Wohl–Aue reaction

Overview

The Wohl–Aue reaction is a chemical reaction used in organic chemistry to synthesize quinoline derivatives. This reaction involves the condensation of an aniline with a _-ketoester in the presence of a Lewis acid catalyst. The reaction is named after the chemists Alfred Wohl and Wilhelm Aue, who first reported it in the early 20th century.

Reaction Mechanism

General scheme of the Wohl–Aue reaction.

The mechanism of the Wohl–Aue reaction involves several key steps:

1. Formation of an Enamine: The reaction begins with the formation of an enamine intermediate from the aniline and the _-ketoester. This step is facilitated by the Lewis acid catalyst, which activates the carbonyl group of the _-ketoester.

2. Cyclization: The enamine intermediate undergoes an intramolecular cyclization to form a dihydroquinoline intermediate. This step is crucial for the formation of the quinoline ring system.

3. Aromatization: The dihydroquinoline intermediate is then oxidized to form the final quinoline product. This step often requires an oxidizing agent to facilitate the removal of hydrogen atoms and the formation of the aromatic quinoline ring.

Applications

The Wohl–Aue reaction is particularly useful in the synthesis of various quinoline derivatives, which are important in the pharmaceutical industry. Quinoline compounds are known for their antimalarial, antibacterial, and antitumor properties. The ability to synthesize these compounds efficiently makes the Wohl–Aue reaction a valuable tool in medicinal chemistry.

Related Reactions

The Wohl–Aue reaction is related to other quinoline synthesis methods, such as the Skraup synthesis and the Doebner–Miller reaction. These reactions also involve the formation of quinoline derivatives but differ in the starting materials and reaction conditions used.

Related Pages

• Quinoline
• Aniline
• _-Ketoester
• Lewis acid
• Skraup synthesis
• Doebner–Miller reaction