Login Register Cart 0
Generic placeholder image

Current Organocatalysis

Editor-in-Chief

ISSN (Print): 2213-3372
ISSN (Online): 2213-3380

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

A Critical Analysis of the Modern Synthetic Procedures Used to Produce Benzimidazole Candidates

Author(s): Shikha Sharma*, Neha Dangi, Nitin Mittal and Naresh Kalra

Volume 11, Issue 1, 2024

Published on: 19 June, 2023

Page: [7 - 32] Pages: 26

DOI: 10.2174/2213337210666230329103657

Price: $65

Abstract

Background: Benzimidazole is a remarkable heterocyclic chemical compound in which the phenyl ring is fused with the imidazole ring at positions 4 and 5. Benzimidazole derivatives have lots of medicinal activity in the pharmaceutical industry. Therefore, the synthesis of benzimidazole derivatives is challenging in this scientific field.

Methods: In benzimidazole synthesis, simple nucleophilic substitution and condensation reactions involving carbonyl compounds and o-phenylenediamine have been used in previous times. Currently, green chemistry aspects such as solvent-free conditions, metal-free conditions, or using nanoparticle catalysts in various ways involving condensation, and cyclization are the methods of the new era.

Results: Green chemistry methods are used widely in various chemical reactions, such as it was observed that the use of solvent-free conditions, metal-free conditions, or using nanoparticle catalysts molecules is a more efficient way to synthesize benzimidazole derivative.

Conclusion: In this review, benzimidazole scaffold syntheses that have only recently been described in the literature through the end of 2021 are covered. Monosubstituted benzimidazoles (MSBs) and disubstituted-benzimidazoles (DSBs) are the primary targets of our research currently. Different ways have been found to make functionalized derivatives of benzimidazole, which are shown in this review as a powerful scaffold.

