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Synlett 2010(9): 1351-1354  
DOI: 10.1055/s-0029-1219917
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient One-Pot Synthesis of Substituted 2-Aminothiophenes via Three-Component Gewald Reaction Catalyzed by l-Proline

Tao Wanga,b, Xian-Gui Huanga,b, Jia Liua,b, Bo Lid, Jin-Jin Wua, Kai-Xian Chend, Wei-Liang Zhua,c, Xiao-Yong Xu*a,b, Bu-Bing Zeng*a,b
a School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. of China
Fax: +86(21)64253689; e-Mail: zengbb@ecust.edu.cn; e-Mail: xyxu@ecust.edu.cn;
b Shanghai Key Laboratory of Chemical Biology, Shanghai 200237, P. R. of China
c Drug Discovery and Design Centre, Shanghai Institute of Materia Medica, Shanghai 201203, P. R. of China
d Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P. R. of China
Further Information

Publication History

Received 19 January 2010
Publication Date:
06 May 2010 (online)

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Abstract

An efficient one-pot procedure for the direct catalytic synthesis of substituted 2-aminothiophenes catalyzed by l-proline under mild reaction conditions has been developed. A variety of functionalized 2-aminothiophene scaffolds were assembled in high yields by this catalytic protocol. Low catalyst loading, simple procedure, and high yields are the important attributes of this methodology.

Key words

Gewald reaction - 2-aminothiophene - one-pot - multicomponent - Knoevenagel reaction

    Primary data for this article are available online and can be cited using the following DOI: 10.4125/pd0002th:
  • Primary Data
    • MS data and associated files for the ¹H and ¹³C NMR spectra for the compounds 3a-o are summarized.

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8

General Procedure for the One-Pot Synthesis of Substituted 2-Aminothiophenes 3
A mixture of carbonyl compound (3.0 mmol), nitrile (3.3 mmol), sulfur (4.5 mmol), l-proline (0.3 mmol), and DMF (3.0 mL) in a 50 mL round bottom flask was stirred at 60 ˚C for 10-24 h. The crude product was directly purified through flash chromatography to give the desired product 3. The spectral data of all compounds 3a-o matched in all respects with reported data.