Multicomponent Synthesis of Lidocaine at Room Temperature
Michelle Lee, Nathan J. Vosburg, Emily A. Shimizu, Manuel A. Rentería‐Gómez, Rocío Gámez‐Montaño, David A. Vosburg
Abstract
A new undergraduate organic laboratory experiment has been developed and implemented for the Ugi three-component synthesis of the topical anesthetic lidocaine with excellent atom economy. Paraformaldehyde, diethylamine, and 2,6-dimethylphenyl isocyanide were combined and conveniently stirred at room temperature for a week in methanol with acetic acid. Students successfully collected their product by precipitation and filtration and then characterized it by NMR spectroscopy (1H, 13C, COSY, DEPT, HSQC), IR spectroscopy, mass spectrometry, and melting point analysis. Students also evaluated multiple lidocaine synthesis procedures using green chemistry principles and explored the reaction mechanisms of both traditional (N-acylation followed by N-alkylation) and multicomponent lidocaine syntheses. Results from both in-person and remote instruction versions of the experiment are included.