Studies On Syntheses Of N-Substituted-4-Piperidone Derivatives

N-Alkyl-4-piperidones and its derivatives were applied widely in the production of medicines, peticides, fine-chemicals because of their pharmaceutical importance. More attention has been paid to the synthesis of chiral piperidones because they are important synthetic blocks.N-alkyl-4-piperidone was selected as the research object in this paper. The synthetic route of N-alkyl-4-piperidones was systematically studied. As a result, The established process is that N-alkyl-4-piperidones were obtained from amines and met- hyl acrylate through Michael addition, Dieckmann cyclocondensation, decarboxyla- tion.N-methyl-4-piperidone was synthesized from methylamine and methyl acrylate (molar ratio = 1∶2.2) through Michael addition under room temperature; Dieckmann cyclocondensation catalysed by sodium methoxide-methanol solution under 95~100℃; decarboxylation catalysed by acid. The total yield is up to 54%. N-benzyl-4-Piperidone was simillarly synthesized from phenylmethylamine and methyl acrylate in the yield of 82%.N-methyl-4-piperidinol was prepared through the hydrogenation of N-methyl- 4-piperidone under 0.4~0.8 Mpa, 75~80℃in the yield of 96%.N-methyl-4-chloropiperidine was yielded through the chlorination of N-methyl- 4-piperidinol by sulfurous dichloride under 80℃in the yield of 49%.On the basis of established process, a few chiral N-substituted-4-piperidones were also obtained from chiral hydroxylamines and methyl acrylate through Michael addition, Dieckmann cyclocondensation, decarboxylation, including S-(+)-1-(1-hydr- oxybutan-2-yl)piperidin-4-one,R-(-)-1-(1-hydroxybutan-2-yl)piperidin-4-one, S-(+)- 1-(1-hydroxypropan-2-yl)piperidin-4-one and 1-(1-hydroxybutan-2-yl)piperidin-4-one, 1-(2-hydroxyethyl)piperidin-4-one .The total yields of all is over 35%.