What is a Rearrangement in Organic Chemistry?
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
1. What is the Fries rearrangement reaction? Explain with an example.
The Fries rearrangement is an organic reaction where an aryl ester is transformed into a hydroxy aryl ketone using a Lewis acid catalyst, typically aluminium chloride (AlCl₃), and aqueous acid. In this reaction, an acyl group migrates from the phenolic oxygen to the carbon atoms of the aromatic ring, primarily at the ortho and para positions.
For example, when phenyl acetate (an aryl ester) is heated with anhydrous AlCl₃, it rearranges to form a mixture of ortho-hydroxy acetophenone and para-hydroxy acetophenone.
2. What is the specific role of the Lewis acid catalyst, like AlCl₃, in the Fries rearrangement?
The Lewis acid catalyst, such as aluminium chloride (AlCl₃), plays a crucial role in activating the ester for rearrangement. Its primary function is to coordinate with the carbonyl oxygen atom of the acyl group. This coordination polarises the bond between the acyl group and the phenolic oxygen, making it weaker. This facilitates the cleavage of the bond to generate a highly reactive electrophile, the acylium carbocation (R-C=O⁺), which is essential for the subsequent attack on the aromatic ring.
3. How does the mechanism for the Fries rearrangement proceed?
The widely accepted mechanism for the Fries rearrangement involves several key steps:
- Step 1: Catalyst Coordination: The Lewis acid (AlCl₃) acts as an electron acceptor and forms a complex with the carbonyl oxygen of the ester, which is a better Lewis base than the phenolic oxygen.
- Step 2: Acylium Ion Formation: The complex formation weakens the ester linkage, leading to the cleavage of the C-O bond and the generation of a free acylium carbocation.
- Step 3: Electrophilic Aromatic Substitution: The positively charged acylium carbocation then attacks the electron-rich benzene ring in an electrophilic aromatic substitution reaction. This attack occurs at the ortho and para positions to form the corresponding hydroxy aryl ketones.
4. How can the major product (ortho or para isomer) be controlled in a Fries rearrangement?
The selectivity for the ortho or para product in a Fries rearrangement is highly dependent on the reaction conditions, particularly temperature and the solvent used.
- Temperature: Low reaction temperatures (around 25°C) favour the formation of the more thermodynamically stable para-product. In contrast, higher temperatures (above 60°C) tend to yield the ortho-product as the major isomer.
- Solvent: The polarity of the solvent also influences the outcome. Using non-polar solvents (like CS₂) generally favours the formation of the ortho-isomer. Conversely, polar solvents favour the formation of the para-isomer.
5. Is the Fries rearrangement an intramolecular or intermolecular reaction?
While it might appear to be a simple intramolecular shift, evidence from crossover experiments suggests that the Fries rearrangement is primarily an intermolecular process. In these experiments, when a mixture of two different aryl esters is used, crossover products are formed. This indicates that the acyl group detaches completely from one molecule to form a free acylium carbocation, which can then attack either its parent ring or the ring of a different ester molecule present in the reaction mixture.
6. What are the key limitations of the Fries rearrangement?
Despite its utility, the Fries rearrangement has several limitations:
- Low Yields: The reaction often provides low to moderate yields, which can make it unsuitable for large-scale industrial production.
- Substituent Effects: The presence of strongly deactivating or meta-directing groups on the aromatic ring significantly reduces the reaction yield.
- Steric Hindrance: Esters with bulky or heavily substituted acyl groups react poorly, resulting in lower yields.
- Mixture of Products: The reaction typically produces a mixture of ortho and para isomers, which requires an additional, often difficult, separation step to isolate the desired product.
7. How does the Photo-Fries rearrangement differ from the standard thermal Fries rearrangement?
The Photo-Fries rearrangement is a photochemical alternative that differs from the thermal version in key aspects:
- Mechanism: The thermal Fries rearrangement proceeds through an ionic mechanism involving an acylium carbocation. In contrast, the Photo-Fries rearrangement occurs via a radical mechanism, initiated by the absorption of UV light.
- Products: The thermal reaction yields [1,2] (ortho) and [1,3] (para) rearranged products. The Photo-Fries rearrangement can also produce these, along with [1,5] products and phenols resulting from radical side reactions.
- Conditions: The thermal reaction requires a Lewis acid catalyst and heat, while the Photo-Fries reaction is carried out in the absence of a catalyst using ultraviolet light.
8. What are the main applications of the Fries rearrangement in chemical synthesis?
The Fries rearrangement is a valuable method for synthesizing acylphenols (hydroxy aryl ketones), which are important intermediates in various industries. These compounds serve as building blocks for:
- Pharmaceuticals: Used in the synthesis of various drugs and active pharmaceutical ingredients.
- Agrochemicals: Utilised in the production of certain pesticides and herbicides.
- Fine Chemicals: Serve as precursors for fragrances, dyes, and other specialised chemical products.
