Editing Pyridine (section)

===Nucleophilic substitutions===
In contrast to benzene ring, pyridine efficiently supports several nucleophilic substitutions. The reason for this is relatively lower electron density of the carbon atoms of the ring. These reactions include substitutions with elimination of a [[hydride]] ion and elimination-additions with formation of an intermediate [[aryne]] configuration, and usually proceed at the 2- or 4-position.<ref name=jou10/><ref name=davies>{{cite book|first=D. T. |last=Davies |title=Aromatic Heterocyclic Chemistry |publisher=Oxford University Press |date=1992 |isbn=0-19-855660-8}}</ref>

[[File:Pyridine-NA-2-position.svg|class=skin-invert-image|500px|center|Nucleophilic substitution in 2-position]]
[[File:Pyridine-NA-3-position.svg|class=skin-invert-image|500px|center|Nucleophilic substitution in 3-position]]
[[File:Pyridine-NA-4-position.svg|class=skin-invert-image|500px|center|Nucleophilic substitution in 4-position]]

Many nucleophilic substitutions occur more easily not with bare pyridine but with pyridine modified with bromine, chlorine, fluorine, or sulfonic acid fragments that then become a leaving group. So fluorine is the best leaving group for the substitution with [[organolithium compound]]s. The nucleophilic attack compounds may be [[alkoxide]]s, thiolates, [[amine]]s, and ammonia (at elevated pressures).<ref>[[#Joule|Joule]], p.&nbsp;133</ref>

In general, the hydride ion is a poor leaving group and occurs only in a few heterocyclic reactions. They include the [[Chichibabin reaction]], which yields pyridine derivatives [[Amination|aminated]] at the 2-position. Here, [[sodium amide]] is used as the nucleophile yielding 2-aminopyridine. The hydride ion released in this reaction combines with a proton of an available amino group, forming a hydrogen molecule.<ref name=davies/><ref>{{cite journal|last1=Shreve|first1=R. Norris|last2=Riechers|first2=E. H.|last3=Rubenkoenig|first3=Harry|last4=Goodman|first4=A. H.|title=Amination in the Heterocyclic Series by Sodium amide|journal=Industrial & Engineering Chemistry|volume=32|pages=173|year=1940|doi=10.1021/ie50362a008|issue=2}}</ref>

Analogous to benzene, nucleophilic substitutions to pyridine can result in the formation of [[pyridyne]] intermediates as hetero[[aryne]]. For this purpose, pyridine derivatives can be eliminated with good leaving groups using strong bases such as sodium and [[potassium tert-butoxide]]. The subsequent addition of a nucleophile to the [[triple bond]] has low selectivity, and the result is a mixture of the two possible adducts.<ref name=jou10/>