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
Research Article

L-Pipecolic Acid-catalyzed Highly Efficient Synthesis of 2,4,5-Trisubstituted Imidazoles and N-cycloalkyl-2,4,5-trisubstituted Imidazoles

Author(s): Anila Mishra, Zeeshan Fatima*, Akash Ved, Sajal Srivastava and Ashok K Singh

Volume 11, Issue 3, 2024

Published on: 26 January, 2024

Page: [248 - 258] Pages: 11

DOI: 10.2174/0122133372285122240103102528

Price: $65

Abstract

Aims: We aimed to conduct an L-Pipecolic acid-catalyzed synthesis of 2,4,5-trisubstituted imidazoles and N-cycloalkyl-2,4,5- trisubstituted imidazoles to develop a novel synthetic route followed by the synthesis of novel series of compounds.

Background: A rapid, highly efficient, and greener approach for the synthesis of a series of 2,4,5- trisubstituted imidazoles and N-cycloalkyl-2,4,5- trisubstituted imidazoles were developed via onepot multicomponent reaction (MCRs).

Objective: The objective of the current study was to discover a new and highly efficient organocatalyzed synthetic route for the synthesis of 2,4,5-trisubstituted imidazoles and 1,2,4,5-tetrasubstituted imidazoles followed by the synthesis of novel series of compounds.

Method: L-Pipecolic acid was used as a bifunctional catalyst in one-pot multicomponent reaction (MCRs) for the cyclo-condensation of 1,2-dicarbonyl compounds, substituted aromatic aldehydes, cycloalkyl amines, and ammonium acetate in ethanol at moderate temperature. Purification of compounds was performed through a non-chromatographic method. Physical and spectral data analysis was carried out to characterize the products.

Result: Employing our newly developed L-Pipecolic acid-catalyzed synthetic route, a series of total twenty-three compounds incorporating 2,4,5-trisubstituted imidazoles (3a-n) and N-cycloalkyl- 2,4,5- trisubstituted imidazoles (4a-i) were synthesized successfully, and a plausible reaction mechanism is proposed based on the results of the experiment.

Conclusion: All the derivatives were afforded high purity and excellent yields (92–97%) in a short reaction time (45–90 min). The newly developed synthetic route is rapid and robust and could be applicable for the synthesis of pharmaceutically active compounds.

