Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition
Abstract
:1. Introduction
2. Results
2.1. Effect of Reaction Solvent
2.2. Effect of Substrate Ratio
2.3. Effect of Reaction Temperature
2.4. Effect of Residence Time
2.5. The Effect of Enzyme Reusability
2.6. The Scope and Limitation of the Synthesis of N-Substituted Benzimidazole Derivatives Catalyzed by Lipozyme TL IM in Continuous-Flow Microreactors
3. Materials and Methods
3.1. Materials
3.2. Experimental Setup and Experiment Conditions
3.3. Analytical Methods
3.3.1. Thin-Layer Chromatography (TLC)
3.3.2. Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS)
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Entry | Solvent | Catalysts | Log P | Yield b (%) |
---|---|---|---|---|
1 | Methanol | None | −0.76 | n.d. |
2 | Methanol | Lipozyme TL IM | −0.76 | 95.4 ± 1.6 |
3 | Tert-amyl alcohol | Lipozyme TL IM | 1.04 | 45.8 ± 1.5 |
4 | DMSO | Lipozyme TL IM | −1.3 | 68.2 ± 1.0 |
5 | Isopropanol | Lipozyme TL IM | 0.39 | 32.3 ± 0.5 |
6 | Acetonitrile | Lipozyme TL IM | −0.33 | 42.5 ± 0.8 |
7 | n-Hexane | Lipozyme TL IM | 3.94 | 66.4 ± 1.1 |
8 | DMF | Lipozyme TL IM | −1.0 | 43.2 ± 0.7 |
Entry | R1 | R2 | EWG | Product | Yield b (%) |
---|---|---|---|---|---|
1 | H | Cl | CN | 3a | 95.4 ± 1.6 |
2 | H | H | CN | 3b | 90.3 ± 0.8 |
3 | H | H | COOMe | 3c | 92.2 ± 1.5 |
4 | H | CH3 | COOMe | 3d | trace |
5 | H | H | SO2Ph | 3e | 97.1 ± 1.2 |
6 | Cl | Cl | CN | 3f | 80.5 ± 0.5 |
7 | Cl | H | CN | 3g | 76.8 ± 0.9 |
8 | Cl | H | COOMe | 3h | 77.4 ± 1.1 |
9 | Cl | CH3 | COOMe | 3i | trace |
10 | Cl | H | SO2Ph | 3j | 80.3 ± 0.7 |
11 | CH3 | Cl | CN | 3k | 95.6 ± 1.4 |
12 | CH3 | H | CN | 3l | 90.4 ± 1.1 |
13 | CH3 | H | COOMe | 3m | 93.2 ± 0.6 |
14 | CH3 | CH3 | COOMe | 3n | trace |
15 | CH3 | H | SO2Ph | 3o | 97.2 ± 0.8 |
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Jiang, R.-K.; Pan, Y.; Du, L.-H.; Zheng, L.-Y.; Sheng, Z.-K.; Zhang, S.-Y.; Lin, H.; Zhang, A.-Y.; Xie, H.-J.; Yang, Z.-K.; et al. Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition. Catalysts 2022, 12, 1658. https://doi.org/10.3390/catal12121658
Jiang R-K, Pan Y, Du L-H, Zheng L-Y, Sheng Z-K, Zhang S-Y, Lin H, Zhang A-Y, Xie H-J, Yang Z-K, et al. Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition. Catalysts. 2022; 12(12):1658. https://doi.org/10.3390/catal12121658
Chicago/Turabian StyleJiang, Rong-Kuan, 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, and et al. 2022. "Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition" Catalysts 12, no. 12: 1658. https://doi.org/10.3390/catal12121658