What is Fries Rearrangement Definition Mechanism and Reaction Conditions
A rearrangement reaction is a class of organic reactions, in this class, a molecule’s carbon skeleton undergoes rearrangement to produce a structural isomer of the original molecule. A substituent moves within the same molecule from one atom to another atom frequently.
Different Rearrangement Reactions:
Curtius Rearrangement or Curtius Reaction:
Curtius’ reaction includes the heating of an acyl azide. This acyl azide loses nitrogen and then gets rearranged to an isocyanate.
Claisen Rearrangement:
The typical claisen rearrangement is the first and slow step of the isomerization of allyl and aryl ethers to ortho alkylated phenols. A cyclohexanone is generated in the actual rearrangement step. It is a [3,3]-sigmatropic rearrangement.
Beckmann Rearrangement:
In this particular rearrangement reaction, an oxime is transformed into an amide.
Hofmann Rearrangement:
The Hofmann rearrangement occurs from the treatment of a primary amide with bromine and hydroxide ion in water. This results in the formation of an amine in which the carbonyl group of the starting amide is lost.
Fries Rearrangement: You are going to study about this rearrangement in detail here.
About Fries Rearrangement:
Fries rearrangement is an exciting reaction in organic chemistry. Fries Rearrangement is a rearrangement reaction of organic chemistry in which an aryl ester is converted to a hydroxy aryl ketone with the assistance of aqueous acid and a Lewis acid catalyst.
In Fries Rearrangement reaction, an acyl group of the phenolic ester gets transferred to the aryl ring. It is also interesting to observe that Fries rearrangement is selective to ortho and para positions, which means that, the acyl group gets attached to the ortho position or para position of the aryl ring. This particular selectivity of the reaction is managed by making specific changes in the reaction conditions (the reaction conditions include the temperature under which the response is made or the solvent used for the reaction).
Example-First phenol is converted to phenylacetate.
For this reaction to take place, phenol is treated with a base (NaOH) in the presence of pyridine to produce a phenoxide ion. And then sodium phenoxide is formed. Sodium phenoxide is later treated with acetyl chloride to produce an ester. In this reaction, NaCl is released. The ester produced is phenylacetate.
When phenylacetate is subjected to a Lewis acid (AlCl3), rearrangement occurs, and ortho hydroxy acetophenone and para hydroxy acetophenone is produced. This particular rearrangement is called fries rearrangement.
There have been many efforts to determine a particular mechanism for Fries rearrangement. A conclusive reaction mechanism for the Fries rearrangement is yet to be determined. There has been evidence for inter-and intramolecular mechanisms which were obtained by crossover experiments with mixed reactants. The Reaction progress is independent of solvent or substrate. There is a widely accepted mechanism present though. This mechanism involves the formation of a carbocation intermediate.
Fries Rearrangement Mechanism
At first, the carbonyl oxygen of the acyl group gives rise to a complex with a Lewis acid catalyst (Aluminium chloride). Since the carbonyl oxygen has more number of electrons, it is, hence, a better Lewis base. Therefore, the formation of this complex with the carbonyl oxygen is favoured over the construction of the complex with the phenolic oxygen.
Thus, the bond between the acyl complex and the phenolic oxygen gets polarized; this results in the rearrangement of the AlCl3 bond to the phenolic oxygen. This furthermore leads to the formation of the acylium carbocation. The acylium carbocation now attacks the aromatic ring utilizing the electrophilic aromatic substitution reaction.
It is also of utmost importance to note that the orientation of this electrophilic aromatic substitution is highly dependent on temperature. Lower reaction temperatures facilitate substitution at the para position. Relatively high temperatures lead to substitution at ortho positions.
The usage of non-polar solvents in this rearrangement reaction also favours the substitution at the ortho position. Highly polar solvents enable para-substituted products in this rearrangement reaction. This particular rearrangement reaction and its mechanism are called fries rearrangement reaction.
Limitations of Fries Rearrangement:
The essential limitations of Fries rearrangement are as follows:
Due to its relatively severe reaction conditions, only esters with somewhat less reactive acyl components can be used in this reaction.
Relatively lower yields are received when heavily substituted acyl components are used.
When deactivating or meta-directing groups are present on the aromatic ring, this also results in relatively lower yields.
