Editing Pyridine

{{short description|Heterocyclic aromatic organic compound}}
{{Distinguish|Pyrimidine|Pyridyne}}
{{Use dmy dates|date=September 2020}}
{{chembox
|Verifiedfields = changed
|Watchedfields  = changed
|verifiedrevid  = 414415928
|Name = Pyridine
|ImageFileL1 = Pyridine-2D-full.svg
|ImageNameL1 = Full structural formula of pyridine
|ImageClassL1 = skin-invert-image
|ImageFileR1_Ref = {{chemboximage|correct|??}}
|ImageFileR1 = Pyridine numbers.svg
|ImageNameR1 = Skeletal formula of pyridine, showing the numbering convention
|ImageClassR1 = skin-invert-image
|ImageFileL2 = Pyridine-CRC-MW-3D-balls.png
| ImageClassL2 = bg-transparent
|ImageNameL2 = Ball-and-stick diagram of pyridine
|ImageFileR2 = Pyridine-CRC-MW-3D-vdW.png
| ImageClassR2 = bg-transparent
|ImageNameR2 = Space-filling model of pyridine
|ImageFile3 = Pyridine sample.jpg
|PIN = Pyridine<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | page = 141 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4}}</ref>
|SystematicName = Azabenzene
|OtherNames = Azine<br />Azinine
|Section1 = {{Chembox Identifiers
|ChEBI_Ref = {{ebicite|changed|EBI}}
|ChEBI = 16227
|SMILES = c1ccncc1
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = NH9L3PP67S
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C00747
|InChI = 1/C5H5N/c1-2-4-6-5-3-1/h1-5H
|InChIKey = JUJWROOIHBZHMG-UHFFFAOYAY
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 266158
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C5H5N/c1-2-4-6-5-3-1/h1-5H
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = JUJWROOIHBZHMG-UHFFFAOYSA-N
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo = 110-86-1
|PubChem = 1049
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 1020
|EINECS = 203-809-9
}}
|Section2 = {{Chembox Properties
|C=5 | H=5 | N=1
|Appearance = Colorless liquid<ref name=ul/>
|Odor = Nauseating, fish-like<ref name=PGCH/>
|Density = 0.9819&nbsp;g/mL (20 °C)<ref name=h1/>
|Solubility = Miscible<ref name=h1/>
|MeltingPtC = −41.63
|MeltingPt_ref = <ref name=h1>[[#Haynes|Haynes]], p. 3.474</ref> 
|BoilingPtC = 115.2
|BoilingPt_ref =<ref name=h1/>
|Viscosity = 0.879&nbsp;[[Poise (unit)|cP]] (25&nbsp;°C)<ref>[[#Haynes|Haynes]], p. 6.246</ref>
|ThermalConductivity = 0.166 W/(m·K)<ref>[[#Haynes|Haynes]], p. 6.258</ref>
|Dipole = 2.215&nbsp;D<ref>[[#Haynes|Haynes]], p. 9.65</ref>
|RefractIndex = 1.5095 (20 °C)<ref name=h1/>
|VaporPressure = 16&nbsp;mmHg (20&nbsp;°C)<ref name=PGCH/>
|pKa = 5.23 (pyridinium)<ref>[[#Haynes|Haynes]], p. 5.95</ref>
|ConjugateAcid = [[Pyridinium]]
|MagSus = −48.7·10<sup>−6</sup> cm<sup>3</sup>/mol<ref>[[#Haynes|Haynes]], p. 3.579</ref>
|LogP =0.65<ref>[[#Haynes|Haynes]], p. 5.176</ref>
}}
|Section3 = {{Chembox Thermochemistry
|DeltaHf = 100.2 kJ/mol
|HeatCapacity = 132.7 J/(mol·K)
|DeltaHc = −2.782{{nbsp}}MJ/mol
|Thermochemistry_ref=<ref>[[#Haynes|Haynes]], pp. 5.34, 5.67</ref> 
}}
|Section4 = {{Chembox Hazards
|MainHazards= Low to moderate hazard<ref>Pyridine: main hazards, precautions and toxicity</ref>
|Hazards_ref = <ref>{{cite web |url=https://fscimage.fishersci.com/msds/19990.htm |title=Pyridine MSDS |website=fishersci.com |publisher=Fisher |access-date=2 February 2010 |archive-date=11 June 2010 |archive-url=https://web.archive.org/web/20100611053419/http://fscimage.fishersci.com/msds/19990.htm |url-status=live }}</ref>
|NFPA-H = 2
|NFPA-F = 3
|NFPA-R = 0
|FlashPtC = 20
|FlashPt_ref = <ref name=hig>[[#Haynes|Haynes]], p. 15.19</ref>
|AutoignitionPtC = 482
|AutoignitionPt_ref=<ref name=hig/>
|TLV-TWA = 5&nbsp;ppm
|GHSPictograms = {{GHS02}}{{GHS07}}<ref name="GESTIS" />
|GHSSignalWord = Danger
|HPhrases = {{H-phrases|225|302|312|332|315|319}}<ref name="GESTIS" />
|PPhrases = {{P-phrases|210|280|301+312|303+361+353|304+340+312|305+351+338}}<ref name="GESTIS" />
|PEL = TWA 5&nbsp;ppm (15&nbsp;mg/m<sup>3</sup>)<ref name=PGCH>{{PGCH|0541}}</ref>
|ExploLimits = 1.8–12.4%<ref name=PGCH/>
|IDLH = 1000&nbsp;ppm<ref name=PGCH/> 
|REL = TWA 5&nbsp;ppm (15&nbsp;mg/m<sup>3</sup>)<ref name=PGCH/>
|LC50 = 9000&nbsp;ppm (rat, 1&nbsp;hr)<ref name=IDLH>{{IDLH|110861|Pyridine}}</ref>
|LD50 = 891&nbsp;mg/kg (rat, oral)<br/>1500&nbsp;mg/kg (mouse, oral)<br/>1580&nbsp;mg/kg (rat, oral)<ref name=IDLH/>
}}
|Section5 = {{Chembox Related
|OtherFunction_label = [[amine]]s
|OtherFunction = [[Picoline]]<br />[[Quinoline]]
|OtherCompounds = [[Aniline]]<br />[[Pyrimidine]]<br />[[Piperidine]]}}
}}

'''Pyridine''' is a [[basic (chemistry)|basic]] [[heterocyclic compound|heterocyclic]] [[organic compound]] with the [[chemical formula]] {{chem2|C5H5N|auto=1}}. It is structurally related to [[benzene]], with one [[methine group]] {{chem2|(\dCH\s)}} replaced by a [[nitrogen]] atom {{chem2|(\dN\s)}}.  It is a highly flammable, weakly [[alkali]]ne, water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated [[Polymer|polymeric]] chains, which show significant [[electrical conductivity]].{{page needed|date=March 2024}}<ref>{{Cite journal |last1=Vaganova |first1=Evgenia |last2=Eliaz |first2=Dror |last3=Shimanovich |first3=Ulyana |last4=Leitus |first4=Gregory |last5=Aqad |first5=Emad |last6=Lokshin |first6=Vladimir |last7=Khodorkovsky |first7=Vladimir |date=January 2021 |title=Light-Induced Reactions within Poly(4-vinyl pyridine)/Pyridine Gels: The 1,6-Polyazaacetylene Oligomers Formation |journal=Molecules |language=en |volume=26 |issue=22 |pages=6925 |doi=10.3390/molecules26226925 |pmid=34834017 |pmc=8621047 |issn=1420-3049|doi-access=free }}</ref>  The pyridine ring occurs in many important compounds, including [[agrochemical]]s, [[pharmaceutical]]s, and [[vitamin]]s. Historically, pyridine was produced from [[coal tar]]. As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.<ref name=ul/>

==Properties==
[[File:PyridineXray.svg|class=skin-invert-image|thumb|142px|left|Internal bond angles and bond distances (in [[picometer|pm]]) for pyridine.<ref name=cox/>]]

===Physical properties===
[[File:Kristallstruktur Pyridin.png|thumb|left|Crystal structure of pyridine]]

Pyridine is [[diamagnetism|diamagnetic]]. Its [[critical point (thermodynamics)|critical parameters]] are: pressure 5.63&nbsp;MPa, temperature 619&nbsp;K and volume 248&nbsp;cm<sup>3</sup>/mol.<ref>[[#Haynes|Haynes]], p.&nbsp;6.80</ref> In the temperature range 340–426&nbsp;°C its vapor pressure ''p'' can be described with the [[Antoine equation]]
:<math>\log_{10} p = A-\frac{B}{C+T}</math>
where ''T'' is temperature, ''A''&nbsp;=&nbsp;4.16272, ''B''&nbsp;=&nbsp;1371.358&nbsp;K and ''C''&nbsp;=&nbsp;−58.496&nbsp;K.<ref>{{cite journal|last1=McCullough|first1=J. P.|last2=Douslin|first2=D. R.|last3=Messerly|first3=J. F.|last4=Hossenlopp|first4=I. A.|last5=Kincheloe|first5=T. C.|last6=Waddington|first6=Guy|title=Pyridine: Experimental and Calculated Chemical Thermodynamic Properties between 0 and 1500&nbsp;K.; a Revised Vibrational Assignment|journal=Journal of the American Chemical Society|volume=79|pages=4289|year=1957|doi=10.1021/ja01573a014|issue=16}}</ref>

===Structure===
Pyridine ring forms a {{chem2|C5N}} hexagon.  Slight variations of the {{chem2|C\sC}} and {{chem2|C\sN}} distances as well as the bond angles are observed.

