Hantzsch pyrrole synthesis

This reaction involves the high-speed vibration milling (HSVM) of ketones with N-iodosuccinimide (NIS) and p-toluenesulfonic acid, to form an α-iodoketone in situ.

This is followed by addition of a primary amine, a β-dicarbonyl compound, cerium(IV) ammonium nitrate (CAN) and silver nitrate, as shown in the scheme below: 2,3-dicarbonylated pyrroles can be synthesized by a version of the Hantzsch Pyrrole Synthesis.

The reaction can also occur between an enamine and an α-haloketone to synthesize substituted indoles, which also have biological significance.

[6][9] A library of substituted pyrrole analogs can be quickly produced by using continuous flow chemistry (reaction times of around 8 min.).

[10] The advantage of using this method, as opposed to the in-flask synthesis, is that this one does not require the work-up and purification of several intermediates, and could therefore lead to a higher percent yield.

The Hantzsch pyrrole synthesis
The Hantzsch pyrrole synthesis
Mechanism for the Hantzsch Pyrrole Synthesis
Mechanism for the Hantzsch Pyrrole Synthesis
Reaction Scheme for Generalized Hantzsch Pyrrole Synthesis
Reaction Scheme for Generalized Hantzsch Pyrrole Synthesis
Reaction Scheme for Generalized Hantzsch Pyrrole Synthesis
Reaction Scheme for Generalized Hantzsch Pyrrole Synthesis
Reaction for Substituted Indols by Hantzsch Pyrrole Synthesis
Reaction for Substituted Indols by Hantzsch Pyrrole Synthesis
Hantzsch Pyrrole Synthesis Using Continuous Flow Chemistry
Hantzsch Pyrrole Synthesis Using Continuous Flow Chemistry