Fragmentation — alkynone synthesis
Eschenmoser-Tanabe fragmentation
How the Eschenmoser-Tanabe fragmentation 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: TsNHNH₂, AcOH (or Et₃N); α,β-epoxy ketone. Conditions: CH₂Cl₂ or AcOH, 0–25 °C. Bonds formed: C≡C; C=O (new carbonyl); N₂; TsH; bonds broken: Cα–Cβ (ring); epoxide C–O; C–N; N–S. Stereochemistry: Alkyne carbons lose stereochemistry. Rate and selectivity: Hydrazone formation, then fast irreversible fragmentation.
At a glance
Step 1: Epoxy ketone + TsNHNH₂ → tosylhydrazone
An α,β-epoxy ketone condenses with tosylhydrazine to form a tosylhydrazone right next to the strained epoxide — positioning two reactive groups adjacent to each other, much like the setup for a Grob fragmentation.
Step 2: Base-triggered fragmentation
Base deprotonates the hydrazone N–H; the resulting anion pushes electrons through the adjacent C–C bond, which breaks as the epoxide ring opens and N₂ and sulfinate are expelled together — a single concerted fragmentation, structurally analogous to Grob fragmentation but built on a hydrazone/epoxide pairing instead of a leaving group/donor pairing.
Step 3: Ring-opened alkynone
The result is a ring-opened alkynone — this fragmentation is a reliable way to convert a cyclic α,β-epoxy ketone directly into an acyclic alkyne bearing a distal carbonyl, cleaving the ring at a very specific, predictable bond.
Abbreviations and terms
- Ts
- Tosyl. p-Toluenesulfonyl (p-CH₃C₆H₄SO₂–).
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- AcOH
- Acetic acid. Weak acid and polar protic solvent.
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Eschenmoser-Tanabe fragmentation | Grob fragmentation | Fischer indole synthesis | |
|---|---|---|---|
| Reagents | TsNHNH₂, AcOH (or Et₃N); α,β-epoxy ketone | Substrate with γ-leaving group and donor (e.g. NR₂, O⁻); often base or heat | Phenylhydrazine, ketone (acetone), acid (ZnCl₂, PPA, H₂SO₄, AcOH) |
| Conditions | CH₂Cl₂ or AcOH, 0–25 °C | Polar solvent, mild heat | 80–180 °C, Brønsted or Lewis acid |
| Stereochemistry | Alkyne carbons lose stereochemistry | Antiperiplanar alignment of donor lone pair, C–C and C–LG | None in product; regiochemistry from ene-hydrazine formation |
| Rate / selectivity | Hydrazone formation, then fast irreversible fragmentation | Concerted; favoured by good LG (OTs) and strong donor | [3,3]-shift is rate-limiting and irreversible |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Eschenmoser-Tanabe fragmentation?
TsNHNH₂, AcOH (or Et₃N); α,β-epoxy ketone. Conditions: CH₂Cl₂ or AcOH, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C≡C; C=O (new carbonyl); N₂; TsH. Broken: Cα–Cβ (ring); epoxide C–O; C–N; N–S.
What is the stereochemical outcome?
Alkyne carbons lose stereochemistry
What controls the rate or the selectivity?
Hydrazone formation, then fast irreversible fragmentation
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti