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The Fries Rearrangement: Mechanism Applications and Karl Theophil Fries

Fries Rearrangement: A Comprehensive Overview

Chemistry is a vast subject, and organic chemistry is an important branch that deals with the study of organic compounds and their properties. The Fries Rearrangement is one of the many organic reactions that have been studied over the years.

In this article, we will explore what the Fries Rearrangement is, how it works, and its applications. We will also learn about Karl Theophil Fries, the German chemist who discovered the reaction.

Fries Rearrangement: Definition

The Fries Rearrangement is an organic reaction that involves the rearrangement of a phenyl ester to form a hydroxy aryl ketone. The reaction occurs in the presence of a Lewis acid catalyst, such as aluminum trichloride or ferric chloride.

The reaction is named after

Karl Theophil Fries, who discovered it in 1908. The Fries Rearrangement involves the migration of the acyl group from the oxygen atom to the carbon atom adjacent to the aryl ring. This rearrangement occurs at the ortho or para position of the aryl ring, depending on the substitution pattern of the ring. The Friedel-Crafts acylation reaction is a common precursor to the Fries Rearrangement.

Examples of Fries Rearrangement

The Fries Rearrangement is used to synthesize a wide range of compounds, including:

  • o- and p-hydroxy acetophenone, which is used as a pharmaceutical and drug intermediate
  • Hydroxyphenyl acetate, which is a key intermediate in the production of agrochemicals

The reaction is also used to synthesize thermographic materials, which are used in the production of antiviral agents.

Mechanism of Fries Rearrangement

The Fries Rearrangement proceeds via a carbocation intermediate. The carbocation is formed when the Lewis acid catalyst coordinates with the carbonyl oxygen of the ester to form a complex. The complex undergoes a proton transfer, resulting in the formation of a carbocation intermediate. The carbocation then undergoes a migration, in which the acyl group shifts to the carbon atom adjacent to the aryl ring. The migration results in the formation of a hydroxy aryl ketone.

Applications of Fries Rearrangement

The Fries Rearrangement is used in the production of a wide range of compounds, including:

  • Pharmaceuticals
  • Drug intermediates
  • Agrochemical intermediates
  • Thermographic materials
  • Antiviral agents

The reaction is particularly useful in the synthesis of o- and p-hydroxy acetophenone, which has been found to have antiviral properties. Hydroxyphenyl acetate, which is produced using the Fries Rearrangement, is used as an intermediate in the production of agrochemicals such as herbicides, pesticides, and fungicides.

Karl Theophil Fries

The Fries Rearrangement is named after Karl Theophil Fries, a German chemist who discovered the reaction in 1908. Fries was born in 1873 in Hesse, Germany. He studied chemistry at the University of Berlin and later at the University of Freiburg. He received his PhD in 1897, and in 1906, he became a professor of chemistry at the University of Breslau. In 1908, Fries published a paper in the Journal of the Chemical Society in which he described a new rearrangement reaction involving phenyl esters. The reaction was later named after him and became known as the Fries Rearrangement. Fries made significant contributions to the field of organic chemistry and is remembered for his work on the synthesis of heterocyclic compounds.

Reaction Conditions: Temperature and Solvent

The Fries Rearrangement is a sensitive reaction that is influenced by various reaction conditions, including the reaction temperature and solvent. The reaction is typically carried out at low temperatures, typically between -20 and 0°C, to minimize the formation of byproducts. At higher temperatures, the reaction can lead to the formation of the ortho product, which can make isolation and purification of the desired product difficult. The solvent used for the reaction also plays a crucial role in the Fries Rearrangement. Polar aprotic solvents, such as dichloromethane, are commonly used because they are effective solvents for both the reactants and products, and they also do not interfere with the Lewis acid catalyst. The use of aromatic solvents, such as benzene and toluene, should be avoided because they can undergo Friedel-Crafts reactions with Lewis acid catalysts. When para-substituted phenyl esters are used as starting materials for the Fries Rearrangement, the reaction can be performed at higher temperatures. This is because the para-substituent increases the stability of the carbocation intermediate, making it less susceptible to rearrangement. However, it is still important to carefully control the reaction conditions to prevent the formation of unwanted byproducts.

Significance and Uses

Pharmaceutical Industry

Pharmaceutical companies use the Fries Rearrangement to synthesize various drug intermediates and active pharmaceutical ingredients. For example, the Fries Rearrangement is used to synthesize o- and p-hydroxyacetophenone, which is an intermediate in the synthesis of antiviral agents. This compound has been found to inhibit the replication of various viruses, including hepatitis C, dengue, and Zika viruses. The Fries Rearrangement is also used in the synthesis of other drug intermediates, such as hydroxyphenyl acetate, which is a key intermediate in the production of pain relief medication.

Agrochemical Industry

The agrochemical industry also uses the Fries Rearrangement to synthesize various intermediates in the production of herbicides, pesticides, and fungicides. For example, hydroxyphenyl acetate, which is synthesized using the Fries Rearrangement, is an intermediate used in the production of herbicides and fungicides. The reaction is also used to synthesize other agrochemical intermediates, such as 2-hydroxybiphenylacetic acid, which is a key intermediate used in the production of insecticides.

Other Industries

The Fries Rearrangement is also used in other industries, such as the production of thermographic materials and the synthesis of antiviral agents. In the production of thermographic materials, the Fries Rearrangement is used to synthesize aromatic ketones, which are used as photoinitiators in the production of thermographic coatings. These coatings are used in the printing industry and for the production of printed circuit boards. The Fries Rearrangement is also used in the synthesis of antiviral agents, such as o- and p-hydroxyacetophenone, which have been found to inhibit the replication of various viruses.

Conclusion

In conclusion, the Fries Rearrangement is an important organic reaction that has found various applications in the production of pharmaceuticals, agrochemicals, and other industrial materials. The reaction is influenced by various reaction conditions, such as the reaction temperature and solvent, which should be carefully controlled to prevent the formation of unwanted byproducts. The Fries Rearrangement is a versatile and useful reaction and is an important tool in the synthesis of various compounds. In conclusion, the Fries Rearrangement is a critical organic reaction that involves the migration of the acyl group from the oxygen atom to the carbon atom adjacent to the aryl ring. The reaction finds widespread applications across various industries such as pharmaceuticals, agrochemicals, and thermographic materials. Careful control of reaction conditions, including temperature and solvent, is essential to prevent the formation of unwanted byproducts. Overall, the Fries Rearrangement is a vital tool in organic synthesis, and its significance in various industries is undeniable.

FAQs:

1. What is the Fries Rearrangement?

The Fries Rearrangement is an organic reaction that involves the rearrangement of a phenyl ester to form a hydroxy aryl ketone.

2. What are the applications of the Fries Rearrangement?

The Fries Rearrangement finds applications in the production of pharmaceuticals, agrochemical intermediates, thermographic materials, antiviral agents, and active agents.

3. What are the reaction conditions for the Fries Rearrangement?

The reaction conditions for the Fries Rearrangement include temperature and solvent. The reaction is typically carried out at a low temperature, and polar aprotic solvents are commonly used.

4. Who discovered the Fries Rearrangement, and what is their contribution to chemistry?

The Fries Rearrangement is named after Karl Theophil Fries, a German chemist who discovered the reaction in 1908. Fries made significant contributions to the field of organic chemistry, particularly in the synthesis of heterocyclic compounds.

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