Study On New Synthesis Method Of Piperidines Analgesics

The traditional synthesis method of piperidines analgesics exists many disadvantages such as long reaction route, low yield, high price of raw material, toxicity. So, it has important application value to explore an efficient, environmentally friendly route to synthesis of piperidines analgesics.During carrying out the synthesis of piperidines analgesics, this paper found that, with benzene acetonitrile as raw material and LDA as deacid reagent, precursor compound alpha, alpha-di (methanesulfonyl ethyl) phenylacetonitrile can be synthesised by one pot method. Then, take this compound as raw materials react with primary amines with different R group, use control variable method to design several control tests, discuss the different effects of various experimental factors on the synthesis reaction, screen out the optimum reaction conditions, in this condition, this paper have successfully synthesized pethidine, anileridine, piminodine.This paper take benzene acetonitrile, ethylene oxide, methanesulfonyl chloride as raw materials, use LDA as deacid reagent and tetrahydrofuran as solvent, synthesis alpha, alpha-di (methanesulfonyl ethyl) phenylacetonitrile by one pot method. On this basis, this paper carry out methodology study on synthesis of pethidine, finally synthesis pethidine after two step reaction. In the research process of synthesis of anileridine, this paper design a new synthetic route of anileridine by inverse synthetic analysis of the product:take2-(4-aminophenyl) ethylamine and alpha, alpha-di (methanesulfonyl ethyl) phenylacetonitrile as raw materials to synthesis anileridine after two step reaction. And in this paper the experimental conditions were optimized, the reaction mechanism is analyzed at a certain degree. Compared with the traditional synthesis method of anileridine, the method proposed in this paper simplifies the synthesis steps, reduce the cost of reaction.In the synthesis method of piminodine of this paper, first of all, take Iodobenzene and diaminopropane as raw material to synthesis compound7, then the compound and alpha, alpha-di (methanesulfonyl ethyl) phenylacetonitrile react to synthesis piminodine by two step reaction.Finally, this paper use characterization methods including1H NMR spectrum,13C NMR spectra, DEPT135spectra, HSQC spectra, HMBC spectrum and HRMS spectrum to determine the molecular structure of product, have confirmed the synthesis of pethidine, anileridine, piminodine. The synthesis method presented in this paper shorten the reaction steps in a certain extent, improve the reaction efficiency, reduce the cost, there is a certain application value of the synthesis method presented in this paper.