化学学报 ›› 2019, Vol. 77 ›› Issue (5): 418-421.DOI: 10.6023/A19020061 上一篇    下一篇

研究通讯

无金属催化的吡啶C2位碳-氢键胺甲酰化反应合成吡啶甲酰胺

王昱赟, 刘云云   

  1. 江西师范大学化学化工学院 南昌 330022
  • 收稿日期:2019-02-11 出版日期:2019-05-15 发布日期:2019-04-09
  • 通讯作者: 刘云云 E-mail:chemliuyunyun@jxnu.edu.cn
  • 基金资助:

    项目受国家自然科学基金(No.21562024)资助.

Metal-Free C2-H Aminocarbonylation of Pyridines for the Synthesis of Picolinamides

Wang Yuyun, Liu Yunyun   

  1. College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022
  • Received:2019-02-11 Online:2019-05-15 Published:2019-04-09
  • Contact: 10.6023/A19020061 E-mail:chemliuyunyun@jxnu.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21562024).

报道了一种无金属催化条件下合成吡啶-2-甲酰胺的方法.在质子酸的促进作用下,简单的吡啶和异氰通过2位碳-氢键的胺甲酰化反应生成吡啶-2-甲酰胺类化合物.产物的形成主要经历二水合草酸存在下异腈对吡啶环的亲电加成、水解和过氧化二叔丁酯氧化下的吡啶环芳构化转化.优化部分的对比实验证实质子酸和氧化剂的存在对于该反应都是必须条件.大体而言,所有反应都是将各反应物和试剂一次性加入,在空气氛围下100℃加热进行良好.环上不同位置含有甲基、叔丁基、环状二烷基、甲氧基、卤素等基团的吡啶底物均展示了良好兼容性.另一方面,烷基和芳基官能化的异腈也都能用于该反应,得到相应的N-烷基和N-芳基吡啶甲酰胺产物.初步结果显示异腈的稳定性对于反应结果有明显影响,相对稳定的2,6-二甲基苯基异腈参与反应生成的产物产率高于其它异腈参与的反应.和已知合成类似产物时采用银、钯盐等催化活化吡啶的2-位碳-氢键的方法相比,本文报道的合成方法优势在于完全无需金属催化剂、专一的碳-2位区域选择性反应、广泛的底物适用性以及高原子经济性.因此,这样的合成方法可望成为对已有合成方法的补充用于合成结构多样和有用的吡啶-2-甲酰胺化合物.

关键词: 无金属, 吡啶, 碳-氢键, 胺甲酰化, 吡啶酰胺

In this paper, a metal-free catalytic method for synthesis of 2-picolinamide derivatives is reported. Under the promotion of proton acid, simple pyridines react with isocyanides to provide 2-picolinamides by means of the aminocarbonylation of the aryl C-H bond in the C2 position of pyridines. The product formation involves in the electrophilic addition of isocyanide to pyridine ring, hydrolysis and the oxidative aromatization regenerating pyridine ring in the presence of Di-t-butyl peroxide (DTBP) and oxalic acid dihydrate. Control experiments in the optimization section disclose the fact that the proton acid and oxidant are both indispensable for this C-H bond aminocarbonylation reaction. Generally, the synthetic reactions run smoothly under air atmosphere by heating all the substrates and reagents in one-pot at 100℃. The pyridine substrates containing methyl, t-butyl, cyclic dialkyl, methoxyl, halogen substituents at different site of the pyridine ring have displayed fine tolerance to the synthesis of corresponding products with diverse substructures in the pyridine ring. On the other hand, both alkyl and aryl functionalized isocyanides have also been found applicable to this synthetic protocol to provide 2-picolinamides containing correspondingly various N-alkyl and N-aryl fragment. The primary results indicate that the stability of the isocyanide substrate evidently influence the reaction result. The reactions employing relatively more stable 2,6-dimethylphenyl isocyanide give corresponding products with higher yield than those ones using other isocyanides. Comparing with those reported methods employing transition metal catalyst such as silver or palladium salt to activate the C2-H bond in pyridines for the synthesis of analogous products, the present method benefits from the distinctive features of totally metal-free catalysis, broad substrate tolerance, specific regioselectivity in transforming C2-H bond, and high atom economy. Therefore, such a synthetic method will reasonably be a practical approach in complementing those already known strategies for the synthesis of structurally diverse and useful 2-picolinamide scaffolds.

Key words: metal-free, pyridines, C-H bond, aminocarbonylation, 2-picolinamides