Multicomponent green synthesis, spectroscopic and structural investigation of multi-substituted imidazoles. Part 1

Abstract

Ten 1,2,4,5-tetra-substituted imidazole derivatives have been synthesized with a 2-hydroxyethy substituent at the 1-nitrogen atom and potentially electron releasing hydroxy-, methoxy-, dimethylamino- or nitro substituents in various positions on the benzene ring located on the 2-carbon atom. The prototypical derivative with an unsubstituted phenyl ring at the 2-position is also reported. The compounds are obtained in excellent yields (average 86%) via a four-component cyclocondensation reaction of benzil, ethanolamine, and the appropriate aromatic carbaldehyde together with ammonium acetate. The reaction uses a novel ionic liquid catalyst, DEAHS (diethyl ammonium hydrogen sulfate), under solvent-free conditions and a green synthetic protocol. The key advantages of this process are high yield, shorter reaction times and ease of work-up. Furthermore, the products can be purified by a non-chromatographic method and the catalyst is re-usable. All of these newly synthesized compounds have been characterized from spectral data; the X-ray structures of three representative molecules are also detailed.

Ionic Liquid Solvation versus Catalysis: Computational Insight from a Multisubstituted Imidazole Synthesis in [Et2NH2][HSO4]

“…cationic and anionic) catalytic effect with much lower activation energies than can be achieved if the IL acts only as a solvent. Our calculations, therefore, rationalize the experimental observations that we reported previously and answer the question “Why is the reaction completed in a very short time with a remarkably high yield?”.…”

“…This interaction strongly facilitates the catalytic activity of the anionic IL component for proton exchange. In contrast, no such ‘assistance’ is required when the cationic component is catalytically active. We have taken the opportunity to perform structural analysis of the product, which was not performed in our previous experimental study . Details can be found in the Supporting Information.…”

“…We have taken the opportunity to perform structural analysis of the product, which was not performed in our previous experimental study . Details can be found in the Supporting Information.…”

“…This type of synthetic procedure is known to be commercially viable and free of toxic intermediate release, and the desired product could be achieved safely. Remarkably, the reaction completed with 98 % yield in only 20 min . This is very surprising, because a similar InCl 3 ⋅3 H 2 O‐catalyzed reaction reaches only 84 % conversion after 6 h .…”

“…The imidazole formation reaction of Scheme is used as an example because of the very efficient conversion in the presence of the IL. We chose benzaldehyde among the array of aldehydes that were used in our experimental work, because of its simple structure, along with other reagents, namely benzil, ethanolamine, ammonium acetate, and [Et 2 NH 2 ][HSO 4 ], to conduct theoretical calculations on the reaction. The one‐pot synthesis of substituted imidazoles is also a suitable example, representing more general nucleophilic addition and cyclocondensation reactions .…”