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{{Short description|Isomers of chemical compounds that interconvert}}
[[File:Amino acid zwitterions.svg|thumb|upright=1.3|alt=An amino acid, illustrated in two different ionization states. First, it has a neutral amine and neutral carboxylic acid. Second, it has a protonated ammonium cation and deprotonated carboxylate anion.| The two tautomers of an amino acid: (1) neutral and (2) [[zwitterion]]ic forms]]

In [[chemistry]], '''tautomers''' ({{IPAc-en|ˈ|t|ɔː|t|ə|m|ɚ
}})<ref>{{cite web |url=https://en.oxforddictionaries.com/definition/tautomer |title=tautomer |website=Oxford Dictionaries - English |url-status=dead |archive-url=https://web.archive.org/web/20180219090719/https://en.oxforddictionaries.com/definition/tautomer
|archive-date=2018-02-19}}</ref> are [[structural isomer]]s (constitutional isomers) of [[chemical compound]]s that readily interconvert.<ref name=Antonov2013>{{cite book |author=Antonov L |title=Tautomerism: Methods and Theories |edition=1st |publisher=Wiley-VCH |location=Weinheim, Germany |year=2013 |isbn=978-3-527-33294-6}}</ref><ref name=Antonov2016>{{cite book |author=Antonov L |title=Tautomerism: Concepts and Applications in Science and Technology |edition=1st |publisher=Wiley-VCH |location=Weinheim, Germany |year=2016 |isbn=978-3-527-33995-2}}</ref><ref name=March>{{cite book |isbn=9781119371809 |title=March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure |last1=Smith |first1=Michael B. |date=19 February 2020 |publisher=Wiley |pages=96–103 |url=https://books.google.com/books?id=7sa4DwAAQBAJ }}
</ref><ref name=Katritzkybook>{{cite book |vauthors=Katritzky AR, Elguero J |author-link=Alan R. Katritzky |title=The Tautomerism of heterocycles |url=https://archive.org/details/tautomerismofhet0000unse |url-access=registration |publisher=[[Academic Press]] |location=New York |year=1976 |isbn=978-0-12-020651-3|display-authors=etal}}</ref> The [[chemical reaction]] interconverting the two is called '''tautomerization'''. This conversion commonly results from the relocation of a [[hydrogen]] atom within the compound. The phenomenon of tautomerization is called '''tautomerism''', also called '''desmotropism'''. Tautomerism is for example relevant to the behavior of [[amino acids]] and [[nucleic acids]], two of the fundamental building blocks of life. The term is derived {{ety|grc|''{{linktext|ταὐτό}}'' (tautó)|the same||''{{linktext|μέρος}}'' (méros)|part}}.

Care should be taken not to confuse tautomers with depictions of "contributing structures" in chemical [[Resonance (chemistry)|resonance]]. Tautomers are distinct [[chemical species]] that can be distinguished by their differing atomic connectivities, molecular geometries, and physicochemical and spectroscopic properties,<ref name=Smith>{{cite journal |last1=Smith |first1=Kyle T. |last2=Young |first2=Sherri C. |last3=DeBlasio |first3=James W. |last4=Hamann |first4=Christian S. |title=Measuring Structural and Electronic Effects on Keto–Enol Equilibrium in 1,3-Dicarbonyl Compounds |journal=Journal of Chemical Education |date=27 January 2016 |volume=93 |issue=4 |pages=790–794 |doi=10.1021/acs.jchemed.5b00170|bibcode=2016JChEd..93..790S }}</ref> whereas resonance forms are merely alternative [[Lewis structure]] ([[valence bond theory]]) depictions of a single chemical species, whose true structure is a [[quantum superposition]], essentially the "average" of the idealized, hypothetical geometries implied by these resonance forms.