« Previous Next »
Graphical Abstract

[1]
Wright, J.B. The chemistry of the benzimidazoles. Chem. Rev., 1951, 48(3), 397-541.
[http://dx.doi.org/10.1021/cr60151a002] [PMID: 24541208]
[2]
Rajasekhar, S.; Maiti, B.; Balamurali, M.M. Chanda, A. A decade update on benzoxazoles, a privileged scaffold in synthetic organic chemistry. Curr. Org. Synth., 2017, 14, 40-60.
[http://dx.doi.org/10.2174/1570179413666160818151932]
[3]
Tiwari, A.K.; Mishra, A.K.; Bajpai, A.; Mishra, P.; Singh, S.; Sinha, D.; Singh, V.K. Synthesis and evaluation of novel benzimidazole derivative [Bz-Im] and its radio/biological studies. Bioorg. Med. Chem. Lett., 2007, 17(10), 2749-2755.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.071] [PMID: 17368898]
[4]
Srivastava, V.; Srivastava, A.M.; Tiwari, A.K.; Srivastava, R.; Sharma, R.; Sharma, H.; Singh, V.K. Disubstituted 4(3H) quinazolones: A novel class of antitumor agents. Chem. Biol. Drug Des., 2009, 74(3), 297-301.
[http://dx.doi.org/10.1111/j.1747-0285.2009.00850.x] [PMID: 19703032]
[5]
Saini, N.; Varshney, R.; Tiwari, A.K.; Kaul, A.; Allard, M.; Ishar, M.P.S.; Mishra, A.K. Synthesis, conjugation and relaxation studies of gadolinium(iii)-4-benzothiazol-2-yl-phenylamine as a potential brain specific MR contrast agent. Dalton Trans., 2013, 42(14), 4994-5003.
[http://dx.doi.org/10.1039/c2dt32391e] [PMID: 23389482]
[6]
Yedluri, A.K.; Kim, H.J. Wearable super-high specific performance supercapacitors using a honeycomb with folded silk-like composite of NiCo2O4 nanoplates decorated with NiMoO4 honeycombs on nickel foam. Dalton Trans., 2018, 47(43), 15545-15554.
[http://dx.doi.org/10.1039/C8DT03598A] [PMID: 30345451]
[7]
Pallavolu, M.R.; Anil Kumar, Y.; Mani, G.; Alshgari, R.A.; Ouladsmane, M.; Joo, S.W. Facile fabrication of novel heterostructured tin disulfide (SnS2)/tin sulfide (SnS)/N-CNO composite with improved energy storage capacity for high-performance supercapacitors. J. Electroanal. Chem., 2021, 899, 115695.
[http://dx.doi.org/10.1016/j.jelechem.2021.115695]
[8]
Shukla, G.; Tiwari, A.K.; Singh, V.K.; Bajpai, A.; Chandra, H.; Mishra, A.K. Effect of a novel series of benzothiazolo-quinazolones on epidermal growth factor receptor (EGFR) and biological evaluations. Chem. Biol. Drug Des., 2008, 72(6), 533-539.
[http://dx.doi.org/10.1111/j.1747-0285.2008.00724.x] [PMID: 19090920]
[9]
El-Feky, S.A.H.; Abd El-Samii, Z.K.; Osman, N.A.; Lashine, J.; Kamel, M.A.; Thabet, H.K. Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II. Bioorg. Chem., 2015, 58, 104-116.
[http://dx.doi.org/10.1016/j.bioorg.2014.12.003] [PMID: 25590381]
[10]
Gaba, M.; Gaba, P.; Uppal, D.; Dhingra, N.; Bahia, M.S.; Silakari, O.; Mohan, C. Benzimidazole derivatives: search for GI-friendly anti-inflammatory analgesic agents. Acta Pharm. Sin. B, 2015, 5(4), 337-342.
[http://dx.doi.org/10.1016/j.apsb.2015.05.003] [PMID: 26579464]
[11]
Alpan, A.S.; Zencir, S.; Zupkó, I.; Coban, G.; Réthy, B.; Gunes, H.S.; Topcu, Z. Biological activity of bis-benzimidazole derivatives on DNA topoisomerase I and HeLa, MCF7 and A431 cells. J. Enzyme Inhib. Med. Chem., 2009, 24(3), 844-849.
[http://dx.doi.org/10.1080/14756360802420831] [PMID: 18951286]
[12]
Sweeney, M.; Conboy, D.; Mirallai, S.I.; Aldabbagh, F. Advances in the synthesis of ring-fused benzimidazoles and imidazobenzimidazoles. Molecules, 2021, 26(9), 2684.
[http://dx.doi.org/10.3390/molecules26092684] [PMID: 34064312]
[13]
Mohammed, A.F.; Abdel-Moty, S.G.; Hussein, M.A.; Abdel-Alim, A.A.M. Design, synthesis and molecular docking of some new 1,2,4-triazolobenzimidazol-3-yl acetohydrazide derivatives with anti-inflammatory-analgesic activities. Arch. Pharm. Res., 2013, 36(12), 1465-1479.
