Copper-Catalyzed Oxidative Amidation of Aldehydes with Amine Salts: Synthesis of Primary, Secondary, and Tertiary Amides

摘要

A practical method for the amidation of aldehydes with economic ammonium chloride or amine hydrochloridensalts has been developed for the synthesis of a wide variety of amides by using inexpensive copper sulfate or copper(I) oxide as ancatalyst and aqueous tert-butyl hydroperoxide as an oxidant. This amidation reaction is operationally straightforward and providesnprimary, secondary, and tertiary amides in good to excellent yields for most cases utilizing inexpensive and readily availablenreagents under mild conditions. In situ formation of amine salts from free amines extends the substrate scope of the reaction.nChiral amides are also synthesized from their corresponding chiral amines without detectable racemization. The practicality ofnthis amide formation reaction has been demonstrated in an efficient synthesis of the antiarrhythmic drug N-acetylprocainamide.