多类型催化体系作用的苯并咪唑合成研究进展
Advances in Benzimidazole Synthesis via Multifarious Catalytic Systems
DOI: 10.12677/hjcet.2026.164027, PDF,    国家自然科学基金支持
作者: 刘文迪, 高道伟, 赵勇昌, 徐明慧, 徐英杰, 王 彬*, 郑庚修*:济南大学化学化工学院,山东 济南
关键词: 苯并咪唑催化合成非均相催化绿色合成Benzimidazole Catalytic Synthesis Heterogeneous Catalysis Green Synthesis
摘要: 苯并咪唑是一类重要含氮杂环化合物,在医药、材料等领域应用广泛,其高效绿色合成是有机催化的研究热点。文章系统综述均相催化、非均相金属与纳米催化、多孔骨架催化、无金属催化、光催化及电化学合成、流动化学与连续流催化合成七大体系,重点梳理不同催化策略的反应机理、工艺条件与底物适用性。研究表明,各催化体系通过活性位点设计、载体修饰、外场辅助等手段,可实现温和条件下苯并咪唑的高收率、高选择性合成,部分体系副产物仅为氢气与水,符合绿色化学要求,非均相与光/电催化体系还具备催化剂易回收、循环稳定性好等优势。综上,多类型催化体系为苯并咪唑的高效、绿色、可控制备提供了丰富路径,未来可进一步聚焦催化机制解析、低成本催化剂开发与工业化放大研究,推动苯并咪唑类化合物的合成与应用发展。
Abstract: Benzimidazoles are an important class of nitrogen-containing heterocyclic compounds with broad applications in pharmaceuticals, materials, and other fields. Efficient and green synthesis of benzimidazoles has become a research hotspot in organic catalysis. This review systematically summarizes seven major catalytic systems, including homogeneous catalysis, heterogeneous metal and nanocatalysis, porous framework catalysis, metal-free catalysis, photocatalysis and electrochemical synthesis, as well as flow chemistry and continuous-flow catalysis. The reaction mechanisms, process conditions, and substrate applicability of these catalytic strategies are comprehensively discussed. Studies show that through active site design, support modification, and external field assistance, these systems can achieve high-yield and highly selective synthesis of benzimidazoles under mild conditions. Some systems generate only hydrogen and water as byproducts, meeting green chemistry principles, while heterogeneous, photocatalytic, and electrocatalytic systems also offer advantages such as facile catalyst recovery and excellent recyclability. In conclusion, diverse catalytic strategies provide versatile routes for the efficient, green, and controllable preparation of benzimidazoles. Future research may focus on mechanistic elucidation, development of low-cost catalysts, and industrial-scale implementation to further advance the synthesis and application of benzimidazole derivatives.
文章引用:刘文迪, 高道伟, 赵勇昌, 徐明慧, 徐英杰, 王彬, 郑庚修. 多类型催化体系作用的苯并咪唑合成研究进展[J]. 化学工程与技术, 2026, 16(4): 283-295. https://doi.org/10.12677/hjcet.2026.164027

参考文献

[1] Uthumange, S.S., Zaki, M.A.F.b.A. and Yeong, K.Y. (2025) Synthesis and Anticancer Potential of New Benzimidazole Theranostic. ChemistryOpen, 14, e202500263. [Google Scholar] [CrossRef] [PubMed]
[2] Shinde, R.B., Pansare, D.N., Shelke, R.N., Sarkate, A.P., Tiwari, S.V., Bangal, M.N., et al. (2023) A Facile Synthesis and Characterization of Some Novel Benzimidazole Derivatives. Results in Chemistry, 6, Article ID: 101134. [Google Scholar] [CrossRef
[3] Kafash, S. and Abdolmaleki, A. (2026) Metal-Free Synthesis of Benzimidazoles via Pyridinium-Catalyzed Silane Activation under Atmospheric CO2. Results in Chemistry, 24, Article ID: 103182. [Google Scholar] [CrossRef
