Study On The Preparative Method Of Piperidone And Its Derivatives

Piperidones and its derivatives have been widely utilized in the production of medicines, pesticides, fine-chemicals because of their pharmaceutical importance.N-Ethyl-4-piperidone was chosen as the target molecule in our work. The synthetic route of N-Ethyl-4-piperidones has been systematically investigated.N-Ethyl-4-piperidone was prepared by double Michael addition reaction, followed subsequently by Dieckmann cyclocondensation catalyzed by sodium methoxide by employing ethylamine and methylacrylate as starting materials.The total yield of N-Ethyl-4-piperidone was about 14 %, due to its thermal and chemical instability during normal purification process.The intermediate, 1,5-Dichloropentan-3-one, was prepared by using classic Friedel-Crafts acylation, in which ethylene gas and 3-chloropropionyl chloride used as starting materials and aluminium chloride used as catalyst. The total yield was>90 %, and the level of purity was about 75 %, determined by Gas Chromatography. The purified 1,5-Dichloropentan-3-one reacted with the primary amine, aniline and ethylamine respectively, giving the target piperidones with a yield ranging from 40-50%.Based on atomic economic principia, we tried to synthesize N-Ethyl-4-piperidone by employing Double-Mannich reaction under various reaction conditions. The reaction was investigated systematically by changing solvents and activators. Although a satisfied yield has not obtained in our study, it sheds some light on improving and optimizing the reaction conditions in the future.