« Previous
Graphical Abstract

[1]
Maleki, B.; Kahoo, G.E.; Tayebee, R. One-pot synthesis of polysubstituted imidazoles catalyzed by an ionic liquid. Org. Prep. Proced. Int., 2015, 47(6), 461-472.
[http://dx.doi.org/10.1080/00304948.2015.1088757]
[2]
Saxer, S.; Marestin, C.; Mercier, R.; Dupuy, J. The multicomponent debus–radziszewski reaction in macromolecular chemistry. Polym. Chem., 2018, 9(15), 1927-1933.
[http://dx.doi.org/10.1039/C8PY00173A]
[3]
Samai, S.; Nandi, G.C.; Singh, P.; Singh, M.S. l-Proline: An efficient catalyst for the one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. Tetrahedron, 2009, 65(49), 10155-10161.
[http://dx.doi.org/10.1016/j.tet.2009.10.019]
[4]
Abrahams, S.L.; Hazen, R.J.; Batson, A.G.; Phillips, A.P. Trifenagrel: A chemically novel platelet aggregation inhibitor. J. Pharmacol. Exp. Ther., 1989, 249(2), 359-365.
[PMID: 2542526]
[5]
Frandsen, P.L.; Håkansson, K.; Holm, A.; Harrit, N.; Elding, L.I.; Trabjerg, I. Peroxide chemistry of triaryl-substituted imidazoles. Fenflumizole, a non-steroidal, anti-inflammatory agent. Acta Chem. Scand., 1991, 45(6), 627-631.
[http://dx.doi.org/10.3891/acta.chem.scand.45-0627] [PMID: 1764333]
[6]
Noriega-Iribe, E.; Díaz-Rubio, L.; Estolano-Cobián, A.; Barajas-Carrillo, V.W.; Padrón, J.M.; Salazar-Aranda, R.; Díaz-Molina, R.; García-González, V.; Chávez-Santoscoy, R.A.; Chávez, D.; Córdova-Guerrero, I. In vitro and in silico screening of 2,4,5-trisubstituted imidazole derivatives as potential xanthine oxidase and acetylcholinesterase inhibitors, antioxidant, and antiproliferative agents. Appl. Sci., 2020, 10(8), 2889.
[http://dx.doi.org/10.3390/app10082889]
[7]
Hu, C.; Shen, J.; Bian, K.; Zhang, R.; Deng, L. Design, synthesis and biological evaluation of 2, 4, 5-triphenylimidazole derivatives with preliminary SAR. Lett. Drug Des. Discov., 2014, 11(6), 762-769.
[http://dx.doi.org/10.2174/1570180811666140116214111]
[8]
Jain, A.K.; Ravichandran, V.; Sisodiya, M.; Agrawal, R.K. Synthesis and antibacterial evaluation of 2–substituted–4,5–diphenyl–N–alkyl imidazole derivatives. Asian Pac. J. Trop. Med., 2010, 3(6), 471-474.
[http://dx.doi.org/10.1016/S1995-7645(10)60113-7]
[9]
Husain, A.; Drabu, S.; Kumar, N.; Alam, M.M.; Bawa, S. Synthesis and biological evaluation of di- and tri-substituted imidazoles as safer anti-inflammatory-antifungal agents. J. Pharm. Bioallied Sci., 2013, 5(2), 154-161.
[http://dx.doi.org/10.4103/0975-7406.111822] [PMID: 23833522]
[10]
Gising, J.; Nilsson, M.T.; Odell, L.R.; Yahiaoui, S.; Lindh, M.; Iyer, H.; Sinha, A.M.; Srinivasa, B.R.; Larhed, M.; Mowbray, S.L.; Karlén, A. Trisubstituted imidazoles as Mycobacterium tuberculosis glutamine synthetase inhibitors. J. Med. Chem., 2012, 55(6), 2894-2898.
[http://dx.doi.org/10.1021/jm201212h] [PMID: 22369127]
[11]
Arora, R.; Gill, N.S.; Kapoor, R.; Aggarwal, A.; Rana, A.C. Synthesis of 2,4,5-triphenylimidazoles novel mannich bases as potential antiinflammatory and analgesic agents. Curr. Res. Chemis., 2012, 4(4), 99-109.
[http://dx.doi.org/10.3923/crc.2012.99.109]
[12]
Debus, H. Ueber die einwirkung des ammoniaks auf glyoxal. Justus Liebigs Ann. Chem., 1858, 107(2), 199-208.
[http://dx.doi.org/10.1002/jlac.18581070209]
[13]