Photo-Fries Rearrangement:
A photochemical variation is also possible in addition to the normal thermal phenyl ester reaction. The photo-Fries rearrangement can give [1,3] and [1,5] products. This includes a radical reaction mechanism. This reaction is can also be done by deactivating substituents on the aromatic group. Since the yields are low, this procedure is not recommended for commercial production.
Anionic Fries Rearrangement:
In this type of Fries rearrangement, ortho-metalation of aryl esters, carbonates, carbamates, with a strong base leads to the rearrangement to produce the ortho-carbonyl species.
FAQs on Fries Rearrangement Reaction in Organic Chemistry
1. What is the Fries rearrangement in organic chemistry?
The Fries rearrangement is a reaction in which an aryl ester is converted into o- and p-hydroxyaryl ketones using a Lewis acid catalyst such as AlCl3. It involves migration of the acyl group (–CO–R) from the oxygen atom to the aromatic ring.
- Starting material: Aryl ester (e.g., phenyl acetate).
- Catalyst: Commonly AlCl3.
- Products: Ortho- and para-acylated phenols.
- It is an example of an intramolecular acyl transfer reaction.
2. What is the general reaction of the Fries rearrangement?
The general reaction of the Fries rearrangement is: Ar–O–CO–R → o- and p-HO–Ar–CO–R in the presence of a Lewis acid such as AlCl3.
- Example: C6H5–O–COCH3 (phenyl acetate)
- Reagent: AlCl3, heat
- Products: o-hydroxyacetophenone and p-hydroxyacetophenone
- The acyl group migrates to the ortho and para positions of the aromatic ring.
3. What is the mechanism of the Fries rearrangement?
The Fries rearrangement mechanism proceeds via Lewis acid activation of the ester followed by acyl migration to the aromatic ring. The key steps are:
- Step 1: Coordination of AlCl3 to the carbonyl oxygen of the ester.
- Step 2: Formation of an acylium ion (R–C≡O+) or acyl–AlCl3 complex.
- Step 3: Electrophilic aromatic substitution at ortho or para position.
- Step 4: Hydrolysis to yield o- and p-hydroxyaryl ketones.
4. What reagents are used in the Fries rearrangement?
The Fries rearrangement requires an aryl ester and a strong Lewis acid catalyst, most commonly AlCl3. Typical reagents and conditions include:
- AlCl3 (most common catalyst)
- Other Lewis acids: FeCl3, BF3
- Heat (often 100–200°C)
- Anhydrous conditions
5. What products are formed in the Fries rearrangement?
The Fries rearrangement forms a mixture of ortho-hydroxyaryl ketones and para-hydroxyaryl ketones. For example:
- Phenyl acetate → o-hydroxyacetophenone
- Phenyl acetate → p-hydroxyacetophenone
6. What is the difference between Fries rearrangement and Friedel–Crafts acylation?
The main difference is that Fries rearrangement is an intramolecular acyl migration from an ester, while Friedel–Crafts acylation is an intermolecular acylation using an acyl halide or anhydride. Key differences include:
- Fries rearrangement: Starts with an aryl ester; acyl group migrates within the molecule.
- Friedel–Crafts acylation: Uses RCOCl or (RCO)2O with AlCl3.
- Fries gives hydroxyaryl ketones; Friedel–Crafts gives aryl ketones.
7. Why does the Fries rearrangement give ortho and para products?
The Fries rearrangement gives ortho and para products because the –O– group activates the aromatic ring and directs substitution to ortho and para positions. Important points:
- The phenoxy group is electron-donating by resonance.
- Ortho and para positions have higher electron density.
- The acylium ion acts as an electrophile.
8. How does temperature affect the Fries rearrangement?
Temperature affects product distribution: lower temperatures favor para products, while higher temperatures favor ortho products. This happens because:
- Low temperature: Para product is favored due to less steric hindrance.
- High temperature: Ortho product increases due to thermodynamic control and possible complex formation.
9. Can you give 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 using AlCl3. The reaction is:
- Phenyl acetate + AlCl3 → o-hydroxyacetophenone + p-hydroxyacetophenone (after hydrolysis)
10. What are the limitations of the Fries rearrangement?
The main limitations of the Fries rearrangement include harsh conditions, side reactions, and substrate sensitivity. Common limitations are:
- Requires strong Lewis acids like AlCl3.
- High temperatures may cause decomposition.
- Polyacylation or resin formation can occur.
- Not suitable for strongly deactivated aromatic rings.
