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.
FAQs on Fries Rearrangement Reaction
1. What is the Fries rearrangement reaction in organic chemistry?
The Fries rearrangement is an organic reaction that involves the conversion of a phenolic ester into a mixture of ortho- and para-hydroxy acylphenones. This transformation is typically carried out by heating the ester with a Lewis acid catalyst, such as anhydrous aluminium chloride (AlCl₃), in an inert solvent.
2. What is the role of the catalyst in the Fries rearrangement?
A Lewis acid catalyst, most commonly anhydrous aluminium chloride (AlCl₃), is essential for the Fries rearrangement. Its primary role is to coordinate with the carbonyl oxygen atom of the ester group. This coordination weakens the acyl-oxygen bond, facilitating its cleavage and the formation of a reactive acylium ion (R-C=O)⁺ intermediate, which then acts as an electrophile to attack the activated benzene ring.
3. What are the major products when phenyl acetate undergoes a Fries rearrangement?
When phenyl acetate undergoes a Fries rearrangement, it yields a mixture of two isomeric hydroxy ketones. The primary products are:
- o-hydroxyacetophenone (the ortho-product)
- p-hydroxyacetophenone (the para-product)
4. How does temperature affect the products of the Fries rearrangement?
Temperature is a critical factor that controls the product distribution in the Fries rearrangement. This is a classic example of thermodynamic versus kinetic control.
- At low temperatures (e.g., below 60°C), the more thermodynamically stable para-product is favoured.
- At high temperatures (e.g., above 160°C), the kinetically favoured ortho-product is the major product, which is often stabilised by intramolecular hydrogen bonding.
5. Why does the acyl group migrate specifically to the ortho and para positions?
The acyl group migrates to the ortho and para positions because the hydroxyl group (-OH), which is attached to the aromatic ring, is a powerful activating and ortho, para-directing group. It increases the electron density at the ortho and para positions through resonance, making these sites highly susceptible to attack by the electrophilic acylium ion that is generated during the reaction.
6. What is the key difference between the Fries rearrangement and the Friedel-Crafts acylation of phenols?
The main difference lies in the starting material. In Friedel-Crafts acylation, a phenol is directly acylated using an acylating agent (like an acyl chloride) and a Lewis acid. In the Fries rearrangement, the starting material is a phenolic ester, which is itself a product of the acylation of a phenol. Essentially, the Fries rearrangement rearranges an existing ester, while Friedel-Crafts acylation adds a new acyl group to a phenol.
7. What are the major limitations of the Fries rearrangement reaction?
The Fries rearrangement has several limitations that can affect its utility. The yields are often poor if the aromatic ring contains strong electron-withdrawing or deactivating groups. Furthermore, the reaction is sensitive to steric hindrance; highly substituted acyl groups or aromatic rings can lead to very low yields. The harsh conditions required also mean that only relatively stable esters can be used as substrates.
8. What is the Photo-Fries rearrangement and how does it differ from the standard reaction?
The Photo-Fries rearrangement is a significant variant that is initiated by UV light instead of a Lewis acid catalyst. It proceeds through a free-radical mechanism where the ester bond breaks homolytically to form a radical pair. These radicals then recombine, primarily at the ortho and para positions, to form the final product. The lack of a catalyst and different mechanism make it suitable for substrates that are sensitive to strong acids.
