Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides.
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.
Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research (A*STAR), 8 Biomedical Grove, Neuros 07-01, Singapore 138665.
Subhash Chandra
SC
Ghosh
Joyce S Y
JS
Ngiam
Abdul M
AM
Seayad
Dang Thanh
DT
Tuan
Christina L L
CL
Chai
Anqi
A
Chen
D000120:Acecainide / Q000138:chemical synthesis* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis; D000588:Amines / Q000138:chemical synthesis; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012492:Salts / Q000737:chemistry*; D020122:tert-Butylhydroperoxide / Q000737:chemistry*
D000447:Aldehydes; D000577:Amides; D000588:Amines; D000889:Anti-Arrhythmia Agents; D012492:Salts; D003300:Copper; D000120:Acecainide; D020122:tert-Butylhydroperoxide