ChemInform Abstract: Iodine Promoted Simple Synthesis of Benzimidazole Acyclonucleosides.

Abstract

In nature, 5,6-dimethyl-1-(α-D-ribofuranosyl)benzimidazole exists as a moiety of vitamin B12 (Ref 1). The furanosyl benzimidazole can be considered as Cnucleoside mimic. Due to its structural similarity to purine, benzimidazole is also an important chemical entity in pharmaceuticals 2 . In one approach, aldobenzimimdazoles are prepared by the condensation of aldonic acid or aldonic δ-lactones with o-phenylenediamine 3 . The condensation reactions are often conducted in strong acidic conditions at elevated temperature (e.g.135°C) 4 . The teritol-1-yl benzimidazoles can be further converted to furanosyl benzimidazoles by Lewis acid promoted dehydrative cyclization 5 . In another approach, aldoses are subjected to oxidative condensation with o-phenylenediamine to give aldobenzimidazoles in a direct manner 6 . This approach mitigates the laborious work in the prior preparation of aldonic acids from the corresponding aldoses 7 . For example, Moore and Link 4 have previously applied this approach to synthesize two monosaccharides benzimidazoles, D-gluco and Dgalactobenzimidazoles, in 24% and 50% yields from D-glucose and D-galactose, respectively, by heating with cupric acetate (2 equiv) at 53°C for 14 hr in aqueous acetic acid solution. Some saccharide bisSchiff bases and quinaxolines also form as side products under such reaction conditions 4-6 . However using catalytic amounts of CuSO4 or replacing the AcOH solvent with MeOH does not give any desired aldo-benzimidazoles 8 . Considering the acid-sesitive internal glycosidic bonds in disaccharides and higher saccharides, it is questionable that the corresponding aldo-benimidazoles can be obtained by the above mentioned reactions involving acidic conditions at high reaction temperature. In continuation of our study, the novel transformation of aldehyde and aldoses by use of amines and iodine 9-12 , we describe herein an improved protocol for the synthesis of various aldo-benzimidazoles by direct oxidative condensation of aldoses, including different mono-saccharides with substituted ophenylenediamine in the presence of iodine.