Fries Rearrangement Reaction

Fries rearrangement in a rearrangement reaction in which the transformation of a phenolic ester to hydroxyl aryl ketone occurs. This organic reaction always takes place in the presence of any suitable catalyst. Brønsted or Lewis acids like AlCl3, HF, SnCl4 are the most suitable catalyst for this reaction. In this organic reaction, the migration of the acyl group that belongs to phenolic ester takes place into the aryl ring. This reaction is ortho or para selective, which means that the acyl group from phenolic ester will attach to ortho or para positions. By changing the conditions (temperature and solvent), one can get the desired product, either ortho or para.

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The above Image Illustrates the Fries Rearrangement Reaction of the Acetoxy Benzene (phenylacetate). 

It is essential to observe that the product can be ortho or para according to the conditions during the reaction.

What is the Fries Rearrangement Reaction Mechanism?

The mechanism of Fries rearrangement reaction is complex and exciting. Let's assume that we are using AlCl3 as a Lewis acid in this reaction. First of all, the AlCl3 forms a coordinate bond with carbonyl oxygen that belongs to the acyl group in this reaction. This carbonyl oxygen is more abundant in electrons, and hence, it acts as a Lewis base. The interaction of carbonyl oxygen and AlCl3 polarizes the bond between phenolic oxygen and acyl residue. It results in the rearrangement of the aluminium chloride group to phenolic oxygen.

 This rearrangement results in the formation of a free acylium carbocation. Then, it reacts with an aromatic ring in a classical electrophilic aromatic substitution. It results in the release of the abstracted proton in the form of hydrochloric acid, whereas the aluminium chloride releases the chlorine during the reaction. It is important to note that the temperature of the substitution reaction defines its orientation. If the reaction takes place at a low temperature, then it results in the para product's formation. However, at high temperatures, the ortho product will form. The non-polar solvents favour the formation of ortho products while the para product ratio increases with increasing polarity of the solution.

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The above Image Shows the Mechanism of the Fries Rearrangement Reaction. Here, the Presence of the Non-polar Solvent Results in the Yielding of Ortho-substituted Products.

Applications of Fries Rearrangement Reaction

The Fries rearrangement reaction has many uses. They are:

  • Fries rearrangement reaction is essential for the synthesis of o- and p-hydroxy acetophenone. Both these compounds are essential intermediates during the preparation of pharmaceuticals.

  • This reaction is useful for the synthesis of α-tocopherol or Vitamin E.

  • Fries rearrangement reaction is necessary for the production of ortho-acyl hydroxy[2.2]paracyclophanes, which has significant industrial importance.

  • In the medical industry, this reaction helps to synthesize various thermographic materials, intermediates, and several antiviral agents. 

Recent Researches and Trends on Fries Rearrangement Reaction

  • Scientists have studied the Thia-fries rearrangement of aryl sulfonates under microwave in solvent-free conditions.

  • Exposing the photoreactive liquid crystalline polymer films to linearly polarized ultraviolet (LPUV) light results in axis-selective photo-Fries rearrangement. Moreover, it exhibited photoinduced optical anisotropy during the process.

  • To synthesize Muricadienin, scientists are employing fries rearrangement. Muricadienin is a putative unsaturated precursor in the biosynthesis of trans- and cis-solamin.

  • Chiral ferrocenyl phosphates yield diastereomeric enriched 1,2-P, O-phosphonates by the anionic phospho-Fries rearrangement. After that, it can be transformed into pure phosphane.

  • When the reaction of aryl esters takes place by Liquid-phase Fries rearrangement mechanism yields Cs2.5H0.5PW12O40. The catalyst present in the reaction is heteropoly acid H3PW12O40 (PW supported on silica or its salt.

  • The Anionic phospho-Fries rearrangement plays a major role in the detailed study of ferrocene chemistry.

Photo Fries Rearrangement

A photochemical variant of the Fries rearrangement reaction is also possible in phenyl ester. This reaction is popular as photo-Fries rearrangement, which can yield products [1,3] and [1,5] likewise. This reaction involves the mechanism of the radical reaction. This reaction can also take place even when the deactivating substituents are present in the aromatic group. However, due to the low yields obtained in this reaction, it is not suitable for commercial purposes.

The photo-fries rearrangement can also happen in nature in daily life. For example, if you expose the water bottle made of polycarbonate to the sun, this reaction can take place. However, the UV light must have a wavelength of 310nm, and it must be heated to a temperature of at least 40oC. In this case, the leaching of phthalate from the plastic can occur by photolysis of ester groups.

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The above Picture Contains a General Example of a Photo-fries Rearrangement along with its Mechanism.

FAQ (Frequently Asked Questions)

Q1. What are the Shortcomings of the Fries Rearrangement Reaction?

Ans. Fries rearrangement reaction has various applications, but it has some limitations too. The biggest drawback of this reaction is that no compounds other than esters are suitable for it. It is because, in harsh conditions of Fries rearrangement, only esters can withstand stable acyl components. Moreover, it is not possible to massively substitute the acyl or aromatic component in this reaction. By doing it, there will be very less chemical yield because of the steric constraints. An adverse effect occurs in this reaction during the deactivating the meta-directing groups on the benzene ring. A similar effect can be seen in the Friedel–Crafts acylation too.

Q2. What are the Different Variants of Fries Rearrangement Reaction?

Ans. There are some variants of Fries rearrangement reaction which are of great importance in chemistry. The first variant of this reaction is the photo-Fries rearrangement reaction. This organic reaction involves the transformation of phenolic esters into hydroxyl ketones without a catalyst. In this reaction, the UV rays work as a catalyst. The other variant of this organic reaction is Thia-Fries rearrangement. In this reaction, aryl triflinates transforms into trifluoromethane sulfinyl phenols. The catalyst present in this reaction is aluminium chloride in dichloromethane. The anionic phospho-Fries rearrangement is another variant of this organic reaction. In this variant reaction of the Fries rearrangement, aryl phosphate ester transforms into ortho-hydroxyaryl phosphonates.