Radziszewski, B. Ueber die Constitution des Lophins und verwandter Verbindungen. Ber. Dtsch. Chem. Ges., 1882, 15(2), 1493-1496.
[http://dx.doi.org/10.1002/cber.18820150207]
[14]
Davidson, D.; Weiss, M.; Jelling, M. The action of ammonia on benzoin. J. Org. Chem., 1937, 2(4), 328-334.
[http://dx.doi.org/10.1021/jo01227a005]
[15]
Matsuoka, Y.; Ishida, Y.; Sasaki, D.; Saigo, K. Synthesis of enantiopure 1-substituted, 1,2-disubstituted, and 1,4,5-trisubstituted imidazoles from 1,2-amino alcohols. Tetrahedron, 2006, 62(34), 8199-8206.
[http://dx.doi.org/10.1016/j.tet.2006.05.079]
[16]
Kim, Y.; Kumar, M.R.; Park, N.; Heo, Y.; Lee, S. Copper-catalyzed, one-pot, three-component synthesis of benzimidazoles by condensation and C-N bond formation. J. Org. Chem., 2011, 76(23), 9577-9583.
[http://dx.doi.org/10.1021/jo2019416] [PMID: 22034860]
[17]
Chawla, A.; Sharma, A.; Sharma, A.K. Review: A convenient approach for the synthesis of imidazolederivatives using microwaves. Pharma Chem., 2012, 4, 116-140.
[18]
Xie, Z.; Deng, J.; Qiu, Z.; Li, J.; Zhu, Q. Copper-mediated C(sp 3)–H azidation with Me 3 SiN 3: Synthesis of imidazoles from ketones and aldehydes. Chem. Commun., 2016, 52(38), 6467-6470.
[http://dx.doi.org/10.1039/C6CC01863G] [PMID: 27101465]
[19]
Le Phuong, H.A.; Cseri, L.; Whitehead, G.F.S.; Garforth, A.; Budd, P.; Szekely, G. Environmentally benign and diastereoselective synthesis of 2,4,5-trisubstituted-2-imidazolines. RSC Advances, 2017, 7(84), 53278-53289.
[http://dx.doi.org/10.1039/C7RA11827A]
[20]
Siddiqui, S.A.; Narkhede, U.C.; Palimkar, S.S.; Daniel, T.; Lahoti, R.J.; Srinivasan, K.V. Room temperature ionic liquid promoted improved and rapid synthesis of 2,4,5-triaryl imidazoles from aryl aldehydes and 1,2-diketones or α-hydroxyketone. Tetrahedron, 2005, 61(14), 3539-3546.
[http://dx.doi.org/10.1016/j.tet.2005.01.116]
[21]
Mohammadi Ziarani, G.; Badiei, A.; Lashgari, N.; Farahani, Z. Efficient one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles using SBA-Pr-SO3H as a green nano catalyst. J. Saudi Chem. Soc., 2016, 20(4), 419-427.
[http://dx.doi.org/10.1016/j.jscs.2013.01.005]
[22]
Shaabani, A.; Rahmati, A. Silica sulfuric acid as an efficient and recoverable catalyst for the synthesis of trisubstituted imidazoles. J. Mol. Catal. Chem., 2006, 249(1-2), 246-248.
[http://dx.doi.org/10.1016/j.molcata.2006.01.006]
[23]
Das Sharma, S.; Hazarika, P.; Konwar, D. An efficient and one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by InCl3•3H2O. Tetrahedron Lett., 2008, 49(14), 2216-2220.
[http://dx.doi.org/10.1016/j.tetlet.2008.02.053]
[24]
Sangshetti, J.N.; Kokare, N.D.; Kotharkara, S.A.; Shinde, D.B. Ceric ammonium nitrate catalysed three component one-pot efficient synthesis of 2,4,5-triaryl-1H-imidazoles. J. Chem. Sci., 2008, 120(5), 463-467.
[http://dx.doi.org/10.1007/s12039-008-0072-6]
[25]
Heravi, M.M.; Bakhtiari, K.; Oskooie, H.A.; Taheri, S. Synthesis of 2,4,5-triaryl-imidazoles catalyzed by NiCl2•6H2O under heterogeneous system. J. Mol. Catal. Chem., 2007, 263(1-2), 279-281.
[http://dx.doi.org/10.1016/j.molcata.2006.08.070]
[26]
Sharma, G.V.M.; Jyothi, Y.; Lakshmi, P.S. Efficient room-temperature synthesis of tri- and tetrasubstituted imidazoles catalyzed by ZrCl 4. Synth. Commun., 2006, 36(20), 2991-3000.
[http://dx.doi.org/10.1080/00397910600773825]
[27]
