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

Abstract

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. 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). 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. 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. 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-cycloalkyl2,4,5- trisubstituted imidazoles (4a-i) were synthesized successfully, and a plausible reaction mechanism is proposed based on the results of the experiment. 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.