Unsaturated cyclic ureas as new nontoxic biodegradable transdermal penetration enhancers I: Synthesis

A new concept was implemented to reduce the toxicity of some new biodegradable transdermal penetration enhancers. These enhancers consist of 1-alkyl-4-imidazolin-2-one and a long-chain alkyl ester group at the N-3 position. The synthesis involves N-alkylation of the parent compound with soft alkylating agents which were prepared in high yields by an improved method. A phase transfer catalysis technique using KOH as the base, tetrabutylammonium bromide as the catalyst, and toluene as the solvent was found to be most effective in the N-alkylation step.