Pfitzinger reaction

The Pfitzinger reaction is the chemical reaction of isatin with base and a carbonyl compound to yield substituted quinoline-4-carboxylic acids.
[Image:Pfitzinger_Reaction_Scheme.png|center|400px|The Pfitzinger reaction]
Several reviews have been published.

Reaction mechanism

[Image:Pfitzinger_Reaction_Mechanism.png|center|650px|The mechanism of the Pfitzinger reaction]
The reaction of isatin with a base such as potassium hydroxide hydrolyses the amide bond to give the keto-acid 2. This intermediate can be isolated, but is typically not. A ketone will react with the aniline to give the imine and the enamine. The enamine will cyclize and dehydrate to give the desired quinoline.

Variations

Halberkann variant

[Image:Pfitzinger Halberkann Modification Scheme.png|center|350px|The Halberkann variant of the Pfitzinger reaction]
Reaction of N-acyl isatins with base gives 2-hydroxy-quinoline-4-carboxylic acids.