Chemistry, Properties, Reactivity, and Synthesis of Pyrrole

Chemistry
of Pyrrole

Session Objectives

By the end of this
session, students will be able to:

• Discuss chemistry, reactivity, method of synthesis of
pyrrole

Chemistry of pyrrole

• Simplest of five membered heterocyclic compound

• Occurs naturally from coal tar, bone oil, products derived
from proteins

• Sub-unit of haem, chlorophyll, vitamin B12,
some bile pigments and most ubiquitous throughout the plant and animal compound

• First obtained by Runge in 1834, from coal tar by Anderson
in 1857 and later synthesized by heating ammonium salt of mucic acid

• Pyrrole gives an intense red colour with p-dimethyl
aminobenzaldehyde, referred as Ehrlich test- characteristic of pyrroles

Molecular properties of Pyrrole

• Looking at the structure shows that, compound has diene
character and can be called as aromatic

• Shows high degree of reactivity towards electrophilic
reagents rather than addition reactions

• Contains sp2 hybridized carbons, planar pentagon, each
ring atom has one electron remaining in pz orbital and heteroatom
contributes two p-electrons to the aromatic sextet

• Can also be expressed using resonance structures

Resonance structures of Pyrrole

• Comparison of pyrrole vs thiophene vs furan: aromaticity
falls in the order of thiophene > pyrrole > furan representing the order
of electronegativity

• Furan is least aromatic i.e., oxygen is reluctant to
release its electrons

• Because of partial delocalization of electrons in pyrrole,
nitrogen atom cannot donate electrons and looses its basic character like
amines

• Pyrrole is extremely weak base among amines

• High electron density in the ring causes extremely
reactive towards electrophilic substitution like nitrosation, coupling with
diazonium salts

Physical properties of Pyrrole

• Colorless liquid with boiling point 130 0C and
is higher than furan and thiophene, resembles that pyrrole forms intermolecular
hydrogen bonding

• Odour resembling that of chloroform

• Slightly soluble in water but freely soluble in organic
solvents

Intermolecular hydrogen
bonding

Synthetic methods of Pyrrole

1) From furans:
commercially obtained from fractional distillation of coal tar or bone oil

Or from furan by passing it over ammonia or amine and steam
and heated 400 0C in the presence of aluminium oxide as
catalyst 

2) From ammonium
mucate:
classical method by heating ammonium mucate

• Here ammonium mucate dissociates into free acid,
dehydrates followed by decarboxylation and cyclization in ammonia yields parent
compound

Chemical properties of Pyrrole

• Pyrrole undergoes electrophilic substitution, condensation
and ring opening reactions. Very reactive and behaves as both acid and base

1) Protonation:
proton attached to nitrogen atom undergoes rapid exchange in acid and alkali

• Exchange of proton attached to carbon atom occurs only in
more acidic conditions, α-protons
exchange at twice rate of β-protons

2) Reaction
with bases
: pka for loss of the N-H hydrogen of pyrrole is 17.5

• It’s a weak acid than phenol, reacts with potassium to
form corresponding salt

• Acidity of pyrrole can be enhanced by putting electron
withdrawing groups at 3rd position, because anion can be stabilized
by resonance

3) Alkylation:

• Position of substitution in pyrrole alkylation depends on
two factors, nature of catalyst and solvating capacity of solvent

• Potassium and sodium salts of pyrrole reacts with alkyl
halides to give good yields of N-alkyl pyrroles

• Electron withdrawing groups favor the alkylation

• Alkyl and benzyl substituents in N-substituted pyrroles
migrate to 2nd and 3rd position in pyrrole ring at high
temperatures (500-600 0C)

• Useful synthetic approach for such isomers

 4) Electrophilic substitution:
occurs similar to benzenoid compounds

• Undergoes predominantly at 2nd position because
of its resonance

• Three resonance forms for substitution at 2nd
position and two forms for substitution at 3rd position

5) Halogenation: pyrrole is extremely reactive
towards halogens- chlorination (SO2Cl2), bromination (Br2/AcOH),
Iodination (I2/KI3) yield corresponding tetrahalo
derivatives

• It is very difficult to prepare mono-halo pyrroles under
very special conditions

• Halopyrroles are very unstable and decompose readily in
air and light

• Monohalogenation occurs in the presence of electron
withdrawing groups on the pyrrole ring

B) Friedel
Crafts reaction
: N-acylation of pyrroles is accomplished by reaction of
alkali metal salts with acid chlorides

• Here pyrrole reacts rapidly even in the absence of
catalyst 

Summary

• Pyrrole Contains sp2 hybridized carbons, planar pentagon,
each ring atom has one electron remaining in pz orbital and
heteroatom contributes two p-electrons to the aromatic sextet

• Pyrrole is extremely weak base among amines

• Pyrrole forms intermolecular hydrogen bonding

• Pyrrole undergoes electrophilic substitution, condensation
and ring opening reactions. Very reactive and behaves as both acid and base

• It is very difficult to prepare mono-halopyrroles under
very special conditions