α-Halogenation of carboxylic acids
Hell-Volhard-Zelinsky reaction
How the Hell-Volhard-Zelinsky 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: 1) PBr₃ (or cat. P), Br₂ 2) H₂O. Conditions: Neat or CCl₄, 80–100 °C; then aqueous workup. Bonds formed: C–Br (α); acyl bromide then COOH; bonds broken: α C–H; acid C–OH. Stereochemistry: Racemic at a new α stereocentre. Rate and selectivity: Enolization of acyl bromide is rate-limiting.
At a glance
Step 1: Acid → acyl bromide
PBr₃ (or catalytic P with Br₂) converts the carboxylic acid into an acyl bromide. Unlike a free acid, an acyl bromide enolizes readily, which is the whole reason this reaction needs phosphorus.
Step 2: Enol attacks Br₂
The acyl bromide tautomerizes to its enol, and the enol's C=C attacks Br₂ at the α-carbon, giving an α-bromo acyl bromide — the same enol-plus-electrophilic-halogen logic as acid-catalyzed α-halogenation of a ketone.
Step 3: Hydrolysis to the α-bromo acid
Aqueous workup hydrolyzes the acyl bromide back to the carboxylic acid (or exchanges with another acid, which regenerates fresh acyl bromide), leaving the α-bromo acid. The α-bromide can then be displaced to make α-amino and α-hydroxy acids.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- PBr3
- Phosphorus tribromide. Converts alcohols to bromides by SN2.
- HBr
- Hydrobromic acid. Strong acid; bromide is a good nucleophile.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
How it compares with related reactions
| Hell-Volhard-Zelinsky reaction | Acid-catalyzed hydrolysis of a nitrile | Haloform reaction of a methyl ketone | |
|---|---|---|---|
| Reagents | 1) PBr₃ (or cat. P), Br₂ 2) H₂O | Nitrile R–C≡N, H₃O⁺ (conc. HCl or H₂SO₄), H₂O | I₂ (or Br₂, Cl₂, NaOCl) and NaOH |
| Conditions | Neat or CCl₄, 80–100 °C; then aqueous workup | Reflux, several hours | Aqueous base, 25 °C; excess halogen |
| Stereochemistry | Racemic at a new α stereocentre | No new stereocentre; α-stereocentres retained | No stereocentre formed |
| Rate / selectivity | Enolization of acyl bromide is rate-limiting | Water attack on the protonated nitrile is rate-limiting; amide hydrolysis is the slower, forcing stage | Each halogenation faster than the last (acidity increases) |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Hell-Volhard-Zelinsky reaction?
1) PBr₃ (or cat. P), Br₂ 2) H₂O. Conditions: Neat or CCl₄, 80–100 °C; then aqueous workup.
Which bonds are formed and which are broken?
Formed: C–Br (α); acyl bromide then COOH. Broken: α C–H; acid C–OH.
What is the stereochemical outcome?
Racemic at a new α stereocentre
What controls the rate or the selectivity?
Enolization of acyl bromide is rate-limiting
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