===Crystallography===
Pyridine crystallizes in an [[orthorhombic crystal system]] with [[space group]] ''Pna2<sub>1</sub>'' and [[lattice parameters]] ''a''&nbsp;=&nbsp;1752&nbsp;[[picometer|pm]], ''b''&nbsp;=&nbsp;897&nbsp;pm, ''c''&nbsp;=&nbsp;1135&nbsp;pm, and 16 [[formula unit]]s per [[unit cell]] (measured at 153&nbsp;K). For comparison, crystalline [[benzene]] is also orthorhombic, with space group ''Pbca'', ''a''&nbsp;=&nbsp;729.2&nbsp;pm, ''b''&nbsp;=&nbsp;947.1&nbsp;pm, ''c''&nbsp;=&nbsp;674.2&nbsp;pm (at 78&nbsp;K), but the number of molecules per cell is only 4.<ref name=cox>{{cite journal|last1=Cox|first1=E.|title=Crystal Structure of Benzene|journal=Reviews of Modern Physics|volume=30|issue=1|pages=159–162|year=1958|doi=10.1103/RevModPhys.30.159|bibcode=1958RvMP...30..159C}}</ref> This difference is partly related to the lower [[Molecular symmetry|symmetry]] of the individual pyridine molecule (C<sub>2v</sub> vs D<sub>6h</sub> for benzene). A tri[[hydrate]] (pyridine·3H<sub>2</sub>O) is known; it also crystallizes in an orthorhombic system in the space group ''Pbca'', lattice parameters ''a''&nbsp;=&nbsp;1244&nbsp;pm, ''b''&nbsp;=&nbsp;1783&nbsp;pm, ''c''&nbsp;=&nbsp;679&nbsp;pm and eight formula units per unit cell (measured at 223&nbsp;K).<ref name=str>{{cite journal|last1=Mootz|first1=D.|title=Crystal structures of pyridine and pyridine trihydrate|journal=The Journal of Chemical Physics|volume=75|pages=1517–1522|year=1981|doi=10.1063/1.442204|issue=3|bibcode = 1981JChPh..75.1517M }}</ref>

===Spectroscopy===
The optical [[Absorption Spectrum|absorption spectrum]] of pyridine in [[hexane]] consists of bands at the [[wavelength]]s of 195, 251, and 270&nbsp;nm.  With respective extinction coefficients (''ε'') of 7500, 2000, and 450&nbsp;L·mol<sup>−1</sup>·cm<sup>−1</sup>, these bands are assigned to π&nbsp;→&nbsp;π*, π&nbsp;→&nbsp;π*, and n&nbsp;→&nbsp;π*  transitions. The compound displays very low [[fluorescence]].<ref>{{cite journal |last1=Varras |first1=Panayiotis C. |last2=Gritzapis |first2=Panagiotis S. |last3=Fylaktakidou |first3=Konstantina C. |title=An explanation of the very low fluorescence and phosphorescence in pyridine: a CASSCF/CASMP2 study |journal=Molecular Physics |date=17 January 2018 |volume=116 |issue=2 |pages=154–170 |doi=10.1080/00268976.2017.1371800|url=https://figshare.com/articles/journal_contribution/5414566 }}</ref>

The <sup>1</sup>H [[nuclear magnetic resonance]] (NMR) spectrum shows signals for α-([[chemical shift|δ]] 8.5), γ-(δ7.5) and β-protons (δ7). By contrast, the proton signal for benzene is found at δ7.27. The larger chemical shifts of the α- and γ-protons in comparison to benzene result from the lower electron density in the α- and γ-positions, which can be derived from the resonance structures. The situation is rather similar for the [[13C NMR|<sup>13</sup>C&nbsp;NMR]] spectra of pyridine and benzene: pyridine shows a triplet at ''δ''(α-C)&nbsp;=&nbsp;150&nbsp;ppm, δ(β-C)&nbsp;=&nbsp;124&nbsp;ppm and δ(γ-C)&nbsp;=&nbsp;136&nbsp;ppm, whereas benzene has a single line at 129&nbsp;ppm. All shifts are quoted for the solvent-free substances.<ref>[[#Joule|Joule]], p.&nbsp;16</ref> Pyridine is conventionally detected by the [[gas chromatography]] and [[mass spectrometry]] methods.<ref name=osha>{{cite book |url=http://monographs.iarc.fr/ENG/Monographs/vol77/mono77-21.pdf |title=Pyridine |work=IARC Monographs 77 |publisher=OSHA |location=Washington DC |date=1985 |access-date=7 January 2011 |archive-date=4 March 2016 |archive-url=https://web.archive.org/web/20160304083832/http://monographs.iarc.fr/ENG/Monographs/vol77/mono77-21.pdf |url-status=live }}</ref>

===Bonding===
[[File:Pyridine-2D-Skeletal.png|class=skin-invert-image|upright=.5|thumb|left|Pyridine with its free electron pair]]
Pyridine has a [[conjugation (organic chemistry)|conjugated]] system of six [[Pi bond|π electrons]] that are delocalized over the ring. The molecule is planar and, thus, follows the [[Hückel rule|Hückel criteria]] for aromatic systems. In contrast to benzene, the [[electron density]] is not evenly distributed over the ring, reflecting the negative [[inductive effect]] of the nitrogen atom. For this reason, pyridine has a dipole moment and a weaker [[Resonance (chemistry)|resonant stabilization]] than benzene ([[Resonance (chemistry)#Resonance energy|resonance energy]] 117&nbsp;kJ/mol in pyridine vs. 150&nbsp;kJ/mol in benzene).<ref>[[#Joule|Joule]], p.&nbsp;7</ref>

The ring atoms in the pyridine molecule are [[orbital hybridisation#sp2 hybrids|sp<sup>2</sup>-hybridized]]. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. The [[lone pair]] is in an sp<sup>2</sup> orbital, projecting outward from the ring in the same plane as the [[σ bond]]s. As a result, the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack.<ref>{{cite book|last=Sundberg|first=Francis A. Carey; Richard J.|title=Advanced Organic Chemistry : Part A: Structure and Mechanisms|year=2007|publisher=Springer US|location=Berlin|isbn=978-0-387-68346-1|edition=5.|page=794}}</ref> However, because of the separation of the lone pair from the aromatic ring system, the nitrogen atom cannot exhibit a positive [[mesomeric effect]].

Many analogues of pyridine are known where N is replaced by other heteroatoms from the same column of the [[Periodic Table of Elements]] (see figure below). Substitution of one C–H in pyridine with a second N gives rise to the [[diazine]] heterocycles (C<sub>4</sub>H<sub>4</sub>N<sub>2</sub>), with the names [[pyridazine]], [[pyrimidine]], and [[pyrazine]].

<div><ul> 
<li style="display: inline-block;">[[File:Bond lengths of group 15 heterobenzenes and benzene.svg|class=skin-invert-image|thumb|center|upright=2|Bond lengths and angles of benzene, pyridine, [[phosphorine]], [[arsabenzene]], [[stibabenzene]], and [[bismabenzene]]]]</li>
<li style="display: inline-block;">[[File:Pyridine-orbitals.svg|class=skin-invert-image|thumb|center|upright=.5|Atomic orbitals in pyridine]]</li>
<li style="display: inline-block;">[[File:Pyridine-10.png|class=skin-invert-image|thumb|center|upright=2.4|Resonance structures of pyridine]]</li>
<li style="display: inline-block;">[[File:Pyridinium-orbitals.svg|class=skin-invert-image|thumb|center|upright=.57|Atomic orbitals in protonated pyridine]]</li>
</ul></div>

==History==
[[File:ThomasAnderson(1819-1874).jpg|thumb|upright|[[Thomas Anderson (chemist)|Thomas Anderson]]]]
Impure pyridine was undoubtedly prepared by early [[Alchemy|alchemists]] by heating animal bones and other organic matter,<ref name=weiss>{{cite book|last1=Weissberger |first1=A. |last2=Klingberg |first2=A. |last3=Barnes |first3=R. A.|last4= Brody |first4=F. |last5=Ruby |first5=P.R. |title=Pyridine and its Derivatives |volume=1 |date=1960 |publisher=Interscience |location=New York}}</ref> but the earliest documented reference is attributed to the Scottish scientist [[Thomas Anderson (chemist)|Thomas Anderson]].<ref>{{cite journal |last1=Anderson |first1=Thomas |title=On the constitution and properties of picoline, a new organic base from coal-tar |journal=Transactions of the Royal Societies of Edinburgh University |date=1849 |volume=16 |issue=2 |pages=123–136 |url=https://babel.hathitrust.org/cgi/pt?id=njp.32101074834258;view=1up;seq=153 |doi=10.1017/S0080456800024984 |s2cid=100301190 |access-date=24 September 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045408/https://babel.hathitrust.org/cgi/pt?id=njp.32101074834258;view=1up;seq=153 |url-status=live }}</ref><ref name="Von1849">{{cite journal|last1=Anderson|first1=T.|title=Producte der trocknen Destillation thierischer Materien|trans-title=Products of the dry distillation of animal matter|journal=Annalen der Chemie und Pharmacie|volume=70|pages=32–38|year=1849|language=de|url=https://babel.hathitrust.org/cgi/pt?id=uiug.30112025848026;view=1up;seq=434|doi=10.1002/jlac.18490700105|access-date=24 September 2018|archive-date=24 May 2020|archive-url=https://web.archive.org/web/20200524045414/https://babel.hathitrust.org/cgi/pt?id=uiug.30112025848026;view=1up;seq=434|url-status=live}}</ref> In 1849, Anderson examined the contents of the [[Dippel's oil|oil obtained through high-temperature heating of animal bones]].<ref name="Von1849" /> Among other substances, he separated from the oil a colorless liquid with unpleasant odor, from which he isolated pure pyridine two years later. He described it as highly soluble in water, readily soluble in concentrated acids and salts upon heating, and only slightly soluble in oils.

