Fries rearrangement
| Fries rearrangement | |
|---|---|
| Named after | Karl Theophil Fries |
| Reaction type | Rearrangement reaction |
| Identifiers | |
| Organic Chemistry Portal | fries-rearrangement |
| RSC ontology ID | RXNO:0000444 |
The Fries rearrangement, named for the German chemist Karl Theophil Fries, is a rearrangement reaction of a phenolic ester to a hydroxy aryl ketone by catalysis of Lewis acids.
It involves migration of an acyl group of phenol ester to the aryl ring. The reaction is ortho and para selective and one of the two products can be favoured by changing reaction conditions, such as temperature and solvent.
Despite many efforts, a definitive reaction mechanism for the Fries rearrangement has not been determined. Evidence for inter- and intramolecular mechanisms have been obtained by crossover experiments with mixed reactants. Reaction progress is not dependent on solvent or substrate. A widely accepted mechanism involves a carbocation intermediate.
In the first reaction step a Lewis acid for instance aluminium chloride AlCl
3 co-ordinates to the carbonyl oxygen atom of the acyl group. This oxygen atom is more electron rich than the phenolic oxygen atom and is the preferred Lewis base. This interaction polarizes the bond between the acyl residue and the phenolic oxygen atom and the aluminium chloride group rearranges to the phenolic oxygen atom. This generates a free acylium carbocation which reacts in a classical electrophilic aromatic substitution with the aromatic ring. The abstracted proton is released as hydrochloric acid where the chlorine is derived from aluminium chloride. The orientation of the substitution reaction is temperature dependent. A low reaction temperature favors para substitution and with high temperatures the ortho product prevails, this can be rationalised as exhibiting classic Thermodynamic versus kinetic reaction control as the ortho product can form a more stable bidentate complex with the Aluminium. Formation of the ortho product is also favoured in non-polar solvents; as the solvent polarity increases, the ratio of the para product also increases.
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