Definition: What is Fries Rearrangement?

The Fries rearrangement is an organic reaction used to convert a phenyl ester to a hydroxy aryl ketone using a Lewis acid catalyst and Brønsted acid work-up. In this reaction, an acyl group belonging to phenol ester migrates to the aryl ring either in the ortho or para position, depending on the reaction temperature and solvent. A low reaction temperature favors para substitution, and with high temperatures, the ortho product dominates ^[1-2].

The history of this reaction goes back to 1908 when German chemist Karl Theophil Fries reported in a journal.

Examples of Fries Rearrangement

This reaction is used to convert phenyl acetate to ortho- and para- hydroxyphenyl acetate ^[2].

Mechanism of Fries Rearrangement

The reaction proceeds through the formation of a carbocation intermediate ^[2-4].

Applications of Fries Rearrangement

Fries rearrangement has the following applications:

• Synthesis of o- and p-hydroxy acetophenone, which are useful intermediates in the manufacture of pharmaceuticals
• Synthesis of drug and agrochemical intermediates, thermographic materials, and active antiviral agents