Inline reaction monitoring of amine-catalyzed acetylation of benzyl alcohol using a microfluidic stripline NMR setup.

We present an in-depth study of the acetylation of benzyl alcohol in the presence of N,N-diisopropylethylamine (DIPEA) by NMR monitoring the reaction from 1.5 seconds to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. In line spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all the three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction in case tertiary amines were present. The pyridine catalyzed reaction proceeds via a different mechanism.