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 B_12, 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 p_z 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 3^rd 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 2^nd and 3^rd 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 2^nd position because of its resonance

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