Pfitzinger reaction

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Pfitzinger reaction
Named after W. Pfitzinger
Reaction type ring-condensation
Reaction
ketone or aldehyde
+
isatin
+
potassium hydroxide
quinoline-4-carboxylic acid
+
water
Conditions
Typical solvents protic

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

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

Reaction mechanism[edit]

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 quiniline (5).

Variations[edit]

Halberkann variant[edit]

The Halberkann variant of the Pfitzinger reaction

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

See also[edit]

References[edit]

  1. ^ Pfitzinger, W. (1886). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. 33: 100. doi:10.1002/prac.18850330110. 
  2. ^ Pfitzinger, W. (1888). "Chinolinderivate aus Isatinsäure". J. Prakt. Chem. 38: 582. doi:10.1002/prac.18880380138. 
  3. ^ Manske, R. H. (1942). Chem. Rev. 30: 126. doi:10.1021/cr60095a006.  Missing or empty |title= (help)
  4. ^ Bergstrom, F. W. (1944). "Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline". Chem. Rev. 35 (2): 152. doi:10.1021/cr60111a001. 
  5. ^ Shvekhgeimer, M. G.-A. (2004). "The Pfitzinger Reaction". Chemistry of Heterocyclic Compounds 40 (3): 257. doi:10.1023/B:COHC.0000028623.41308.e5. )
  6. ^ Halberkann, J. (1921). "Abkömmlinge der Chininsäure". Chemische Berichte 54 (11): 3090. doi:10.1002/cber.19210541118.