Owing to its flammability, Anderson named the new substance ''pyridine'', after {{langx|el|[[wikt:πῦρ|πῦρ]]}} (pyr) meaning ''fire''. The suffix ''[[wikt:-idine|idine]]'' was added in compliance with the chemical nomenclature, as in ''[[toluidine]]'', to indicate a [[cyclic compound]] containing a nitrogen atom.<ref>{{cite journal |last1=Anderson |first1=Thomas |title=On the products of the destructive distillation of animal substances. Part II. |journal=Transactions of the Royal Society of Edinburgh |date=1851 |volume=20 |issue=2 |pages=247–260 |url=https://babel.hathitrust.org/cgi/pt?id=njp.32101074834290;view=1up;seq=287 |doi=10.1017/S0080456800033160 |s2cid=102143621 |access-date=24 September 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045301/https://babel.hathitrust.org/cgi/pt?id=njp.32101074834290;view=1up;seq=287 |url-status=live }}  From p. 253: "Pyridine. The first of these bases, to which I give the name of pyridine, … "</ref><ref name=anderson2>{{cite journal |last1=Anderson |first1=T. |title=Ueber die Producte der trocknen Destillation thierischer Materien |trans-title=On the products of dry distillation of animal matter |journal=Annalen der Chemie und Pharmacie |volume=80 |pages=44–65 |year=1851 |language=de |url=https://babel.hathitrust.org/cgi/pt?id=uiug.30112025848422;view=1up;seq=444 |doi=10.1002/jlac.18510800104 |access-date=24 September 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045314/https://babel.hathitrust.org/cgi/pt?id=uiug.30112025848422;view=1up;seq=444 |url-status=live }}</ref>

The chemical structure of pyridine was determined decades after its discovery. [[Wilhelm Körner]] (1869)<ref>{{cite journal |last1=Koerner |first1=W. |title=Synthèse d'une base isomère à la toluidine |journal=Giornale di Scienze Naturali ed Economiche (Journal of Natural Science and Economics (Palermo, Italy)) |date=1869 |volume=5 |pages=111–114 |url=https://books.google.com/books?id=J00_AAAAcAAJ&pg=PA111 |trans-title=Synthesis of a base [that is] isomeric to toluidine |language=fr}}</ref> and [[James Dewar]] (1871)<ref>{{cite journal |last1=Dewar |first1=James |title=On the oxidation products of picoline |journal=Chemical News |date=27 January 1871 |volume=23 |pages=38–41 |url=https://babel.hathitrust.org/cgi/pt?id=uc1.$c193335;view=1up;seq=46 |access-date=27 September 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045420/https://babel.hathitrust.org/cgi/pt?id=uc1.$c193335;view=1up;seq=46 |url-status=live }}</ref><ref>{{cite journal |title=Koerner, Dewar and the Structure of Pyridine |first=Alan J. |last=Rocke |journal=Bulletin for the History of Chemistry |volume=2 |date=1988 |page=4 |url=http://www.scs.illinois.edu/~mainzv/HIST/bulletin_open_access/bull88-num2.php |access-date=5 May 2016 |archive-date=24 September 2018 |archive-url=https://web.archive.org/web/20180924105914/http://www.scs.illinois.edu/~mainzv/HIST/bulletin_open_access/bull88-num2.php |url-status=live }} {{open access}}</ref> suggested that, in analogy between [[quinoline]] and [[naphthalene]], the structure of pyridine is derived from [[benzene]] by substituting one C–H unit with a nitrogen atom.<ref>{{cite book |author-link=Albert Ladenburg |last=Ladenburg |first=Albert |url=http://www.sciencemadness.org/library/books/lectures_on_the_history_of_the_development_of_chemistry.pdf |title=Lectures on the history of the development of chemistry since the time of Lavoisier |pages=283–287 |year=1911|access-date=7 January 2011 |archive-date=20 September 2018 |archive-url=https://web.archive.org/web/20180920134805/http://www.sciencemadness.org/library/books/lectures_on_the_history_of_the_development_of_chemistry.pdf |url-status=live }} {{open access}}</ref><ref>{{cite book|last=Bansal |first=Raj K. |url=https://books.google.com/books?id=RH1l_VQcFDQC&pg=PA216 |title=Heterocyclic Chemistry |date=1999 |isbn=81-224-1212-2 |page=216|publisher=New Age International }}</ref> The suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to [[piperidine]] with [[sodium]] in [[ethanol]].<ref>{{cite journal |last1=Ladenburg |first1=A. |title=Synthese des Piperidins |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1884 |volume=17 |page=156 |url=https://babel.hathitrust.org/cgi/pt?id=uc1.31210011601398;view=1up;seq=164 |trans-title=Synthesis of piperidine |language=de |doi=10.1002/cber.18840170143 |access-date=15 October 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045307/https://babel.hathitrust.org/cgi/pt?id=uc1.31210011601398;view=1up;seq=164 |url-status=live }}</ref><ref>{{cite journal |last1=Ladenburg |first1=A. |title=Synthese des Piperidins und seiner Homologen |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1884 |volume=17 |pages=388–391 |url=https://babel.hathitrust.org/cgi/pt?id=uc1.31210011601398;view=1up;seq=396 |trans-title=Synthesis of piperidine and its homologues |language=de |doi=10.1002/cber.188401701110 |access-date=15 October 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045355/https://babel.hathitrust.org/cgi/pt?id=uc1.31210011601398;view=1up;seq=396 |url-status=live }}</ref> In 1876, [[William Ramsay]] combined [[acetylene]] and [[hydrogen cyanide]] into pyridine in a [[Red heat|red-hot]] iron-tube furnace.<ref>{{cite journal |last1=Ramsay |first1=William |title=On picoline and its derivatives |journal=Philosophical Magazine |date=1876 |volume=2 |pages=269–281 |url=https://babel.hathitrust.org/cgi/pt?id=uiug.30112098008771;view=1up;seq=283 |series=5th series |issue=11 |doi=10.1080/14786447608639105 |access-date=24 September 2018 |archive-date=24 May 2020 |archive-url=https://web.archive.org/web/20200524045452/https://babel.hathitrust.org/cgi/pt?id=uiug.30112098008771;view=1up;seq=283 |url-status=live }}</ref> This was the first synthesis of a heteroaromatic compound.<ref name=osha/><ref>{{cite journal|title=A. Henninger, aus Paris. 12. April 1877|journal=Berichte der Deutschen Chemischen Gesellschaft|volume=10|pages=727–737|year=1877|doi=10.1002/cber.187701001202|type=Correspondence}}</ref>

The first major synthesis of pyridine derivatives was described in 1881 by [[Arthur Rudolf Hantzsch]].<ref>{{cite journal|last1=Hantzsch|first1=A.|title=Condensationsprodukte aus Aldehydammoniak und ketonartigen Verbindungen|trans-title=Condensation products from aldehyde ammonia and ketone-type compounds|journal=Berichte der Deutschen Chemischen Gesellschaft|volume=14|pages=1637–1638|year=1881|doi=10.1002/cber.18810140214|issue=2|url=https://zenodo.org/record/1425236|access-date=6 September 2019|archive-date=22 January 2021|archive-url=https://web.archive.org/web/20210122224737/https://zenodo.org/record/1425236|url-status=live}}</ref> The [[Hantzsch pyridine synthesis]] typically uses a 2:1:1 mixture of a β-[[keto acid]] (often [[Acetoacetic acid|acetoacetate]]), an [[aldehyde]] (often [[formaldehyde]]), and [[ammonia]] or its salt as the nitrogen donor. First, a double [[Hydration reaction|hydrogenated]] pyridine is obtained, which is then oxidized to the corresponding pyridine derivative. [[Emil Knoevenagel]] showed that asymmetrically substituted pyridine derivatives can be produced with this process.<ref>{{cite journal|last1=Knoevenagel|first1=E.|last2=Fries|first2=A.|title=Synthesen in der Pyridinreihe. Ueber eine Erweiterung der Hantzsch'schen Dihydropyridinsynthese|trans-title=Syntheses in the pyridine series. On an extension of the Hantzsch dihydropyridine synthesis|journal=Berichte der Deutschen Chemischen Gesellschaft|volume=31|pages=761–767|year=1898|doi=10.1002/cber.189803101157|url=https://zenodo.org/record/1425894|access-date=29 June 2019|archive-date=15 January 2020|archive-url=https://web.archive.org/web/20200115174109/https://zenodo.org/record/1425894|url-status=live}}</ref>

[[File:Hantzsch pyridine synthesis.svg|class=skin-invert-image|800px|thumb|center|[[Hantzsch pyridine synthesis]] with acetoacetate, formaldehyde and [[ammonium acetate]], and [[iron(III) chloride]] as the oxidizer.]]

The contemporary methods of pyridine production had a low yield, and the increasing demand for the new compound urged to search for more efficient routes. A breakthrough came in 1924 when the Russian chemist [[Aleksei Chichibabin]] invented a [[Chichibabin pyridine synthesis|pyridine synthesis reaction]], which was based on inexpensive reagents.<ref name=tschi>{{cite journal
| last = Chichibabin
| first = A. E.
| trans-title = On condensation of aldehydes with ammonia to make pyridines
| title = Über Kondensation der Aldehyde mit Ammoniak zu Pyridinebasen
| url = http://gallica.bnf.fr/ark:/12148/bpt6k90877m/f132.chemindefer
| journal = Journal für Praktische Chemie
| year = 1924
| volume = 107
| pages = 122
| doi = 10.1002/prac.19241070110
| access-date = 7 January 2011
| archive-date = 20 September 2018
| archive-url = https://web.archive.org/web/20180920134841/https://gallica.bnf.fr/ark:/12148/bpt6k90877m/f132.chemindefer
| url-status = live
}}</ref> This method is still used for the industrial production of pyridine.<ref name=ul/>

==Occurrence==
Pyridine is not abundant in nature, except for the leaves and roots of belladonna (''[[Atropa belladonna]]'')<ref>{{cite book|editor-last=Burdock |editor-first=G. A. |title=Fenaroli's Handbook of Flavor Ingredients |volume=2 |edition=3rd |publisher=CRC Press |location=Boca Raton |date=1995 |isbn=0-8493-2710-5}}</ref> and in marshmallow (''[[Althaea officinalis]]'').<ref>{{cite book|last1=Täufel |first1=A. |last2=Ternes |first2=W. |last3=Tunger |first3=L. |last4=Zobel |first4=M. |title=Lebensmittel-Lexikon |edition=4th |page=450 |publisher=Behr |date=2005 |isbn=3-89947-165-2}}</ref> Pyridine derivatives, however, are often part of biomolecules such as [[alkaloid]]s.

