Synthesis of unsaturated N-(2-Propylpentanoyl) urea analogues

Abstract

This investigation was to study the synthetic route of four unsaturated N-(2-propylpentanoyl) urea analogues which were expected to possess anticonvulsant activity. N-(4-Methyl-2-propyl-4-pentenoyl) urea, N-(2-propyl-4-pentenoyl) urea, N-(4-methyl-2-(2’-methyl-2’-propenyl)-4-pentenoyl) urea and N-(2-allyl-4-pentenoyl) urea were synthesized as potential anticonvulsants. Diethyl malonate was reacted with n-propyl bromide in sodium ethoxide solution to yield diethyl propylmalonate. Then, it was alkylated with 3-chloro-2-methyl-1-propene or allylbromide to obtain diethyl (2-methyl-2-propenyl) propylmalonate and diethyl ally(propyl)malonate, respectively. Diethyl di(2-methyl-2-propenyl) malonate and diethyl diallylmalonate were synthesized by using 2-equivalent of sodium ethoxide and alkylating agents, 3-chloro-2-methyl-l-propene or allyl bromide to react with diethyl malonate. Four disubstituted malonic esters were refluxed with LiCl-H2O-DMSO to give the corresponding decarbethoxylated products, monoesters. The monoesters were hydrolyzed in 80% alcoholic potassium hydroxide solution. The carboxylic acid products were heated with thionyl chloride to acquire the acid chloride which were reacted with urea in dry benzene with the present of potassium carbonate. The final products were obtained. The structures of the synthesized compounds were confirmed by Infrared, 1H- and 13C-Nuclear Magnetic Resonance, and Mass Spectrometry techniques.