Syn elimination — amine oxide
Cope elimination
How the Cope elimination 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: H₂O₂ or mCPBA (oxidation); then heat. Conditions: Oxidation 0–25 °C; elimination 80–160 °C (milder in DMSO/THF). Bonds formed: C=C; O–H (hydroxylamine); bonds broken: β C–H; C–N (amine oxide). Stereochemistry: Syn elimination via planar 5-membered TS. Rate and selectivity: Intramolecular, first order; faster in polar aprotic solvents.
At a glance
Step 1: Amine is oxidized to the amine oxide
A tertiary amine is oxidized to an amine oxide (with H₂O₂ or mCPBA), placing a nucleophilic, negatively-polarized oxygen directly on nitrogen.
Step 2: Syn five-membered cyclic transition state
On mild heating, that oxygen reaches intramolecularly for a β-hydrogen in a five-membered cyclic transition state, syn-periplanar by geometric necessity — the same concerted, intramolecular logic as the Chugaev elimination, just using an amine oxide instead of a xanthate.
Step 3: Alkene + hydroxylamine
The C–H and C–N bonds break as a new alkene π bond forms, releasing a hydroxylamine byproduct — because no external base or strongly acidic conditions are needed, this is a mild way to convert an amine directly into an alkene with predictable syn stereochemistry.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- DMSO
- Dimethyl sulfoxide. Polar aprotic solvent; also the oxidant in Swern/Kornblum-type reactions.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- mCPBA
- meta-Chloroperoxybenzoic acid. Peracid that transfers an electrophilic oxygen (epoxidation, Baeyer–Villiger).
- H2O2
- Hydrogen peroxide. Oxidant; its anion HOO⁻ is an excellent nucleophile.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Cope elimination | Chugaev elimination | Aldol condensation | |
|---|---|---|---|
| Reagents | H₂O₂ or mCPBA (oxidation); then heat | 1) NaH, CS₂, CH₃I 2) heat | NaOH or KOH (cat.) |
| Conditions | Oxidation 0–25 °C; elimination 80–160 °C (milder in DMSO/THF) | Neat or inert solvent, 100–250 °C | H₂O/EtOH, heat 50–100 °C |
| Stereochemistry | Syn elimination via planar 5-membered TS | Syn elimination via cyclic 6-membered TS | Mostly E-enal (thermodynamic) |
| Rate / selectivity | Intramolecular, first order; faster in polar aprotic solvents | Intramolecular, first order; no base needed | E1cB; loss of HO⁻ from the enolate is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Cope elimination?
H₂O₂ or mCPBA (oxidation); then heat. Conditions: Oxidation 0–25 °C; elimination 80–160 °C (milder in DMSO/THF).
Which bonds are formed and which are broken?
Formed: C=C; O–H (hydroxylamine). Broken: β C–H; C–N (amine oxide).
What is the stereochemical outcome?
Syn elimination via planar 5-membered TS
What controls the rate or the selectivity?
Intramolecular, first order; faster in polar aprotic solvents
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go