In daily life, trace amounts of pyridine are components of the [[volatile organic compound]]s that are produced in roasting and [[canning]] processes, e.g. in fried chicken,<ref>{{cite journal|last1=Tang|first1=Jian|last2=Jin|first2=Qi Zhang|last3=Shen|first3=Guo Hui|last4=Ho|first4=Chi Tang|last5=Chang|first5=Stephen S.|title=Isolation and identification of volatile compounds from fried chicken|journal=Journal of Agricultural and Food Chemistry|volume=31|pages=1287|year=1983|doi=10.1021/jf00120a035|issue=6}}</ref> [[sukiyaki]],<ref>{{cite journal|last1=Shibamoto|first1=Takayuki|last2=Kamiya|first2=Yoko|last3=Mihara|first3=Satoru|title=Isolation and identification of volatile compounds in cooked meat: sukiyaki|journal=Journal of Agricultural and Food Chemistry|volume=29|pages=57–63|year=1981|doi=10.1021/jf00103a015}}</ref> roasted coffee,<ref>{{cite journal|last1=Aeschbacher|first1=HU|last2=Wolleb|first2=U |last3=Löliger|first3=J|last4=Spadone|first4=JC|last5=Liardon|first5=R|title=Contribution of coffee aroma constituents to the mutagenicity of coffee|journal=[[Food and Chemical Toxicology]] |volume=27|issue=4|pages=227–232|year=1989|pmid=2659457|doi=10.1016/0278-6915(89)90160-9|doi-access=free}}</ref> potato chips,<ref>{{cite journal |last1=Buttery |first1=Ron G. |last2=Seifert |first2=Richard M. |last3=Guadagni |first3=Dante G. |last4=Ling |first4=Louisa C. |year=1971 |title=Characterization of Volatile Pyrazine and Pyridine Components of Potato Chips |journal=Journal of Agricultural and Food Chemistry |volume=19 |issue=5 | pages= 969–971|location= Washington, DC|publisher=ACS |doi= 10.1021/jf60177a020 }}</ref> and fried [[bacon]].<ref>{{cite journal|last1=Ho|first1=Chi Tang|last2=Lee|first2=Ken N.|last3=Jin|first3=Qi Zhang|title=Isolation and identification of volatile flavor compounds in fried bacon|journal=Journal of Agricultural and Food Chemistry|volume=31|pages=336|year=1983|doi=10.1021/jf00116a038|issue=2}}</ref> Traces of pyridine can be found in [[Beaufort (cheese)|Beaufort cheese]],<ref>{{cite journal|last1=Dumont|first1=Jean Pierre|last2=Adda|first2=Jacques|title=Occurrence of sesquiterpene in mountain cheese volatiles|journal=Journal of Agricultural and Food Chemistry|volume=26|pages=364|year=1978|doi=10.1021/jf60216a037|issue=2}}</ref> [[Vaginal lubrication|vaginal secretion]]s,<ref>{{cite book |last1= Labows | first1= John N. Jr. |editor1-first=Howard R. |editor1-last= Moskowitz |last2= Warren|first2= Craig B.|title= Odor Quality and Chemical Structure |year=1981 |publisher=American Chemical Society |location=Washington, DC|isbn= 9780841206076 |doi= 10.1021/bk-1981-0148.fw001 |pages=195–210 |chapter= Odorants as Chemical Messengers}}</ref> [[black tea]],<ref>{{cite journal|last1=Vitzthum|first1=Otto G.|last2=Werkhoff|first2=Peter|last3=Hubert|first3=Peter|title=New volatile constituents of black tea flavor|journal=Journal of Agricultural and Food Chemistry|volume=23|pages=999|year=1975|doi=10.1021/jf60201a032|issue=5}}</ref> saliva of those suffering from [[gingivitis]],<ref>{{cite journal |last1=Kostelc |first1=J. G. |last2=Preti |first2=G. |last3=Nelson |first3=P. R. |last4=Brauner |first4=L. |last5=Baehni |first5=P. |year=1984 |title= Oral Odors in Early Experimental Gingivitis |journal= Journal of Periodontal Research |volume=19 |pages=303–312|doi= 10.1111/j.1600-0765.1984.tb00821.x |issue= 3 |pmid= 6235346}}</ref> and [[Monofloral honey|sunflower honey]].<ref>{{cite book|last1=Täufel |first1=A. |last2=Ternes |first2=W. |last3=Tunger |first3=L. |last4=Zobel |first4=M. |title=Lebensmittel-Lexikon |edition=4th |page=226 |publisher=Behr |date=2005 |isbn=3-89947-165-2}}</ref>

<gallery class="centered skin-invert-image">
File:4-Bromopyridine.svg|4-bromopyridine
File:2,2'-Bipyridine.svg|2,2'-[[bipyridine]]
File:Dipicolinic acid.svg|pyridine-2,6-dicarboxylic acid ([[dipicolinic acid]])
File:PyridiniumVerbindungen.svg|General form of the [[pyridinium]] cation
</gallery>

Trace amounts of up to 16&nbsp;μg/m<sup>3</sup> have been detected in tobacco smoke.<ref name=osha/> Minor amounts of pyridine are released into environment from some industrial processes such as steel manufacture,<ref>{{cite journal|last1=Junk|first1=G. A.|last2=Ford|first2=C. S.|title=A review of organic emissions from selected combustion processes|journal=Chemosphere|volume=9|pages=187|year=1980|doi=10.1016/0045-6535(80)90079-X|issue=4|bibcode=1980Chmsp...9..187J|osti=5295035 }}</ref> processing of [[oil shale]], [[coal gasification]], [[coking]] plants and [[Incineration|incinerators]].<ref name=osha/> The atmosphere at oil shale processing plants can contain pyridine concentrations of up to 13&nbsp;μg/m<sup>3</sup>,<ref>{{cite journal|last1=Hawthorne|first1=Steven B.|last2=Sievers|first2=Robert E.|title=Emissions of organic air pollutants from shale oil wastewaters|journal=Environmental Science & Technology|volume=18|pages=483–90|year=1984|doi=10.1021/es00124a016|issue=6|pmid=22247953|bibcode = 1984EnST...18..483H }}</ref> and 53&nbsp;μg/m<sup>3</sup> levels were measured in the [[groundwater]] in the vicinity of a coal gasification plant.<ref>{{cite journal|last1=Stuermer|first1=Daniel H.|last2=Ng|first2=Douglas J.|last3=Morris|first3=Clarence J.|title=Organic contaminants in groundwater near to underground coal gasification site in northeastern Wyoming|journal=Environmental Science & Technology|volume=16|pages=582–7|year=1982|doi=10.1021/es00103a009|issue=9|pmid=22284199|bibcode = 1982EnST...16..582S }}</ref> According to a study by the US [[National Institute for Occupational Safety and Health]], about 43,000 Americans work in contact with pyridine.<ref>{{cite book|title=National Occupational Exposure Survey 1981–83 |location=Cincinnati, OH |publisher=Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occuptional Safety and Health}}</ref>

===In foods===
Pyridine has historically been added to foods to give them a bitter flavour, although this practise is now banned in the U.S.<ref>{{Federal Register|83|50490}}</ref><ref>{{Cite news|url=https://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm622475.htm|title=FDA Removes 7 Synthetic Flavoring Substances from Food Additives List|date=5 October 2018|access-date=8 October 2018|archive-date=7 October 2018|archive-url=https://web.archive.org/web/20181007053921/https://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm622475.htm|url-status=live}}</ref> It may still be added to [[ethanol]] to make it unsuitable for drinking.<ref name=roempp/>

==Production==
Historically, pyridine was extracted from [[coal tar]] or obtained as a byproduct of coal [[gasification]]. The process is labor-consuming and inefficient: [[coal tar]] contains only about 0.1% pyridine,<ref>{{cite book|first=A. |last=Gossauer |title=Struktur und Reaktivität der Biomoleküle |date=2006 |page=488 |publisher=Wiley-VCH |location=Weinheim |isbn=3-906390-29-2}}</ref> and therefore a multi-stage purification was required, which further reduced the output. Nowadays, most pyridines are synthesized from ammonia, aldehydes, and nitriles, a few combinations of which are suited for pyridine itself.   Various [[name reaction]]s are also known, but they are not practiced on scale.<ref name=ul>{{Ullmann|first1=S. |last1=Shimizu |first2=N. |last2=Watanabe |first3=T. |last3=Kataoka |first4=T. |last4=Shoji |first5=N. |last5=Abe |first6=S. |last6=Morishita |first7=H. |last7=Ichimura |title=Pyridine and Pyridine Derivatives |doi=10.1002/14356007.a22_399}}</ref>

In 1989, 26,000 tonnes of pyridine was produced worldwide.  Other major derivatives are [[2-methylpyridine|2-]], [[3-methylpyridine|3-]], [[4-methylpyridine]]s and [[5-ethyl-2-methylpyridine]].  The combined scale of these alkylpyridines matches that of pyridine itself.<ref name=ul/> Among the largest 25 production sites for pyridine, eleven are located in Europe (as of 1999).<ref name=osha/> The major producers of pyridine include [[Evonik Industries]], Rütgers Chemicals, [[Jubilant Life Sciences]], [[Imperial Chemical Industries]], and Koei Chemical.<ref name=ul/> Pyridine production significantly increased in the early 2000s, with an annual production capacity of 30,000 tonnes in mainland China alone.<ref>{{cite web |url=http://www.agrochemex.net/en/press/2010/05/11/Pyridine_s_Development_in_China/ |title=Pyridine's Development in China |publisher=[[AgroChemEx]] |date=11 May 2010 |access-date=7 January 2011 |archive-url=https://web.archive.org/web/20180920134906/http://www.agrochemex.net/en/press/2010/05/11/Pyridine_s_Development_in_China/ |archive-date=20 September 2018 |url-status=dead }}</ref> The US–Chinese joint venture Vertellus is currently the world leader in pyridine production.<ref>{{cite web |url=http://www.vertellus.com/company.aspx |title=About Vertellus |website=vertellus.com |access-date=7 January 2011 |archive-url=https://archive.today/20120918012717/http://www.vertellus.com/company.aspx |archive-date=18 September 2012 |url-status=dead }}</ref>

