Rearrangement — aryl ester to ketone
Fries rearrangement
How the Fries rearrangement 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: AlCl₃ (≥1 equiv; or BF₃, TfOH). Conditions: Low T (<60 °C) favors para; high T (>160 °C) favors ortho; neat or PhNO₂. Bonds formed: C–C (aryl–acyl); phenol O–H (after work-up); bonds broken: C(acyl)–O (aryl ester); aromatic C–H. Stereochemistry: Regiochemistry: para (kinetic, low T) vs ortho (chelated, high T). Rate and selectivity: Acylium formation and EAS both contribute; needs stoichiometric AlCl₃.
At a glance
Step 1: AlCl₃ complexes C=O, acylium forms
AlCl₃ coordinates an aryl ester's carbonyl oxygen, weakening the O–aryl bond and eventually promoting its ionization to release a resonance-stabilized acylium ion — the same acylium electrophile used in Friedel-Crafts acylation, generated intramolecularly instead of from an acid chloride.
Step 2: Ring π attacks the acylium (para shown)
This acylium ion, still tethered nearby by the aluminum-phenoxide complex, is attacked by the ring's own π electrons in the same electrophilic aromatic substitution mechanism used throughout this library, reacting preferentially ortho or para to the original ester oxygen.
Step 3: Deprotonation, work-up
Loss of a proton restores aromaticity, giving a hydroxyaryl ketone — this converts an aryl ester directly into an ortho- or para-acylated phenol, using nothing but the ester's own acyl group as the incoming electrophile.
Abbreviations and terms
- Lewis acid
- Lewis acid. Electron-pair acceptor (AlCl₃, BF₃, TiCl₄…) that activates carbonyls and halides.
- AlCl3
- Aluminium chloride. Strong Lewis acid for Friedel–Crafts reactions.
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- HCl
- Hydrochloric acid / hydrogen chloride. Strong acid; chloride is the nucleophile in additions/substitutions.
- EAS
- Electrophilic aromatic substitution. An electrophile replaces H on an arene via a Wheland intermediate.
- Wheland
- Wheland intermediate (arenium ion). The cyclohexadienyl cation formed when an electrophile adds to a benzene ring.
How it compares with related reactions
| Fries rearrangement | Bamberger rearrangement | Beckmann rearrangement | |
|---|---|---|---|
| Reagents | AlCl₃ (≥1 equiv; or BF₃, TfOH) | N-Phenylhydroxylamine, dilute H₂SO₄ (aq) | H₂SO₄, PCl₅, TsCl or PPA |
| Conditions | Low T (<60 °C) favors para; high T (>160 °C) favors ortho; neat or PhNO₂ | H₂O, 25–60 °C | Acid, 100–130 °C (industrial: oleum) |
| Stereochemistry | Regiochemistry: para (kinetic, low T) vs ortho (chelated, high T) | None; para-selective | Group anti to OH migrates, with retention |
| Rate / selectivity | Acylium formation and EAS both contribute; needs stoichiometric AlCl₃ | Loss of water to give the nitrenium ion is rate-limiting | Migration is rate-limiting; leaving-group ability of N–OX matters |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Fries rearrangement?
AlCl₃ (≥1 equiv; or BF₃, TfOH). Conditions: Low T (<60 °C) favors para; high T (>160 °C) favors ortho; neat or PhNO₂.
Which bonds are formed and which are broken?
Formed: C–C (aryl–acyl); phenol O–H (after work-up). Broken: C(acyl)–O (aryl ester); aromatic C–H.
What is the stereochemical outcome?
Regiochemistry: para (kinetic, low T) vs ortho (chelated, high T)
What controls the rate or the selectivity?
Acylium formation and EAS both contribute; needs stoichiometric AlCl₃
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti