Lossen rearrangement

The Lossen rearrangement is the conversion of an acyl hydroxamate to an isocyanate and carboxylic acid side product.^[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.

General reaction scheme for the Lossen rearrangement.

Lossen rearrangement
Named after	Wilhelm Lossen
Reaction type	Rearrangement reaction
Identifiers
RSC ontology ID	RXNO:0000156

Reaction mechanism

The acyl hydroxamate is first converted to its conjugate base. A concerted rearrangement event then occurs in which the amide substituent migrates to the amide nitrogen, the nitrogen donates a pair of electrons to form the isocyanate C=N double bond, and the N–O σ-bond breaks.

Arrow pushing mechanism for the Lossen rearrangement.

Historical references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.

See also

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