Introduction
The Steglich esterification is a commonly used reaction in which esters are formed from carboxylic acids and alcohols through the use of a carbodiimide coupling reagent (dicyclohexylcarbodimide, DCC) and catalyst (4-(dimethylamino)pyridine, DMAP). This reaction is often run in anhydrous chlorinated solvents or dimethylformamide, which are hazardous to human health and the environment. Our research focuses on the development of a more green methodology for the Steglich esterification as well as a study of the kinetics of the reaction in real-time using NMR spectroscopy.
Greener Steglich esterification
We have developed a modified method for esterification using DMAP and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in acetonitrile, which was used to synthesize a small library of cinnamyl ester derivatives. (link) Using NMR, we have shown that the relative rate of reaction in non-anhydrous acetonitrile under air is comparable to the rate of the reaction in other commonly used more toxic solvent systems. In addition, the methodology used eliminates the need for a chromatography step or other post-extraction purification. We are currently applying this methodology to other carboxylic acid substrates.
REaction kinetics
We are using kinetic proton and fluorine NMR experiments to measure reaction rates and to probe the mechanistic pathway of the esterification in deuterated chloroform and acetonitrile solvent systems. In addition, we are investigating the rate effects of alcohol sterics, electron donating and withdrawing groups on the acid, and reagent concentration.