Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (12): 1603-1606.DOI: 10.6023/A13091000 Previous Articles     Next Articles



胡露丹a, 高令峰b, 万常峰a, 汪志勇b   

  1. a 江西师范大学化学化工学院 南昌 330022;
    b 中国科学技术大学化学系 合肥 230026
  • 投稿日期:2013-10-08 发布日期:2013-11-14
  • 通讯作者: 万常峰, 汪志勇;
  • 基金资助:

    项目受国家自然科学基金(Nos. 21172205,21272222)资助.

A Practical Iodine-Catalyzed Sequential Process:Assembly of Imidazo[1,5-a]pyridines From Aldehydes

Hu Ludana, Gao Lingfengb, Wan Changfenga, Wang Zhiyongb   

  1. a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China;
    b Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
  • Received:2013-10-08 Published:2013-11-14
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21172205, 21272222).

Imidazo[1,5-a]pyridines represent an important class of heterocyclic compounds because of their largely potential application in photophysical and biological areas. These substances have been widely investigated in the context of organic light-emitting diodes (OLED) and organic thinlayer field effect transistors (FET). Furthermore, they have been explored in a wide range of potential pharmaceutical applications, including HIV-protease inhibitors, and Thromboxane A2 synthesis inhibitors. However, literature survey found that only some strategies for the synthesis of imidazo[1,5-a]pyridine derivatives were reported. Traditionally, substituted imidazo[1,5-a]pyridines were accessed via Vilsmeier-type cyclizations of N-2-pyridylmethyl amides. Recently, Murai's group reported several methods for the construction of imidazo-[1,5-a]pyridine rings. Although these methods provided useful access to substituted imidazo[1,5-a]pyridine derivatives, they suffered from some drawbacks, such as the use of strong acid and high temperature, moreover, study on the preparation of 3-arylated imidazo[1,5-a]pyridines and 1,3-diarylated imidazo[1,5-a]pyridines in a procedure is rare. Therefore, developing more efficient and practical protocols for the preparation of 3-arylated imidazo[1,5-a]pyridines and 1,3-diarylated imidazo[1,5-a]pyridines still are highly desirable. As part of a program targeting new methods for constructing some useful heterocycles probably found application in pharmaceutical and industry areas. We chose pyridin-2-ylmethanamine and aldehydes as the reaction substrates to achieve the synthesis of imidazo[1,5-a]pyridines in the presence of iodine and TBHP. Moreover, α-substituted pyridin-2-ylmethanamine used as substrate reacted with aldehydes to also provide 1,3-diarylated imidazo[1,5-a]pyridines. Therefore, 3-aryl imidazo[1,5-a]pyridines and 1,3-diaryl imidazo[1,5-a]pyridines can be obtained through this method. Herein, we report a simple and efficient iodine-catalyzed synthesis of 3-substituted and 1,3-disubstituted imidazo[1,5-a]pyridines from easily available aldehydes under mild conditions. The optimization of reaction conditions showed that N,N-dimethylformamide was the only effective solvent and 70 ℃ was the proper reaction temperature. The investigation on the scope of suitable substrates showed that the electronic effect of substituent on the aldehydes had a major impact on the success of the process. Aldehydes bearing electron-deficient substituents proven more favorable for the reaction, while electron-rich groups didn't offer good reaction result despite of prolonging the reaction time.

Key words: iodine catalyze, oxidation, tandem cyclization, heterocycles syntheses, imidazo[1,5-a]pyridines