Eco-Friendly Synthesis of Polyhydroquinolines using TBAB/CS₂CO₃ in Aqueous PEG-600

A sustainable and efficient one-pot, four-component protocol was developed for the synthesis of polyhydroquinoline derivatives. The reaction involves the condensation of an aromatic aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol), and ammonium acetate (1.5 mmol) using a dual catalytic system of tetrabutylammonium bromide (5 mol%) and cesium carbonate (5 mol%). The reaction was performed in an environmentally benign PEG-600/water medium. Initially, the reaction mixture was stirred at room temperature for 5 minutes, followed by heating at 80 °C until completion, as monitored by TLC. The work-up involved reducing the reaction in ice-cold water, followed by extraction with ethyl acetate. The crude products were isolated as yellow solids and purified by recrystallization from hot ethanol or by short silica gel column chromatography using 10-15% ethyl acetate in hexane. This method afforded the target polyhydroquinoline derivatives in good to excellent yields. The key features of this protocol include mild reaction conditions, operational simplicity, use of a recyclable green solvent system, and easy product isolation. The PEG-600/water medium enhances the reaction rate and allows for catalyst recovery, making this approach eco-friendly and suitable for gram-scale synthesis.