Hofmann Rearrangement-百灵威

Hofmann Rearrangement

时间: Invalid Date

作者: 百灵威

Amides are converted to primary amines that are one carbon shorter via the Hofmann rearrangement. The base deprotonates the amide, which attacks the halogen, forming an N-haloamide. The N-haloamide is then deprotonated by the base, forming an N-haloamide salt that quickly undergoes a concerted rearrangement to produce isocyanate. Water attacks isocyanate, creating carbamic acid, which releases carbon dioxide gas to make the 1° amine.

Reagents: Halide Source (X₂, NaBrO₂, Alkali Hypobromite or Hypochlorite, etc.), Base (Alkali Hydroxide), H₂O
Reactant: 1° Amide
Product: One Carbon Shorter 1° Amine
Type of Reaction: Rearrangement

Mechanism

Original Paper

Hofmann, A. W. Ueber Die Einwirkung Des Broms in Alkalischer Lösung Auf Amide Berichte der deutschen chemischen Gesellschaft 1881, 14 (2), 2725-2736.

Top Citations

A Mild and Efficient Modified Hofmann Rearrangement. J. Org. Chem. 1997, 62 (21), 7495–7496.

A Microfluidic Flow Chemistry Platform for Organic Synthesis: The Hofmann Rearrangement. Tetrahedron Letters 2009, 50 (26), 3287–3289.

A Facile Synthesis of 2-Oxazolidinones via Hofmann Rearrangement Mediated by Bis(Trifluoroacetoxy)Iodobenzene. Tetrahedron Letters 2001,42 (8), 1449–1452.

Related Compounds

Halogens

Bases