Standard Article

The Schmidt Reaction

  1. Aaron Wrobleski,
  2. Thomas C. Coombs,
  3. Chan Woo Huh,
  4. Sze-Wan Li,
  5. Jeffrey Aubé

Published Online: 31 OCT 2012

DOI: 10.1002/0471264180.or078.01

Organic Reactions

Organic Reactions

How to Cite

Wrobleski, A., Coombs, T. C., Huh, C. W., Li, S.-W. and Aubé, J. 2012. The Schmidt Reaction. Organic Reactions. 78:1:1–320.

Author Information

  1. The University of Kansas, Department of Medicinal Chemistry, Lawrence, Kansas, 66045-7582, U.S.A.

Publication History

  1. Published Online: 31 OCT 2012

Abstract

The classical form of the Schmidt reaction involves the reaction of a carbon-centered electrophile with hydrazoic acid with loss of nitrogen, usually with a rearrangement that forms a new carbon-nitrogen bond. Although the conversion of a ketone into an amide is the most commonly used variation, mechanistically related versions utilize an aldehyde, acid, or a carbocation generated from an alkene or alcohol as the electrophilic component. In recent years, the definition of the Schmidt reaction has been modified to include analogous reactions in which the hydrazoic acid is replaced by an alkyl azide, promoted by Lewis acids. The use of an alkyl azide uniquely permits the formulation of intramolecular Schmidt reactions of the azide with a carbonyl or carbocationic electrophile.

Keywords:

  • alkyl azide;
  • amide synthesis;
  • hydrazoic acid;
  • lactam synthesis;
  • rearrangement;
  • ring expansion;
  • Schmidt reaction