Annelation of Benzimidazoles with α,β-Acetylenic γ-Hydroxyacid Nitriles and Hydrolytic Rearrangement of the Cycloadducts on Alumina

• Published in: European Journal of Organic Chemistry 2007-02, Vol.2007 (6), p.1018-1025
• Main Authors: Trofimov, Boris A., Andriyankova, Ludmila V., Mal'kina, Anastasiya G., Belyaeva, Kseniya V., Nikitina, Lina P., Dyachenko, Oleg A., Kazheva, Olga N., Chekhlov, Anatolii N., Shilov, Gennadii V., Afonin, Andrei V., Ushakov, Igor' A., Baikalova, Ludmila V.
• Format: Article
• Language: English
• Subjects: Annelation; Benzimidazoles; Formamides; Nitriles; Rearrangement
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200600776

1‐Substituted benzimidazoles are readily annelated regio‐ and stereoselectively with α,β‐acetylenic γ‐hydroxyacidnitriles under mild conditions (20–25 °C, no catalyst, no solvent) to form new polyfunctional condensed systems, 4‐cyanomethylene‐1,3‐oxazolobenzimidazoles (30–88 % yield). Unexpectedly, the latter, when chromatographed on neutral Al2O3 at room temperature, undergo a complex multi‐position hydrolytic rearrangement involving the cleavage of the imidazole ring to aminophenyl N‐substituted formamides with an aminodihydrofuran moiety in the aminophenylsubstituent, N‐(2‐{[5‐amino‐2,2‐dialkyl‐3(2H)‐furanylidene]amino}phenyl)‐N‐substituted formamides, a novel class of highly functionalized pharmacophoric compounds. The results contribute to the basic benzimidazole chemistry and provide for prospective families of drug candidates.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)