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

• Published in: Catalysts Vol. 12; no. 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: Journal Article
• Language: English
• Published: Basel MDPI AG 01.12.2022
• Subjects: Acrylonitriles; Benzimidazoles; Carbonyl compounds; Carbonyls; Catalysis; Catalysts; Chemical properties; Chemical reactions; Continuous flow; Efficiency; Enzymes; Esters; Hypertension; Lipase; Microfluidics; Microreactors; Nitrogen; Pharmaceutical research; Pharmaceuticals; R&D; Reaction time; Research & development; Solvents; Substitutes; Substitution reactions; Substrates; Sustainable development; Synthesis; China
• ISSN: 2073-4344; 2073-4344
• DOI: 10.3390/catal12121658

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.