Alcohol activation
Appel reaction: alcohol → alkyl halide
How the Appel 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: PPh₃, CBr₄ (or CCl₄). Conditions: CH₂Cl₂, 0–25 °C. Bonds formed: C–Br; P=O; bonds broken: C–O; P–Br. Stereochemistry: Inversion at carbon (SN2). Rate and selectivity: Driven by strong P=O bond; works best on 1° and 2° alcohols.
At a glance
Step 1: O attacks activated phosphorus
The alcohol's oxygen attacks electrophilic PPh₃ (already activated by CBr₄ or CCl₄), displacing a halide and forming an oxyphosphonium salt — a phosphorus-based leaving group far better than plain OH.
Step 2: Bromide displaces Ph₃P=O (SN2)
The liberated halide ion then performs a backside SN2 attack on the carbon bearing that activated oxygen, exactly as it would on any good leaving group.
Step 3: Alkyl bromide + Ph₃P=O
Triphenylphosphine oxide (a very stable, thermodynamically favorable byproduct) is what drives this reaction forward, giving the alkyl halide with inversion of configuration.
Abbreviations and terms
- Ph
- Phenyl. –C₆H₅.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- PPh3
- Triphenylphosphine. Nucleophilic phosphine; forms very strong P=O bonds, driving Wittig, Appel and Mitsunobu reactions.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
How it compares with related reactions
| Appel reaction | Mitsunobu reaction | Polonovski reaction | |
|---|---|---|---|
| Reagents | PPh₃, CBr₄ (or CCl₄) | PPh₃, DEAD (or DIAD), acidic H–Nu (pKa < 13) | Tertiary amine N-oxide, Ac₂O (or TFAA); then Nu⁻ (CN⁻, H⁻, enol) |
| Conditions | CH₂Cl₂, 0–25 °C | THF, 0 °C → 25 °C | CH₂Cl₂, 0–25 °C |
| Stereochemistry | Inversion at carbon (SN2) | Clean inversion at the alcohol carbon | Iminium regiochemistry set by the more acidic/accessible α-H |
| Rate / selectivity | Driven by strong P=O bond; works best on 1° and 2° alcohols | Betaine formation fast; SN2 step rate-limiting | O-acylation fast; elimination is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Appel reaction?
PPh₃, CBr₄ (or CCl₄). Conditions: CH₂Cl₂, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C–Br; P=O. Broken: C–O; P–Br.
What is the stereochemical outcome?
Inversion at carbon (SN2)
What controls the rate or the selectivity?
Driven by strong P=O bond; works best on 1° and 2° alcohols
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