Alkene synthesis from hydrazone
Shapiro reaction
How the Shapiro reaction 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; 2 equiv n-BuLi; then H₂O. Conditions: THF or TMEDA, –78 °C → 25 °C. Bonds formed: C=C; N₂; Ts⁻; bonds broken: α C–H; N–H; C–N; N–S. Stereochemistry: Less substituted alkene (kinetic deprotonation). Rate and selectivity: Dianion formation fast; N₂ loss irreversible.
At a glance
Step 1: Tosylhydrazone, then dianion
A ketone condenses with tosylhydrazine to form a tosylhydrazone, then two equivalents of strong base deprotonate both the N–H and an alpha C–H.
Step 2: Loss of Ts⁻ and N₂
Loss of the sulfinate leaving group (Ts⁻) and N₂ gas occurs in a concerted fragmentation, forming a vinyl anion directly at the former carbonyl carbon.
Step 3: Protonation
Aqueous workup protonates the vinyl anion, giving the less substituted alkene — a useful complement to Wittig or E2 methods when that regiochemistry is hard to access otherwise.
Abbreviations and terms
- Ts
- Tosyl. p-Toluenesulfonyl (p-CH₃C₆H₄SO₂–).
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- n-BuLi
- n-Butyllithium. Very strong base/nucleophile (pKa of butane ≈ 50); deprotonates alkynes and does lithium–halogen exchange.
- TMEDA
- N,N,N′,N′-Tetramethylethylenediamine. Chelates Li⁺ and breaks up RLi aggregates, making them more reactive.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- E2
- Bimolecular elimination. Concerted base removal of β-H and loss of the leaving group (anti-periplanar).
How it compares with related reactions
| Shapiro reaction | Bamford-Stevens reaction | Horner-Wadsworth-Emmons (HWE) reaction | |
|---|---|---|---|
| Reagents | TsNHNH₂; 2 equiv n-BuLi; then H₂O | Tosylhydrazone, strong base (NaOMe, NaH, or NaOEt) | Phosphonate ester (EtO)₂P(O)CH₂CO₂Et, NaH or NaOMe, aldehyde |
| Conditions | THF or TMEDA, –78 °C → 25 °C | Aprotic solvent (diglyme, toluene), 100–200 °C | THF or DME, 0–25 °C |
| Stereochemistry | Less substituted alkene (kinetic deprotonation) | Mixture of E/Z; thermodynamic (more substituted) alkene favoured | Strong E-selectivity (trans) |
| Rate / selectivity | Dianion formation fast; N₂ loss irreversible | Diazo decomposition to carbene is rate-limiting | Aldehyde addition rate-limiting; water-soluble phosphate easily removed |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Shapiro reaction?
TsNHNH₂; 2 equiv n-BuLi; then H₂O. Conditions: THF or TMEDA, –78 °C → 25 °C.
Which bonds are formed and which are broken?
Formed: C=C; N₂; Ts⁻. Broken: α C–H; N–H; C–N; N–S.
What is the stereochemical outcome?
Less substituted alkene (kinetic deprotonation)
What controls the rate or the selectivity?
Dianion formation fast; N₂ loss irreversible
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