Combinatorial synthesis of biheterocyclic benzimidazoles by microwave irradiation.
Liquid phasel synthesis of biheterocyclic benzimidazoles by controlled microwave irradiation was investigated. Polymer immobilized o-phenylenediamines was synthesized under microwave irradiation. The resulting PEG bound diamines was N-acylated with 4-fluoro-3-nitrobenzoic acid selectively in primary aromatic amino moiety. Nucleophilic aromatic substitution of amide was performed with various amines then cyclized to form the first benzimidazole scaffold in acidic condition. Successive reduction, cyclization with isothiocyanates yielded 5-(benzimidazol-2-yl)benzimidazoles. The desired products were released from the polymer support to afford the tri-substituted bis-benzimidazoles in good yields and purity.
Yeh
Wen-Bing
WB
Laboratory of Combinatorial Drug Design, National Tong Hwa University, Shou-Feng, Hualien 974, Taiwan.
Lin
Mei-Jung
MJ
Sun
Chung-Ming
CM
D000215:Acylation; D000577:Amides / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D003959:Diamines / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D017879:Isothiocyanates / Q000737:chemistry; D008872:Microwaves; D015394:Molecular Structure; D009579:Nitrobenzoates / Q000737:chemistry; D010655:Phenylenediamines / Q000737:chemistry
D000577:Amides; D001562:Benzimidazoles; D003959:Diamines; D006571:Heterocyclic Compounds; D017879:Isothiocyanates; D009579:Nitrobenzoates; D010655:Phenylenediamines; C009712:bis-benzimidazole; C081549:4-fluoro-3-nitrobenzoic acid; C034193:1,2-diaminobenzene