A sustainable metal and base-free direct amidation of esters using water as a green solvent

Herein, we report a simple and efficient synthetic approach for direct amidation of esters via C(acyl)-O bond cleavage without any additional reagents or catalysts, using only water as a green solvent. Subsequently, the reaction byproduct is recovered and utilized for the next phase of ester synthesis. This method emphasized metal-free, additive-free, and base-free characteristics making it a new, sustainable, and eco-friendly way to realize direct amide bond formation. In addition, the synthesis of the drug molecule diethyltoluamide and the Gram-scale synthesis of a representative amide are demonstrated.

Automated summary

Herein, we propose a straightforward and efficient method to directly convert esters into amides by breaking the C(acyl)-O bond, without the need for additional reagents or catalysts, using only water as a green solvent. Furthermore, the byproduct of the reaction can be recovered and used for subsequent ester synthesis. This metal-free, additive-free, and base-free approach offers a novel, sustainable, and eco-friendly strategy for amide bond formation. Additionally, we demonstrate the synthesis of the drug molecule diethyltoluamide and the Gram-scale synthesis of a representative amide.