:Pfitzinger reaction
{{Short description|Chemical reaction}}
{{Reactionbox
| verifiedrevid =
| Reference =
| Type = ring-condensation
| NamedAfter = Wilhelm Pfitzinger
| Section1 = {{Reactionbox Conditions
| Solvent = protic
}}
| Section3 = {{Reactionbox Identifiers
| RSC_ontology_id = 0000109
}}
| Reaction = {{Reactionbox Reaction
| Reactant1 = ketone or aldehyde
| Reactant2 = isatin
| Reactant3 = potassium hydroxide
| Product1 = quinoline-4-carboxylic acid
| Sideproduct1 = water
}}
}}
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.{{cite journal|author=Pfitzinger, W.|journal=J. Prakt. Chem.|year=1886|volume=33|issue=1|page=100|doi=10.1002/prac.18850330110|title=Chinolinderivate aus Isatinsäure|language = German|url=https://zenodo.org/record/1427906}}{{cite journal|author=Pfitzinger, W. |journal=J. Prakt. Chem.|year=1888|volume=38|issue=1|pages=582–584|doi=10.1002/prac.18880380138|title=Chinolinderivate aus Isatinsäure|language = German|url=https://zenodo.org/record/1427906}}
Image:Pfitzinger_Reaction_Scheme.png
Several reviews have been published.{{cite journal|last1=Manske|first1=R. H.|title=The Chemistry of Quinolines.|journal=Chem. Rev.|volume=30|issue=1|year=1942|pages=113–144|doi=10.1021/cr60095a006}}{{cite journal|author=Bergstrom, F. W.|journal=Chem. Rev.|year=1944|volume=35|issue=2|pages=77–277|doi=10.1021/cr60111a001|title=Heterocyclic Nitrogen Compounds. Part IIA. Hexacyclic Compounds: Pyridine, Quinoline, and Isoquinoline}}{{cite journal|author=Shvekhgeimer, M. G.-A. |doi=10.1023/B:COHC.0000028623.41308.e5|title=The Pfitzinger Reaction|year=2004|journal=Chem. Heterocycl. Compd.|volume=40|issue=3|pages=257–294|s2cid=97698676}})
Reaction mechanism
Image: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
=Halberkann variant=
Image:Pfitzinger Halberkann Modification Scheme.png
Reaction of N-acyl isatins with base gives 2-hydroxy-quinoline-4-carboxylic acids.{{cite journal|author=Halberkann, J.|journal=Chem. Ber.|year=1921|volume=54|issue=11|pages= 3090–3107|title=Abkömmlinge der Chininsäure|doi=10.1002/cber.19210541118|language=German|url=https://zenodo.org/record/1426711}}