An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water

作者：Jiang, Yu-qin^*; Jia, Shu-hong; Li, Xi-yong; Sun, Ya-min; Li, Wei; Zhang, Wei-wei; Xu, Gui-qing

来源：CHEMICAL PAPERS, 2018, 72(5): 1265-1276.

DOI：10.1007/s11696-017-0367-5

• NaHSO3
• Chemoselective synthesis
• 2-Substituted benzimidazoles
• In water
• 1,2,3-Triazole

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.

• 出版日期2018-5
• 单位河南师范大学