Synthesis of benzimidazole derivatives (2-aryl-1H-benzo[d]imidazoles) using ultrasonic energy, in the absence of solvents and catalysts
DOI:
https://doi.org/10.19136/jobs.a12n33.6678Keywords:
Ultrasound, Benzimidazoles, Green chemistry, SynthesisAbstract
This paper presents a new methodology for the synthesis of benzimidazole derivatives in the framework of green chemistry. The methodology is promoted by ultrasound, in the absence of solvents and catalysts and proceeds in a time of 2 hours. Under the optimized conditions, benzimidazoles were obtained with yields of 20-83%. This methodology promises to be efficient for obtaining benzimidazoles with great pharmacological potential, so the study of their possible synthetic scope is promising
References
[1] V. R. Mishra, C. W. Ghanavatkar, S. N. Mali, S. I. Qureshi, H. K. Chaudhari, y N. Sekar, “Design, synthesis, antimicrobial activity and computational studies of novel azo linked substituted benzimidazole, benzoxazole and benzothiazole derivatives”, Comput Biol Chem, vol. 78, pp. 330–337, feb. 2019, doi: 10.1016/j.compbiolchem.2019.01.003. DOI: https://doi.org/10.1016/j.compbiolchem.2019.01.003
[2] M. Abdel-Motaal, K. Almohawes, y M. A. Tantawy, “Antimicrobial evaluation and docking study of some new substituted benzimidazole-2yl derivatives”, Bioorg Chem, vol. 101, p. 103972, ago. 2020, doi: 10.1016/J.BIOORG.2020.103972. DOI: https://doi.org/10.1016/j.bioorg.2020.103972
[3] S. R. Brishty, M. J. Hossain, M. U. Khandaker, M. R. I. Faruque, H. Osman, y S. M. A. Rahman, “A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives”, Front Pharmacol, vol. 12, nov. 2021, doi: 10.3389/FPHAR.2021.762807. DOI: https://doi.org/10.3389/fphar.2021.762807
[4] H. R. M. Rashdan, A. H. Abdelmonsef, M. M. Abou-Krisha, y T. A. Yousef, “Synthesis, identification, computer-aided docking studies, and admet prediction of novel benzimidazo-1,2,3-triazole based molecules as potential antimicrobial agents”, Molecules, vol. 26, núm. 23, dic. 2021, doi: 10.3390/molecules26237119. DOI: https://doi.org/10.3390/molecules26237119
[5] S. Nashaat, M. A. Henen, S. M. El-Messery, y H. Eisa, “Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer”, Bioorg Med Chem, vol. 28, núm. 11, jun. 2020, doi: 10.1016/j.bmc.2020.115495. DOI: https://doi.org/10.1016/j.bmc.2020.115495
[6] F. M. Suk, C. L. Liu, M. H. Hsu, Y. T. Chuang, J. P. Wang, y Y. J. Liao, “Treatment with a new benzimidazole derivative bearing a pyrrolidine side chain overcomes sorafenib resistance in hepatocellular carcinoma”, Sci Rep, vol. 9, núm. 1, dic. 2019, doi: 10.1038/s41598-019-53863-2. DOI: https://doi.org/10.1038/s41598-019-53863-2
[7] Z. Wu et al., “Design, synthesis and biological evaluation of novel fluoro-substituted benzimidazole derivatives with anti-hypertension activities”, Bioorg Chem, vol. 101, ago. 2020, doi: 10.1016/j.bioorg.2020.104042. DOI: https://doi.org/10.1016/j.bioorg.2020.104042
[8] O. A. Ramos Rodríguez et al., “Synthesis, crystal structure, antioxidant activity and dft study of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-One”, J Mol Struct, vol. 1199, ene. 2020, doi: 10.1016/j.molstruc.2019.127036. DOI: https://doi.org/10.1016/j.molstruc.2019.127036
[9] R. Srivastava et al., “Alkylated benzimidazoles: Design, synthesis, docking, DFT analysis, ADMET property, molecular dynamics and activity against HIV and YFV”, Comput Biol Chem, vol. 89, dic. 2020, doi: 10.1016/j.compbiolchem.2020.107400. DOI: https://doi.org/10.1016/j.compbiolchem.2020.107400
