What Is Fries Rearrangement Reaction Definition Mechanism Examples and Applications
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 in Organic Chemistry
1. What is the Fries rearrangement reaction?
The Fries rearrangement reaction is a chemical reaction in which an aryl ester is converted into a mixture of ortho- and para-hydroxy aryl ketones in the presence of a Lewis acid such as AlCl3. It involves migration of the acyl group from the oxygen atom to the aromatic ring under acidic conditions. This rearrangement is widely used in organic chemistry to synthesize substituted hydroxy ketones from phenolic esters.
2. What is the general reaction of the Fries rearrangement?
The general reaction of the Fries rearrangement is the conversion of an aryl ester into ortho- and para-acylated phenols using a Lewis acid catalyst. For example:
C6H5OCOCH3 → o- and p-HOC6H4COCH3 (in presence of AlCl3)
- Substrate: aryl ester (e.g., phenyl acetate)
- Catalyst: Lewis acid such as AlCl3
- Products: ortho- and para-hydroxy aryl ketones
3. What is the mechanism of the Fries rearrangement?
The mechanism of the Fries rearrangement involves Lewis acid activation of the ester followed by acyl migration to the aromatic ring. The key steps are:
- Coordination of AlCl3 with the carbonyl oxygen of the ester
- Formation of an acylium ion-like species (RCO+)
- Electrophilic aromatic substitution at the ortho or para position
- Hydrolysis to give hydroxy aryl ketones
4. What reagents are used in the Fries rearrangement?
The Fries rearrangement typically uses a Lewis acid catalyst such as AlCl3 to promote acyl migration. Common reagents include:
- Aryl ester (e.g., phenyl acetate)
- AlCl3 (most common catalyst)
- Heat to facilitate rearrangement
5. Why does the Fries rearrangement give both ortho and para products?
The Fries rearrangement gives both ortho and para products because the acylium ion attacks the activated aromatic ring at positions directed by the phenolic oxygen. The –OH group formed during rearrangement is:
- Ortho/para-directing
- Electron-donating by resonance
6. What is an example of the Fries rearrangement reaction?
A classic example of the Fries rearrangement is the conversion of phenyl acetate into o- and p-hydroxyacetophenone. The reaction is:
C6H5OCOCH3 → o-HOC6H4COCH3 + p-HOC6H4COCH3 (in presence of AlCl3)
This demonstrates intramolecular migration of the acetyl group from oxygen to the aromatic ring.
7. What is the difference between Fries rearrangement and Friedel–Crafts acylation?
The key difference is that Fries rearrangement involves migration of an acyl group within an aryl ester, while Friedel–Crafts acylation introduces a new acyl group onto an aromatic ring. Differences include:
- Fries: starts from an aryl ester
- Friedel–Crafts: uses acyl chloride (RCOCl) or anhydride
- Fries: intramolecular rearrangement
- Friedel–Crafts: intermolecular electrophilic substitution
8. How does temperature affect the Fries rearrangement?
Temperature affects the ortho/para ratio in the Fries rearrangement, with higher temperatures generally favoring the ortho product. Specifically:
- Low temperature → more para product
- High temperature → more ortho product
9. Is the Fries rearrangement intramolecular or intermolecular?
The Fries rearrangement is primarily an intramolecular rearrangement because the acyl group migrates within the same molecule. The acyl group moves from the oxygen atom of the ester to the aromatic ring, forming hydroxy aryl ketones. However, in some conditions, intermolecular pathways may also contribute.
10. What are the applications of the Fries rearrangement in organic chemistry?
The Fries rearrangement is used to synthesize hydroxy aryl ketones, which are important intermediates in pharmaceuticals and dyes. Applications include:
- Preparation of substituted acetophenones
- Synthesis of fragrance and dye intermediates
- Production of pharmaceutical precursors