[http://dx.doi.org/10.1007/s12272-013-0153-z] [PMID: 23712380]
[14]
Küçükbay, H.; Durmaz, R.; Okyucu, N.; Günal, S. Antifungal activity of some bis-5-methylbenzimidazole compounds. Folia Microbiol. (Praha), 2003, 48(5), 679-681.
[http://dx.doi.org/10.1007/BF02993478] [PMID: 14976728]
[15]
Kucukbay, H.; Yilmaz, U.; Sirec, N.; Onganer, A.N. Synthesis and antimicrobial activities of some bridged bis-benzimidazole derivatives. Turk. J. Chem., 2011, 35, 561-571.
[16]
Kankate, R.S.; Gide, P.S.; Belsare, D.P. Design, synthesis and antifungal evaluation of novel benzimidazole tertiary amine type of fluconazole analogues. Arab. J. Chem., 2019, 12(8), 2224-2235.
[http://dx.doi.org/10.1016/j.arabjc.2015.02.002]
[17]
Sharma, M.C.; Sharma, S.; Sahu, N.K.; Kohli, D.V. 3D QSAR kNN-MFA studies on 6-substituted benzimidazoles derivatives as nonpeptide angiotensin ii receptor antagonists: A rational approach to antihypertensive agents. J. Saudi Chem. Soc., 2013, 17(2), 167-176.
[http://dx.doi.org/10.1016/j.jscs.2011.03.005]
[18]
Hranjec, M.; Pavlović, G.; Karminski-Zamola, G. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2-a]benzimidazoles. J. Mol. Struct., 2012, 1007, 242-251.
[http://dx.doi.org/10.1016/j.molstruc.2011.10.054]
[19]
Mavrova, A.T.; Wesselinova, D.; Vassilev, N.; Tsenov, J.A. Design, synthesis and antiproliferative properties of some new 5-substituted-2-iminobenzimidazole derivatives. Eur. J. Med. Chem., 2013, 63, 696-701.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.010] [PMID: 23567959]
[20]
Evans, C.W.; Atkins, C.; Pathak, A.; Gilbert, B.E.; Noah, J.W. Benzimidazole analogs inhibit respiratory syncytial virus G protein function. Antiviral Res., 2015, 121, 31-38.
[http://dx.doi.org/10.1016/j.antiviral.2015.06.016] [PMID: 26116756]
[21]
Zhang, Z.; Ojo, K.K.; Johnson, S.M.; Larson, E.T.; He, P.; Geiger, J.A.; Castellanos-Gonzalez, A.; White, A.C., Jr; Parsons, M.; Merritt, E.A.; Maly, D.J.; Verlinde, C.L.M.J.; Van Voorhis, W.C.; Fan, E. Benzoylbenzimidazole-based selective inhibitors targeting Cryptosporidium parvum and Toxoplasma gondii calcium-dependent protein kinase-1. Bioorg. Med. Chem. Lett., 2012, 22(16), 5264-5267.
[http://dx.doi.org/10.1016/j.bmcl.2012.06.050] [PMID: 22795629]
[22]
Chen, Q.; Tian, W.; Han, G.; Qi, J.; Zheng, C.; Zhou, Y.; Ding, L.; Zhao, J.; Zhu, J.; Lv, J.; Sheng, C. Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping. Eur. J. Med. Chem., 2013, 59, 176-182.
[http://dx.doi.org/10.1016/j.ejmech.2012.11.005] [PMID: 23220646]
[23]
Hobrecker, F. Berichte der Deutschen Chemischen Gesellschaft 1872, (5), 920-924.
[24]
Ladenburg, A. Derivate von Diaminen. Ber. Dtsch. Chem. Ges., 1875, 8(1), 677-678.
[http://dx.doi.org/10.1002/cber.187500801209]
[25]
Furniss, B.S.; Hannaford, A.J.; Tatchell, A.R. Vogel’s Textbook of Practical Organic Chemistry; Pearson Education: London, 1989, p. 1514.
[26]
Wagner, E.C.; Millett, W.H. Benzimidazole. Org. Synth., 1939, 19, 12.
[27]
Shriller, R.L.; Upson, R.W. Synthesis of bis-benzimidazoles from diabasic acids. J. Am. Chem. Soc., 1941, 63, 2277-2278.
[28]
John b. Wright. chemistry of the benzimidazoles. Chem. Rev., 1951, 48(3), 397-541.
[29]
Wang, L.; Sheng, J.; Tian, H.; Qian, C. An efficient procedure for the synthesis of Benzimidazole derivatives using Yb(OTf)3 as catalyst under solvent‐free conditions. Synth. Commun., 2004, 34(23), 4265-4272.
[http://dx.doi.org/10.1081/SCC-200039340]
[30]
Trivedi, R.; De, S.K.; Gibbs, R.A. A convenient one-pot synthesis of 2-substituted benzimidazoles. J. Mol. Catal. Chem., 2006, 245(1-2), 8-11.