[10] “Telmisartán: Usos, interacciones y mecanismo de acción | DrugBank Online”. Consultado: el 5 de julio de 2025. [En línea]. Disponible en: https://go.drugbank.com/drugs/DB00966
[11] “Droperidol: Usos, interacciones y mecanismo de acción | DrugBank Online”. Consultado: el 5 de julio de 2025. [En línea]. Disponible en: https://go.drugbank.com/drugs/DB00450
[12] “Albendazol: Usos, interacciones y mecanismo de acción | DrugBank Online”. Consultado: el 5 de julio de 2025. [En línea]. Disponible en: https://go.drugbank.com/drugs/DB00518
[13] “Omeprazol: Usos, interacciones y mecanismo de acción | DrugBank Online”. Consultado: el 5 de julio de 2025. [En línea]. Disponible en: https://go.drugbank.com/drugs/DB00338
[14] N. Sridhar Goud et al., “Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, 18F-radiolabeling & galectin-1 inhibition studies”, Bioorg Chem, vol. 102, sep. 2020, doi: 10.1016/j.bioorg.2020.104125. DOI: https://doi.org/10.1016/j.bioorg.2020.104125
[15] C. S. Radatz, R. B. Silva, G. Perin, E. J. Lenardão, R. G. Jacob, y D. Alves, “Catalyst-free synthesis of benzodiazepines and benzimidazoles using glycerol as recyclable solvent”, Tetrahedron Lett, vol. 52, núm. 32, pp. 4132–4136, ago. 2011, doi: 10.1016/j.tetlet.2011.05.142. DOI: https://doi.org/10.1016/j.tetlet.2011.05.142
[16] D. Raja, A. Philips, P. Palani, W. Y. Lin, S. Devikala, y G. C. Senadi, “Metal-Free Synthesis of Benzimidazoles via Oxidative Cyclization of d -Glucose with o-Phenylenediamines in Water”, Journal of Organic Chemistry, vol. 85, núm. 17, pp. 11531–11540, sep. 2020, doi: 10.1021/acs.joc.0c01053. DOI: https://doi.org/10.1021/acs.joc.0c01053
[17] Santosh Rangnath Deshmukh, Archana Subhash Nalkar, y Shankar Ramchandra Thopate, “Water-Mediated Green Synthesis of Benzimidazoles Using Pyruvic Acid: A Comparable Study of Ultra-sonication versus Conventional Heating”, Lett Org Chem, vol. 19, núm. 7, pp. 511–519, jun. 2022. DOI: https://doi.org/10.2174/1570178618666211105092142
[18] S. D. Pardeshi et al., “Sonicated assisted synthesis of benzimidazoles, benzoxazoles and benzothiazoles in aqueous media”, Journal of the Chilean Chemical Society, vol. 59, núm. 1, pp. 2335–2340, 2014, doi: 10.4067/S0717-97072014000100020. DOI: https://doi.org/10.4067/S0717-97072014000100020
[19] M. Bharathi, S. Indira, G. Vinoth, T. Mahalakshmi, E. Induja, y K. Shanmuga Bharathi, “Green synthesis of benzimidazole derivatives under ultrasound irradiation using Cu-Schiff base complexes embedded over MCM-41 as efficient and reusable catalysts”, J Coord Chem, vol. 73, núm. 4, pp. 653–670, feb. 2020, doi: 10.1080/00958972.2020.1730335. DOI: https://doi.org/10.1080/00958972.2020.1730335
[20] D. Shah et al., “Ultrasound-Assisted Synthesis of Benzimidazole Derivatives: A Catalyst-Free Green Chemistry Approach”, Russian Journal of Organic Chemistry, vol. 59, núm. 8, pp. 1397–1406, ago. 2023, doi: 10.1134/S1070428023080146. DOI: https://doi.org/10.1134/S1070428023080146
[21] A. Avila-Sorrosa, L. A. Gil-Ruiz, M. E. Vargas-Diaz, B. Torres-Nogueda, y D. Morales-Morales, “Green synthesis and in vitro anticancer evaluation of 1,2-disubstituted benzimidazole derivatives”, Results Chem, vol. 14, p. 102134, mar. 2025, doi: 10.1016/J.RECHEM.2025.102134. DOI: https://doi.org/10.1016/j.rechem.2025.102134
