Microwave-Assisted Benzimidazole Cyclization by Bismuth Chloride

Abstract

We have developed a multi-step, microwave-assisted method for the bismuth chloride catalyzed synthesis of 1,2-disubstituted benzimidazoles. Biologically interesting benzimidazoles were readily assembled using a S_NAr reaction, reduction, and finally a bismuth(III)-mediated cyclization under microwave irradiation. The desired products were then liberated from the soluble matrix in excellent yield and purity after cleavage. Each step of the synthetic sequence was performed under microwave conditions.

Key words

bismuth chloride - combinatorial chemistry - liquid-phase method - microwave assisted synthesis - scaffold

References

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10

The control reaction was also performed under normal thermal heating in refluxing chloroform (pre-heated oil bath) for four minutes, using identical stoichiometry. However, after cleavage we obtained only the unreacted compound 4. The same reaction reached completion in two hours by conventional heating. Similar enhancement through microwave irradiation was also observed during the cleavage step. Compared to conventional thermal hearting, microwave irradiation decreased the reaction time on the support from several hours to several minutes.

11

All the microwave assisted polymer-supported reactions described here were performed in a CEM Discover Microwave System at a frequency of 2450 Hz (0-300 W).