[http://dx.doi.org/10.1016/j.molcata.2005.09.025]
[31]
Yang, D.; Fu, H.; Hu, L.; Jiang, Y.; Zhao, Y. Copper-catalyzed synthesis of benzimidazoles via cascade reactions of o-haloacetanilide derivatives with amidine hydrochlorides. J. Org. Chem., 2008, 73(19), 7841-7844.
[http://dx.doi.org/10.1021/jo8014984] [PMID: 18754576]
[32]
Peng, J.; Zong, M.Ye.; Feng, F.; Hu, L.; Wang, X.; Wang, Y.; Chen, C. Copper-catalyzed synthesis of benzimidazoles via cascade reactions of o-haloacetanilide derivatives with amidine hydrochlorides. J. Org. Chem., 2010, 76, 716-719.
[http://dx.doi.org/10.1021/jo1021426] [PMID: 21175149]
[33]
Rekha, M.; Hamza, A.; Venugopal, B.R.; Nagaraju, N. Synthesis of 2-substituted benzimidazoles and 1,5-disubstituted benzodiazepines on alumina and zirconia. Catalysts chin. J. Catal., 2012, 33(2-3), 439-446.
[http://dx.doi.org/10.1016/S1872-2067(11)60338-0]
[34]
Nguyen, T.B.; Ermolenko, L.; Al-Mourabit, A. Iron sulfide catalyzed redox/condensation cascade reaction between 2-amino/hydroxy nitrobenzenes and activated methyl groups: A straightforward atom economical approach to 2-hetaryl-benzimidazoles and -benzoxazoles. J. Am. Chem. Soc., 2013, 135(1), 118-121.
[http://dx.doi.org/10.1021/ja311780a] [PMID: 23249371]
[35]
Nguyen, T.B.; Ermolenko, L.; Corbin, M.; Al-Mourabit, A. Fe/S-catalyzed decarboxylative redox condensation of arylacetic acids with nitroarenes. Org. Chem. Front., 2014, 1(10), 1157-1160.
[http://dx.doi.org/10.1039/C4QO00221K]
[36]
Das, K.; Mondal, A.; Srimani, D. Selective synthesis of 2-Substituted and 1,2-disubstituted benzimidazoles directly from aromatic diamines and alcohols catalyzed by molecularly defined nonphosphine Manganese(I). Complex. J. Org. Chem., 2018, 83(16), 9553-9560.
[http://dx.doi.org/10.1021/acs.joc.8b01316] [PMID: 29993244]
[37]
Tzani, M.A.; Gabriel, C.; Lykakis, I.N. Selective synthesis of Benzimidazoles from o-Phenylenediamine and aldehydes promoted by supported gold nanoparticles. Nanomaterials, 2020, 10(12), 2405.
[http://dx.doi.org/10.3390/nano10122405] [PMID: 33271922]
[38]
Ibrahim, K.S.; Begum, J. Synthesis and antimicrobial activity of some benzimidazole derivative with ibuprofen. Int. J. Pharma Sci., 2011, 2, 298.
[39]
Nguyen, T.B.; Ermolenko, L.; Dean, W.A.; Al-Mourabit, A. Benzazoles from aliphatic amines and o-amino/mercaptan/hydro-xyanilines: Elemental sulfur as a highly efficient and traceless oxidizing agent. Org. Lett., 2012, 14(23), 5948-5951.
[http://dx.doi.org/10.1021/ol302856w] [PMID: 23171411]
[40]
Tran, M.Q.; Ermolenko, L.; Retailleau, P.; Nguyen, T.B.; Al-Mourabit, A. Reaction of quinones and guanidine derivatives: Simple access to bis-2-aminobenzimidazole moiety of benzosceptrin and other benzazole motifs. Org. Lett., 2014, 16(3), 920-923.
[http://dx.doi.org/10.1021/ol403672p] [PMID: 24479902]
[41]
Majumdar, S.; Chakraborty, M.; Pramanik, N.; Maiti, D.K. Grindstone chemistry: Protic ionic liquid-substrate tuned green synthesis of 1,2-disubstituted and 2-substituted benzimidazoles with outstanding selectivity. RSC Advances, 2015, 5(63), 51012-51018.
[http://dx.doi.org/10.1039/C5RA08183A]
[42]
Nguyen, T.B.; Ermolenko, L.; Al-Mourabit, A. Formic acid as a sustainable and complementary reductant: an approach to fused benzimidazoles by molecular iodine-catalyzed reductive redox cyclization of o-nitro-t-anilines. Green Chem., 2016, 18(10), 2966-2970.
[http://dx.doi.org/10.1039/C6GC00902F]
[43]
Feizpour, F.; Jafarpour, M.; Rezaeifard, A. A tandem aerobic photocatalytic synthesis of benzimidazoles by cobalt ascorbic acid complex coated on TiO2 nanoparticles under visible light. Catal. Lett., 2018, 148(1), 30-40.
