Rearrangement — amine oxide [2,3]-shift
Meisenheimer rearrangement
How the Meisenheimer 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: Allylic tertiary amine N-oxide. Conditions: Heat, 25–100 °C (neutral). Bonds formed: O–C (allyl); C=C (shifted); bonds broken: N–C (allyl); C=C (original). Stereochemistry: Suprafacial [2,3]; chirality transfer from N-oxide to carbon. Rate and selectivity: Concerted, 5-membered envelope TS; unimolecular.
At a glance
Step 1: Allylic N-oxide
An allylic tertiary amine N-oxide has its nitrogen-bound oxygen positioned directly adjacent to the allylic system — the same structural setup as the allylic sulfoxides that undergo Mislow-Evans rearrangement.
Step 2: [2,3]-Sigmatropic shift (TS)
Heating promotes a [2,3]-sigmatropic shift through a five-membered cyclic transition state — the nitrogen analog of the Mislow-Evans rearrangement, with oxygen migrating from nitrogen onto the allylic terminus as the double bond shifts position.
Step 3: O-allyl hydroxylamine
The product is an O-allylic hydroxylamine ether — this and the Mislow-Evans rearrangement are two faces of the identical pericyclic logic, just swapping which heteroatom (N or S) carries the migrating oxygen.
Abbreviations and terms
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- Meisenheimer
- Meisenheimer complex. The anionic cyclohexadienyl intermediate of SNAr stabilised by electron-withdrawing groups.
How it compares with related reactions
| Meisenheimer rearrangement | Boekelheide rearrangement | Pinacol rearrangement | |
|---|---|---|---|
| Reagents | Allylic tertiary amine N-oxide | 2-Methylpyridine N-oxide, Ac₂O (or TFAA); then aqueous base | Cat. H₂SO₄ or other strong acid |
| Conditions | Heat, 25–100 °C (neutral) | Ac₂O, reflux (TFAA works at 25 °C) | Heat, aqueous or neat acid |
| Stereochemistry | Suprafacial [2,3]; chirality transfer from N-oxide to carbon | None (achiral product) | Migratory aptitude: aryl, H > tertiary alkyl > methyl |
| Rate / selectivity | Concerted, 5-membered envelope TS; unimolecular | N-acylation fast; [3,3] shift rate-limiting | Ionisation to the cation is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Meisenheimer rearrangement?
Allylic tertiary amine N-oxide. Conditions: Heat, 25–100 °C (neutral).
Which bonds are formed and which are broken?
Formed: O–C (allyl); C=C (shifted). Broken: N–C (allyl); C=C (original).
What is the stereochemical outcome?
Suprafacial [2,3]; chirality transfer from N-oxide to carbon
What controls the rate or the selectivity?
Concerted, 5-membered envelope TS; unimolecular
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti