Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition

Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters,...

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Bibliographic Details
Published in:Catalysts 2022-12, Vol.12 (12), p.1658
Main Authors: Jiang, Rong-Kuan, Pan, Yue, Du, Li-Hua, Zheng, Ling-Yan, Sheng, Zhi-Kai, Zhang, Shi-Yi, Lin, Hang, Zhang, Ao-Ying, Xie, Han-Jia, Yang, Zhi-Kai, Luo, Xi-Ping
Format: Article
Language:English
Subjects:
Acrylonitriles
aza-Michael addition
benzimidazole derivatives
Benzimidazoles
Carbonyl compounds
Carbonyls
Catalysis
Catalysts
Chemical properties
Chemical reactions
Continuous flow
continuous-flow microreactor
continuous-flow reaction technology
Efficiency
enzymatic synthesis
Enzymes
Esters
Hypertension
Lipase
Microfluidics
Microreactors
Nitrogen
Pharmaceutical research
Pharmaceuticals
R&D
Reaction time
Research & development
Solvents
Substitutes
Substitution reactions
Substrates
Sustainable development
Synthesis
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Summary:Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters, phenyl vinyl sulfone) catalyzed by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Investigations were conducted on reaction parameters such as solvent, substrate ratio, reaction temperature, reactant donor/acceptor structures, and reaction time. The transformation is promoted by inexpensive and readily available lipase in methanol at 45 °C for 35 min. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds were efficiently and selectively synthesized in high yields (76–97%). All in all, a microfluidic biocatalysis system was applied to the synthesis of N-substituted benzimidazole derivatives, and could serve as a promising fast synthesis strategy for further research to develop novel and highly potent active drugs.
ISSN:2073-4344
2073-4344
DOI:10.3390/catal12121658