[http://dx.doi.org/10.1007/s10562-017-2232-0]
[44]
Liu, X.; Cao, H.; Bie, F.; Yan, P.; Han, Y. C N bond formation and cyclization: A straightforward and metal-free synthesis of N-1-alkyl-2-unsubstituted benzimidazoles. Tetrahedron Lett., 2019, 60(15), 1057-1059.
[http://dx.doi.org/10.1016/j.tetlet.2019.03.028]
[45]
Senapak, W.; Saeeng, R.; Jaratjaroonphong, J.; Promarak, V.; Sirion, U. Metal-free selective synthesis of 2-substituted benzimidazoles catalyzed by Brönsted acidic ionic liquid: Convenient access to one-pot synthesis of N-alkylated 1,2-disubstituted benzimidazoles. Tetrahedron, 2019, 75(26), 3543-3552.
[http://dx.doi.org/10.1016/j.tet.2019.05.014]
[46]
Raja, D.; Philips, A.; Palani, P.; Lin, W.Y.; Devikala, S.; Senadi, G.C. Metal-free synthesis of benzimidazoles via oxidative cyclization of d-glucose with o-phenylenediamines in water. J. Org. Chem., 2020, 85(17), 11531-11540.
[http://dx.doi.org/10.1021/acs.joc.0c01053] [PMID: 32786645]
[47]
Kidwai, M.; Jahan, A.; Bhatnagar, D. Polyethylene glycol: A recyclable solvent system for the synthesis of benzimidazole derivatives using CAN as catalyst. J. Chem. Sci., 2010, 122(4), 607-612.
[http://dx.doi.org/10.1007/s12039-010-0095-7]
[48]
Azarifar, D.; Pirhayati, M.; Maleki, B.; Sanginabadi, M.; Yami, N. Acetic acid-promoted condensation of o-phenylenediamine with aldehydes into 2-aryl-1-(arylmethyl)-1H-benzimidazoles under microwave irradiation. J. Serb. Chem. Soc., 2010, 75(9), 1181-1189.
[http://dx.doi.org/10.2298/JSC090901096A]
[49]
Shaikh, K.A.; Patil, V.A. An efficient solvent-free synthesis of imidazolines and benzimidazoles using K4[Fe(CN)6] catalysis. Org. Commun, 2012, 5, 12-17.
[50]
Karimi-Jaberi, Z.; Amiri, M. An efficient and inexpensive synthesis of 2-substituted benzimidazoles in water using boric acid at room temperature. J. Chem., 2012, 9, 167-170.
[51]
Chen, C.; Chen, C.; Li, B.; Tao, J.; Peng, J. Aqueous synthesis of 1-H-2-substituted benzimidazoles via transition-metal-free intramolecular amination of aryl iodides. Molecules, 2012, 17(11), 12506-12520.
[http://dx.doi.org/10.3390/molecules171112506] [PMID: 23095894]
[52]
Samanta, S.; Das, S.; Biswas, P. Photocatalysis by 3,6-disubstituted-s-tetrazine: Visible-light driven metal-free green synthesis of 2-substituted benzimidazole and benzothiazole. J. Org. Chem., 2013, 78(22), 11184-11193.
[http://dx.doi.org/10.1021/jo401445j] [PMID: 24134516]
[53]
Nguyen, T.B.; Ermolenko, L.; Al-Mourabit, A. Selective autoxidation of benzylamines: Application to the synthesis of some nitrogen heterocycles. Green Chem., 2013, 15(10), 2713-2717.
[http://dx.doi.org/10.1039/c3gc41186a]
[54]
Khunt, M.D.; Kotadiya, V.C.; Viradiya, D.J.; Baria, B.H.; Bhoya, U.C. Easy, simplistic and green synthesis of various Benzimidazole and Benzoxazole derivatives using PEG400 as a Green Solvent. Int. Lett. Chem. Phys. Astronomy, 2014, 25, 61-68.
[http://dx.doi.org/10.56431/p-9vy9eu]
[55]
Yu, Z.Y.; Zhou, J.; Fang, Q.S.; Chen, L.; Song, Z.B. Chemoselective synthesis of 1,2-disubstituted benzimidazoles in lactic acid without additive. Chem. Pap., 2016, 70(9), 1293-1298.
[http://dx.doi.org/10.1515/chempap-2016-0056]
[56]
Di Gioia, M.L.; Cassano, R.; Costanzo, P.; Herrera Cano, N.; Maiuolo, L.; Nardi, M.; Nicoletta, F.P.; Oliverio, M.; Procopio, A. Green synthesis of privileged benzimidazole scaffolds using active deep eutectic solvent. Molecules, 2019, 24(16), 2885.
[http://dx.doi.org/10.3390/molecules24162885] [PMID: 31398916]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy