title: Combinatorial liquid-phase synthesis of structurally diverse benzimidazole libraries.
abstract: An expedient liquid-phase synthesis for construction of the diverse benzimidazole libraries is described. Nucleophilic aryl substitution of poly(ethylene glycol)-supported 4-fluoro-3-nitrobenzoic acid 3 with several primary amines under basic conditions, followed by Zn/NH(4)Cl mediated nitro group reduction, gave the PEG bound diamines 5. Subsequent cyclization of immobilized o-phenylenediamine 5 using thiocarbonyldiimidazole (TCD) or thiophosgene in dichloromethane furnished benzimidazole-2-thiones 6. Treatment of 6 with alkyl halides and benzylic halides in the presence of triethylamine provided 1-substituted-2-alkylthio-5-carbamoylbenzimidazoles on the support. The desired products 8 were severed from the PEG under mild conditions in high yield and high purity.
authors.affiliation: Department of Chemistry, National Dong Hwa University, Shou-Feng, Hualien 974, Taiwan.
authors.forename: C M
authors.initials: CM
authors.lastname: Yeh
authors.forename: C L
authors.initials: CL
authors.lastname: Tung
authors.forename: C M
authors.initials: CM
authors.lastname: Sun
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D007202:Indicators and Reagents