A simple synthesis of Hantzsch esters derivatives as proton donors in the hydrogenation transfer reaction

The Hantzsch esters derivatives have been attracted much attention for their pharmacological properties. The primary pharmaceutical application of these compounds are the treatment of cardiovascular diseases, such as hypertension. It has also found to show many promising bioactivities such as antibacterial, antioxidant, and anticancer. Besides, the Hantzsch esters also powerful reducing agents in the hydrogenation transfer reaction. Therefore, several methods to afford Hantzsch esters have been developed, such as the classical method, the use of microwaves, including the utilization of various catalysts. However, these methods have disadvantages such as long reaction time, low yields, relatively expensive reagents, and challenge in separation. In continuation of effort towards the development of efficient synthetic procedures, Hantzsch ester synthesis research carried out of the one-pot three-components reaction of aldehydes, ethyl acetoacetate, and ammonium acetate in ethanol solvents using the reflux method which is monitored by TLC. The pure products have obtained by recrystallization. The product structure has been confirmed by melting point and spectroscopc data including UV, IR, 1H-NMR, 13C-NMR, HSQC, and HMBC. In conclusion, a simple and highly efficient method for one-pot three-component synthesis of Hantzsch esters from various aromatic and aliphatic aldehydes, ethyl acetoacetate, and ammonium acetate get a good yield. The simple experimental protocol, mild conditions, avoiding the use of any catalyst, and good yields are the advantages of this procedure. This research is part of the synthesis of dihydrochalcone through the hydrogenation transfer reaction.