Efficient Solid-Phase Organic Synthesis of Prochiral Schiff Bases from Asymmetric Ketones on Merrifield Resin

Resumo

A solid-phase organic synthesis protocol is presented for the preparation of asymmetric Schiff bases derived from prochiral ketones using functionalized Merrifield resins. Due to the lower electrophilicity of ketones compared to aldehydes, solid-phase imine formation from ketones remains scarcely reported. In this study, 1,2-ethylenediamine was covalently attached to Merrifield resins with chloride loadings of 1.4 mmol/g and 3.5–4.5 mmol/g, followed by condensation with the asymmetric ketones in anhydrous tetrahydrofuran. Reaction conditions were systematically evaluated by varying solvent, temperature (25–70 °C), and reaction time (1–24 h). While reactions at room temperature afforded low yields (20%), reflux at 70 °C for 5 h significantly improved conversions, affording resin-supported prochiral imines in yields ranging from 90 to 99%. The formation of the C=N bond was confirmed by Fourier-transform infrared spectroscopy (1634–1650 cm^–1), and fluorescence monitoring indicated that imine formation approached completion within 5 h under reflux conditions. The solid-phase organic synthesis methodology eliminates the need for chromatographic purification, as products were isolated by vacuum filtration followed by drying at 50 °C. This approach provides a practical and reproducible route for the preparation of solid-supported prochiral imines with potential applications as precursors of chiral ligands and functional materials.