[4] Nardi, M., Bonacci, S., Herrera Cano, N., Oliverio, M. and Procopio, A. (2022) The Highly Efficient Synthesis of 1,2-Disubstituted Benzimidazoles Using Microwave Irradiation. Molecules, 27, Article No. 1751. [Google Scholar] [CrossRef] [PubMed]
[5] Yao, X.R., Rao, C.H., Jia, M.Z., Miao, X.L. and Zhang, J. (2023) Metal-Free Photocatalyst with Redox Center and Lewis Acid Site for Selective Synthesis of Mono-and Disubstituted Benzimidazoles via Alcohol and Aromatic Diamine Cross-Dehydrocoupling. ACS Sustainable Chemistry & Engineering, 11, 14056-14067. [Google Scholar] [CrossRef
[6] Li, J.S., Yang, P.P., Xie, X.Y., Jiang, S., Tao, L., Li, Z., et al. (2020) Catalyst‐Free Electrosynthesis of Benzimidazolones through Intramolecular Oxidative C-N Coupling. Advanced Synthesis & Catalysis, 362, 1977-1981. [Google Scholar] [CrossRef
[7] Ma, D., Ji, X., Wu, Z., Cheng, C., Zhou, B. and Zhang, Y. (2019) Synthesis of Benzimidazoles through Palladium‐Catalyzed Amination of 2‐Iodobenzimines with Diaziridinone. Advanced Synthesis & Catalysis, 361, 739-746. [Google Scholar] [CrossRef
[8] Xu, F., Zhang, S., Huo, J., Zeng, F., Zhou, F. and Barboni, L. (2026) Rh(III)-Catalyzed Cascade C-H Activation/Amination Enables the Synthesis of 1,2-Disubstituted Benzimidazoles from Amidines and Arynes. Organic & Biomolecular Chemistry, 24, 3218-3222. [Google Scholar] [CrossRef
[9] Anandaraj, P., Ramesh, R. and Malecki, J.G. (2023) Direct Synthesis of Benzimidazoles by Pd(II) N^N^S-Pincer Type Complexes via Acceptorless Dehydrogenative Coupling of Alcohols with Diamines. Journal of Organometallic Chemistry, 985, Article ID: 122577. [Google Scholar] [CrossRef
[10] Zhong, R.Y., Xiong, W.L., Zhang, H.Y., Zeng, T.T., Gong, S.S. and Sun, Q. (2022) Highly Efficient and Ambient-Temperature Synthesis of Benzimidazoles via Co(III)/Co(II)-Mediated Redox Catalysis. Catalysts, 12, Article No. 59. [Google Scholar] [CrossRef
[11] Mohaghegh, F. and Jafarpour, F. (2025) Copper-Catalyzed Synthesis of Polysubstituted Benzimidazoles: An Efficient One-Pot Synthetic Approach to n-Enylated Benzimidazoles. Organic & Biomolecular Chemistry, 23, 7742-7745. [Google Scholar] [CrossRef] [PubMed]
[12] Rodrigues, F.S., de Almeida, H.B., Bortoluzzi, A.J., Cuin, A., de Almeida, E.T., de Góis, E.P., et al. (2022) Unexpected Synthesis of Benzimidazole from Schiff Base Mediated by Lanthanide Chloride and Citotoxic Activities. Journal of Molecular Structure, 1252, Article ID: 132140. [Google Scholar] [CrossRef
[13] Vinayagam, V., Karre, S.K., Kasu, S.R., Srinath, R., Bathula, H.S.N.B. and Sadhukhan, S.K. (2022) AlCl3-Mediated CHF2 Transfer and Cyclocondensation of Difluoromethoxy Functionalized o-Phenylenediamines to Access N-Substituted Benzimidazoles. Organic Letters, 24, 6142-6147. [Google Scholar] [CrossRef] [PubMed]
[14] Sun, J., Li, S., Meng, M., Xue, Q., Chen, X., Qin, Q., et al. (2023) Divergent Synthesis of 1,5-Benzodiazepines and Benzimidazoles via a BiCl3-Catalyzed One-Pot Condensation-Cyclization Process. Chemistry of Heterocyclic Compounds, 59, 564-573. [Google Scholar] [CrossRef
