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

Ghosh, Subhash Chandra, Ngiam, Joyce S. Y., Seayad, Abdul M., Tuan, Dang Thanh, Chai, Christina L. L., Chen, Anqi
Journal of organic chemistry 2012 v.77 no.18 pp. 8007-8015
aldehydes, amides, amines, ammonium chloride, catalysts, copper sulfate, drugs, organic chemistry, oxidants
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 tert-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 N-acetylprocainamide.