What is Gatterman aldehyde synthesis?

The Gattermann aldehyde synthesis, also known as the Gattermann reaction, is a method for the synthesis of aromatic aldehydes from aromatic compounds bearing electron-donating substituents. It was developed by the German chemist Ludwig Gattermann in the early 20th century.

The reaction involves the use of a mixture of hydrogen cyanide (HCN) and hydrogen chloride (HCl) in the presence of a Lewis acid catalyst such as aluminum chloride (AlCl₃). The reaction proceeds via an electrophilic aromatic substitution mechanism.

Here are the general steps of the Gattermann aldehyde synthesis:

Activation of the aromatic ring: The Lewis acid catalyst, typically AlCl₃, reacts with the hydrogen cyanide to form a complex. This complex activates the aromatic ring by coordinating with it, making it more susceptible to electrophilic attack.

Electrophilic attack: The hydrogen chloride (HCl) reacts with the activated aromatic ring, generating an electrophilic species, the "chloronium ion." This ion is formed by the addition of an H⁺ ion to the aromatic ring.

Cyanide substitution: The activated aromatic ring then undergoes a nucleophilic substitution with the cyanide ion (CN⁻), which is generated by the dissociation of hydrogen cyanide (HCN). This substitution reaction replaces the chloride group with a cyano group (CN).

Acid hydrolysis: The resulting cyano group is then hydrolyzed in the presence of an acid, typically dilute sulfuric acid (H₂SO₄). This step converts the cyano group (-CN) into a carboxylic acid group (-COOH).

Reduction to aldehyde: Finally, the carboxylic acid group is reduced to an aldehyde group (-CHO) by treatment with reducing agents such as zinc (Zn) and hydrochloric acid (HCl).

The Gattermann aldehyde synthesis is a useful method for introducing aldehyde functional groups into aromatic compounds and has applications in the synthesis of various aromatic aldehydes used in the pharmaceutical, agrochemical, and fragrance industries. However, it is important to note that the use of hydrogen cyanide (HCN) in this reaction poses safety and environmental concerns, so alternative methods have been developed to achieve similar transformations.