===Chichibabin synthesis===
The [[Chichibabin pyridine synthesis]] was reported in 1924 and the basic approach underpins several industrial routes.<ref name=tschi/> In its general form, the reaction involves the [[condensation reaction]] of [[aldehydes]], [[ketones]], [[α,β-Unsaturated carbonyl compound|α,β-unsaturated carbonyl compounds]], or any combination of the above, in [[ammonia]] or [[amine|ammonia derivatives]]. Application of the Chichibabin pyridine synthesis suffer from low yields, often about 30%,<ref name='Frank1949'>{{cite journal
|last1=Frank|first1= R. L. |last2=Seven|first2= R. P.| title = Pyridines. IV. A Study of the Chichibabin Synthesis
| journal = Journal of the American Chemical Society
| year = 1949
| volume = 71
| issue = 8
| pages = 2629–2635
| doi = 10.1021/ja01176a008}}</ref> however the precursors are inexpensive. In particular, unsubstituted pyridine is produced from [[formaldehyde]] and [[acetaldehyde]]. First, [[acrolein]] is formed in a [[Knoevenagel condensation]] from the acetaldehyde and formaldehyde. The acrolein then [[condensation reaction|condenses]] with acetaldehyde and ammonia to give [[dihydropyridine]], which is oxidized to pyridine. This process is carried out in a gas phase at 400–450&nbsp;°C. Typical catalysts are modified forms of [[alumina]] and [[silica]]. The reaction has been tailored to produce various [[methylpyridine]]s.<ref name=ul/>

[[File:AcroleinDarstellung.svg|class=skin-invert-image|500px|center|thumb|Formation of acrolein from acetaldehyde and formaldehyde]]
[[File:Pyridin aus Acrolein.svg|class=skin-invert-image|500px|center|thumb|Condensation of pyridine from acrolein and acetaldehyde]]

===Dealkylation and decarboxylation of substituted pyridines===
Pyridine can be prepared by dealkylation of alkylated pyridines, which are obtained as byproducts in the syntheses of other pyridines. The oxidative dealkylation is carried out either using air over [[vanadium(V) oxide]] catalyst,<ref>{{cite patent|status=patent |country=DE |number=1917037 |gdate=1968|title=Verfahren zur Herstellung von Pyridin und Methylpyridinen|inventor=Swift, Graham}}</ref> by vapor-dealkylation on [[nickel]]-based catalyst,<ref>{{cite patent|status=patent |inventor=Nippon Kayaku |country=JP |number=7039545 |gdate=1967|title=Electrically-assisted bicycle, driving system thereof, and manufacturing method}}</ref><ref>{{cite patent|status=patent |country=BE |number=758201 |gdate=1969|title=Procede de preparation de bases pyridiques|inventor=
Koei Chemical}}</ref> or hydrodealkylation with a [[silver]]- or [[platinum]]-based catalyst.<ref>{{cite journal|title=Hydrodealkylierung von Pyridinbasen bei Normaldruck|author=Mensch, F. |year=1969|journal= Erdöl Kohle Erdgas Petrochemie|volume= 2|pages= 67–71}}</ref> Yields of pyridine up to be 93% can be achieved with the nickel-based catalyst.<ref name=ul/> Pyridine can also be produced by the [[decarboxylation]] of [[nicotinic acid]] with [[copper chromite]].<ref>{{cite journal|title = A method for the Degradation of Radioactive Nicotinic Acid|journal = Biochemical Journal|volume=102|issue=1|pages=87–93|author1=Scott, T. A.|doi=10.1042/bj1020087|pmc = 1270213|year = 1967|pmid=6030305}}</ref>

===Bönnemann cyclization===
[[File:BönnemannEn.png|class=skin-invert-image|thumb|Bönnemann cyclization]]
The [[trimerization]] of a part of a [[nitrile]] molecule and two parts of [[acetylene]] into pyridine is called '''Bönnemann cyclization'''. This modification of the [[Walter Reppe|Reppe synthesis]] can be activated either by heat or by [[Photochemistry|light]]. While the [[thermal activation]] requires high pressures and temperatures, the photoinduced [[cycloaddition]] proceeds at ambient conditions with CoCp<sub>2</sub>(cod) (Cp = cyclopentadienyl, cod = [[1,5-cyclooctadiene]]) as a catalyst, and can be performed even in water.<ref>{{cite book|last=Behr |first=A. |date=2008 |title=Angewandte homogene Katalyse |page=722 |publisher=Wiley-VCH |location=Weinheim |isbn=978-3-527-31666-3}}</ref> A series of pyridine derivatives can be produced in this way. When using [[acetonitrile]] as the nitrile, 2-methylpyridine is obtained, which can be dealkylated to pyridine.

===Other methods===
The [[Kröhnke pyridine synthesis]] provides a fairly general method for generating substituted pyridines using pyridine itself as a reagent which does not become incorporated into the final product. The reaction of pyridine with bromomethyl ketones gives the related [[pyridinium]] salt, wherein the [[methylene group]] is highly acidic. This species undergoes a [[Michael addition|Michael-like addition]] to [[Α,β-Unsaturated carbonyl compound|α,β-unsaturated carbonyls]] in the presence of [[ammonium acetate]] to undergo ring closure and formation of the targeted substituted pyridine as well as pyridinium bromide.<ref>{{cite journal|first=Fritz |last=Kroehnke |title=The Specific Synthesis of Pyridines and Oligopyridines |journal=Synthesis |date=1976 |volume=1976 |issue=1 |pages=1–24 |doi=10.1055/s-1976-23941|s2cid=95238046 }}.</ref>
[[File:Kroehnke Pyridine Figure 1.png|class=skin-invert-image|600px|Figure 1|center]]
{{clear}}

The Ciamician–Dennstedt rearrangement<ref>{{Cite journal |last1=Ciamician |first1=G. L. |last2=Dennstedt |first2=M. |date=1881 |title=Ueber die Einwirkung des Chloroforms auf die Kaliumverbindung Pyrrols |url=https://onlinelibrary.wiley.com/doi/10.1002/cber.188101401240 |journal=Berichte der Deutschen Chemischen Gesellschaft |language=en |volume=14 |issue=1 |pages=1153–1163 |doi=10.1002/cber.188101401240 |issn=0365-9496}}</ref> entails the ring-expansion of [[pyrrole]] with [[dichlorocarbene]] to [[3-Chloropyridine|3-chloropyridine]].<ref>{{cite journal|doi=10.1021/ja01541a070|last1=Skell |first1=P. S. |last2=Sandler |first2=R. S. |journal= Journal of the American Chemical Society |volume=80|pages= 2024 |year=1958|issue=8|title=Reactions of 1,1-Dihalocyclopropanes with Electrophilic Reagents. Synthetic Route for Inserting a Carbon Atom Between the Atoms of a Double Bond}}</ref><ref>{{cite journal|doi=10.1039/J39690002249|title=Mechanism of heterocyclic ring expansions. Part III. Reaction of pyrroles with dichlorocarbene|year=1969|last1=Jones|first1=R. L.|last2=Rees|first2=C. W.|journal=Journal of the Chemical Society C: Organic|issue=18|pages=2249}}</ref><ref>{{cite journal|last1=Gambacorta |first1=A. |last2=Nicoletti |first2=R. |last3=Cerrini |first3=S. |last4=Fedeli |first4=W. |last5=Gavuzzo |first5=E. |doi=10.1016/S0040-4039(01)94795-1|title=Trapping and structure determination of an intermediate in the reaction between 2-methyl-5-''t''-butylpyrrole and dichlorocarbene|year=1978|journal=Tetrahedron Letters|volume=19|issue=27|pages=2439}}</ref>
[[File:Ciamician-Dennstedt Rearrangement.png|class=skin-invert-image|500px|center|Ciamician–Dennstedt Rearrangement]]
{{clear}}

In the Gattermann–Skita synthesis,<ref>{{cite journal|title = Eine Synthese von Pyridin-Derivaten|trans-title = A synthesis of pyridine derivatives|journal = Chemische Berichte|volume = 49|issue = 1|year = 1916|pages = 494–501|last1 = Gattermann|first1 = L.|last2 = Skita|first2 = A.|doi = 10.1002/cber.19160490155|url = https://zenodo.org/record/1426601|access-date = 29 June 2019|archive-date = 25 September 2020|archive-url = https://web.archive.org/web/20200925145302/https://zenodo.org/record/1426601|url-status = live}}</ref> a [[Malonic ester synthesis|malonate ester]] salt reacts with dichloro[[methylamine]].<ref>{{cite web|archive-url=https://web.archive.org/web/20060616020955/http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/gattermann-skita.htm |url=http://www.pmf.ukim.edu.mk/PMF/Chemistry/reactions/gattermann-skita.htm |title=Gattermann–Skita |publisher=Institute of Chemistry, Skopje |archive-date=2006-06-16}}</ref>
[[File:Gattermann-Skita Syntesis.png|class=skin-invert-image|500px|center|Gattermann–Skita synthesis]]
{{clear}}

Other methods include the [[Boger pyridine synthesis]] and [[Diels–Alder reaction]] of an [[alkene]] and an [[oxazole]].<ref>{{Cite journal |author1=Karpeiskii, Y.|author2=Florent'ev V. L. |date=1969 |title=Condensation of Oxazoles with Dienophiles — a New Method for the Synthesis of Pyridine Bases |journal=Russian Chemical Reviews |volume=38 |issue=7 |pages=540–546 |doi=10.1070/RC1969v038n07ABEH001760 |bibcode=1969RuCRv..38..540K |s2cid=250852496 }}</ref>

===Biosynthesis===
Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, [[nicotinic acid]] (vitamin B<sub>3</sub>) occurs in some [[bacteria]], [[fungi]], and [[mammal]]s. Mammals synthesize nicotinic acid through oxidation of the [[amino acid]] [[tryptophan]], where an intermediate product, the [[aniline]] derivative [[kynurenine]], creates a pyridine derivative, [[quinolinate]] and then nicotinic acid. On the contrary, the bacteria ''[[Mycobacterium tuberculosis]]'' and ''[[Escherichia coli]]'' produce nicotinic acid by condensation of [[glyceraldehyde 3-phosphate]] and [[aspartic acid]].<ref>{{cite journal|doi=10.1104/pp.69.3.553|last1=Tarr|pmc=426252|pmid=16662247|first1=J. B.|year=1982|pages=553–556|issue=3|volume=69|last2=Arditti|journal=Plant Physiology|first2=J.|title=Niacin Biosynthesis in Seedlings of ''Zea mays''}}</ref>

