Key Reactions and Applications of Pyrrole in Chemistry
Pyrrole is a colourless volatile liquid. It is an aromatic organic compound that is also heterocyclic. It is in the form of a five-membered ring with the formula C4H5N. When it is exposed to air it darkens. The substituted derivatives of pyrrole are called pyrroles such as N-methyl pyrrole, C4H4NCH3. An example of trisubstituted pyrrole is porphobilinogen, which is the biosynthetic type of precursor to many natural products such as heme. In the more complex macrocycles, the components of pyrrole are found for example the porphyrinogens and products derived including chlorins, porphyrins of heme, chlorophylls and bacteriochlorins.
Pyrrole Structure
The structure of pyrrole has three pairs of delocalized pi electrons. Two of the pairs are shown in the figure as double bonds and the third pair is as a pair of nonbonding electrons on the nitrogen which is a heteroatom in the structure. These non-bonding electrons are in an sp2 hybrid orbital perpendicular to the p-orbitals. It is cyclic, a planar molecule with three pairs of delocalized electrons and also fulfils the criteria for aromaticity.
(Image Will be Updated Soon)
Properties of Pyrrole
Some major physical and chemical properties of pyrrole are given below.
The odour of pyrrole is a kind of nutty odour. It is a colourless volatile liquid but when exposed to air it changes its colour easily and darkens. Before any application, it is usually purified.
The IUPAC name of pyrrole is 1H-Pyrrole.
Similar to thiophene and futon compounds it is also a five-membered aromatic heterocyclic compound.
Unlike furan and thiophene, it features a dipole in which the end with a positive charge is on the side of the heteroatom with a dipole moment of 1.58 D.
Pyrrole is a weakly basic compound with a conjugate acid dissociation constant of (pKa) of −3.8.
The pyrrolinium cation (C4H6N+) which is most thermodynamically stable is formed through protonation at the 2nd position.
When pyrrole is substituted with substituents of alkyl it provides a more basic molecule, for example, tetramethyl pyrrole has a conjugate acid pKa of +3.7.
It is also a weakly acidic compound at the nitrogen and hydrogen position, with an acid dissociation constant value of 16.5.
The molecular weight of pyrrole is 67.09 g/mole.
The boiling point is 130.5°C (266.9°F) and the melting point is -23°C (-9.4°F).
Synthesis of Pyrrole
Some methods of pyrrole synthesis are given below with the reaction.
Hantzsch pyrrole synthesis
In the Hantzsch pyrrole synthesis, the reaction involves β-ketoesters (1) with ammonia or primary amines and α-halo ketones to give substituted pyrroles. The reaction is given below.
(Image Will be Updated Soon)
Knorr pyrrole synthesis
An activated methylene compound reacts with an α-aminoketone (an α-amino-β-ketoester) in the Knorr pyrrole synthesis. The method involves the reaction of an α-aminoketone and a methylene group-containing compound to (bonded to the next carbon too) a carbonyl group.
(Image Will be Updated Soon)
Paal - Knorr pyrrole synthesis
A 1,4-dicarbonyl compound reacts with ammonia or a primary amine to form a substituted pyrrole in the Paal - Knorr pyrrole synthesis. The reaction of pyrrole synthesis is given below.
(Image Will be Updated Soon)
Van Leusen reaction
For the synthesis of pyrrole one more method of synthesis is popular which is the Van Leusen reaction. In this reaction, an enone reacts with tosylmethyl isocyanide (TosMIC) in the presence of a base, in addition to Michael. The five-membered ring is formed by five-endo cyclization where the tosyl group is eliminated. The last step of this reaction is the tautomerization of the pyrrole.
(Image Will be Updated Soon)
Piloty -Robinson pyrrole synthesis
In the Piloty–Robinson pyrrole synthesis, the initiating materials named for Gertrude and Robert Robinson and Oskar Piloty are the two equivalents of an aldehyde and hydrazine. The product of this reaction is a pyrrole with substituents at the 3rd and 4th positions. Rearrangement reaction takes place in the second step which is a [3,3]-sigmatropic reaction of rearrangement. The ring closure and loss of ammonia to form the pyrrole is due to the addition of hydrochloric acid. The mechanism was developed by the Robinsons. The reaction is given below.
(Image Will be Updated Soon)
Biosynthesis of pyrroles
The synthesis of pyrrole through the biosynthesis method starts with aminolevulinic acid that can be prepared from glycine and succinyl-CoA.
PBG(porphobilinogen ) is formed when aminolevulinic acid dehydratase catalyses the condensation of two molecules of aminolevulinic acid by forming a Knorr-type ring.
(Image Will be Updated Soon)
Uses of Pyrrole
Some important uses of pyrrole are as follows.
