Pfitzinger reaction
Appearance
Pfitzinger reaction | |||||||||||||
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Named after | Wilhelm Pfitzinger | ||||||||||||
Reaction type | ring-condensation | ||||||||||||
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Typical solvents | protic | ||||||||||||
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RSC ontology ID | RXNO:0000109 | ||||||||||||
The Pfitzinger reaction (also known as the Pfitzinger-Borsche reaction) is the chemical reaction of isatin with base and a carbonyl compound to yield substituted quinoline-4-carboxylic acids.[1][2]
![The Pfitzinger reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b7/Pfitzinger_Reaction_Scheme.png/400px-Pfitzinger_Reaction_Scheme.png)
Several reviews have been published.[3][4][5]
Reaction mechanism
[edit]![The mechanism of the Pfitzinger reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Pfitzinger_Reaction_Mechanism.png/650px-Pfitzinger_Reaction_Mechanism.png)
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 (or aldehyde) will react with the aniline to give the imine (3) and the enamine (4). The enamine will cyclize and dehydrate to give the desired quinoline (5).
Variations
[edit]Halberkann variant
[edit]![The Halberkann variant of the Pfitzinger reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/9/9a/Pfitzinger_Halberkann_Modification_Scheme.png/350px-Pfitzinger_Halberkann_Modification_Scheme.png)
Reaction of N-acyl isatins with base gives 2-hydroxy-quinoline-4-carboxylic acids.[6]
See also
[edit]- Camps quinoline synthesis
- Friedländer synthesis
- Niementowski quinazoline synthesis
- Doebner reaction
- Talnetant, Cinchocaine
References
[edit]- ^ Pfitzinger, W. (1886). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. (in German). 33 (1): 100. doi:10.1002/prac.18850330110.
- ^ Pfitzinger, W. (1888). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. (in German). 38 (1): 582–584. doi:10.1002/prac.18880380138.
- ^ Manske, R. H. (1942). "The Chemistry of Quinolines". Chem. Rev. 30 (1): 113–144. doi:10.1021/cr60095a006.
- ^ Bergstrom, F. W. (1944). "Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline". Chem. Rev. 35 (2): 77–277. doi:10.1021/cr60111a001.
- ^ Shvekhgeimer, M. G.-A. (2004). "The Pfitzinger Reaction". Chem. Heterocycl. Compd. 40 (3): 257–294. doi:10.1023/B:COHC.0000028623.41308.e5. S2CID 97698676.)
- ^ Halberkann, J. (1921). "Abkömmlinge der Chininsäure". Chem. Ber. (in German). 54 (11): 3090–3107. doi:10.1002/cber.19210541118.