Green Ugi-3CR Method for the Synthesis of α-Aminoamides in Water Using SLS

Introduction: Quinoline-based α-aminoamides are promising scaffolds in drug discovery due to their enhanced pharmaceutical properties and biological relevance. Developing efficient and environmentally friendly synthetic methods remain a key goal in pharmaceutical chemistry. Methods: In this study, we developed a green synthetic approach using a Ugi three-component reaction (Ugi-3CR). The reaction involves 2-chloroquinoline-3-carbaldehyde, various aldehydes, and isocyanides in the presence of sodium lauryl sulfate (SLS) as a surfactant in water. Results: The optimized reaction conditions afforded the desired α-aminoamide products in moderate to good yields (59-79%), depending on the substrate used. The reaction worked well with a broad range of starting materials, showing its versatility and efficiency. The use of SLS in water not only promotes reaction efficiency but also aligns with green chemistry principles. Discussion: This work highlights how multicomponent reactions like the Ugi-3CR can simplify the synthesis of structurally diverse, biologically relevant molecules. The use of water and SLS also aligns with green chemistry goals, making the process both practical and environmentally conscious. Conclusion: Our study presents a practical, green, and versatile strategy for the synthesis of quinoline- based α-aminoamides via Ugi-3CR, supporting their continued development in medicinal chemistry.