Chemistry, Reactivity, Properties and Synthesis of Pyridine

Chemistry of Pyridine

Session Objectives

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

• Discuss the chemistry, reactivity, properties and method
of synthesis of pyridine

Chemistry
of Pyridine

• Simplest and best known heterocyclic compound

• First discovered by Anderson from bone oil, occurs in coal
tar as well

• Highly distributed in nature as pyridine derivatives and
in many important alkaloids

• Nitrogen atom in pyridine is assigned position-1

• Presence of nitrogen introduces an element of asymmetry
into the aromatic ring

• Position in a mono substituted pyridine can be designated
either by numbering system or by greek alphabet

• Alkyl derivatives and reduced pyridines

Physical properties of Pyridine:

• Colorless liquid with boiling point 115 0C and
freezing point -42 0C and benzene boils at 80 0C and
freezes at -5.5 0C

• Large intermolecular association in pyridine because of
its greater polarity accounts for higher boiling point

• Presence of alkyl groups increases boiling point, for
example 2,6-lutidine (144 0C), 2,4-lutidine (157 0C) and
2,4,6-collidine (170 0C)

• But the alkyl group adjacent to nitrogen atom boils lower
than other- 2-methylpyridine (129 0C)

• Pyridine is completely soluble in water (because of
excellent hydrogen bonding) and most organic solvents

• Characteristic unpleasant odor

• Dried by keeping it over potassium hydroxide or barium
oxide   

Molecular properties of Pyridine:

• In benzene each carbon atom is sp2 hybridized state, while
in pyridine this is slightly disturbed as the bond angles are not quite 1200

• Pyridine possess sextet of electrons, five of them
provided by five carbon atoms and sixth by nitrogen atom  

• The nitrogen lone pair is located in an sp2 hybridized orbital
which is perpendicular to π-system
of the ring

• Structural feature is that lone pair on the nitrogen atom
is not associated with the ring and is available for protonation

• Pyridine behaves as a tertiary base and has pka of 5.17

• Basicity becomes more pronounced if electron donating
groups are present on 2nd and 6th positions,

• Because they alter the electron availability on nitrogen
atom by resonance

• Substituents at positions 3 and 5 act by inductive effects
and their influence is less pronounced

• Shows that basicity does not differ much

• More basic than pyrrole but less than aliphatic tertiary
amine

• Here electrons are drawn closer to the nitrogen nucleus
and held more tightly by it, making it less available for bonding- drop in
basicity

Tautomerism in Pyridines:

• Tautomeric structures involve the transfer of a proton to
ring nitrogen atom in pyridine

• A tautomeric structure between 2-hydroxypyridine and
pyridon-2-one is one between a benzenoid and non-benzenoid structure

• The electronic distribution in the ring may be changed
significantly from one tautomer to another leading to large differences in
non-specific polar solvents

• Since polar solvents stabilizes polar forms, predominance
of hydroxyl tautomer is predicted in solvents less polar than water 

Synthetic of Pyridine:

• Pyridine and several of its simple alkyl derivatives were
obtained from coal tar in enough quantity

• Can be produced commercially by the gas phase interaction
of a mixture of crotonaldehyde, formaldehyde, steam, air and ammonia on
silica-alumina catalyst at 400 0C in yield of about 60-70%

• Large number of synthetic procedures are available for the
preparation of pyridines in laboratory

1. Hantzsch Synthesis:

• Most important method of synthesis

• Involves condensation of aldehyde with two moles of β-dicarbonyl compound and ammonia

Ammonia
reacts with acetoacetic acid ester to yield
β-aminocrotonic ester while the aldehyde Molecule undergoes a base
catalysed condensation with second molecule of the ester to produce alkylidene
acetoacetic acid ester.

Addition
of
β-aminocrotonic ester across the double bond of
alkylidene acetoacetic acid ester takes Place.

Subsequent
cyclisation via dehydration yields a 1,4 – dihydropyridine.

This is
then oxidized insitu by a mixture of HNO3 & H2SO4 and then by alkaline
hydrolysis & decarboxylationto give 2,6-dimethyl pyridine.

2) From other
ring systems
:

• Various heterocyclic ring systems such as furans, pyrroles
and condensed ring systems rearrange to pyridines under appropriate conditions

• Here 2-acetyl furans react with ammonia and ammonium
chloride at high temperatures to give 3-hydroxypyridines

Chemical reactions of Pyridine:

• Simple pyridines are basic in nature, extremely stable and
possess penetrating odors

• Ring remains intact in most of its chemical reactions

• Much specially used as solvents

1) Reactions
with acids
:

• Strength of an organic base depends on the electron
density at nitrogen atom and its availability for donation

• For pyridine, electron pair on the nitrogen atom in
pyridine is available for extra bonding

• Forms crystalline salts with most protic acids

• With HCl it forms pyridinium chloride

• Pyridine is frequently employed as catalyst for acylation
of phenols, alcohols and amines using acyl chloride or anhydride

• Actual acylating species is the reactive acylpyridinium
salt

Mechanism of acylation

2. Electrophilic
substitution
:

• Pyridine with an electronegative nitrogen atom causes π-deficiency at carbon atoms and
deactivates towards electrophiles

• Extreme difficulty and possible under severe experimental
conditions

• Further deactivation in case of acidic medium, as nitrogen
gets protonated

• Substitution at 3rd position is preferable

3. Halogenation:

• Occurs only under vigorous conditions

• Reaction of chlorine with pyridine in the presence of
large excess of aluminium chloride gives 3-chloropyridine (30-35%) along with
3,5-dichloropyridine

Summary

• Highly distributed in nature as pyridine derivatives and
in many important alkaloids

• Presence of nitrogen introduces an element of asymmetry
into the aromatic ring- three monosubstituted pyridines

• Large intermolecular association in pyridine because of
its greater polarity accounts for higher boiling point

• Pyridine is completely soluble in water (because of
excellent hydrogen bonding) and most organic solvents

• Structural feature is that lone pair on the nitrogen atom
is not associated with the ring and is available for protonation

• More basic than pyrrole but less than aliphatic tertiary
amine

• Pyridine with an electronegative nitrogen atom causes π-deficiency at carbon atoms and deactivates
towards electrophiles

 

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