[15] Tu, X.W., Chen, Y.T., Sun, C., Hu, Y., Zhu, S.X., Qu, J.Y., et al. (2024) A Novel CO2 Fixation Catalyst FCO@NWs to Synthesize Benzimidazole at Atmospheric Pressure. Journal of Environmental Chemical Engineering, 12, Article ID: 112097. [Google Scholar] [CrossRef
[16] Srinivasappa, P.M., Singh, C., Alla, S.C., Gholap, S.S., Samal, A.K., Chaudhari, N.K., et al. (2024) Hollow CeO2 Nanospheres as Catalyst for the Conversion of Aromatic Diamines to Benzimidazoles. ACS Applied Nano Materials, 7, 2956-2970. [Google Scholar] [CrossRef
[17] Prasad, D., Srinivasappa, P.M., Raju, N.A., Samal, A.K. and Jadhav, A.H. (2023) Stable Engineered Trimetallic Oxide Scaffold as a Catalyst for Enhanced Solvent-Free Conversion of CO2 into Value-Added Products. Energy & Fuels, 37, 1187-1206. [Google Scholar] [CrossRef
[18] Rasal, K.B. and Yadav, G.D. (2018) One-Pot Synthesis of Benzimidazole Using DMF as a Multitasking Reagent in Presence CuFe2O4 as Catalyst. Catalysis Today, 309, 51-60. [Google Scholar] [CrossRef
[19] Borade, R.M., Kale, S.B., Tekale, S.U., Jadhav, K.M. and Pawar, R.P. (2021) Cobalt Ferrite Magnetic Nanoparticles as Highly Efficient Catalyst for the Mechanochemical Synthesis of 2-Aryl Benzimidazoles. Catalysis Communications, 159, Article ID: 106349. [Google Scholar] [CrossRef
[20] Kadam, U.D., Pandav, R.S., Arde, S.M., Hossain, M.S., Dinesh, A., Radhakrishnan, K., et al. (2025) Green Synthesis of Benzimidazole Scaffolds Using Copper-Substituted Zinc Aluminate in a Sol-Gel Process. Journal of the Indian Chemical Society, 102, Article ID: 101494. [Google Scholar] [CrossRef
[21] Zhang, L., Tu, X.W., Han, W.H., Chen, L.C., Chen, Y.T. and Zheng, H. (2023) The Efficient CO2 Fixation Catalyzed by Fe-Based Catalyst for Synthesizing Benzimidazoles. Catalysis Letters, 153, 3383-3391. [Google Scholar] [CrossRef
[22] Sun, X.H., Chen, Y.J., Ji, M.M., Zhang, W.Y., Sun, Z.Z., Chu, W.Y. and Wang, X. (2023) Design and Synthesis of Ni3ZnC0.7 Catalyst Derived from a Bimetallic Ni/Zn Metal-Organic Frameworks for Efficient Synthesis of 2-Arylbenzimidazole. Applied Surface Science, 628, Article ID: 157353. [Google Scholar] [CrossRef
[23] del Río‐Rodríguez, J.L., Gutiérrez‐Tarriño, S., Chinchilla, L.E., Holgado, J.P., Villar‐García, I.J., Pérez‐Dieste, V., et al. (2024) Multifunctional Heterogeneous Cobalt Catalyst for the One‐Pot Synthesis of Benzimidazoles by Reductive Coupling of Dinitroarenes with Aldehydes in Water. ChemSusChem, 18, e202402141. [Google Scholar] [CrossRef] [PubMed]
[24] del Río-Rodríguez, J.L., Gutiérrez-Tarriño, S., Molina, M.A., Costley-Wood, L., Falcini, C., Beale, A.M., et al. (2025) Green One-Pot Synthesis of Benzimidazoles from Dinitroarenes in Water Using a Ru-Doped Co-Based Heterogeneous Catalyst. ACS Sustainable Chemistry & Engineering, 13, 15533-15546. [Google Scholar] [CrossRef
