Paal-Knorr furan synthesis

What is Paal-Knorr furan synthesis?

In 1885, Paal and Knorr reported the acid-catalyzed conversion of 1,4-dicarbonyl compounds into furan derivatives, which is commonly referred to as the Paal-Knorr furan synthesisPaal-Knorr reaction or Paal-Knorr synthesis.

Paal-Knorr furan synthesis - general reaction scheme - Paal-Knorr reaction - Paal-Knorr synthesis
Paal-Knorr furan synthesis

R1, R2 = H, alkyl, aryl (see list of acronyms)
Various acidic catalysts, including P2O5 (in EtOH), p-TsOH or ZnCl2 (in Ac2O), and polyphosphoric acid, have been reported. The rate of cyclization depends on the substitution pattern of the diastereomers. For instance, meso-diastereomers containing electron-donating methyl groups cyclize faster, whereas the dl-isomers with bulky substituents cyclize faster.

The mechanism of this reaction involves the protonation of the carbonyl group, followed by tautomerization to enol, which attacks the second protonated carbonyl group. Although Paal-Knorr furan synthesis is important for the synthesis of furan derivatives, its application in organic synthesis is limited due to the limited availability of appropriate 1,4-dicarbonyl compounds.