Heterocyclic Chemistry at a Glance

Pyrroles 83

Ring synthesis – disconnections

There are three important disconnections for the construction of pyrroles, summarised below, with the new bonds
made in the processes shown.

Synthesis of pyrroles from 1,4-dicarbonyl compounds

(1,2- and 1,5-bonds made)

The most obvious route to pyrroles involves the interaction of ammonia, or a primary amine, with a 1,4-dicarbonyl
compound – the Paal-Knorr synthesis. Successive intermolecular then intramolecular nucleophilic additions of ammo-
nia/amine nitrogen to the two carbonyl groups, followed by loss of two molecules of water and fi nally tautomerism,
leads to the aromatic molecule.

Synthesis of pyrroles from -amino-ketones (1,2- and 3,4-bonds made)

This route, often referred to as the Knorr synthesis, rests on the one-pot, sequential condensations of an -amino-
ketone with a 1,3-diketone or 1,3-keto-ester, which contain the relatively acidifi ed central methylene (CH 2 ) necessary
for the reaction to proceed. Clearly, aldol-type condensation to form the C-3-C-4 bond and amine-to-ketone-carbonyl