[25] Chen, J.Y., Li, K.M., Sun, Y.X., Xiao, Y., Guo, F.S., Huang, Y.B. and Lu, Q. (2024) An Atomically Dispersed Co Catalyst for Efficient Oxidative Fabrication of Benzoheterocycles under Ambient Oxygen Conditions. Green Chemistry, 26, 4834-4843. [Google Scholar] [CrossRef
[26] Wang, B.Y., Li, M.R., Zhang, S.D., Wu, H.G., Liao, Y.H. and Li, H. (2023) Synergistic Effect between Co Single Atoms and Nanoparticles Enables Selective Synthesis of Bio-Based Benzimidazoles. Applied Catalysis B: Environmental, 327, Article ID: 122454. [Google Scholar] [CrossRef
[27] Ma, Z., Zhang, B.Y., He, Z., Xu, T., Cheng, Y.H., Cui, Y.B. and Chen, Z.P. (2025) Atomically Dispersed Fe-n-c-Catalyzed Intermolecular Reductive Coupling toward the Synthesis of Benzimidazoles. ACS Catalysis, 15, 11875-11885. [Google Scholar] [CrossRef
[28] Dani, S.H., Gouda, A., Verma, A. and Pratap, U.R. (2023) Zinc‐Embedded Porous Organic Framework Catalyzed Synthesis of 2‐Phenyl Benzimidazoles. ChemistrySelect, 8, e202302193. [Google Scholar] [CrossRef
[29] Ye, Z.C. and Chen, J.Z. (2021) Sulfonate-Grafted Metal-Organic Frameworks for Reductive Functionalization of CO2 to Benzimidazoles and n-Formamides. ACS Catalysis, 11, 13983-13999. [Google Scholar] [CrossRef
[30] Wei, S.Y., Yu, B.L., Wang, Y., Wang, H., Li, M., Li, J.W. and Huang, J.H. (2025) In Situ Engineering of Zwitterionic Betaine‐Based Covalent Organic Frameworks Boost Cooperative CO2 Catalytic Conversion. Small, 21, e202505352. [Google Scholar] [CrossRef
[31] Chaudhary, G., Verma, A., Manna, B., Shrivastav, A., Prabhakar, A. and Verma, D. (2025) Potassium Periodate Catalysis for Benzimidazoles Synthesis: Analysis of Microwave Irradiation versus Conventional Methods. ChemistrySelect, 10, e202501206. [Google Scholar] [CrossRef
[32] Bai, J.Y., Wu, T.B., Dong, B., Ma, J.W., Liang, Y. and Shi, Z.Z. (2025) A Streamlined Approach to Indoles, Pyrroles, and Benzimidazoles via Redox‐Neutral Aromatization and CO Reduction Mediated by Cs2CO3. Angewandte Chemie International Edition, 64, e202511725. [Google Scholar] [CrossRef] [PubMed]
[33] Luo, Z.B., Huang, M.L., Wang, X.Y., Wang, X.Y., Hu, Z.H., Zhao, L. and Huang, T. (2025) Synthesis of Benzimidazoles from o-Phenylenediamines with Α-Keto Acids via Amino Acid Catalysis. RSC Advances, 15, 36803-36807. [Google Scholar] [CrossRef
[34] Liu, L.S., Xie, Z.B., Zhang, C., Fu, L.H., Zhu, H.B. and Le, Z.G. (2018) α-Chymotrypsin-Catalyzed Synthesis of 2-Substituted Benzimidazole through Retro-Claisen Reaction. Green Chemistry Letters and Reviews, 11, 503-507. [Google Scholar] [CrossRef
[35] Maphupha, M., Juma, W.P., de Koning, C.B. and Brady, D. (2018) A Modern and Practical Laccase-Catalysed Route Suitable for the Synthesis of 2-Arylbenzimidazoles and 2-Arylbenzothiazoles. RSC Advances, 8, 39496-39510. [Google Scholar] [CrossRef] [PubMed]
