Fries Rearrangement | Chemistry Optional Notes for UPSC PDF Download

Introduction

The Fries rearrangement represents an organic chemical transformation employed to change a phenyl ester into a hydroxy aryl ketone. This process involves the use of a Lewis acid catalyst and a Brønsted acid work-up. During the reaction, the acyl group from the phenol ester relocates to the aryl ring, positioning itself either in the ortho or para position. The choice between ortho and para placement is influenced by the reaction temperature and solvent. At lower temperatures, para substitution is favored, while higher temperatures tend to result in the dominance of the ortho product.

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

Examples

This reaction is used to convert phenyl acetate to ortho- and para- hydroxyphenyl acetate.

Fries Rearrangement for Phenyl Acetate

Mechanism of Fries Rearrangement

The reaction proceeds through the formation of a carbocation intermediate

Step 1: co-ordination of the ester to the Lewis acid follwed by rearrangement, resulting in electrophullic acylium carbonation

Step 2: Attack of the alkyl via electrophilic aromatic sustitution followed by deprotonation to restore aromaticity

Step 3: Acid work up to regenerates the  lewis acid and results in the final product (ortho)

Applications of Fries Rearrangement

Fries rearrangement has the following applications:

• The production of o- and p-hydroxy acetophenone, valuable precursors in pharmaceutical manufacturing. 
• The creation of intermediates for drugs, agrochemicals, thermographic materials, and potent antiviral agents.