The Study On Synthesizing The Compounds Of N-Methyl-4-Piperidines

The compounds of N-methyl-4-piperidines have an important value in the research of medical synthesis,and the study on these compounds has been a hotspot in the chemical field. N-methyl-4-chloro-piperidine can react easily with magnesium in THF.The product has a very high activation in chemical reaction. Its intermedias piperidone and piperidol have some active group such as carbonyl and hydroxyl. So the intermedias can turn into amine, nitrile, ester and formaldehyde under certain response conditions easily. Methyl has some special functions in Pharmacology.So N-methyl-4-chloro-piperidine and its intermedias N-methyl-4-piperidone, N-methyl-4-piperidol have an extensive use in the sythesis of medicine directly and indirectly. Until now there was little correlative report on the synthesis of N-methyl-4-chlor-piperidine and its intermediates mainly depended on importing. So the study on their synthesis is of great practical significance. The synthesis of N-methyl-4-piperid one,N-methyl-4-piperidol,N-methyl-4- chloro-piperidine is the major work of this paper. The final products were identified by IR and 1HNMR.The method of ring is economical and feasible. Methylamine was treated with ethylacryate at 50℃for 3h to afford methyl-di-(β-carbethoxyethyl)-amine.Then it was added in a thin stream into a solution of sodium ethoxide and toluene, heating under reflux ..Then hydrochloric acid was added and kept the solution refuxing.The acid solution was neutralised to basic and extracted with ethyl acetate. The extraction was dried and fractionally distilled under reduced pressure to give 1-methyl-4-piperidone.Total yield of this procedure reached 59.7%.The route has advantages of mild conditions, easy operation and cheap material which laid an elementary foundation for large-scale industrialized production.methyl-4-piperidone hydrochloride was synthesized efficiently and fast with methylamine and ethyl acrylate via a series of addition, Dieckmann condensation and hydrolysis decarboxylafio -n reactions.The total yield of this procedure reached to 75.6%.Reducting piperidone is a very useful method for synthesizing piperidol at present.This text chose three methods to reduce piperidone.They were Mg-Cd2+ reduction, NaBH4- Amberlyst-15(H+)reduction and NaBH4-ZnCl2 reduction.The system of NaBH 4 - Amberlyst-15(H+)was on key study.The optimum reaction condition was gained.The yield of reduction reached to 87.9%.Piperidol was first chloridized with thionyl chloride to afford hydrochloride of N-methyl-4- chloro-piperidine, then the hydrochloride was neutralised to prepare N-methyl-4-chloro-piperidine. Finally, the objective product was obstained by the oxalate through alkalescence hydrolyzation. Effects of reaction time, temperature and dosage of solvent were studied. In the optimum reaction condition,the yield was up to 78.1%.The success of synthesizing the three intermediates laid foundation for large-scale industrialized production.And it also provides a consult value for synthesizing other compounds of Piperidines.