Abstract
An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO3 in water had been developed. The amount of NaHSO3 had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO3 was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO3 was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.
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This work was supported financially by Innovative Talents Program of Henan Province (Nos. 164100510015, 174100510025 and 18A150030), Foundation of Henan Educational Committee (Nos. 15A150054 and 16A350015), Scientific Research Foundation for Doctors (No. qd16106) and Youth Foundation (No. 2016QK09) of Henan Normal University.
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Jiang, Yq., Jia, Sh., Li, Xy. et al. An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water. Chem. Pap. 72, 1265–1276 (2018). https://doi.org/10.1007/s11696-017-0367-5
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DOI: https://doi.org/10.1007/s11696-017-0367-5