What Is A Sandmeyer Reaction?

June 22, 2021 by No Comments

What Is A Sandmeyer Reaction?

The Sandmeyer reaction is a chemical reaction that uses copper salts as reagents or catalysts to manufacture aryl halides from aryl diazonium salts. A radical-nucleophilic aromatic substitution is an example. The Sandmeyer reaction allows for the creation of novel benzene transformations such as halogenation, cyanation, trifluoromethylation, and hydroxylation.

When Swiss chemist Traugott Sandmeyer attempted to manufacture phenylacetylene from benzenediazonium chloride and cuprous acetylide in 1884, he found the reaction. However, phenyl chloride was the primary product he identified. In current times, the Sandmeyer reaction refers to any approach for substituting an aromatic amino group with a nucleophile in the presence of catalytic copper salts by preparing its diazonium salt and then displacing it with a nucleophile. Even when catalysis is possible, a stoichiometric quantity is generally used for greater reactivity due to the inexpensive cost of copper salts. The chlorination, bromination, cyanation, and hydroxylation processes, which use CuCl, CuBr respectively, are the most often used Sandmeyer reactions. Trifluoromethylation of diazonium salts, sometimes known as a Sandmeyer-type reaction, was developed more recently. Diazonium salts react with boronates, iodide, thiols, water, and other compounds, while fluorination can be accomplished with tetrafluoroborate anions, this is known as Balz–Schiemann reaction. These reactions aren’t commonly referred to as Sandmeyer reactions because they don’t require a metal catalyst. Other transition metal salts, such as copper, iron, and cobalt, have been used in a number of different variations. The Sandmeyer reaction, like other diazonium compound transformations, is complementary to electrophilic aromatic substitution because of its extensive synthetic application.

Conditions and mechanism of reaction:

Sodium nitrite and acid are generally used to make nitrous acid in situ. One equivalent step of water is lost after two protonation steps to generate the nitrosonium ion. After passing through a nitrosamine intermediate, the nitrosonium ion functions as an electrophile in a reaction with an aromatic amine, such as aniline, to create a diazonium salt. The following are typical conditions for the reaction:

A radical-nucleophilic aromatic substitution is exemplified by the Sandmeyer reaction. The discovery of biarylbyproducts supports the radical mechanism of the Sandmeyer reaction. A one-electron transfer mechanism catalysed by copper initiates the substitution of the aromatic diazo group with a halogen or pseudohalogen, resulting in the formation of an aryl radical with the loss of nitrogen gas. To synthesise the substituted arene and regenerate the copper catalyst, direct transfer of Cl, Br, CN, or OH from a copper type to the aryl radical could be used. A transient copper intermediate produced from coupling of the aryl radical with the copper species undergoes quick reductive elimination to offer the product and renew copper in an alternative suggestion. The evidence for such an organocopper intermediate is, however, limited and primarily circumstantial, and the exact pathway may vary depending on the substrate and reaction conditions.

Synthetic Applications Of The Sandmeyer Reaction

The Sandmeyer Reaction has numerous synthetic applications and few of the major ones are elaborated below:

Halogenation:

The production of aryl halides is one of the most important applications of the Sandmeyer reaction. Diiodomethane is the preferred solvent for the synthesis of aryl iodides, while bromoform is employed for the production of aryl bromides. Chloroform is the preferred solvent for the production of aryl chlorides. The Sandmeyer reaction is used to replace an amine group with a bromo group in the production of curcuphenol, a bioactive molecule with antifungal and anticancer properties. The Balz–Schiemann reaction employs tetrafluoroborate to produce fluorobenzene, a halide-substituted product that cannot be produced with copper fluorides. The Sandmeyer reaction is represented by motifs in this reaction.

Cyanation:

The Sandmeyer reaction is also used for cyanation, which results in the synthesis of benzonitriles, a class of chemical molecules. The Sandmeyer reaction is used to produce a critical step in the manufacture of the antipsychotic medication Fluanxol. The Sandmeyer reaction was also used to make neoamphimedine, a chemical that could be used as an anti-cancer medication by targeting topoisomerase II.

Trifluoromethylation:

It has been shown that Sandmeyer-type reactions can be employed to produce aryl compounds with trifluoromethyl substituent groups. Trifluoromethylation is a chemical procedure that produces unique chemical characteristics with a wide range of practical applications. Pharmaceuticals containing CF3 groups, in particular, have improved metabolic stability, lipophilicity, and bioavailability. In comparison to prior methods of trifluoromethylation, Sandmeyer-type trifluoromethylation processes have mild reaction conditions and improved functional group tolerance.

Hydroxylation:

The Sandmeyer reaction can also be used to convert aryl amines to phenols by first forming an aryl diazonium salt. This reaction occurs quickly at room temperature when a copper catalyst is present. The process can be achieved with the use of cuprous oxide and an excess of cupric nitrate in neutral water.

Leave a Comment

Your email address will not be published. Required fields are marked *