Fries Rearrangement

The Reaction

The Fries rearrangement reaction is an organic name reaction which involves the conversion of phenolic esters into hydroxyaryl ketones on heating in the presence of a catalyst. Suitable catalysts for this reaction are Brønsted or Lewis acids such as HF, AlCl3, BF3, TiCl4, or SnCl4. The Fries rearrangement reaction is an ortho, para-selective reaction, and is used in the preparation of acyl phenols.1 This organic reaction has been named after German chemist Karl Theophil Fries.

The photo-Fries rearrangement involves a similar conversion of phenolic esters into hydroxy ketones in the presence of UV light without catalyst.1

The thia-Fries rearrangement involves the conversion of aryl triflinates to trifluoromethanesulfinyl phenols in the presence of aluminum chloride in dichloromethane.2

The anionic phospho-Fries rearrangement involves the conversion of an aryl phosphate ester [ArOP(=O)(OR)2] into an ortho-hydroxyarylphosphonate [o-HO-Ar-P(=O)(OR)2]. This rearrangement yields phenols with an ortho C-P bond.3

Materials

     

Applications

The Fries rearrangement has found application in the following areas:

  • The use of an ionic melt [1-butyl-3-methylimidazolium chloroaluminate, ([BMIm]Cl·xAlCl3)] as both solvent and Lewis acid catalyst was investigated. The reaction with phenyl benzoate yields ortho- and para‑hydroxybenzophenone.4



  • Synthesis of o- and p-hydroxyacetophenones (useful intermediates in the manufacture of pharmaceuticals).5
  • Total synthesis of α-tocopherol (vitamin E).6
  • Regioselective synthesis of ortho-acylhydroxy[2.2]paracyclophanes, via TiCl4-catalyzed Fries rearrangement and direct regioselective acylation reaction.7
  • Synthesis of drug and agrochemical intermediates, thermographic materials, and effective antiviral agents.8
  • Synthesis of hydroxynaphthyl ketones, via scandium trifluoromethanesulfonate catalyzed Fries rearrangement of acyloxynaphthalenes.9
  • Photochemical one-pot synthesis of 5-, 6-, and 7-substituted chroman-4-ones from aryl 3-methyl-2-butenoate esters, via a photo-Fries rearrangement and a base-catalyzed intramolecular oxa-Michael addition reaction.10

Scheme of the above syntheses:

Recent Research and Trends

  • Thia–Fries rearrangement of aryl sulfonates in solvent-free conditions under microwave dielectric heating has been studied.8
  • Photoreactive liquid crystalline polymer films were reported to undergo axis-selective photo-Fries rearrangement, and exhibited photoinduced optical anisotropy when exposed to linearly polarized ultraviolet (LPUV) light.11
  • Fries rearrangement has been employed in the key steps in the total synthesis of muricadienin, the unsaturated putative precursor in the biosynthesis of trans- and cis-solamin.10
  • The anionic phospho-Fries rearrangement of chiral ferrocenyl phosphates yields diastereomeric enriched 1,2-P,O-phosphonates, which can then be converted into an enantiomerically pure phosphane.13
  • Liquid-phase Fries rearrangement of aryl esters catalyzed by heteropoly acid H3PW12O40 (PW) supported on silica or its salt Cs2.5H0.5PW12O40 (CsPW) has been reported.14
  • Anionic phospho-Fries rearrangement has been successfully applied to investigate ferrocene chemistry.15
  • Fries rearrangement is employed for the synthesis of the antiviral flavonoid lead ladanein, starting from 2,6-dimethoxyquinone.16



  • Heteropoly acid H3PW12O40 has been reported as an efficient and environmentally benign catalyst for the Fries rearrangement of phenyl acetate.17

V-06/15-1

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