Lossen rearrangement

The Lossen rearrangement is the conversion of a hydroxamate ester to an isocyanate. Typically O-acyl, sulfonyl, or phosphoryl O-derivative are employed.^[1][2][3][4] The isocyanate can be used further to generate ureas in the presence of amines or generate amines in the presence of H₂O.

Reaction mechanism

The mechanism below begins with an O-acylated hydroxamic acid derivative that is treated with base to form an isocyanate that generates an amine and CO₂ gas in the presence of H₂O. The hydroxamic acid derivative is first converted to its conjugate base by abstraction of a hydrogen by a base. Spontaneous rearrangement releases a carboxylate anion to produce the isocyanate intermediate. The isocyanate is then hydrolyzed in the presence of H₂O. Finally, the respective amine and CO₂ are generated by abstraction of a proton with a base and decarboxylation.

Hydroxamic acids are commonly synthesized from their corresponding esters.^[5]

Historical references

• Lossen, W. (1872). "Ueber Benzoylderivate des Hydroxylamins". Justus Liebigs Annalen der Chemie. 161 (2–3): 347–362.
  doi:10.1002/jlac.18721610219
  .
• Lossen, W. (1875). "Ueber die Structurformel des Hydroxylamins und seiner amidartigen Derivate". Justus Liebigs Annalen der Chemie. 175 (3): 271–304.
  doi:10.1002/jlac.18751750303
  .
• Lossen, W. (1875). "Methode, die Carboxylgruppe aromatischer Säuren durch die Amidgruppe zu ersetzen". Justus Liebigs Annalen der Chemie. 175 (3): 313–325.
  doi:10.1002/jlac.18751750305
  .

• Curtius rearrangement
• Hofmann rearrangement
• Schmidt reaction
• Beckmann rearrangement
• Gabapentin

References