Amides contain the paramount functional group in the field of chemistry as well as biology and they play a unique role in pharmaceutical industries. Amide bond formation is a prevalent reaction using coupling reagents, usually metal catalysts and additives etc. In this context, herein, we developed a simple and efficient synthetic approach for the direct amidation through esters, simply in water, affording the desired products in good to excellent yields. Interestingly, this method features metal-free, additive-free, and base-free characteristics, and it also uses water as a green solvent. Therefore, it is a new and eco-friendly way to realize the direct amide bond formation. Applying this methodology, we prepared over 30 different amides including the drug molecule Diethyltoluamide in good yield. Finally, this approach was successfully applied to the gram-scale synthesis of a representative amide product.

A metal and base-free effective synthetic approach for the direct amidation of esters via C(acyl)–O bond cleavage, using water as a green-solvent.