Operationally Simple Synthesis of N,N-Diethyl-3-methylbenzamide (DEET) Using COMU as a Coupling Reagent

Abstract

A novel procedure is described where students use COMU [(1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate], as a nonhazardous partner, in the one-pot coupling of a carboxylic acid and amine producing N,N-diethyl-3-methylbenzamide (DEET). Fundamental principles of carbonyl reactivity are understood, with potential for expansion to new methods of amide bond formation. The reaction can be monitored visually by virtue of the color change associated with the conversion, and all byproducts are conveniently water-soluble. This modern, microscale reaction is appropriate for a second-semester introductory undergraduate organic chemistry course: it can be performed during a 3 h laboratory period and is operationally straightforward. Curricular flexibility allows for this protocol to serve as a meaningful discussion of mechanistic organic chemistry and spectroscopy.