== Examples ==
[[File:Tautomers.svg|thumb|upright=2|right|Some examples of tautomers]]
[[File:Acetylacetone keto-enol tautomerism.svg|thumb|upright=1.5|right|Keto-enol tautomerization typically strongly favors the keto tautomer, but an important exception is the case of 1,3-diketones such as [[acetylacetone]].<ref name=Smith/>]]
Tautomerization is pervasive in [[organic chemistry]].<ref name=Antonov2013/><ref name=IUPAC>{{GoldBookRef|title=Tautomerism|file=T06252}}</ref> It is typically associated with polar molecules and ions containing functional groups that are at least weakly acidic.  Most common tautomers exist in pairs, which means that the hydrogen is located at one of two positions, and even more specifically the most common form involves a hydrogen changing places with a double bond: {{chem2|H\sX\sY\dZ <-> X\dY\sZ\sH}}.  Common tautomeric pairs include:<ref name=Antonov2016/><ref name=March/>
* [[ketone]] – [[enol]]: {{chem2|H\sO\sC\dC <-> O\dC\sC\sH}}, see [[keto–enol tautomerism]]
* [[enamine]] – [[imine]]: {{chem2|H\sN\sC\dC <-> N\dC\sC\sH}}
**[[cyanamide]] – [[carbodiimide]]
**[[guanidine]] – guanidine – guanidine: With a central carbon surrounded by three [[Nitrogen|nitrogens]], a guanidine group allows this transform in three possible orientations<!--Not in <ref name=March/>, included as an example of more than two.  Picture at File:Guanidinium-ion-canonical-forms-2D-skeletal.png -->
* [[amide]] – [[imidic acid]]: {{chem2|H\sN\sC\dO <-> N\dC\sO\sH}} (e.g., the latter is encountered during [[nitrile]] [[hydrolysis]] reactions)
**[[lactam]] – [[lactim]], a cyclic form of amide-imidic acid tautomerism in [[2-pyridone]] and derived structures such as the [[nucleobase]]s [[guanine]], [[thymine]], and [[cytosine]]<ref name=Katritzkybook/>
* imine – imine, e.g., during [[pyridoxal phosphate]] catalyzed [[enzymatic]] reactions 
**{{chem2|R^{1}R^{2}C(\dNCHR^{3}R^{4}) <-> (R^{1}R^{2}CHN\d)CR^{3}R^{4} }}
*nitro – ''aci''-nitro (nitronic acid): {{chem2|RR'HC–N+(\dO)(O-) <-> RR'C\dN+(O-)(OH)}}
* [[nitroso]] – [[oxime]]: {{chem2|H\sC\sN\dO <-> C\dN\sO\sH}}
* [[ketene]] – [[ynol]], which involves a triple bond: {{chem2|H\sC\dC\dO <-> C≡C\sO\sH}}
* [[amino acid]] – ammonium carboxylate, which applies to the building blocks of the proteins.  This shifts the proton more than two atoms away, producing a [[zwitterion]] rather than shifting a double bond: {{chem2|H2N\sCH2\sCOOH <-> H3N+\sCH2\sCO2-}}
*[[Phosphite ester|phosphite]] – [[phosphonate]]: {{chem2|P(OR)2(OH) <-> HP(OR)2(\dO)}} between trivalent and pentavalent phosphorus.

==Prototropy==
'''Prototropy''' is the most common form of tautomerism and refers to the relocation of a hydrogen atom.<ref name=IUPAC/> Prototropic tautomerism may be considered a subset of [[acid-base]] behavior. Prototropic tautomers are sets of isomeric [[protonation]] states with the same [[empirical formula]] and total [[charge (physics)|charge]]. Tautomerizations are [[Catalysis|catalyzed]] by:<ref name=March/>
* [[Base (chemistry)|base]]s, involving a series of steps: deprotonation, formation of a [[delocalized]] [[anion]] (e.g., an [[enolate]]), and [[protonation]] at a different position of the anion; and
* [[acid]]s, involving a series of steps: protonation, formation of a delocalized cation, and deprotonation at a different position adjacent to the cation).

[[Image:Glucose Fisher to Haworth.gif|thumb|upright=1.2|[[Glucose]] can exist in both a straight-chain and ring form.]]
Two specific further subcategories of tautomerizations:
*Annular tautomerism is a type of prototropic tautomerism wherein a proton can occupy two or more positions of the [[heterocyclic]] systems found in many drugs, for example, 1''H''- and 3''H''-[[imidazole]]; 1''H''-, 2''H''- and 4''H''- [[1,2,4-triazole]]; 1''H''- and 2''H''- [[isoindole]].<ref name=Katritzky>{{cite journal |doi=10.1007/s10822-010-9359-z |title=Tautomerism in drug discovery |year=2010 |last1=Katritzky |first1=Alan R. |last2=Hall |first2=C. Dennis |last3=El-Gendy |first3=Bahaa El-Dien M. |last4=Draghici |first4=Bogdan |journal=Journal of Computer-Aided Molecular Design |volume=24 |issue=6–7 |pages=475–484 |pmid=20490619 |bibcode=2010JCAMD..24..475K |s2cid=1811678 }}</ref>
*Ring–chain tautomers occur when the movement of the proton is accompanied by a change from an open structure to a ring, such as the [[open chain]] and cyclic [[hemiacetal]] (typically [[pyranose]] or [[furanose]] forms) of many sugars.<ref name=March/>{{rp|102}}  (See {{slink|Carbohydrate|Ring-straight chain isomerism}}.)  The tautomeric shift can be described as H−O&thinsp;⋅&thinsp;C=O ⇌ O−C−O−H, where the "⋅" indicates the initial absence of a bond.

== Valence tautomerism ==
'''Valence tautomerism''' is a type of tautomerism in which single and/or double bonds are rapidly formed and ruptured, without migration of atoms or groups.<ref name=Gold>{{GoldBookRef |title=valence tautomerization |file=V06591.html }}</ref> It is distinct from prototropic tautomerism, and involves processes with rapid reorganisation of bonding electrons.

