Fries Rearrangement

In the early 1900s, K. Fries and colleagues reacted phenolic esters of acetic and chloroacetic acid with aluminum chloride, isolating a mixture of ortho- and para-acetyl and chloroacetyl phenols. Fries realized that this rearrangement of phenolic esters was general, and for this the transformation of phenolic esters to corresponding ketones and aldehydes in the presence of Lewis or Bronsted acids (e.g. HF, HClO_4, PPA) became known as the Fries rearrangement.

There are two main types of Fries rearrangement: an anionic reaction where ortho-lithiated O-aryl carbamates are converted to substituted salicylamides, and a photochemical reaction where light-irradiated phenolic esters are converted to the corresponding phenols.

The Friedel-Crafts acylation of phenols is often a two-stage process, formation of the phenolic ester followed by a Fries rearrangement.

One application of the Fries rearrangement is in the synthesis of the potent protein kinase C inhibitor (-)-balanol.