Nitrogen-extrusion rearrangement family
Lossen rearrangement
How the Lossen rearrangement works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Hydroxamic acid, activator (Ac₂O, TsCl), base. Conditions: Mild base, 25–100 °C, then H₂O. Bonds formed: R–N; N=C=O; bonds broken: C–R; N–O. Stereochemistry: Migrating group retains configuration. Rate and selectivity: Rate set by leaving-group ability of the O-acyl/O-sulfonyl group.
At a glance
Step 1: Activate the N–OH
A hydroxamic acid's OH is converted to a good leaving group (typically an O-acyl or O-sulfonyl ester).
Step 2: Deprotonation, 1,2-shift
Base removes the remaining N–H; as the leaving group departs from oxygen, the R group migrates from carbon to nitrogen in the same concerted 1,2-shift used by Hofmann, Curtius, and Beckmann, forming an isocyanate.
Step 3: Hydrolysis and decarboxylation
Water adds to the isocyanate and loses CO₂, giving a primary amine — proof that this whole rearrangement family (Hofmann, Curtius, Lossen, Schmidt) converges on the identical nitrogen-migration mechanism, just with different leaving groups.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- TsCl
- p-Toluenesulfonyl chloride. Turns an alcohol OH into a good leaving group (tosylate).
- Ac2O
- Acetic anhydride. Acetylating agent.
- Hofmann
- Hofmann product/rule. Elimination giving the less substituted alkene (bulky base or leaving group).
How it compares with related reactions
| Lossen rearrangement | Hofmann rearrangement | Schmidt reaction | |
|---|---|---|---|
| Reagents | Hydroxamic acid, activator (Ac₂O, TsCl), base | Br₂, NaOH (or NaOBr), H₂O | HN₃ (or NaN₃), H₂SO₄ or polyphosphoric acid |
| Conditions | Mild base, 25–100 °C, then H₂O | 0 °C then 50–70 °C | Strong acid, 25–80 °C; HN₃ is toxic and explosive |
| Stereochemistry | Migrating group retains configuration | Migrating group retains configuration | Migrating group retains configuration |
| Rate / selectivity | Rate set by leaving-group ability of the O-acyl/O-sulfonyl group | Concerted 1,2-shift is rate-determining; amine has one carbon fewer | N₂ loss and R-shift are concerted and irreversible |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Lossen rearrangement?
Hydroxamic acid, activator (Ac₂O, TsCl), base. Conditions: Mild base, 25–100 °C, then H₂O.
Which bonds are formed and which are broken?
Formed: R–N; N=C=O. Broken: C–R; N–O.
What is the stereochemical outcome?
Migrating group retains configuration
What controls the rate or the selectivity?
Rate set by leaving-group ability of the O-acyl/O-sulfonyl group
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti