Knorr pyrrole synthesis

The Knorr pyrrole is a common reaction to the synthesis of substituted pyrroles. It is named after its discoverer, the German chemist Ludwig Knorr, named and is one of the named reactions. In this reaction, α -amino- β -keto esters and ketones are reacted to form pyrroles. The reaction is carried out in the presence of zinc and will take place due to the high reactivity of the α -amino- ketone at room temperature. Since α -amino ketones are not stable and undergo a condensation reaction itself, they must be in situ, for example, of the oximes released. Heterocycles obtained are referred to as Knorr pyrrole.

Reaction mechanism

In the first step of the β -keto ester is protonated and attacked the port from the α -amino ketone. After intramolecular proton transfer from the ammonium to the hydroxyl group and elimination of water, the imine formed after final deprotonation. This tautomerization to an enamine. By attack of the double bond on the electron-deficient carbonyl carbon now forms an N- heterocycle. In the next step, the negatively charged oxygen atom is protonated by the formation of an imine to the hydroxyl group, which eventually forms after final elimination of water and formation of a further double bond with renewed imine / enamine tautomerism the pyrrole.

In the original Knorr pyrrole two equivalents of ethyl acetoacetate were implemented. In this case, an equivalent by glacial acetic acid and sodium nitrite was converted to 2- Oximinoacetessigsäureester. Zinc dust now reduced the oxime to the active amine and the condensation reaction can begin.

There are many modern variations on the classic method of Knorr. From Levi and Zanetti exists an extension of the Knorr pyrrole on acetylacetone (2,4- pentanedione ), which is reacted with the oxime to pyrroles.