The derivatives of pyrrole and pyrrole themselves are widely used as an intermediate in the synthesis of agrochemicals, medicines, dyes, pharmaceuticals, perfumes, photographic chemicals and other organic compounds. For example, heme and chlorophyll are the derivatives of pyrrole that are made by four pyrrole ring formation of the porphyrin ring system.
Pyrrole derivatives are used in medicinal uses such as enzyme inhibiting, anti-microbial, anti-viral, antitubercular, anti-malarial, anti-inflammatory and anticancer properties. Compounds formed with rings of the pyrrole are also precursors to certain drugs.
Pyrroles are taken in the application as scarlet, lightfast red and carmine pigments.
Do you know?
F. F. Runge was the first one who detected pyrrole in 1834, as a constituent of coal tar. It was isolated from the pyrolysate of bone in 1857. Its name comes from the Greek pyrrhos which means reddish. This word has come from the reaction used to detect the red colour that it imparts to wood when moistened with hydrochloric acid.
Hans Fischer was recognized by the Nobel Prize because of his contribution to the syntheses of pyrrole-containing haemin.
Conclusion
The chemical pyrrole formula is C4H5N. The above article on pyrrole covers all the related important information of pyrrole such as its properties, reaction of pyrrole, methods of synthesis and uses as well. Pyrrole structure consists of a five-carbon ring.FAQs on Pyrrole Explained: Structure, Properties, Synthesis & Uses
1. What is pyrrole and what is its chemical formula?
Pyrrole is a heterocyclic aromatic organic compound. It consists of a five-membered ring structure containing four carbon atoms and one nitrogen atom. As a foundational member of the pyrrole family of compounds, its chemical formula is C₄H₅N. It is a colourless volatile liquid that darkens upon exposure to air.
2. What are the key uses and natural sources of pyrrole?
While pyrrole itself is not abundant in nature, its derivatives are crucial components in many biological systems and have significant applications.
- Natural Occurrences: The pyrrole ring system is a core part of vital natural products like heme in haemoglobin, chlorophyll in plants, and vitamin B12. It is also found in bile pigments such as bilirubin.
- Industrial Uses: It is a precursor in the synthesis of pharmaceuticals and agrochemicals. It is also used to create polypyrrole, a conductive polymer with applications in electronics and sensors.
3. Why is pyrrole classified as an aromatic compound?
Pyrrole is classified as an aromatic compound because it perfectly fits Hückel's rule for aromaticity. It has a planar, cyclic, and fully conjugated system with 6 π-electrons (4n+2, where n=1). These 6 electrons come from the four carbons in the double bonds (4 electrons) and the lone pair of electrons from the nitrogen atom (2 electrons), which are delocalised across the entire ring.
4. What is the hybridization of each atom in the pyrrole ring?
In the pyrrole molecule, all five atoms in the ring—the four carbon atoms and the one nitrogen atom—are sp² hybridised. This sp² hybridization results in a planar ring structure. Each atom uses its unhybridized p-orbital to contribute to the delocalised π-electron cloud, which lies above and below the plane of the ring and is responsible for its aromatic character.
5. Why does electrophilic substitution in pyrrole happen at the C-2 position instead of C-3?
Electrophilic substitution in pyrrole preferentially occurs at the C-2 (or alpha) position because it leads to a more stable intermediate carbocation. When an electrophile attacks at the C-2 position, the resulting positive charge is delocalised over three atoms, leading to three stable resonance structures. In contrast, an attack at the C-3 (or beta) position results in an intermediate with only two resonance structures, making it less stable. The greater stability of the C-2 attack intermediate makes this pathway energetically favourable.
6. Why is pyrrole a much weaker base than other amines like pyridine?
Pyrrole is an extremely weak base because the lone pair of electrons on its nitrogen atom is integral to its aromaticity. These electrons are delocalised within the ring to form the 6 π-electron aromatic system. For pyrrole to act as a base, it would need to donate this lone pair, which would break the aromatic stabilization of the ring. This process is highly unfavourable, making pyrrole significantly less basic than pyridine, where the nitrogen's lone pair is in an sp² orbital outside the aromatic system and is readily available for donation.
7. How do resonance structures explain pyrrole's high reactivity in electrophilic substitution reactions?
The resonance structures of pyrrole show the delocalisation of the nitrogen's lone pair of electrons into the carbon ring. This places a partial negative charge on the carbon atoms, making the ring electron-rich. An electron-rich ring is highly attractive to electrophiles (electron-seeking species). This increased electron density makes pyrrole much more reactive towards electrophilic substitution than benzene, often reacting under milder conditions.
8. What is the Paal-Knorr synthesis of pyrrole?
The Paal-Knorr synthesis is a widely used method for preparing pyrroles. The process involves the reaction of a 1,4-dicarbonyl compound (a molecule with two carbonyl groups separated by two carbon atoms) with an excess of ammonia or a primary amine. The reaction proceeds through a series of steps involving nucleophilic attack followed by cyclization and dehydration (loss of water) to form the stable pyrrole ring.
