Direct synthesis of amides from alcohols and amines with liberation of H2

Chidambaram Gunanathan, Yehoshoa Ben-David, David Milstein

Research output: Contribution to journalArticle

861 Citations (Scopus)

Abstract

Given the widespread importance of amides in biochemical and chemical systems, an efficient synthesis that avoids wasteful use of stoichiometric coupling reagents or corrosive acidic and basic media is highly desirable. We report a reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen (the only products) in high yields and high turnover numbers. This reaction is catalyzed by a ruthenium complex based on a dearomatized PNN-type ligand [where PNN is 2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine], and no base or acid promoters are required. Use of primary diamines in the reaction leads to bis-amides, whereas with a mixed primary-secondary amine substrate, chemoselective acylation of the primary amine group takes place. The proposed mechanism involves dehydrogenation of hemiaminal intermediates formed by the reaction of an aldehyde intermediate with the amine.

Original languageEnglish
Pages (from-to)790-792
Number of pages3
JournalScience
Volume317
Issue number5839
DOIs
Publication statusPublished - Aug 10 2007

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Amides
Amines
Alcohols
Acylation
Caustics
Diamines
Ruthenium
Dehydrogenation
Aldehydes
Hydrogen
Ligands
Acids
Substrates

ASJC Scopus subject areas

  • General

Cite this

Direct synthesis of amides from alcohols and amines with liberation of H2 . / Gunanathan, Chidambaram; Ben-David, Yehoshoa; Milstein, David.

In: Science, Vol. 317, No. 5839, 10.08.2007, p. 790-792.

Research output: Contribution to journalArticle

Gunanathan, Chidambaram ; Ben-David, Yehoshoa ; Milstein, David. / Direct synthesis of amides from alcohols and amines with liberation of H2 . In: Science. 2007 ; Vol. 317, No. 5839. pp. 790-792.
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