N-Heterocyclic Carbene-Catalyzed Alcohol Acetylation: An Organic Experiment Using Organocatalysis

Abstract

Undergraduate students in the teaching laboratory have successfully used N-heterocyclic carbenes (NHCs) as organocatalysts for the acetylation of primary alcohols, despite the high water sensitivity of uncomplexed (free) NHCs. The free NHC readily reacted with chloroform, resulting in an air- and moisture-stable adduct that liberates the free NHC when heated to temperatures above 45 °C in solution. The free NHC is a kinetically competent catalyst for the acetylation of benzyl, n-amyl, and isoamyl alcohols, a process that was monitored by gas chromatography (GC) and nuclear magnetic resonance (NMR) spectroscopy. Using the method of initial rates, students have calculated the relative rates for the three alcohol substrates, noting the trend: rate of benzyl > rate of n-amyl > rate of isoamyl alcohol. In their reports, students used these rates to demonstrate how NHC catalysts are sensitive to the steric bulk of the alcohol substrates. Overall, students were exposed to all aspects of chemical catalysis: synthesis of a catalyst, collection of initial rate data, development of a steric model to explain the data, and postulation of catalyst modification for increased activity based on their model.