H-Bond Driven Solvent-Free Rapid Access of β -enamino Esters/Ketones using 230-400 Mesh Silica Gel as a Catalyst

Purpose This study aimed to develop a cheap and eco-friendly protocol for the synthesis of β-enamino esters and β-enaminones by the catalysis of silica gel (230-400 mesh) under solvent-free conditions. Methods Targeted enamino esters and enaminones are very important synthetic intermediates for the construction of biologically relevant heterocycles due to the presence of multiple reactive sites in their structures. Commercially available different silica-gel was chosen as catalysts as the size of silica-gel can be tunned without compromising with the price. Results The developed protocol was found to be a quick, easy, and effective process for the synthesis of enamino esters or enamino ketones with the primary amines in high yield in the presence of silica gel of smaller particle size and high specific surface area. The present approach is also applicable to ammonium acetate as an amine source. This strategy provides the β-enamino ester and β-enaminone derivatives in excellent to outstanding yields (up to 98%) in a short period of time at 100°C and is suitable to a wide range of aromatic/aliphatic and chiral amines. Reversibility of the protocol is inhibited by the presence of N-H in the final product which is a key for the success of the current protocol as it forms a six-membered H-bonding which provides extra stability of the product. The existence of a H-bond in the product was ascertained by X-ray crystallographic studies. Conclusion We have exploited a size-selective efficient catalytic property of silica-gel towards the eco-friendly synthesis of enamino esters or enamino ketones reactive intermediates. It is believed that the present strategy can provide an alternative, highly efficient, and much more economical protocol for the synthesis of enaminones and enaminoates intermediates than the existing protocols. Graphical abstract