Research on the Experimental Preparation of New Analgesic and Anti-Tussive Drug ethyl 1, 1-diphenyl-3-piperidinopropylsulfone (I), ethyl 1, 1-diphenyl-3-piperidinobutylsulfone (II) and 3-piperidino-1, 1-di-2′-thienylbut-1-ene (III)

Abstract

At the present time, India is the only cultivating country of poppy in the world. The necessary amount of opium in Japan is said to be 57-61 ton by year. As the imported amount of opium from India to Japan is at the most 50 ton by year, so the shortage of it is replaced with the synthetic petidine hydrochloride. Consequently the trial of experimental preparation of three methadone allied compounds such as ethyl 1, 1-diphenyl-3-piperidino propyl sulfone (I), ethyl 1, 1-diphenyl-3-piperidino butyl sulfone (II) and 3-piperiodino-1, 1-di-2′-thienyl but-1-ene (III) was requested us by the Ministry of Welfare. In the experiments of synthesis, the whole steps except the last step went well without any trouble and we could get the products with high yields in every steps. However in the last step of the condensation of sulfone with β-piperiodino alkyl chloride, it was proved to be the occurrence of side-reaction producing the diethylene-bis-piperidinium dichloride from β-piperidino ethyl chloride, and ammonium chloride and immonium-ion formation from β-piperidino propyl chloride during the condensation. By adjusting the reaction temperature at 75-80°, and using pure Na-NH_2, pure new prepared β-piperidino alkyl chloride and absolute water free solvent and prolonging the condensation time to 15 hrs, we were able to get I and II with 60% and 56% yields of the theoretical amount of sulfone, respectively. The preparation of 3-piperidino-1, 1-di-2′-thienyl but-1-ene was carried out without any difficulty as described in the literature.