==Reactions==
Because of the [[Electronegativity|electronegative]] [[nitrogen]] in the pyridine ring, pyridine enters less readily into [[electrophilic aromatic substitution]] reactions than benzene derivatives.<ref>{{cite book|last=Sundberg|first=Francis A. Carey; Richard J.|title=Advanced Organic Chemistry : Part A: Structure and Mechanisms|year=2007|publisher=Springer US|location=Berlin|isbn=978-0-387-68346-1|edition=5.|page=794}}</ref> Instead, in terms of its reactivity, pyridine resembles [[nitrobenzene]].<ref>{{cite journal|title=Adrien Albert and the Rationalization of Heterocyclic chemistry|first1=E. |last1=Campaigne|journal=J. Chem. Educ.|year=1986|volume=63|issue=10|page=860|doi=10.1021/ed063p860|bibcode=1986JChEd..63..860C }}</ref>

Correspondingly pyridine is more prone to [[nucleophilic substitution]], as evidenced by the ease of [[metalation]] by strong [[Organometallic chemistry|organometallic]] bases.<ref name=jou10/><ref name=davies/> The reactivity of pyridine can be distinguished for three chemical groups. With [[electrophile]]s, [[electrophilic substitution]] takes place where pyridine expresses aromatic properties. With [[nucleophile]]s, pyridine reacts at positions 2 and 4 and thus behaves similar to [[imine]]s and [[carbonyl]]s. The reaction with many [[Lewis acid]]s results in the addition to the nitrogen atom of pyridine, which is similar to the reactivity of tertiary amines. The ability of pyridine and its derivatives to oxidize, forming [[amine oxide]]s (''N''-oxides), is also a feature of tertiary amines.<ref>{{cite book|first1=R. |last1=Milcent |first2=F. |last2=Chau |title=Chimie organique hétérocyclique: Structures fondamentales |pages=241–282 |publisher=EDP Sciences |date=2002 |isbn=2-86883-583-X}}</ref>

The nitrogen center of pyridine features a basic [[lone pair]] of [[electron]]s. This lone pair does not overlap with the aromatic π-system ring, consequently pyridine is [[Base (chemistry)|basic]], having chemical properties similar to those of [[tertiary amine]]s. [[Protonation]] gives [[pyridinium]], C<sub>5</sub>H<sub>5</sub>NH<sup>+</sup>.The [[pKa|p''K''<sub>a</sub>]] of the [[conjugate acid]] (the pyridinium cation) is 5.25. The structures of pyridine and pyridinium are almost identical.<ref>{{cite journal|last1=Krygowski |first1=T. M. |last2=Szatyowicz |first2=H. |last3=Zachara |first3=J. E. |journal = J. Org. Chem.|doi = 10.1021/jo051354h|pmid = 16238319|title = How H-bonding Modifies Molecular Structure and π-Electron Delocalization in the Ring of Pyridine/Pyridinium Derivatives Involved in H-Bond Complexation|year = 2005|volume = 70|issue = 22|pages = 8859–8865}}</ref> The pyridinium cation is [[isoelectronic]] with benzene. Pyridinium ''p''-[[toluenesulfonic acid|toluenesulfonate]] (PPTS) is an illustrative pyridinium salt; it is produced by treating pyridine with [[P-Toluenesulfonic acid|''p''-toluenesulfonic acid]]. In addition to [[protonation]], pyridine undergoes N-centred [[alkylation]], [[acylation]], and [[N-oxidation|''N''-oxidation]]. Pyridine and poly(4-vinyl) pyridine have been shown to form conducting [[Molecular wire|molecular wires]] with remarkable polyenimine structure on [[UV irradiation]], a process which accounts for at least some of the visible light absorption by aged pyridine samples. These wires have been theoretically predicted to be both highly efficient electron donors and acceptors, and yet are resistant to air oxidation.<ref>{{Cite journal |last1=Vaganova |first1=Evgenia |last2=Eliaz |first2=Dror |last3=Shimanovich |first3=Ulyana |last4=Leitus |first4=Gregory |last5=Aqad |first5=Emad |last6=Lokshin |first6=Vladimir |last7=Khodorkovsky |first7=Vladimir |date=January 2021 |title=Light-Induced Reactions within Poly(4-vinyl pyridine)/Pyridine Gels: The 1,6-Polyazaacetylene Oligomers Formation |journal=Molecules |language=en |volume=26 |issue=22 |pages=6925 |doi=10.3390/molecules26226925 |pmid=34834017 |pmc=8621047 |issn=1420-3049|doi-access=free }}</ref>

===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>

===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/>

===Radical reactions===
Pyridine supports a series of radical reactions, which is used in its [[Dimer (chemistry)|dimerization]] to bipyridines. Radical dimerization of pyridine with elemental [[sodium]] or [[Raney nickel]] selectively yields [[4,4'-bipyridine]],<ref>{{cite book|last1=Badger|first1=G|last2=Sasse|first2=W|chapter=The Action of Metal Catalysts on Pyridines|volume=2|pages=179–202|year=1963|doi=10.1016/S0065-2725(08)60749-7|title=Advances in Heterocyclic Chemistry Volume 2|pmid=14279523|isbn=9780120206025}}</ref> or [[2,2'-bipyridine]],<ref>{{cite journal|author=Sasse, W. H. F.|title=2,2'-bipyridine|journal=Organic Syntheses|year=1966|volume=46|pages=5–8|doi=10.1002/0471264180.os046.02|df=dmy-all}}</ref> which are important precursor reagents in the chemical industry. One of the [[name reactions]] involving free radicals is the [[Minisci reaction]]. It can produce 2-''tert''-butylpyridine upon reacting pyridine with [[pivalic acid]], [[silver nitrate]] and [[ammonium]] in [[sulfuric acid]] with a yield of 97%.<ref name=jou10>[[#Joule|Joule]], pp. 125–141</ref>

===Reactions on the nitrogen atom===
[[File:Pyridine-complex.svg|class=skin-invert-image|thumb|upright=1.5|Additions of various [[Lewis acid]]s to pyridine]]
[[Lewis acid]]s easily add to the nitrogen atom of pyridine, forming pyridinium salts. The reaction with [[alkyl halide]]s leads to [[alkylation]] of the nitrogen atom. This creates a positive charge in the ring that increases the reactivity of pyridine to both oxidation and reduction. The [[Zincke reaction]] is used for the selective introduction of radicals in pyridinium compounds (it has no relation to the chemical element [[zinc]]).

===Hydrogenation and reduction===
[[File:Piperidin Reaktionsschema.svg|class=skin-invert-image|left|thumb|Reduction of pyridine ('''1''') to piperidine ('''2''') with [[Raney nickel]]]]

[[Piperidine]] is produced by [[hydrogenation]] of pyridine with a [[nickel]]-, [[cobalt]]-, or [[ruthenium]]-based catalyst at elevated temperatures.<ref>{{Ullmann|last1=Eller |first1=K. |last2=Henkes |first2=E. |last3=Rossbacher |first3=R. |last4=Hoke |first4=H. |title=Amines, aliphatic}}</ref> The hydrogenation of pyridine to piperidine releases 193.8&nbsp;kJ/mol,<ref name="Cox">{{cite book|last1=Cox |first1=J. D. |last2=Pilcher |first2=G. |date=1970 |title=Thermochemistry of Organic and Organometallic Compounds |publisher=Academic Press |location=New York |pages=1–636 |isbn=0-12-194350-X}}</ref> which is slightly less than the energy of the hydrogenation of [[benzene]] (205.3&nbsp;kJ/mol).<ref name="Cox"/>

Partially hydrogenated derivatives are obtained under milder conditions. For example, reduction with [[lithium aluminium hydride]] yields a mixture of 1,4-dihydropyridine, 1,2-dihydropyridine, and 2,5-dihydropyridine.<ref>{{cite journal|last1=Tanner|first1=Dennis D.|last2=Yang|first2=Chi Ming|title=On the structure and mechanism of formation of the Lansbury reagent, lithium tetrakis(''N''-dihydropyridyl) aluminate|journal=The Journal of Organic Chemistry|volume=58|pages=1840|year=1993|doi=10.1021/jo00059a041|issue=7}}</ref> Selective synthesis of 1,4-dihydropyridine is achieved in the presence of organometallic complexes of [[magnesium]] and [[zinc]],<ref>{{cite journal|last1=De Koning|first1=A.|title=Specific and selective reduction of aromatic nitrogen heterocycles with the bis-pyridine complexes of bis(1,4-dihydro-1-pyridyl)zinc and bis(1,4-dihydro-1-pyridyl)magnesium|journal=Journal of Organometallic Chemistry|volume=199|pages=153|year=1980|doi=10.1016/S0022-328X(00)83849-8|issue=2|last2=Budzelaar|first2=P. H. M.|last3=Boersma|first3=J.|last4=Van Der Kerk|first4=G. J. M.}}</ref> and (Δ3,4)-tetrahydropyridine is obtained by electrochemical reduction of pyridine.<ref>{{cite journal | last=Ferles | first=M. | title=Studies in the pyridine series. II. Ladenburg and electrolytic reductions of pyridine bases | journal=Collection of Czechoslovak Chemical Communications | publisher=Institute of Organic Chemistry & Biochemistry | volume=24 | issue=4 | year=1959 | doi=10.1135/cccc19591029 | pages=1029–1035}}</ref> [[Birch reduction]] converts pyridine to dihydropyridines.<ref>{{cite journal |doi=10.1021/ol0065930|title=Partial Reduction of Electron-Deficient Pyridines |year=2000 |last1=Donohoe |first1=Timothy J. |last2=McRiner |first2=Andrew J. |last3=Sheldrake |first3=Peter |journal=Organic Letters |volume=2 |issue=24 |pages=3861–3863 |pmid=11101438 }}</ref>

===Lewis basicity and coordination compounds===
Pyridine is a [[Lewis base]], donating its pair of electrons to a Lewis acid. Its Lewis base properties are discussed in the [[ECW model]]. Its relative donor strength toward a series of acids, versus other Lewis bases, can be illustrated by [[ECW model|C-B plots]].<ref>Laurence, C. and Gal, J-F. (2010) ''Lewis Basicity and Affinity Scales, Data and Measurement''. Wiley. pp. 50–51. {{ISBN|978-0-470-74957-9}}</ref><ref>{{cite journal|author1=Cramer, R. E. |author2=Bopp, T. T. |year=1977|title= Graphical display of the enthalpies of adduct formation for Lewis acids and bases |journal= Journal of Chemical Education |volume=54|pages=612–613|doi= 10.1021/ed054p612}} The plots shown in this paper used older parameters. Improved E&C parameters are listed in [[ECW model]].</ref> One example is the [[sulfur trioxide pyridine complex]] (melting point 175&nbsp;°C), which is a [[sulfation]] agent used to convert alcohols to [[sulfate ester]]s. Pyridine-[[borane]] ({{chem2|C5H5NBH3}}, melting point 10–11&nbsp;°C) is a mild reducing agent.

