Microwave-Assisted Solvent-Free Cyclotrimerization of Enaminones to 1,3,5-Trisubstituted Benzenes Using Amberlite IR-120H as a Recyclable Heterogeneous Catalyst

Abstract

Abstract 1,3,5-Trisubstituted benzenes are a valuable class of aromatic compounds that function as key motifs in drug design, rigid scaffolds in supramolecular chemistry, and important chromophores in advanced materials. However, constructing these densely substituted benzene frameworks through C−C bond formation remains challenging and has drawn significant attention. In the present study, we developed a sustainable and efficient microwave-assisted protocol for the synthesis of 1,3,5-triarylbenzene derivatives via the cyclotrimerization of enaminones using Amberlite IR-120H resin as a heterogeneous acid catalyst. The method operates under solvent-free conditions and provides significantly enhanced reaction rates and yields compared to conventional approaches, delivering the desired 1,3,5-triarylbenzene derivatives in 74–90% yield. Optimization studies identified Amberlite IR-120H resin as the most effective catalyst, with the highest conversion achieved at 120 °C for 30 min under microwave irradiation. The protocol exhibits broad substrate scope, tolerating electron-donating, electron-withdrawing, heteroaryl, and naphthyl substituents. The turnover number (TON) and turnover frequency (TOF) values for the catalytic cycle ranged from 203 to 353 and 405 to 706 h−1, respectively, confirming consistently high catalytic activity and excellent productivity. The protocol also showed favorable green-chemistry metrics for the model reaction, including an E-factor (0.497), PMI (1.497), RME (66.76%), and an Eco-score of 78. Structural confirmation of all products (4a–n) was achieved through FT-IR,1H NMR, and ESI-MS analyses. Overall, this study establishes a rapid, metal-free, solvent-free, and environmentally benign synthetic route for constructing 1,3,5-trisubstituted benzene frameworks, demonstrating clear advantages in efficiency, sustainability, and operational simplicity. Graphical AbstractDiagram detailing the cyclotrimerization of enaminones using Amberlite IR 120 H resin beads, showcasing process stages and advantages.The figure outlines the cyclotrimerization of enaminones to 1,3,5-triaryl benzenes with Amberlite IR 120 H resin beads. It shows enaminone structures, the Anton Paar Monowave 400 reactor setup, and catalyst details. The resulting triaryl benzene structures are featured alongside key advantages including microwave assistance, solvent-free and metal-free processes, environmental benefits, high yield (74-90%), and ease of purification. Each section is distinct for clarity, employing color-coded elements.