pyridine model

Pyridine behaves as a base through the lone pair of the nitrogen atom. In the presence of acids, it is protonated, generating pyridinium salts.


a) Alkylation reaction

Pyridine reacts with alkyl halides, alkanoyl halides, and anhydrides to form pyridinium salts. The reaction proceeds through the nucleophilic attack of the lone pair of nitrogen on the electrophilic carbon of said reagents.


The pyridine ring is capable of attacking electrophiles, analogously to benzene, giving the aromatic electrophilic substitution reaction. Due to the electronegativity of nitrogen, pyridine is much less reactive than benzene in SE, requiring more drastic reaction conditions.


This reaction forms organolithiums from a halogenated pyridine. Organolithics allow the attack of very varied carbon electrophiles, such as: primary alkyl halides, aldehydes, ketones, nitriles, esters, epoxides...

pyridine lithiation 01

Hard nucleophiles (organometallic, amide, lithium aluminum hydride) attack position 2 of the pyridine ring, giving rise to nucleophilic addition reactions. In the event that a final oxidation stage occurs, with loss of hydride, we can speak of nucleophilic substitution.

a) Addition of organometallics

an organometallic pyridine 01

Rearomatization of the ring is possible by adding an oxidant that removes "H 2 "

an organometallic pyridine 02

b) Addition of amide. Chichibabin's reaction

an pyridine chichibabin 01

Pyridines with leaving groups at positions 2,4 react with nucleophiles, resulting in substitution of the leaving group for the nucleophile. The reaction follows an addition-elimination mechanism.

pyridine nucleophilic substitution 01

Pyridines with leaving groups in position 3 do not give nucleophilic substitutions, but can undergo elimination in the presence of strong bases, leading to an intermediate called pyridine (equivalent to benzyne), which is attacked by the nucleophile in the middle.

pyridine 01

Pyridines with 2,4-alkyl groups have acidic hydrogens in the neighboring position of the ring. These hydrogens can be removed by using strong bases such as tert-butyllithium, LDA, etc.

alkyl vinyl pyridines 01

The base obtained has an important nucleophilic character, which allows the chain to be lengthened by attacking different electrophiles.

molecular-model-pyridine The pyridine molecule can be obtained by reacting enamines with a,b-unsaturated. Thus, the reaction between ethenamine and propenal, followed by oxidation, produces pyridine.


The condensation of two molecules of ethanal and one of methane produces a 1,5-dicarbonyl compound that reacts with ammonia to generate pyridine.


The Kröhnke synthesis of pyridine starts from a pyridinium ylide and an alpha, beta-unsaturated to yield 1,5-dicarbonyl, which by reaction with ammonia gives the final pyridine.

The Guareschi Thorpe synthesis prepares 2-pyridones from cyanoacetamide as the nitrogenous component, together with a 1,3-diketone or 3-ketoester.