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.
Keywords: One-pot multicomponent reactions (MCRs), L-Pipecolic acid, 2, 4, 5-trisubstituted imidazoles, N-cycloalkylated-2, 5- trisubstituted imidazoles, bifunctional catalyst, non-chromatographic method.
[http://dx.doi.org/10.1080/00304948.2015.1088757]
[http://dx.doi.org/10.1039/C8PY00173A]
[http://dx.doi.org/10.1016/j.tet.2009.10.019]
[PMID: 2542526]
[http://dx.doi.org/10.3891/acta.chem.scand.45-0627] [PMID: 1764333]
[http://dx.doi.org/10.3390/app10082889]
[http://dx.doi.org/10.2174/1570180811666140116214111]
[http://dx.doi.org/10.1016/S1995-7645(10)60113-7]
[http://dx.doi.org/10.4103/0975-7406.111822] [PMID: 23833522]
[http://dx.doi.org/10.1021/jm201212h] [PMID: 22369127]
[http://dx.doi.org/10.3923/crc.2012.99.109]
[http://dx.doi.org/10.1002/jlac.18581070209]
[http://dx.doi.org/10.1002/cber.18820150207]
[http://dx.doi.org/10.1021/jo01227a005]
[http://dx.doi.org/10.1016/j.tet.2006.05.079]
[http://dx.doi.org/10.1021/jo2019416] [PMID: 22034860]
[http://dx.doi.org/10.1039/C6CC01863G] [PMID: 27101465]
[http://dx.doi.org/10.1039/C7RA11827A]
[http://dx.doi.org/10.1016/j.tet.2005.01.116]
[http://dx.doi.org/10.1016/j.jscs.2013.01.005]
[http://dx.doi.org/10.1016/j.molcata.2006.01.006]
[http://dx.doi.org/10.1016/j.tetlet.2008.02.053]
[http://dx.doi.org/10.1007/s12039-008-0072-6]
[http://dx.doi.org/10.1016/j.molcata.2006.08.070]
[http://dx.doi.org/10.1080/00397910600773825]
[http://dx.doi.org/10.1021/ol049682b] [PMID: 15101765]
[http://dx.doi.org/10.1016/j.catcom.2006.04.004]
[http://dx.doi.org/10.1007/s11030-009-9197-x] [PMID: 19866367]
[http://dx.doi.org/10.1016/j.molcata.2006.10.048]
[http://dx.doi.org/10.1016/j.tetlet.2008.02.100]
[http://dx.doi.org/10.1039/b006201o]
[http://dx.doi.org/10.1021/ja994280y]
[http://dx.doi.org/10.1021/ol0513544] [PMID: 16119914]
[http://dx.doi.org/10.1021/ol052861o] [PMID: 16494447]
[http://dx.doi.org/10.1016/j.tetlet.2010.02.143] [PMID: 21785516]
[http://dx.doi.org/10.1039/c2gc35668f]
[http://dx.doi.org/10.1016/j.tetlet.2006.11.010]
[http://dx.doi.org/10.1021/ja028812d] [PMID: 12603135]
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