Study On Synthesis Of N-Alkyl-Substituted-4-Piperidones

N-alkyl-substituted-4-piperidones,a important pharmacological active group, are essential in the development of new drugs. This kind of derivatives were applied widely in the production of medicines, pesticides, fine-chemicals because of their pharmaceutical importance.The syntheses of derivatives of N-alkyl-2(3)-substituted-4-piperidones and a compound of dipeperidones which was prepared by 1,2-ethanediamine were studied in this paper.; The artworks of N-propyl-2-methyl-4-piperidone, 1-(2-(4-oxopiperidin-1-yl)ethyl)piperidin-4 were optimized and the platform of the syntheses of piperidone derivatives was constructed.Firstly, the syntheses of N-alkyl-2(3)-substituted-4-piperidones were studied. A series of N-alkyl-2(3)-substituted-4-piperidones were synthesized from amines and ethyl crotonate(methyl methacrylate),methyl acrylate through Michael addition, Dieckmann cyclization, decarboxylation, and the parameters of the synthetic route were optimized. The total yield of N-methyl(ethyl, propyl, butyl, benzyl)-2-methyl-4- piperidone and N-methyl(ethyl, propyl, butyl, benzyl)-3-methyl-4-piperidone , in over 35%yeild, and 99% GC purity. Similarly, a compound of 1-(2-(4-oxopiperidin-1-yl)ethyl)piperidin-4 was synthesized from 1,2-ethanediamine and methyl acrylate through Michael addition, Dieckmann cyclization, decarboxylation, 98% GC purity. And the parameters of the synthetic route were optimized.as the catalyst in over 52% and 26% yield. The chemical structures were comfirmed by NMR.Secondly, a compound of 1,3,5-trimethyl-2,6-diphenylpiperidin-4-one was synthesized from methanamine, benzaldehyde and pentan-3-one through Mannich reaction. This method proceeded with fewer steps, under mild conditions. Thus it is an ideal synthetic route for the piperidones derivatives in special constraction.