Reaction of Orthoesters with Amine Hydrochlorides: An Introductory Organic Lab Experiment Combining Synthesis, Spectral Analysis, and Mechanistic Discovery

Abstract

While orthoesters are often used by chemists as alkylating, acylating, and formylating agents, they are rarely encountered in introductory organic chemistry curricula. We describe a second-semester organic chemistry laboratory experiment in which students acetylate unknown amine hydrochloride salts with trimethyl orthoacetate (TMOA) in the absence of solvent, monitor the progress of the reaction chromatographically, identify the amide product spectroscopically, and propose a mechanism supported by spectral detection of a transient imidate intermediate in an aliquot removed from the reaction mixture. This operationally straightforward experiment combines synthesis with spectral analysis as part of a mechanistic investigation.