Editing Pyridine (section)

===Electrophilic substitutions===
Owing to the decreased electron density in the aromatic system, [[electrophilic substitution]]s are suppressed in pyridine and its derivatives. [[Friedel–Crafts reaction|Friedel–Crafts alkylation or acylation]], usually fail for pyridine because they lead only to the addition at the nitrogen atom. Substitutions usually occur at the 3-position, which is the most electron-rich carbon atom in the ring and is, therefore, more susceptible to an electrophilic addition.

[[File:Pyridine-EAS-2-position-2D-skeletal.png|class=skin-invert-image|520px|center|substitution in the 2-position]]
[[File:Pyridine-EAS-3-position-2D-skeletal.png|class=skin-invert-image|500px|center|substitution in the 3-position]]
[[File:Pyridine-EAS-4-position-2D-skeletal.png|class=skin-invert-image|430px|center|Substitution in 4-position]]

Direct [[nitration]] of pyridine is sluggish.<ref>{{cite journal|last1=Bakke|first1=Jan M.|last2=Hegbom|first2=Ingrid|title=Dinitrogen Pentoxide-Sulfur Dioxide, a New nitrate ion system|journal=Acta Chemica Scandinavica|volume=48|pages=181–182|year=1994|doi=10.3891/acta.chem.scand.48-0181|last10=Stidsen|first10=Carsten E.|doi-access=free}}</ref><ref>{{cite journal|last1=Ono|first1=Noboru|last2=Murashima|first2=Takashi|last3=Nishi|first3=Keiji|last4=Nakamoto|first4=Ken-Ichi|last5=Kato|first5=Atsushi|last6=Tamai|first6=Ryuji|last7=Uno|first7=Hidemitsu|title=Preparation of Novel Heteroisoindoles from nitropyridines and Nitropyridones|journal=Heterocycles|volume=58|pages=301|year=2002|doi=10.3987/COM-02-S(M)22|doi-access=free}}</ref> Pyridine derivatives wherein the nitrogen atom is screened sterically and/or electronically can be obtained by nitration with [[nitronium tetrafluoroborate]] (NO<sub>2</sub>BF<sub>4</sub>). In this way, 3-nitropyridine can be obtained via the synthesis of 2,6-dibromopyridine followed by nitration and debromination.<ref>{{cite journal|last1=Duffy |first1=Joseph L. |last2=Laali |first2=Kenneth K. |title=Aprotic Nitration ({{chem|NO|2|+|BF|4|−}}) of 2-Halo- and 2,6-Dihalopyridines and Transfer-Nitration Chemistry of Their ''N''-Nitropyridinium Cations|journal=The Journal of Organic Chemistry|volume=56|pages=3006|year=1991|doi=10.1021/jo00009a015|issue=9}}</ref><ref>[[#Joule|Joule]], p.&nbsp;126</ref>

[[Sulfonation]] of pyridine is even more difficult than nitration.   However, pyridine-3-sulfonic acid can be obtained. Reaction with the SO<sub>3</sub> group also facilitates addition of sulfur to the nitrogen atom, especially in the presence of a [[mercury(II) sulfate]] catalyst.<ref name=jou10/><ref>{{cite journal|last1=Möller|first1=Ernst Friedrich|last2=Birkofer|first2=Leonhard|title=Konstitutionsspezifität der Nicotinsäure als Wuchsstoff bei ''Proteus vulgaris'' und ''Streptobacterium plantarum''|trans-title=Constitutional specificity of nicotinic acid as a growth factor in ''Proteus vulgaris'' and ''Streptobacterium plantarum''|journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series)|volume=75|pages=1108|year=1942|doi=10.1002/cber.19420750912|issue=9}}</ref>

In contrast to the sluggish nitrations and sulfonations, the [[bromination]] and [[chlorination reaction|chlorination]] of pyridine proceed well.<ref name=ul/>
[[File:simple chlorination.png|class=skin-invert-image|500px|center]]

====Pyridine ''N''-oxide====
[[File:Pyridine N-oxide.png|class=skin-invert-image|thumb|upright=.4|Structure of pyridine ''N''-oxide]]
Oxidation of pyridine occurs at nitrogen to give [[Pyridine-N-oxide|pyridine ''N''-oxide]]. The oxidation can be achieved with [[peracid]]s:<ref name = "pyridine-N-oxide hydrochloride">{{cite journal |first1 = H. S.|last1 = Mosher |first2 = L.|last2 = Turner |first3 = A.|last3 = Carlsmith |title = Pyridine-''N''-oxide |journal=Org. Synth. |year = 1953 |volume=33 |page=79 |doi = 10.15227/orgsyn.033.0079}}</ref>
:C<sub>5</sub>H<sub>5</sub>N + RCO<sub>3</sub>H &rarr; C<sub>5</sub>H<sub>5</sub>NO +  RCO<sub>2</sub>H

Some electrophilic substitutions on the pyridine are usefully effected using pyridine ''N''-oxide followed by deoxygenation. Addition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed, e.g., using zinc dust.<ref>{{cite journal|title=Synthesis of 2-aryl Pyridines By Palladium-catalyzed Direct Arylation of Pyridine ''N''-oxides|author1=Campeau, Louis-Charles |author2=Fagnou, Keith |journal=Org. Synth.|year=2011|volume=88|pages=22|doi=10.15227/orgsyn.088.0022|doi-access=free}}</ref>