Fries Rearrangement

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What is a Rearrangement in Organic Chemistry?

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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.

FAQ (Frequently Asked Questions)

1. How Fries' Reaction is Useful for us?

Ans: Chemistry Fries rearrangement plays a vital role. In this reaction, phenolic easter easily gets converted into a hydroxy ketone by applying normal heat and the presence of catalyst within a few moments. Like this, a site-specific reaction means attack only on ortho and para position, so involved in the preparation of acyl phenol. As these synthesis processes are done with much ease, it is beneficial for the pharmaceutical industry. Synthesis of some agrochemicals, materials for therapy, and the drug can be quickly synthesized.

2. What are the Demerits of Fries Rearrangement?

Ans: Although Fries rearrangement is very useful for some industrial purposes, It has some of these advantages.

Primarily the yield we get from the synthesis is low to moderate. There is a possibility that the initially formed easters will convert to a mixture of two heterocyclic compounds. So it involved an additional step and required more time. Although we have advanced techniques, still it isn't easy to know Isomeric benzopyrones. Another demerit of the reaction is that we can not control the response when it starts, so separating the required product is quite tricky.