[22] N. Mishra, A. S. Singh, A. K. Agrahari, S. K. Singh, M. Singh, y V. K. Tiwari, “Synthesis of Benz-Fused Azoles via C-Heteroatom Coupling Reactions Catalyzed by Cu(I) in the Presence of Glycosyltriazole Ligands”, ACS Comb Sci, vol. 21, núm. 5, pp. 389–399, may 2019, doi: 10.1021/ACSCOMBSCI.9B00004/SUPPL_FILE/CO9B00004_SI_004.PDF. DOI: https://doi.org/10.1021/acscombsci.9b00004
[23] S. V. Patil, S. S. Patil, y V. D. Bobade, “A simple and efficient approach to the synthesis of 2-substituted benzimidazole via sp3 C–H functionalization”, Arabian Journal of Chemistry, vol. 9, pp. S515–S521, sep. 2016, doi: 10.1016/J.ARABJC.2011.06.017. DOI: https://doi.org/10.1016/j.arabjc.2011.06.017
[24] R. Karmakar y C. Mukhopadhyay, “Ultrasonication under catalyst-free condition: an advanced synthetic technique toward the green synthesis of bioactive heterocycles”, Green Synthetic Approaches for Biologically Relevant Heterocycles: Volume 1: Advanced Synthetic Techniques, pp. 497–562, ene. 2021, doi: 10.1016/B978-0-12-820586-0.00014-5. DOI: https://doi.org/10.1016/B978-0-12-820586-0.00014-5
[25] K. Das, A. Mondal, y D. Srimani, “Selective Synthesis of 2-Substituted and 1,2-Disubstituted Benzimidazoles Directly from Aromatic Diamines and Alcohols Catalyzed by Molecularly Defined Nonphosphine Manganese(I) Complex”, Journal of Organic Chemistry, vol. 83, núm. 16, pp. 9553–9560, ago. 2018, doi: 10.1021/acs.joc.8b01316. DOI: https://doi.org/10.1021/acs.joc.8b01316
[26] J. Fu et al., “PTSA-catalyzed selective synthesis and antibacterial evaluation of 1,2-disubstituted benzimidazoles”, Mol Divers, vol. 27, núm. 2, pp. 873–887, abr. 2023, doi: 10.1007/s11030-022-10460-2. DOI: https://doi.org/10.1007/s11030-022-10460-2
[27] N. T. Chung, V. C. Dung, y D. X. Duc, “Recent achievements in the synthesis of benzimidazole derivatives”, el 7 de noviembre de 2023, Royal Society of Chemistry. doi: 10.1039/d3ra05960j. DOI: https://doi.org/10.1039/D3RA05960J
[28] M. Nardi et al., “A Review on the Green Synthesis of Benzimidazole Derivatives and Their Pharmacological Activities”, el 1 de febrero de 2023, MDPI. doi: 10.3390/catal13020392. DOI: https://doi.org/10.3390/catal13020392
Downloads
Published
Issue
Section
License
Copyright (c) 2026 JOURNAL OF BASIC SCIENCES
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Usted es libre de:
- Compartir — copiar y redistribuir el material en cualquier medio o formato
- La licenciante no puede revocar estas libertades en tanto usted siga los términos de la licencia
Bajo los siguientes términos:
- Atribución — Usted debe dar crédito de manera adecuada , brindar un enlace a la licencia, e indicar si se han realizado cambios . Puede hacerlo en cualquier forma razonable, pero no de forma tal que sugiera que usted o su uso tienen el apoyo de la licenciante.
- NoComercial — Usted no puede hacer uso del material con propósitos comerciales .
- SinDerivadas — Si remezcla, transforma o crea a partir del material, no podrá distribuir el material modificado.
- No hay restricciones adicionales — No puede aplicar términos legales ni medidas tecnológicas que restrinjan legalmente a otras a hacer cualquier uso permitido por la licencia.
Avisos:
No tiene que cumplir con la licencia para elementos del material en el dominio público o cuando su uso esté permitido por una excepción o limitación aplicable.
No se dan garantías. La licencia podría no darle todos los permisos que necesita para el uso que tenga previsto. Por ejemplo, otros derechos como publicidad, privacidad, o derechos morales pueden limitar la forma en que utilice el material.
