Copper-Catalyzed Oxidative
Amidation of Aldehydes
with Amine Salts: Synthesis of Primary, Secondary, and Tertiary Amides
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Abstract
A practical method for the amidation of aldehydes with
economic
ammonium chloride or amine hydrochloride salts has been developed
for the synthesis of a wide variety of amides by using inexpensive
copper sulfate or copper(I) oxide as a catalyst and aqueous <i>tert</i>-butyl hydroperoxide as an oxidant. This amidation reaction
is operationally straightforward and provides primary, secondary,
and tertiary amides in good to excellent yields for most cases utilizing
inexpensive and readily available reagents under mild conditions.
In situ formation of amine salts from free amines extends the substrate
scope of the reaction. Chiral amides are also synthesized from their
corresponding chiral amines without detectable racemization. The practicality
of this amide formation reaction has been demonstrated in an efficient
synthesis of the antiarrhythmic drug <i>N</i>-acetylprocainamide