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Pfitzinger reaction

From Wikipedia, the free encyclopedia
Pfitzinger reaction
Named after Wilhelm Pfitzinger
Reaction type ring-condensation
Reaction
ketone or aldehyde
+
isatin
+
potassium hydroxide
quinoline-4-carboxylic acid
+
water
Conditions
Typical solvents protic
Identifiers
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
The Pfitzinger reaction

Several reviews have been published.[3][4][5]

Reaction mechanism

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The mechanism of the Pfitzinger reaction
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 (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

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Halberkann variant

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The Halberkann variant of the Pfitzinger reaction
The Halberkann variant of the Pfitzinger reaction

Reaction of N-acyl isatins with base gives 2-hydroxy-quinoline-4-carboxylic acids.[6]

See also

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References

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  1. ^ Pfitzinger, W. (1886). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. (in German). 33 (1): 100. doi:10.1002/prac.18850330110.
  2. ^ Pfitzinger, W. (1888). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. (in German). 38 (1): 582–584. doi:10.1002/prac.18880380138.
  3. ^ Manske, R. H. (1942). "The Chemistry of Quinolines". Chem. Rev. 30 (1): 113–144. doi:10.1021/cr60095a006.
  4. ^ 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.
  5. ^ 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.)
  6. ^ Halberkann, J. (1921). "Abkömmlinge der Chininsäure". Chem. Ber. (in German). 54 (11): 3090–3107. doi:10.1002/cber.19210541118.