[[File:Crabtree.svg|class=skin-invert-image|thumb|structure of the [[Crabtree's catalyst]]]]

[[Transition metal pyridine complexes]] are numerous.<ref name =nakamoto>{{cite book|last=Nakamoto|first=K.|title=Infrared and Raman spectra of Inorganic and Coordination compounds|edition=5th|series=Part A|year=1997|publisher=Wiley|isbn=0-471-16394-5}}</ref><ref>{{cite book|last=Nakamoto|first=K.|title=Infrared and Raman spectra of Inorganic and Coordination compounds|edition=5th|series=Part B|isbn=0-471-16392-9|page=24|date=31 July 1997}}</ref> 
Typical octahedral complexes have the stoichiometry {{chem2|MCl2(py)4}} and {{chem2|MCl3(py)3}}. Octahedral homoleptic complexes of the type {{chem2|M(py)6(+)}} are rare or tend to dissociate pyridine. Numerous square planar complexes are known, such as [[Crabtree's catalyst]].<ref>{{cite journal |last1=Crabtree |first1=Robert |title=Iridium compounds in catalysis |journal=Accounts of Chemical Research |volume=12 |pages=331–337 |year=1979 |doi=10.1021/ar50141a005|issue=9}}</ref> The pyridine ligand replaced during the reaction is restored after its completion.

The ''η''<sup>6</sup> coordination mode, as occurs in ''η''<sup>6</sup> benzene complexes, is observed only in [[Steric effects|sterically encumbered]] derivatives that block the nitrogen center.<ref name="Elschenbroich 2008 524–525">{{cite book|last=Elschenbroich |first=C. |title=Organometallchemie |edition=6th |pages=524–525 |publisher=Vieweg & Teubner |date=2008 |isbn=978-3-8351-0167-8}}</ref>

==Applications==
===Pesticides and pharmaceuticals===
The main use of pyridine is as a precursor to the herbicides [[paraquat]] and [[diquat]].<ref name=ul/> The first synthesis step of insecticide [[chlorpyrifos]] consists of the chlorination of pyridine. Pyridine is also the starting compound for the preparation of [[pyrithione]]-based [[fungicide]]s.<ref name=osha/> [[Cetylpyridinium chloride|Cetylpyridinium]] and laurylpyridinium, which can be produced from pyridine with a [[Zincke reaction]], are used as [[antiseptic]] in oral and dental care products.<ref name=roempp>{{cite book|work=Thieme Chemistry|title=RÖMPP Online – Version 3.5|publisher=Georg Thieme |place=Stuttgart|year=2009}}</ref> Pyridine is easily attacked by alkylating agents to give ''N''-alkylpyridinium salts. One example is [[cetylpyridinium chloride]].

[[File:Synthesis of paraquat.png|class=skin-invert-image|thumb|center|585px|Synthesis of [[paraquat]]<ref>{{cite web |url=http://www.inchem.org/documents/ehc/ehc/ehc39.htm |title=Environmental and health criteria for paraquat and diquat |publisher=World Health Organization |location=Geneva |date=1984 |access-date=7 January 2011 |archive-date=6 October 2018 |archive-url=https://web.archive.org/web/20181006030023/http://www.inchem.org/documents/ehc/ehc/ehc39.htm |url-status=live }}</ref>]]

It is also used in the textile industry to improve network capacity of cotton.<ref name=roempp/>

===Laboratory use===
Pyridine is used as a polar, basic, low-reactive solvent, for example in [[Knoevenagel condensation]]s.<ref name=osha/><ref>{{cite book |ref=Carey |year=2007 |title=Advanced Organic Chemistry: Part B: Reactions and Synthesis |edition=5th |publisher=Springer |place=New York |author1=Carey, Francis A. |author2=Sundberg, Richard J. |isbn=978-0387683546|page=147}}</ref> It is especially suitable for the dehalogenation, where it acts as the base for the [[elimination reaction]]. In [[esterification]]s and acylations, pyridine activates the carboxylic [[acid chloride]]s and anhydrides. Even more active in these reactions are the derivatives [[4-dimethylaminopyridine]] (DMAP) and 4-(1-pyrrolidinyl) pyridine. Pyridine is also used as a base in some [[condensation reaction]]s.<ref>{{cite encyclopedia|last=Sherman |first=A. R. |encyclopedia=e-EROS (Encyclopedia of Reagents for Organic Synthesis) |editor-first=L. |editor-last=Paquette |date=2004 |publisher=J. Wiley & Sons |location=New York |doi=10.1002/047084289X.rp280|chapter=Pyridine |title=Encyclopedia of Reagents for Organic Synthesis |isbn=0471936235 }}</ref>

[[File:Chlorocyclopentane elimination.svg|class=skin-invert-image|thumb|center|400px|Elimination reaction with pyridine to form pyridinium]]

===Reagents===
[[File:Alcohol oxidation with Collins reagent.svg|class=skin-invert-image|thumb|Oxidation of an alcohol to aldehyde with the [[Collins reagent]]]]
As a base, pyridine can be used as the [[Karl Fischer reagent]], but it is usually replaced by alternatives with a more pleasant odor, such as [[imidazole]].<ref>{{cite web |url=http://www.ipc.uni-jena.de/downloads/IPC/Lehre/IA_Pharm_12_Karl-Fischer-Titration.pdf |title=Wasserbestimmung mit Karl-Fischer-Titration |trans-title=Water analysis with the Karl Fischer titration |publisher=Jena University |url-status=dead |archive-url=https://web.archive.org/web/20110719105206/http://www.ipc.uni-jena.de/downloads/IPC/Lehre/IA_Pharm_12_Karl-Fischer-Titration.pdf |archive-date=19 July 2011 |df=dmy-all }}</ref>

[[Pyridinium chlorochromate]], [[Cornforth reagent|pyridinium dichromate]], and the [[Collins reagent]] (the complex of [[chromium trioxide|chromium(VI) oxide]]) are used for the oxidation of alcohols.<ref name=b1>{{cite book|last1=Tojo |first1=G. |last2=Fernandez |first2=M. |title = Oxidation of alcohols to aldehydes and ketones: a guide to current common practice|year = 2006|publisher = Springer|location = New York|isbn = 0-387-23607-4|url=https://books.google.com/books?id=O6USLyDIBOUC&pg=PA86|pages=28, 29, 86}}</ref>

==Hazards==
Pyridine is a toxic, flammable liquid with a strong and unpleasant fishy odour. Its [[odour threshold]] of 0.04 to 20 ppm is close to its [[threshold limit value|threshold limit]] of 5&nbsp;ppm for adverse effects,<ref>{{cite web |url=http://www.alfa.com/content/msds/english/19378.pdf |title=Pyridine MSDS |publisher=Alfa Aesar |access-date=3 June 2010 |archive-date=3 April 2015 |archive-url=https://web.archive.org/web/20150403012740/http://www.alfa.com/content/msds/english/19378.pdf |url-status=dead }}</ref> thus most (but not all) adults will be able to tell when it is present at harmful levels. Pyridine easily dissolves in water and harms both animals and plants in aquatic systems.<ref>{{cite web |url=http://cfpub.epa.gov/ecotox/ |title=Database of the (EPA) |publisher=U.S. [[Environmental Protection Agency]] |access-date=7 January 2011 |archive-date=18 September 2011 |archive-url=https://web.archive.org/web/20110918110610/http://cfpub.epa.gov/ecotox/ |url-status=live }}</ref>

===Fire===
Pyridine has a [[flash point]] of 20&nbsp;°C and is therefore highly flammable. Combustion produces toxic fumes which can include [[bipyridine]]s, [[nitrogen oxide]]s, and [[carbon monoxide]].<ref name="GESTIS">{{GESTIS|ZVG=13850|Name=Pyridine}}</ref>

===Short-term exposure===
Pyridine can cause chemical burns on contact with the skin and its fumes may be irritating to the eyes or upon inhalation.<ref name = Aylward>{{cite book|last=Aylward |first=G |date=2008 |title=SI Chemical Data |publisher=Wiley |edition=6th |isbn=978-0-470-81638-7}}</ref> Pyridine depresses the [[nervous system]] giving symptoms similar to intoxication with vapor concentrations of above 3600&nbsp;[[parts per million|ppm]] posing a greater health risk.<ref name=ul/> The effects may have a delayed onset of several hours and include dizziness, headache, [[ataxia|lack of coordination]], nausea, [[saliva]]tion, and loss of appetite. They may progress into abdominal pain, [[pulmonary congestion]] and unconsciousness.<ref name="IARC1">{{cite web|last = International Agency for Research on Cancer (IARC)|author-link = International Agency for Research on Cancer|title = Pyridine Summary & Evaluation|work = IARC Summaries & Evaluations|publisher = IPCS INCHEM|date = 22 August 2000|url = http://www.inchem.org/documents/iarc/vol77/77-16.html|access-date = 17 January 2007|archive-date = 2 October 2018|archive-url = https://web.archive.org/web/20181002182604/http://www.inchem.org/documents/iarc/vol77/77-16.html|url-status = live}}</ref> The lowest known [[lethal dose]] (LD<sub>Lo</sub>) for the ingestion of pyridine in humans is 500&nbsp;mg/kg.

