Combinatorial liquid-phase synthesis of structurally diverse benzimidazole libraries.
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.
Yeh
C M
CM
Department of Chemistry, National Dong Hwa University, Shou-Feng, Hualien 974, Taiwan.
Tung
C L
CL
Sun
C M
CM
D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D007202:Indicators and Reagents