Sandmeyer Reaction Mechanism

What Is the Sandmeyer Reaction?

The Sandmeyer reaction is a type of substitution reaction that is widely used in the production of aryl halides from aryl diazonium salts. Copper salts like chloride, bromide or iodide ions are used as catalysts in this reaction. Notably, the Sandmeyer reaction can be used to perform unique transformations on benzene. The transformations include hydroxylation, trifluoromethylation, cyanation, and halogenation.

Table of Contents

• Sandmeyer Reaction Mechanism
• Formation of Nitrosonium Ion
• Benzenediazonium Ion Formation
• Importance
• Applications of the Sandmeyer Reaction
• FAQs

The reaction was first discovered in the year 1884, when Traugott Sandmeyer, a Swiss chemist, was conducting an experiment to synthesise phenylacetylene from benzene diazonium chloride and cuprous acetylide. However, at the end of the experiment, he obtained phenyl chloride as the main product.

The Sandmeyer reaction is believed to be a great example of a radical-nucleophilic aromatic substitution. This reaction is a useful tool by which an amino group on an aromatic ring can be replaced with different substituents. During the Sandmeyer reaction, the amino group that is attached to an aromatic ring is converted into a diazonium salt that can be transformed into various functional groups.

The Sandmeyer Reaction Mechanism

The Sandmeyer reaction follows a free radical mechanism. The reaction is actually a two-step process, where the synthesis of aryl halides from primary aryl amines involves the formation of diazonium salts and the transformation of diazo intermediates into aryl halides (displacement with a nucleophile). Interestingly, the nucleophile can be a halide anion, cyanide, water, etc.

To elucidate further, the Sandmeyer reaction mechanism commences with a transfer of a single electron from the copper to the diazonium. This results in the formation of a non-participating diazo radical as well as copper(II) halide. A molecule of nitrogen gas is then released by the diazo radical to give aryl radical, which then reacts with the copper(II) halide to restore the catalyst [copper(I) halide]. After all this, the final product, aryl halide, is obtained.

Sandmeyer Reaction Mechanism

Formation of Nitrosonium Ion

We will look at the Sandmeyer reaction mechanism during the formation of the nitrosonium ion. In the experiment, we take sodium nitrite and acid to form nitrous acid. What follows next is the two protonation steps where one equivalent of water is removed. This results in the generation of the nitrosonium ion (nitrogen monoxide cation).

The ion acts as an electrophile when it is reacted further with an aromatic or heterocyclic amine (for example, aniline). Finally, the diazonium salt is formed. The reaction is carried out at temperatures ranging between 25-30^oC.

Sandmeyer Reaction Mechanism – Formation of Nitrosonium Ion

Benzenediazonium Ion Formation

Students can also go through the below diagram, highlighting the Benzenediazonium ion formation to understand the Sandmeyer reaction mechanism more clearly.

Sandmeyer Reaction Mechanism – Formation of Benzenediazonium Ion

Example

Importance of the Sandmeyer Reaction

• The Sandmeyer reaction is very important when we are studying aromatic chemistry. The reaction can be used to generate substitution patterns that are sometimes not possible to achieve by direct substitution.
• In the reaction, a primary arylamine is mainly diazotized to create an aryl diazonium salt which is further reacted with a halide ion to produce the desired aryl halide product.
• It follows an electron-transfer mechanism, including free radicals.
• The Sandmeyer reaction has wide synthetic applicability and is complementary to electrophilic aromatic substitution.

Applications of the Sandmeyer Reaction

Today, a lot of variations of the Sandmeyer reaction have been developed. As a result of these developments, the reaction has multiple synthetic applications. The different adaptations help in the synthesis of aryl thioethers, aryl fluorides (the Schiemann reaction), phenols, and aryl nitriles.

The common uses of the Sandmeyer reaction are listed below:

• It is used in hydroxylation to convert aryl amines to phenols, leading to the formation of an aryl diazonium salt.
• To create aryl compounds during the process of trifluoromethylation. The compounds inherit unique chemical properties with a wide variety of practical applications.
• The Sandmeyer reaction is used for the formation of benzonitriles through the process of cyanation. The reaction is also found during the synthesis of neoamphimedine, a chemical compound that targets topoisomerase II as an anti-cancer drug.
• To create aryl halides. Some of the solvents used in this process are diiodomethane to synthesise aryl iodides, bromoform to synthesise aryl bromides, and chloroform to synthesise aryl chlorides.