===Long-term exposure===
Prolonged exposure to pyridine may result in liver, heart and kidney damage.<ref name="GESTIS"/><ref name=osha/><ref name=bonnard/> Evaluations as a possible [[carcinogenic]] agent showed that there is inadequate evidence in humans for the carcinogenicity of pyridine, although there is sufficient evidence in experimental animals. Therefore, [[International Agency for Research on Cancer|IARC]] considers pyridine as possibly carcinogenic to humans (Group 2B).<ref>{{Cite book|last=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|url=https://publications.iarc.fr/_publications/media/download/5722/be54378b09f7c8f559e7a529f6947cf8aa0515a6.pdf|title=Some chemicals that cause tumours of the urinary tract in rodents|date=2019|others=[[International Agency for Research on Cancer]]|pages=173–198|isbn=978-92-832-0186-1|location=Lyon, France|oclc=1086392170|access-date=2 June 2021|archive-date=6 May 2021|archive-url=https://web.archive.org/web/20210506214036/https://publications.iarc.fr/_publications/media/download/5722/be54378b09f7c8f559e7a529f6947cf8aa0515a6.pdf|url-status=live}}</ref>

==Metabolism==
[[File:Pyridin-Metabolisierung.png|class=skin-invert-image|thumb|upright=1.5|Metabolism of pyridine]]
Exposure to pyridine would normally lead to its inhalation and absorption in the lungs and gastrointestinal tract, where it either remains unchanged or is [[metabolism|metabolized]]. The major products of pyridine metabolism are ''N''-methylpyridiniumhydroxide, which are formed by [[N-methyltransferase|''N''-methyltransferase]]s (e.g., [[pyridine N-methyltransferase|pyridine ''N''-methyltransferase]]), as well as pyridine ''N''-oxide, and 2-, 3-, and 4-hydroxypyridine, which are generated by the action of [[monooxygenase]]. In humans, pyridine is metabolized only into ''N''-methylpyridiniumhydroxide.<ref name="GESTIS"/><ref name=bonnard>{{cite web |last1=Bonnard |first1=N. |last2=Brondeau |first2=M. T. |last3=Miraval |first3=S. |last4=Pillière |first4=F. |last5=Protois |first5=J. C. |last6=Schneider |first6=O. |title=Pyridine |work=Fiche Toxicologique |publisher=INRS |year=2011 |language=fr |url=https://www.inrs.fr/dms/ficheTox/FicheFicheTox/FICHETOX_85-4/FicheTox_85.pdf |access-date=2 June 2021 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602214228/https://www.inrs.fr/dms/ficheTox/FicheFicheTox/FICHETOX_85-4/FicheTox_85.pdf |url-status=live }}</ref>

==Environmental fate==
Pyridine is readily degraded by bacteria to ammonia and carbon dioxide.<ref>{{cite journal|last1=Sims |first1=G. K. |last2=O'Loughlin |first2=E. J. |title = Degradation of pyridines in the environment|journal = CRC Critical Reviews in Environmental Control|year = 1989|volume = 19|issue = 4|pages = 309–340|doi = 10.1080/10643388909388372|bibcode=1989CRvEC..19..309S }}</ref> The unsubstituted pyridine ring degrades more rapidly than [[picoline]], [[lutidine]], [[chloropyridine]], or [[aminopyridine]]s<!-- no disambiguation needed-->,<ref>{{cite journal|doi = 10.1002/etc.5620050601|last1=Sims|first1= G. K. |first2=L.E. |last2=Sommers |year = 1986|title = Biodegradation of pyridine derivatives in soil suspensions| journal = Environmental Toxicology and Chemistry|volume = 5|pages = 503–509|issue = 6}}</ref> and a number of pyridine degraders have been shown to overproduce [[riboflavin]] in the presence of pyridine.<ref>{{cite journal|last1=Sims |first1=G. K. |first2=E.J. |last2=O'Loughlin |year = 1992|title = Riboflavin production during growth of ''Micrococcus luteus'' on pyridine|journal = [[Applied and Environmental Microbiology]]|volume = 58|issue = 10|pages = 3423–3425|doi=10.1128/AEM.58.10.3423-3425.1992 |pmc = 183117|pmid = 16348793|bibcode=1992ApEnM..58.3423S }}</ref> Ionizable ''N''-heterocyclic compounds, including pyridine, interact with environmental surfaces (such as soils and sediments) via multiple pH-dependent mechanisms, including partitioning to [[soil organic matter]], [[cation exchange]], and surface complexation.<ref>{{cite journal | last1 = Bi | first1 = E. | last2 = Schmidt | first2 = T. C. | last3 = Haderlein | first3 = S. B. | year = 2006 | title = Sorption of heterocyclic organic compounds to reference soils: column studies for process identification | journal = Environ Sci Technol | volume = 40 | issue = 19| pages = 5962–5970 | doi=10.1021/es060470e| pmid = 17051786 | bibcode = 2006EnST...40.5962B }}</ref> Such [[adsorption]] to surfaces reduces bioavailability of pyridines for microbial degraders and other organisms, thus slowing degradation rates and reducing [[ecotoxicity]].<ref>{{cite journal | last1 = O'Loughlin | first1 = E. J | last2 = Traina | first2 = S. J. | last3 = Sims | first3 = G. K. | year = 2000 | title = Effects of sorption on the biodegradation of 2-methylpyridine in aqueous suspensions of reference clay minerals | journal = Environmental Toxicology and Chemistry | volume = 19 | issue = 9| pages = 2168–2174 | doi=10.1002/etc.5620190904| s2cid = 98654832 }}</ref>

==Nomenclature==
The systematic name of pyridine, within the [[Hantzsch–Widman nomenclature]] recommended by the [[IUPAC]], is ''{{chem name|azinine}}''. However, systematic names for simple compounds are used very rarely; instead, heterocyclic nomenclature follows historically established common names. IUPAC discourages the use of {{chem name|azinine''/''azine}} in favor of ''pyridine''.<ref>{{cite journal|doi=10.1351/pac198855020409|last=Powell|first=W. H.|title=Revision of the extended Hantzsch-Widman system of nomenclature for hetero mono-cycles|journal=Pure and Applied Chemistry|year=1983|volume=55|pages=409–416|url=http://www.iupac.org/publications/pac/1983/pdf/5502x0409.pdf|issue=2|s2cid=4686578|access-date=7 January 2011|archive-date=20 September 2018|archive-url=https://web.archive.org/web/20180920135014/http://www.iupac.org/publications/pac/1983/pdf/5502x0409.pdf|url-status=live}}</ref> The numbering of the ring atoms in pyridine starts at the nitrogen (see infobox). An allocation of positions by letter of the [[Greek alphabet]] (α-γ) and the [[Arene substitution patterns|substitution pattern]] nomenclature common for homoaromatic systems (''ortho'', ''meta'', ''para'') are used sometimes. Here α (''ortho''), β (''meta''), and γ (''para'') refer to the 2, 3, and 4 position, respectively. The systematic name for the pyridine derivatives is ''pyridinyl'', wherein the position of the substituted atom is preceded by a number. However, the historical name ''pyridyl'' is encouraged by the IUPAC and used instead of the systematic name.<ref>{{cite book|first=D. |last=Hellwinkel |title=Die systematische Nomenklatur der Organischen Chemie |edition=4th |page=45 |publisher=Springer |location=Berlin |date=1998 |isbn=3-540-63221-2}}</ref> The [[cation]]ic derivative formed by the addition of an [[electrophile]] to the nitrogen atom is called ''[[pyridinium]]''.

==See also==
* 6-membered aromatic rings with one carbon replaced by another group: [[borabenzene]], [[silabenzene]], [[germabenzene]], [[stannabenzene]], pyridine, [[phosphorine]], [[arsabenzene]], [[stibabenzene]], [[bismabenzene]], [[pyrylium]], [[thiopyrylium]], [[selenopyrylium]], [[telluropyrylium]]
* 6-membered rings with two nitrogen atoms: [[diazine]]s
* 6-membered rings with three nitrogen atoms: [[triazine]]s
* 6-membered rings with four nitrogen atoms: [[tetrazine]]s
* 6-membered rings with five nitrogen atoms: [[pentazine]]
* 6-membered rings with six nitrogen atoms: [[hexazine]]

==References==
{{Reflist|30em}}

==Bibliography==
*{{cite book|last=Sundberg|first=Francis A. Carey; Richard J.|title=Advanced Organic Chemistry : Part A: Structure and Mechanisms|year=2007|publisher=Springer US|location=Berlin|isbn=978-0-387-68346-1|edition=5.}}
*{{cite book |ref =Haynes | editor= Haynes, William M. | date = 2016| title = [[CRC Handbook of Chemistry and Physics]] | edition = 97th | publisher = [[CRC Press]] | isbn = 9781498754293}}
*{{cite book|last1=Joule |first1=J. A. |last2=Mills |first2=K. |ref=Joule|url=https://books.google.com/books?id=cwe-Ebc64bkC |title=Heterocyclic Chemistry|edition=5th|publisher= Blackwell Publishing|place= Chichester|year= 2010|isbn=978-1-4051-3300-5}}

==External links==
{{Commons category}}
*[http://www.chemsynthesis.com/six-membered-ring/pyridines/page-1.html Synthesis and properties of pyridines] at chemsynthesis.com
*[http://www.inchem.org/documents/icsc/icsc/eics0323.htm International Chemical Safety Card 0323]
*[https://www.cdc.gov/niosh/npg/npgd0541.html NIOSH Pocket Guide to Chemical Hazards]
*[https://www.organic-chemistry.org/synthesis/heterocycles/pyridines.shtm Synthesis of pyridines (overview of recent methods)]

{{Functional Groups}}

{{Authority control}}

[[Category:Pyridines| ]]
[[Category:Amine solvents]]
[[Category:Foul-smelling chemicals]]
[[Category:Aromatic bases]]
[[Category:Simple aromatic rings]]
[[Category:Functional groups]]
[[Category:Aromatic solvents]]