Pyrrole: synthesis and reactivity

Porphyrin synthesis

Porphyrins are an extremely important class of molecules, just think that are the fundamental consistuent of EME group, and, above all, of clorophyll. They are characterized by an heterocyclic skeleton made of four pyrrole molecules linked by four methylene group, sp2 carbon atoms. The reaction is simpler than it seems, and consists just in a series of electrophilic substitution on pyrrole in acidic environment.

Sintesi della porfirinaThe last step is an oxidation reaction. It's obtained a high-conjugated planar system (π interaction between p orbitals), with free circulation of electrons  (4H lost from 4 sp3 carbons and 2 from pyrroles):

sintesi porfirina ossidazione

Porphyrin synthesized this way is a dark blue solid. Notice that two nitrogen atoms are now "pirydine-like", this means that they have a lone pair in an sp2 orbital, available to chelate metallic cations (like, for example Mg2+)

Pyrrole synthesis

  • Paal - Knorr synthesis

Paal - Knorr synthesis allows to generate furan, tiophene or pyrrole starting from 1-4 dicarbonyl compounds. In this article we're just going to see the mechanism of pyrrole synthesis (furan and tiophene synthesis)

Sintesi del pirrolo

Altough the mechanism is nowadays not completely clear, the logic of the proposed mechanism is very easy to understand. Initially the amine (ammonia or primary amine) attacks one ot the two carbonyl groups. As we should know, the resulting product is an intermediate called imine. The nitrogen of the imine afterwars attacks the last free carbonyl, in a fast intramolecular reaction. in subsequent steps, the heterocycle spontaneously proceeds, moves through its aromatic form. In order to let this happen,the loss of water (H2O) is necessary, and we'll therefore conduct the reaction in dehydrating environment or providing heat. The dehydratation as well as the imine formation are favored by a slighty acidic environment (→ imine synthesis).