A facile, environmentally friendly one-pot multicomponent protocol for the synthesis of dihydropyrimidinone (DHPM) and dihydropyrimidin(thio)one (DHPMT) derivatives has been developed using alumina-silica-supported MnO 2 as a catalyst in ethanol, demonstrating a green chemistry approach. The Biginelli-type reaction between aryl aldehyde, ethyl acetoacetate, and urea/thiourea afforded DHPM/DHPMT in 85-92% yield within 45 min. Essential features of this protocol include a short reaction time, the use of a heterogeneous catalyst, and convenient catalyst separation.
A group of 2-(4-aryl)-3-(cyclohexylimino)-2-hydroxy-2,3-dihydro-1 H -imidazo[1,2- a ]pyridin-4-ium chlorides was successfully synthesized in moderate yields through the reaction of Nef-Adducts (alpha-keto imidoyl chlorides), which were generated from the interaction of N -cyclohexyl isocyanide with aryl carbonyl chlorides, followed by the incorporation of 2-aminopyridine. The imidazo[1,2- a ]pyridin-4-ium chlorides produced were thoroughly characterized in this study, and the X-ray crystal structures of their salts were determined. This research examines the antimicrobial properties of the prepared compounds against various microbial strains. The findings suggest that compounds 7b and 7d exhibit the broadest and most potent activity.
Pyridyl-substituted imidazoles are privileged scaffolds in medicinal chemistry and homogeneous catalysis, yet their efficient and modular synthesis has long been a persistent challenge. The established synthetic methods mainly rely on precious metal catalysts, harsh reaction conditions, or multi-step operations, and are largely limited to aryl/alkyl-substituted imidazoles. Mild and efficient methods for the construction of multi-pyridyl-substituted imidazole frameworks remain exceptionally rare. Herein, we report a straightforward manganese-catalyzed one-step cyclization reaction that enables the direct synthesis of 2,4,5-trisubstituted pyridylimidazole derivatives from readily available pyridine-2-carboxaldehyde derivatives and ammonium acetate. This protocol features mild reaction conditions, no requirement for precious metals or strong bases, a broad substrate scope, excellent functional group tolerance, and good to excellent isolated yields (70-95%). This work provides a general and practical synthetic access to multi-pyridyl-substituted imidazoles, which will facilitate their widespread applications in drug discovery and transition-metal catalysis.
A potassium tert-butoxide (t-BuOK)-mediated transamidation system for aromatic amines has been established in this study, enabling efficient transition-metal-free transamidation between aromatic amines/heterocyclic amines and multiple acyl donors. A total of 49 amide compounds were synthesized with yields ranging from 30% to 96%. Notably, the protocol features mild reaction conditions (<= 50 degrees C, no microwave assistance) and achieves room-temperature trifluoroacetylation of heterocyclic amines, providing a green route for the synthesis of fluorine-containing pharmaceutical intermediates and complex heterocyclic amide skeletons. Mechanistic investigations, including radical scavenger experiments and 18-crown-6 chelation studies, reveal that the reaction proceeds via a K + dual-coordination-driven nucleophilic addition-elimination pathway. Specifically, K + acts as a hard Lewis acid to form an "aniline-K +-acyl donor" ternary complex, synergistically activating both the nucleophilic amine and electrophilic acyl donor, thereby facilitating amide C-N bond cleavage and target product formation.
In this study, copper oxide nanoparticles (CuO NPs) were prepared and evaluated as a powerful, reusable heterogeneous catalyst for the production of β-aminocarbonyl derivatives via the Mannich reaction. The CuO nanoparticles were prepared using a chemical reduction-precipitation method, then calcined and characterized in detail using FT-IR, XRD, SEM, TEM, and UV- visible spectroscopy to ascertain the formation of crystalline monoclinic CuO with the proper morphology and surface characteristics. The catalytic activity of the CuO nanoparticles was tested in a three-component, one-pot Mannich reaction of aromatic amines, benzaldehyde, and ketones under mild reaction conditions in the green solvent ethanol. Optimization experiments revealed that product yields were good with a low catalyst loading of 0.015 mol% at ambient temperature. A wide range of aromatic amines, including aniline and substituted anilines, were successfully utilized, as were cyclic and aromatic ketones, which also produced the respective Mannich bases in good to excellent yields. The efficiency of the CuO nanoparticles was also compared with that of ammonium chloride, a traditional homogeneous catalyst. It was found to be more efficient, require less catalyst, and be easily recovered. In addition, the CuO catalyst could be reused in consecutive cycles with negligible loss of catalytic activity. The developed protocol provides an easy, effective, and environmentally benign method for the synthesis of β-amino carbonyl compounds. It demonstrates the potential of CuO nanoparticles as a viable heterogeneous catalyst for multicomponent organic reactions.