[36] Shrivas, P., Zodape, S., Wankhade, A. and Pratap, U. (2020) Facile Synthesis of Benzazoles through Biocatalytic Cyclization and Dehydrogenation Employing Catalase in Water. Enzyme and Microbial Technology, 138, Article ID: 109562. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, Y.F., Qi, M.Y., Conte, M., Tang, Z.R. and Xu, Y.J. (2023) New Radical Route and Insight for the Highly Efficient Synthesis of Benzimidazoles Integrated with Hydrogen Evolution. Angewandte Chemie International Edition, 62, e202304306. [Google Scholar] [CrossRef] [PubMed]
[38] Xie, Y.Y., Tan, C.L., Mao, L., Tang, Z.R. and Xu, Y.J. (2026) Highly Efficient Hydroxyethyl Radicals-Mediated Photocatalytic Benzimidazole Synthesis and Hydrogen Evolution over Defect-Engineered Pt/Nb2O5. Chinese Journal of Catalysis, 83, 132-142. [Google Scholar] [CrossRef
[39] Shiogai, Y., Oka, M., Miyake, H. and Iida, H. (2024) Aerobic Oxidative Synthesis of Benzimidazoles by Flavin Photocatalysis. Organic & Biomolecular Chemistry, 22, 4450-4454. [Google Scholar] [CrossRef] [PubMed]
[40] Liu, W., Zhang, H., Zhang, Z., Ji, Y., Xu, T., Li, X., et al. (2025) Two Birds with One Stone: S-Scheme Charge Transfer Enables Simultaneous Efficient Photocatalytic Complete Methanation of CO2 and Benzimidazole Synthesis. Chemical Engineering Journal, 521, Article ID: 166914. [Google Scholar] [CrossRef
[41] Zhao, H.B., Zhuang, J.L. and Xu, H.C. (2021) Electrochemical Synthesis of Benzimidazoles via Dehydrogenative Cyclization of Amidines. ChemSusChem, 14, 1692-1695. [Google Scholar] [CrossRef] [PubMed]
[42] Shi, T.T., Wang, S.Z., Yang, Z., Wang, Y., Liu, C.K., He, W., Fang, Z. and Guo, K. (2021) Enzymatic Electrochemical Continuous Flow Cascade Synthesis of Substituted Benzimidazoles. Reaction Chemistry & Engineering, 6, 937-943. [Google Scholar] [CrossRef
[43] Thadathil, D.A., Bharath, M., Varghese, A. and Ghosh, M. (2022) Anchored Ferrocene Based Heterogeneous Electrocatalyst for the Synthesis of Benzimidazoles. Electrochimica Acta, 435, Article ID: 141399. [Google Scholar] [CrossRef
[44] Jayan, K. and Varghese, A. (2026) Redox-Active Tetra-Amino Cobalt Phthalocyanine Electrocatalyst for Sustainable Electrochemical Synthesis of 2-(Pyridin-4-yl)-1h-benzo[d]imidazole. Molecular Catalysis, 597, Article ID: 115932. [Google Scholar] [CrossRef
[45] Zou, J., Xu, J., Li, L., Yang, Z. and Zhou, C. (2025) Electrochemical Oxidation of Primary Amines for the Synthesis of Benzimidazole, Benzothiazole, Quinazolinone, and Quinoxaline. The Journal of Organic Chemistry, 90, 7793-7800. [Google Scholar] [CrossRef] [PubMed]
[46] Feng, F., Ye, J., Cheng, Z., Xu, X., Zhang, Q., Ma, L., et al. (2016) Cu-Pd/γ-Al2O3 Catalyzed the Coupling of Multi-Step Reactions: Direct Synthesis of Benzimidazole Derivatives. RSC Advances, 6, 72750-72755. [Google Scholar] [CrossRef
[47] Hood, S., O’Connor, C. and Browne, D.L. (2020) Telescoped Continuous Flow Synthesis of Benzimidazoles from o-Phenylenediamines and Carboxylic Acids. Organic & Biomolecular Chemistry, 18, 8945-8952.
[48] Kutsyk, N., Nenajdenko, V. and Akhrem, I. (2024) Phototransposition of Indazoles to Benzimidazoles: Tautomer-Dependent Reactivity, Wavelength Dependence, and Continuous Flow Studies. Advanced Synthesis & Catalysis, 366, 1123-1131.