Homologation — carbene chemistry
Arndt-Eistert homologation
How the Arndt-Eistert homologation 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: SOCl₂; CH₂N₂ (2 equiv.); Ag₂O (or hν / Δ), H₂O. Conditions: Et₂O 0 °C, then H₂O / dioxane 50–70 °C. Bonds formed: α-diazoketone; ketene; R–CH₂–COOH; bonds broken: C–Cl; N₂ (gas). Stereochemistry: Wolff shift retains configuration at the migrating carbon. Rate and selectivity: Ag(I) catalyses N₂ loss; second CH₂N₂ scavenges HCl.
At a glance
Step 1: Diazomethane acylation
An acid chloride reacts with diazomethane; the diazomethane carbon attacks the electrophilic carbonyl, and loss of chloride and N₂ generates an α-diazoketone.
Step 2: Wolff rearrangement
Silver catalysis (Ag₂O) triggers loss of N₂ from the diazoketone to form a reactive carbene, which immediately undergoes a 1,2-shift — the Wolff rearrangement — where the R group migrates to the carbene carbon, forming a ketene.
Step 3: Water adds to the ketene
Water adds across the ketene's strained C=C=O, giving a carboxylic acid with one more carbon than the starting acid chloride — a reliable one-carbon homologation.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- Et2O
- Diethyl ether. Low-boiling ether solvent, classic for Grignard reagents.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- SOCl2
- Thionyl chloride. Converts acids/alcohols to chlorides; byproducts SO₂ and HCl leave as gases.
- HCl
- Hydrochloric acid / hydrogen chloride. Strong acid; chloride is the nucleophile in additions/substitutions.
- Δ
- Heat. Reaction is run at elevated temperature.
- hν
- Light. Photochemical activation.
How it compares with related reactions
| Arndt-Eistert homologation | Aldol condensation | Bamford-Stevens reaction | |
|---|---|---|---|
| Reagents | SOCl₂; CH₂N₂ (2 equiv.); Ag₂O (or hν / Δ), H₂O | NaOH or KOH (cat.) | Tosylhydrazone, strong base (NaOMe, NaH, or NaOEt) |
| Conditions | Et₂O 0 °C, then H₂O / dioxane 50–70 °C | H₂O/EtOH, heat 50–100 °C | Aprotic solvent (diglyme, toluene), 100–200 °C |
| Stereochemistry | Wolff shift retains configuration at the migrating carbon | Mostly E-enal (thermodynamic) | Mixture of E/Z; thermodynamic (more substituted) alkene favoured |
| Rate / selectivity | Ag(I) catalyses N₂ loss; second CH₂N₂ scavenges HCl | E1cB; loss of HO⁻ from the enolate is rate-determining | Diazo decomposition to carbene is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Arndt-Eistert homologation?
SOCl₂; CH₂N₂ (2 equiv.); Ag₂O (or hν / Δ), H₂O. Conditions: Et₂O 0 °C, then H₂O / dioxane 50–70 °C.
Which bonds are formed and which are broken?
Formed: α-diazoketone; ketene; R–CH₂–COOH. Broken: C–Cl; N₂ (gas).
What is the stereochemical outcome?
Wolff shift retains configuration at the migrating carbon
What controls the rate or the selectivity?
Ag(I) catalyses N₂ loss; second CH₂N₂ scavenges HCl
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