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Synlett 2012(4): 589-594  
DOI: 10.1055/s-0031-1290340
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Simple and Efficient Copper-Catalyzed Synthesis of N-Alkynylimidazoles

Man-Gang Wang, Jun Wu*, Zhi-Cai Shang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87951895; e-Mail: shangzc@zju.edu.cn;
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Publication History

Received 6 November 2011
Publication Date:
08 February 2012 (online)

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Abstract

A simple and efficient method for the synthesis of N-alkynylheteroarenes from 1,1-dibromo-1-alkenes was developed via a copper-catalyzed cross-coupling reaction. Generally superior yields and functional-group tolerance were obtained with TMEDA as ligand using imidazole and benzimidazole substrates in dioxane.

Key words

N-alkynylimidazoles - 1,1-dibromo-1-alkenes - copper - cross-coupling reaction - alkynylation

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Typical Procedure for the Synthesis of N -Alkynyl-imidazole A vessel with a magnetic stir bar was charged with imidazole (1a, 68 mg, 1 mmol), CuI (10 mg, 0.05 mmol), Cs2CO3 (1.3 g, 4 mmol), and TMEDA (12 mg, 0.1 mmol) under a nitrogen atmosphere. The reaction vessel was evacuated and backfilled with nitrogen three times. In a separate flask, a solution of dry dioxane (2 mL) containing the (2,2-dibromo-vinyl)benzene (2a, 1.5 mmol) was evacuated and back-filled with nitrogen gas three times. The dioxane solution was then added to the reaction flask with a syringe, and the reaction mixture was heated to 80 ˚C for 24 h. The reaction mixture was cooled to r.t., quenched with a sat. NH4Cl solution (5 mL), and extracted with EtOAc (3 × 20 mL). The combined organic phases were dried over anhyd Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography with EtOAc and PE (1:4) as eluent to afford the 1-(phenylethynyl)-1H-imidazole (3a) as a yellow oil; yield 82%. ¹H NMR (500 MHz, CDCl3): δ = 7.82 (s, 1 H), 7.61-7.45 (m, 2 H), 7.42-7.32 (m, 3 H), 7.20 (d, J = 1.1 Hz, 1 H), 7.09 (s, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 140.2, 131.9, 129.4, 129.2, 128.7, 121.9, 78.2, 70.6. ESI-MS: m/z = 169.1 [M + H]+.