Paal–Knorr synthesis

The Paal -Knorr synthesis is a name reaction in organic chemistry, which was described by Ludwig Knorr and Carl Paal first time in 1884. The method is the synthesis of five-membered heterocycles, ie, substituted furans, thiophenes and pyrroles, starting from 1,4 -diketones ( γ -diketones ).

Overview of reactions

In the Paal -Knorr - Synthesis of 1,4- diketones are reacted to heteroaromatic Hetereocyclpentadienen either with acid catalysts, amines or phosphorus (V ) sulphide.

• The furan synthesis requires acid catalysts, there arise 2,5 -disubstituted furans:

• In the pyrrole synthesis caused by the use of primary amines, 2,5-substituted pyrroles:

• For the preparation of 2,5 - di- disubstituierterThiophene phosphorus pentasulfide is required:

For the compounds of the various R groups are organyl, for example, alkyl groups.

Mechanism

Furan synthesis

In the first step, a carbonyl group of the diketone 1 is protonated, thus the cation 2 is formed. In the next step, the oxygen atom of the other carbonyl group is added nuklephil with ring closure to the protonated carbonyl group. Simultaneously, a proton is split off, causing the Hydroxyfuran 3 is formed.

The hydroxy group of Hydroxyfurans 3 is protonated so that the reactive intermediate 4 is formed. This responds by dehydration and deprotonation on the furan 5

Pyrrole synthesis

After Amaranth 's publication of the mechanism probably occurs as a direct introduction of a hemiaminal. This optimism is supported adoption of its research results, according to which the stereochemical configuration of the parent compound is retained.

It is assumed that initially there is a nucleophilic addition of the amine as a nucleophile to the carbon atom of a carbonyl group of the Diketons1. The result is a reactive intermediate 2, which reacts by proton transfer to Ketoaminol 3. Ketoaminol this may be referred to as a hemiaminal, if one considers the nitrogen with hydroxy superficially.

In the next step, a further nucleophilic addition takes place. The nitrogen of the Aminols 3 is added under nucleophilic ring closure to the second carbonyl group and responds to a polar intermediate 4 Protonation of the oxygen atom with simultaneous deprotonation of the nitrogen, the Diaminol forms 5 Under dehydration, the pyrrole derivative produced 6

Thiophene synthesis

A possible mechanism of the synthesis of a thiophene was proposed by Foye.

First, the 1,4- diketone 1 with phosphorus (V ) sulphide is added. Phosphorus pentasulfide is Thionierungs - and dehydrating reagent, which could favor the formation of furan (see above). However Foye has been experimentally found that no furan intermediate of thiophene synthesis. By the introduction of sulfur into the dicarbonyl compound 1 to react this thioketone 2 The oxygen atom is protonated so that the cation 3 is formed.

The sulfur takes up the carbon atom of the hydroxyl of nucleophile, followed by 3, the heterocyclic thiohemiacetal 4 formed under deprotonation of the compound. Meanwhile, elimination of water causes the formation of the 2,5-disubstituted thiophene 5