Fries Rearrangement
The Fries rearrangement is an organic reaction where phenolic esters are heated with a Lewis acid such as anhydrous aluminium chloride (AlCl3). This causes the acyl group of the ester to migrate to the aromatic ring, forming phenolic ketones.
A common example is the conversion of phenyl acetate into a mixture of ortho-hydroxyacetophenone and para-hydroxyacetophenone.
Important Points
- The reaction is influenced by temperature, solvent, and the amount of AlCl3.
- Low temperatures (< 60°C) favor formation of the para product.
- High temperatures (> 160°C) favor formation of the ortho product.
- The products can be separated by steam distillation, since ortho-isomers form intramolecular hydrogen bonds and are more volatile.
Mechanism of Fries Rearrangement
The mechanism is not completely certain. Evidence shows that both intermolecular and intramolecular pathways may occur at the same time.
1. Intermolecular Mechanism
In this mechanism, the Lewis acid generates an acylium ion. This intermediate then reacts through a Friedel–Crafts type acylation, attacking the aromatic ring at the ortho or para position.
2. Intramolecular Mechanism
In this mechanism, the acyl group migrates within the same molecule without detaching completely. This pathway is considered more common under certain conditions.
Applications
- Used to synthesize o- and p-hydroxyacetophenone, which are important pharmaceutical intermediates.
- Allows the preparation of compounds like 2-hydroxy-4,6-dimethylacetophenone in high yields.
- Useful for preparing 2,5-dihydroxyacetophenone from hydroquinone diacetate, which cannot be made by normal Friedel–Crafts acylation.
- Applied in the synthesis of antiviral agents, agrochemical intermediates, and photographic materials.
Photo-Fries Rearrangement
When phenolic esters are exposed to UV light (photolysis), they undergo a similar rearrangement without a catalyst. This process mainly proceeds through a free radical mechanism and is mostly intramolecular.
Additional Notes
The Fries rearrangement converts phenyl esters into hydroxy aryl ketones using Lewis acid catalysis. Reaction temperature controls whether the ortho or para product dominates.
Detailed Notes:
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