Stereospecific Synthesis of (Z)-1,3-Oxazolobenzimidazoles from Imidazole- and Benzene-Ring-Substituted Benzimidazoles and α,β-Acetylenic γ-Hydroxynitriles

• Published in: Synthesis (Stuttgart) 2010-08, Vol.2010 (16), p.2828-2840
• Main Authors: Andriyankova, Ludmila V., Belyaeva, Kseniya V., Nikitina, Lina P., Mal’kina, Anastasiya G., Afonin, Andrei V., Trofimov, Boris A.
• Format: Article
• Language: English
• ISSN: 0039-7881; 1437-210X
• DOI: 10.1055/s-0030-1258152

Abstract A stereospecific, facile synthesis of (Z)-1,3-oxazolobenz­imidazoles from imidazole- and benzene-ring-substituted benzimidazoles and α,β-acetylenic γ-hydroxynitriles has been elaborated. The reaction proceeds smoothly in acetonitrile without catalyst (room temperature, 3-5 days or 35-40 ˚C, 20-72 h) to afford the target compounds in 33-90% yields. The annulation involves an intermediate vinyl carbanion with zwitterionic character, which, after transformation into an O-centered zwitterion, is further inserted into the aromatic system of the imidazole ring. The synthesis contributes to the basic benzimidazole and acetylene chemistry and drug design.