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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MDPI AG
2022-12-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/12/12/1658 |
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| author | Rong-Kuan Jiang Yue Pan Li-Hua Du Ling-Yan Zheng Zhi-Kai Sheng Shi-Yi Zhang Hang Lin Ao-Ying Zhang Han-Jia Xie Zhi-Kai Yang Xi-Ping Luo |
| author_facet | Rong-Kuan Jiang Yue Pan Li-Hua Du Ling-Yan Zheng Zhi-Kai Sheng Shi-Yi Zhang Hang Lin Ao-Ying Zhang Han-Jia Xie Zhi-Kai Yang Xi-Ping Luo |
| author_sort | Rong-Kuan Jiang |
| collection | DOAJ |
| description | 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 <i>Thermomyces lanuginosus</i> 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. |
| first_indexed | 2024-03-09T17:13:02Z |
| format | Article |
| id | doaj.art-1ba5fcf10c93444cab0a0ce5d6407f7e |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-09T17:13:02Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-1ba5fcf10c93444cab0a0ce5d6407f7e2023-11-24T13:52:49ZengMDPI AGCatalysts2073-43442022-12-011212165810.3390/catal12121658Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael AdditionRong-Kuan Jiang0Yue Pan1Li-Hua Du2Ling-Yan Zheng3Zhi-Kai Sheng4Shi-Yi Zhang5Hang Lin6Ao-Ying Zhang7Han-Jia Xie8Zhi-Kai Yang9Xi-Ping Luo10College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaCollege of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, ChinaZhejiang Provincial Key Laboratory of Chemical Utilization of Forestry Biomass, Zhejiang A&F University, Hangzhou 311300, ChinaBenzimidazole 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 <i>Thermomyces lanuginosus</i> 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.https://www.mdpi.com/2073-4344/12/12/1658enzymatic synthesisbenzimidazole derivativescontinuous-flow reaction technologycontinuous-flow microreactoraza-Michael addition |
| spellingShingle | Rong-Kuan Jiang Yue Pan Li-Hua Du Ling-Yan Zheng Zhi-Kai Sheng Shi-Yi Zhang Hang Lin Ao-Ying Zhang Han-Jia Xie Zhi-Kai Yang Xi-Ping Luo Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition Catalysts enzymatic synthesis benzimidazole derivatives continuous-flow reaction technology continuous-flow microreactor aza-Michael addition |
| title | Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition |
| title_full | Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition |
| title_fullStr | Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition |
| title_full_unstemmed | Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition |
| title_short | Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition |
| title_sort | microfluidics biocatalysis system applied for the synthesis of n substituted benzimidazole derivatives by aza michael addition |
| topic | enzymatic synthesis benzimidazole derivatives continuous-flow reaction technology continuous-flow microreactor aza-Michael addition |
| url | https://www.mdpi.com/2073-4344/12/12/1658 |
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