Organic Chemistry: Properties of Pyridine

Structure and Properties of Pyridine

• Pyridine is a planar molecule, similar to benzene, due to sp2-hybridized carbon and nitrogen atoms.
• The lone pair of electrons on the nitrogen atom lies in the plane of the ring.
• Pyridine is an aromatic compound, following the Huckel rule of aromaticity (4n+2 π-electrons).
• The nitrogen's lone pair of electrons is in an sp2 orbital, perpendicular to the p orbitals of the ring, making it basic.

Synthesis of Pyridine

• Pyridine can be represented as a resonance hybrid of several structures.
• It can be synthesized through Bonnemann cyclization and Diels-Alder reaction.

Reactions of Pyridine

• Pyridine undergoes electrophilic and nucleophilic substitution reactions typical of aromatic rings.
• Pyridine acts as a base or nucleophile, with reactions involving the nitrogen atom directly.

Basic Character of Pyridine

• Pyridine is basic in nature, with a pKa of 8.75.
• It reacts with strong acids to form salts and is also known as piperidine.

Electrophilic Substitution Reactions

• Pyridine is less aromatic than benzene and pyrrole, making it a highly deactivated aromatic nucleus towards electrophilic substitution reactions.
• The reaction proceeds in two steps, with the rate of the first step determining the overall reaction rate.

Nucleophilic Substitution Reactions

• Nucleophilic attack at the 4-position yields a carbanion that is a hybrid of structures, which is especially stable due to the negative charge on the nitrogen atom.
• Attack at the 3-position yields a carbanion that is also a hybrid of structures.
• Pyridine is more reactive towards nucleophilic substitution than benzene, and more reactive at the 2- and 4-positions than at the 3-position.

Other Reactions of Pyridine

• Reaction with potassium hydroxide yields 2-hydroxypyridine through keto-enol tautomerism.
• Reaction with organometallic compounds, such as butyllithium, yields 2-butylpyridine.
• Reaction with sodium amide yields pyridinium chloride.

Pyridine as a Nucleophile

• As a tertiary amine, pyridine has nucleophilic properties, reacting with electrophiles to form products such as pyridinium chloride.

Pyridine Synthesis

• Hantzsch Synthesis: condensation of beta-dicarbonyl compound, ammonia, and aldehyde leads to 1,4-dihydropyridine derivative, which on oxidation with HNO3 yields pyridine derivative.
• From Pyrrole: Pyrrole heated with methylene chloride in presence of sodium ethoxide forms pyridine.
• From Picoline: Beta-picoline on oxidation with potassium dichromate and sulfuric acid gives nicotinic acid, which on decarboxylation with calcium oxide gives pyridine.

Electrophilic Substitution in Pyridine

• Pyridine is less reactive towards electrophilic substitution reactions due to:
  • Higher electronegativity of nitrogen atom reduces electron density on nitrogen atom.
  • Pyridine forms pyridinium cation with electrophile, decreasing electron density on nitrogen atom.
• Substitution reactions occur mainly at the 3-position (or β-position) due to the stability of the resulting intermediate.

Comparison with Pyrrole

• In pyrrole, nitrogen bears a positive charge, which is a stable state due to every atom having an octet of electrons.
• In pyridine, nitrogen bearing a positive charge is unstable due to nitrogen having only a sextet of electrons.

Reactivity of Pyridine

• Pyridine undergoes nitration, sulfonation, and halogenation only under vigorous conditions.
• Pyridine does not undergo Friedel-Crafts reaction.