Titration of Organolithium Reagents

Described herein is an organic experiment involving the titration of organolithium reagents, which are air- and moisture-sensitive. This experiment begins with the preparation of the titration standard (N -pivaloyl-o -toluidine or N -pivaloyl-o-benzylaniline) via a nucleophilic acyl substitution from the corresponding amine. Characterization of this compound by proton NMR also includes a facile hydrogen–deuterium exchange to help assign the amide proton in the spectrum. Upon synthesis and characterization, this compound is conveniently applied both as the titration standard and color indicator in the titration of an organolithium reagent. This experiment is pedagogically valuable because it revisits the fundamental concepts and techniques in a titration, but also features advanced topics involving the structures and reactivities of organolithium reagents. Furthermore, it shows students how to effectively manipulate air- and moisture-sensitive materials with a Schlenk line, syringes, and cannulae under an inert atmosphere, as well as how to distill anhydrous solvents.