An Improved Method for Synthesis of N‐stearoyl and N‐palmitoylethanolamine

Abstract

AbstractCertain N‐acylethanolamines interact with cannabinoid receptors and have anorexic and neuroprotective effects. Traditional methods for the synthesis of N‐acylethanolamines use fatty acid chlorides, fatty acid methyl esters, free fatty acids and triacylglycerols as acyl donors to react with ethanolamine. In the present study, we investigated the feasibility of using fatty acid vinyl esters as the acyl donor to synthesize N‐stearoyl and N‐palmitoylethanolamine. Theoretically, the use of fatty acid vinyl esters should lead to an irreversible reaction because the volatile acetaldehyde by‐product is easily removed. Four reaction conditions, i.e. catalyst concentration, substrate ratio, temperature, and time were evaluated. The reaction performed at mild temperatures and with an excess amount of ethanolamine which acted as both reactant and solvent resulted in the formation of high purity N‐stearoyl and N‐palmitoylethanolamine. When 20 mmol ethanolamine was reacted with 1 mmol vinyl stearate at 80 °C for 1 h with 1% sodium methoxide as catalyst, N‐stearoylethanolamine with 96% purity was obtained after the removal of excess ethanolamine without further purification, while N‐palmitoylethanolamine with 98% purity was obtained by reacting with the same substrate ratio at 60 °C for 1.5 h with 3% catalyst. Complete conversion of vinyl stearate and palmitate was achieved.