The Hofmann rearrangement converts an amide into a primary amine with the loss of one carbon atom. First, a base deprotonates the amide. The deprotonated amide then attacks a halogen, forming an N‑haloamide. Subsequently, the N‑haloamide is deprotonated by base to give an N‑haloamide anion salt. This salt rapidly undergoes rearrangement to yield an isocyanate. Water attacks the isocyanate to form a carbamic acid, which subsequently releases carbon dioxide gas to produce a primary amine.

• Reagents: Halide Source (X₂, NaBrO₂, Alkali Hypobromite or Hypochlorite, etc.), Base (Alkali Hydroxide), H₂O
• Reactant: Primary Amine
• Product: Primary Amine with one less carbon atom
• Type of Reaction: Rearrangement

Reaction Mechanism:

Original Literature:

• 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