Wolkenberg, S.E.; Wisnoski, D.D.; Leister, W.H.; Wang, Y.; Zhao, Z.; Lindsley, C.W. Efficient synthesis of imidazoles from aldehydes and 1,2-diketones using microwave irradiation. Org. Lett., 2004, 6(9), 1453-1456.
[http://dx.doi.org/10.1021/ol049682b] [PMID: 15101765]
[28]
Karimi, A.R.; Alimohammadi, Z.; Azizian, J.; Mohammadi, A.A.; Mohammadizadeh, M.R. Solvent-free synthesis of tetrasubstituted imidazoles on silica gel/NaHSO4 support. Catal. Commun., 2006, 7(9), 728-732.
[http://dx.doi.org/10.1016/j.catcom.2006.04.004]
[29]
Karimi, A.R.; Alimohammadi, Z.; Amini, M.M. Wells–Dawson heteropolyacid supported on silica: A highly efficient catalyst for synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. Mol. Divers., 2010, 14(4), 635-641.
[http://dx.doi.org/10.1007/s11030-009-9197-x] [PMID: 19866367]
[30]
Kantevari, S.; Vuppalapati, S.V.N.; Biradar, D.O.; Nagarapu, L. Highly efficient, one-pot, solvent-free synthesis of tetrasubstituted imidazoles using HClO4–SiO2 as novel heterogeneous catalyst. J. Mol. Catal. Chem., 2007, 266(1-2), 109-113.
[http://dx.doi.org/10.1016/j.molcata.2006.10.048]
[31]
Sadeghi, B.; Mirjalili, B.B.F.; Hashemi, M.M. BF3•SiO2: An efficient reagent system for the one-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles. Tetrahedron Lett., 2008, 49(16), 2575-2577.
[http://dx.doi.org/10.1016/j.tetlet.2008.02.100]
[32]
Balalaie, S.; Arabanian, A. One-pot synthesis of tetrasubstituted imidazoles catalyzed by zeolite HY and silica gel under microwave irradiation. Green Chem., 2000, 2(6), 274-276.
[http://dx.doi.org/10.1039/b006201o]
[33]
List, B.; Lerner, R.A.; Barbas, C.F. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc., 2000, 122(10), 2395-2396.
[http://dx.doi.org/10.1021/ja994280y]
[34]
Aroyan, C.E.; Vasbinder, M.M.; Miller, S.J. Dual catalyst control in the enantioselective intramolecular Morita-Baylis-Hillman reaction. Org. Lett., 2005, 7(18), 3849-3851.
[http://dx.doi.org/10.1021/ol0513544] [PMID: 16119914]
[35]
Cheong, P.H.Y.; Zhang, H.; Thayumanavan, R.; Tanaka, F.; Houk, K.N.; Barbas, C.F., III Pipecolic acid-catalyzed direct asymmetric mannich reactions. Org. Lett., 2006, 8(5), 811-814.
[http://dx.doi.org/10.1021/ol052861o] [PMID: 16494447]
[36]
Das, B.C.; Mohapatra, S.; Campbell, P.D.; Nayak, S.; Mahalingam, S.M.; Evans, T. Synthesis of function-oriented 2-phenyl-2H-chromene derivatives using l-pipecolinic acid and substituted guanidine organocatalysts. Tetrahedron Lett., 2010, 51(19), 2567-2570.
[http://dx.doi.org/10.1016/j.tetlet.2010.02.143] [PMID: 21785516]
[37]
Li, M.; Zhang, B.; Gu, Y. Facile construction of densely functionalized 4H-chromenes via three-component reactions catalyzed by l-proline. Green Chem., 2012, 14(9), 2421-2428.
[http://dx.doi.org/10.1039/c2gc35668f]
[38]
Varala, R.; Nasreen, A.; Enugala, R.; Adapa, S.R. l-Proline catalyzed selective synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles. Tetrahedron Lett., 2007, 48(1), 69-72.
[http://dx.doi.org/10.1016/j.tetlet.2006.11.010]
[39]
Bahmanyar, S.; Houk, K.N.; Martin, H.J.; List, B. Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolecular aldol reactions. J. Am. Chem. Soc., 2003, 125(9), 2475-2479.
[http://dx.doi.org/10.1021/ja028812d] [PMID: 12603135]

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