SUBSTITUTED DIOXYPIPERIDINES AND PROCESS FOR THE PREPARATION THEREOF

摘要

1374820 1 - [2 - (4,4 - Ethylenedioxypiperidino)ethyl] - 3 - phenyl 2 - imidazolidinones ALDRICH CHEMICAL CO Inc 23 Dec 1971 [28 Dec 1970] 59902/71 Heading C2C Novel 1 - [2 - (4,4 - ethylenedioxypiperidino) ethyl] - 3 - phenyl - 2 - imidazolidinones of the general formula wherein R1 is a hydrogen atom or a C 1 -C 8 alkyl, phenyl or benzyl group and each of R2 and R3 is a chlorine, bromine or iodine atom or a trifluoromethyl group, and non-toxic, pharmaceutically acceptable acid addition salts thereof are prepared by reaction of a 4,4-ethylene-dioxypiperidine of the general formula wherein X is a chlorine or bromine atom or a tosyloxy radical, with a 1-phenyl-2-imidazolidinone of the general formula followed optionally by salification of the product 4,4-Ethylenedioxy-piperidines of the second general formula above are prepared by reaction of a compound of the general formula with ethylene chlorohydrin and reaction of the resulting 1 - (2 - hydroxyethyl) - 4,4 - ethylenedioxy-piperidine of the general formula with thionyl chloride or bromide or p-toluenesulphonyl chloride. 1-Phenyl-2-imidazolidinones of the third general formula above are prepared by reaction of an aniline of the general formula with 2-bromoethylamine hydrobromide, reaction of the resulting N-phenyl-ethylenediamine of the general formula with potassium cyanate in the presence of hydrochloric acid and cyclization of the resulting N-(2-anilinoethyl)-urea of the general formula by heating at about 190‹ C. 1-Phenyl-2-imidazolidinones of the fourth general formula above are prepared by reaction of a 1-phenyl-2-imidazolidinone of the third general formula above with sodium, sodamide or an alkali metal hydride, followed by 2-(2- chloroethoxy)-tetrahydropyran, treatment of the resulting 1-[2-(2-tetrahydropyranyloxy)- ethyl]-3-phenyl-2-imidazolidinone of the general formula with a strong acid and reaction of the resulting 1-(2-hydroxyethyl)-3-phenyl-2-imidazolidone of the general formula with p-toluenesulphonyl chloride. Pharmaceutical compositions having tranquillizing and anti-emetic activity comprise, as active ingredient, a 1-[2-(4,4-ethylenedioxypiperidino)ethyl]-3-phenyl-2-imidazolidinone of the first general formula above or a non-toxic pharmaceutically acceptable salt thereof, together with a pharmaceutical carrier therefor, and may be administered orally or parenterally.