Research On Synthetic Methodology Of Heterocyclic Ketene Aminals, Aromatic Aldehydes And Cyclic Secondary Amines

Organic synthetic methodology is an indispensable part of organic chemistry. Heterocyclic ketene aminals (HKAs) are significant intermediates and skeletal structures with biological activity in organic synthesis. Based on the synthetic methodology of HKAs, we studied the reactions of HKAs with aromatic aldehydes and cyclic secondary amines affording two series of Mannich-like deravatives and dihydropyridones. All the compounds were confirmed by 1HNMR, 13CNMR, HRMS and other analysis methods.One-pot three-component synthesis of Mannich-like deravatives was investigated starting from 2-(nitromethylene)imidazolidine, aromatic aldehydes and cyclic secondary amines using fluorinated alcohol such as 2,2,2-trifluroethanol (TFE) as an additive due to its high hydrogen bonding donor ability and acidic character. Twenty-four novel compounds were synthesized via this method, which expanded the reaction diversity of heterocyclic ketene aminals. Then representative Mannich-like derivatives were selected as reactive intermediates to prepare the corresponding products such as ethers, ketal and carbonyl compound, which would be a potential method for access to carbonyl compounds from piperidine deravatives.Ethyl 2-(imidazolidin-2-ylidene)acetate reacted with aromatic aldehydes to prepare dihydropyridones using cyclic secondary amines piperidine as a base catalyst, affording 26 dihydropyridone compounds. Compared to the reported method, this method has the advantages of shorter reaction time and higher yields.