An efficient one-pot two catalyst system in the construction of 2-substituted benzimidazoles: synthesis of benzimidazo[1,2-c] quinazolines

• Published in: Organic & biomolecular chemistry Vol. 13; no. 48; pp. 11687 - 11695
• Main Authors: Cimarelli, Cristina, Di Nicola, Matteo, Diomedi, Simone, Giovannini, Riccardo, Hamprecht, Dieter, Properzi, Roberta, Sorana, Federico, Marcantoni, Enrico
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2015
• Subjects: Aniline Compounds - chemistry; Benzimidazoles - chemistry; Catalysis; Chemistry; Chemistry Techniques, Analytical - methods; Chemistry, Organic; Molecular Structure; Physical Sciences; Quinazolines - chemical synthesis; Quinazolines - chemistry; Schiff Bases - chemistry; Science & Technology; OXIDATION; ACIDS; ARYLATION; BIOLOGICAL EVALUATION; PRIMARY AMINES; COPPER; 2-ARYLBENZIMIDAZOLES; INDUCTION; 1,2-DISUBSTITUTED BENZIMIDAZOLES; DERIVATIVES
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01777g

The benzimidazole core is a common moiety in a large number of natural products and pharmacologically active small molecules. The synthesis of novel benzimidazole derivatives remains a main focus in medicinal research. In continuation of the efforts towards Ce(III) catalysts for organic transformations, we observed for the first time the activity of the iodide ion and copper cation in activating CeCl3 center dot 7H(2)O in the selective formation of prototypical 2-substituted benzimidazoles. The one-pot CeCl3 center dot 7H(2)O-CuI catalytic system procedure includes the cyclo-dehydrogenation of aniline Schiff's bases, generated in situ from the condensation of 1,2-phenylenediamine and aldehydes, followed by the oxidation with iodine, which works as a hydrogen sponge. Mild reaction conditions, good to excellent yields, and clean reactions make the procedure a useful contribution to the synthesis of biologically active fused heterocycles containing benzimidazoquinazolines.