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Weinreb Amide Formation

(Weinreb Amidation)

Published Online: 15 SEP 2010

DOI: 10.1002/9780470638859.conrr660

Comprehensive Organic Name Reactions and Reagents

Comprehensive Organic Name Reactions and Reagents

How to Cite

2010. Weinreb Amide Formation. Comprehensive Organic Name Reactions and Reagents. 660:2956–2962.

Publication History

  1. Published Online: 15 SEP 2010

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Abstract

The preparation of N-methoxyl-N-methyl amides from N,O-dimethyl hydroxylamine in the presence of a coupling reagent (e.g., AlMe3) is generally known as the Weinreb amide formation or Weinreb amidation. The corresponding amides are called as the Weinreb amides. The Weinreb amide is an important acylation reagent (i.e., equivalent to an acyl group) and been widely used in organic synthesis, such as Weinreb aldehyde synthesis. Several methods have been developed for the preparation of Weinreb amides and the most frequently used one is the treatment of the mixture of carboxylic acid and N,O-dimethyl hydroxylamine hydrochloride with trimethyl aluminum (AlMe3). However, due to its pyrophoric property, AlMe3 is not suitable for large-scale preparation, so that many other coupling reagents have been used for the preparation of the Weinreb amides. This reaction currently plays an important role in the preparation of aldehydes and ketones.

Keywords:

  • α-N-methyl-N-methoxy metal alkoxide;
  • alkynyllithium;
  • N-methoxyl-N-methyl amides;
  • trimethyl aluminum