Pfitzinger reaction

What is Pfitzinger reaction?

The Pfitzinger reaction is a base-promoted condensation reported by Pfitzinger in 1886, between an enolizable carbonyl compound and isatinate from isatin, resulting in 2- or 2,3-disubstituted quinoline or cinchoninic acid derivatives. This reaction is also referred to as the Pfitzinger condensation, Pfitzinger synthesis, or Pfitzinger quinoline synthesis.

Pfitzinger reaction - general reaction scheme - Pfitzinger condensation - Pfitzinger synthesis - Pfitzinger quinoline synthesis
Pfitzinger reaction

Isatins used for this reaction include 5-sulfamoylisatin, 5-methylisatin, methyl isatin-4-carboxylate, 5-bromoisatin, isatin, and isatic acid. Enolizable carbonyl compounds suitable for this reaction include acetone, methyl aryl ketones, methyl heteroaryl ketones, cyclohexanone, cyclopentanone, cyclooctanone, cyclopentadecanone, malonates, keto esters, keto ethers, anhydride, chalcones, 2-undecanone, phloroglucinol, 2-acetylphenothiazine, and lactam acetal. Methyl ketones often result in the formation of 2-alkyl quinolines, while unsymmetrical methyl ketones tend to produce 2-alkyl quinolines. However, alkyl aryl ketones with n < 3 and ketones with a general form of ArC(O)CH2Ar don’t undergo this reaction due to steric hindrance, especially when Ar carries a large ortho-substituent.

References

Pfitzinger, W. (1886), Chinolinderivate aus Isatinsäure. J. Prakt. Chem., 33: 100-100. https://doi.org/10.1002/prac.18850330110

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