Hantzsch pyrrole synthesis

The Hantzschsche pyrrole ( pyrrole Hantzsch'sche ), also known as the Hantzsch pyrrole synthesis, is a name reaction in organic chemistry. It was named after the German chemist Arthur Hantzsch (1857-1935), who published them in 1890. It is used for the synthesis of pyrrole and its derivatives.

The reaction is related to the Paal -Knorr synthesis, and the Knorr pyrrole.

Survey

During the synthesis of β -keto esters react (black) with an amine ( blue) and subsequently closing a ring with an α - halo ketone (green ) to a pyrrole derivative:

Instead of an amine and ammonia can be used for the reaction. Then an unsubstituted at the nitrogen atom of pyrrole forms.

Mechanism

The mechanism with a universal β -ketoester illustrates an α - halo ketone and a primary amine.

At the beginning of the β -keto ester 1 reacts with a primary amine through several intermediate steps to a enamine 2 Then the enamine accesses in the course of the nucleophilic substitution, the α - halo ketone and a halide is split off. This splits off a hydrogen halide from the nitrogen 3 and leaves the reaction as a hydrogen halide (shown here as HX ). 4 so that an imine is formed, the imine is rotated in the next step 5 is followed by an isomerization of the imine to enamine tautomer then the 6 carbon atom of the carbonyl group is attacked by the amino group 6 and thus the five-membered ring 7 is closed. After the rearrangement of a proton 7 Water is cleaved from the molecule 8. The result is the product 9 in the form of pyrroles.

Modifications

Instead of the three original reactants, the reaction can also be conducted between an enamine of the β -keto ester and an α - haloketone. Moreover, the reaction can be used to indole or carbazole synthesized by the choice of starting materials. Thus, for example, react o- amino acetophenone and α - chloroacetophenone 2 -benzoyl -3-methyl -indole: