn
  • 基金资助:

    项目受国家自然科学基金(No. 21172162)、国家青年自然科学基金(No. 21202111)及江苏省青年自然科学基金(No. BK2012174)资助

Copper-Catalyzed Cyclization of Oxime Acetates with 2-Benzylidenemalononitriles for Synthesis of 2?Aminonicotinonitriles

Cai Zhongjian, Lu Xinmou, Wang Shunyi, Ji Shunjun   

  1. Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou 215123
  • Received:2014-04-09 Online:2014-08-14 Published:2014-06-05
  • Supported by:

    Project supported by Natural Science Foundation of China (No. 21172162), Young National Natural Science Foundation of China (No. 21202111) and Young Natural Science Foundation of Jiangsu Province (No. BK2012174).

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.

关键词: 铜(I), 苯乙酮肟的衍生物, 苄烯丙二腈, 环化反应, 2-氨基吡啶

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) to afford the desired product 4,6-diphenylpyridin-2-amine 3a.

Key words: copper, oxime esters, 2-benzylidenemalononitrile, cyclization, 2-aminopyridine