[[Image:Oxepin-benzene oxide.png|thumb|left|Oxepin – benzene oxide equilibrium]]
A pair of valence tautomers with formula C<sub>6</sub>H<sub>6</sub>O are benzene oxide and [[oxepin]].<ref name=Gold/><ref>{{cite journal | doi = 10.1002/anie.196703851 | journal = Angewandte Chemie International Edition in English | title=Benzene Oxide-Oxepin Valence Tautomerism| volume=6 |issue=5 |pages =385–401 |author=E. Vogel and H. Günther | year = 1967}}</ref>

Other examples of this type of tautomerism can be found in [[bullvalene]], and in open and closed forms of certain [[heterocycle]]s, such as organic [[azide]]s and [[tetrazole]]s,<ref>{{cite journal | doi=10.1021/jo902342z | pmid=20297785 | volume=75 | issue=8 | title=Azide−Tetrazole Equilibrium of C-6 Azidopurine Nucleosides and Their Ligation Reactions with Alkynes | year=2010 | journal=The Journal of Organic Chemistry | pages=2461–2473 | author1=Lakshman, Mahesh K. | author2=Singh, Manish K. | author3=Parrish, Damon | author4=Balachandran, Raghavan | author5=Day, Billy W. | pmc=2877261}}</ref> or [[mesoionic]] [[münchnone]] and acylamino ketene.

Valence tautomerism requires a change in molecular geometry and should not be confused with canonical [[resonance structures]] or mesomers.
{{Clear|left}}

== Inorganic materials ==

In inorganic extended solids, valence tautomerism can manifest itself in the change of oxidation states its spatial distribution upon the change of macroscopic thermodynamic conditions. Such effects have been called [[charge ordering]] or valence mixing to describe the behavior in inorganic oxides.<ref>{{Cite journal |last1=Karen |first1=Pavel |last2=McArdle |first2=Patrick |last3=Takats |first3=Josef |date=2014-06-18 |title=Toward a comprehensive definition of oxidation state (IUPAC Technical Report) |journal=Pure and Applied Chemistry |language=en |volume=86 |issue=6 |pages=1017–1081 |doi=10.1515/pac-2013-0505 |s2cid=95381734 |issn=1365-3075|doi-access=free }}</ref>
==Consequences for chemical databases==
The existence of multiple possible tautomers for individual [[chemical substance]]s can lead to confusion. For example, samples of 2-pyridone and [[2-hydroxypyridine]] do not exist as separate isolatable materials: the two tautomeric forms are interconvertible and the proportion of each depends on factors such as temperature, solvent, and additional [[substituent]]s attached to the main ring.<ref name=Katritzky/><ref>{{cite journal |doi=10.3998/ark.5550190.0003.b18 |doi-access=free |title=Reinvestigation of the tautomerism of some substituted 2-hydroxypyridines |year=2002 |last1=Forlani |first1=Luciano |last2=Cristoni |first2=Giampiero |last3=Boga |first3=Carla |last4=Todesco |first4=Paolo E. |last5=Vecchio |first5=Erminia Del |last6=Selva |first6=Simona |last7=Monari |first7=Magda |journal=Arkivoc |volume=2002 |issue=11 |pages=198–215 |hdl=2027/spo.5550190.0003.b18 |hdl-access=free }}</ref>
:[[File:2-pyridone-chemical-tautomer.svg|2-pyridone-chemical-tautomer.svg]]
Historically, each form of the substance was entered into databases such as those maintained by the [[Chemical Abstracts Service]] and given separate [[CAS Registry Number]]s.<ref>{{cite web |url=https://www.cas.org/support/documentation/chemical-substances/faqs |title=CAS REGISTRY and CAS Registry Number FAQs |access-date=2022-08-10 |publisher=CAS, a division of the American Chemical Society}}</ref> 2-Pyridone was assigned [142-08-5]<ref>{{cite web |url=https://commonchemistry.cas.org/detail?cas_rn=142-08-5 |title=2-Pyridone |publisher=CAS Common Chemistry |access-date=2022-08-10}}</ref> and 2-hydroxypyridine [109-10-4].<ref>{{cite web |url=https://commonchemistry.cas.org/detail?cas_rn=109-10-4 |title=2-Pyridone ("other name") |publisher=CAS Common Chemistry |access-date=2022-08-10}}</ref> The latter is now a  "replaced" registry number so that look-up by either identifier reaches the same entry. The facility to automatically recognise such potential tautomerism and ensure that all tautomers are indexed together has been greatly facilitated by the creation of the [[International Chemical Identifier]] (InChI) and associated software.<ref>{{cite journal |doi= 10.1186/1758-2946-5-7 |doi-access=free |title= InChI - the worldwide chemical structure identifier standard |year= 2013 |last1= Heller |first1= Stephen |last2= McNaught |first2= Alan |last3= Stein |first3= Stephen |last4= Tchekhovskoi |first4= Dmitrii |last5= Pletnev |first5= Igor |journal= Journal of Cheminformatics |volume= 5 |issue= 1 |page= 7 |pmid= 23343401 |pmc= 3599061 }}</ref><ref>{{cite journal |doi=10.1002/wcms.36 |title=Representation of chemical structures |year=2011 |last1=Warr |first1=Wendy A. |journal=Wiley Interdisciplinary Reviews: Computational Molecular Science |volume=1 |issue=4 |pages=557–579 |s2cid=29780903 |doi-access=free }}</ref><ref>{{cite journal |doi=10.1186/s13321-020-00460-5 |doi-access=free |url=https://jcheminf.biomedcentral.com/track/pdf/10.1186/s13321-020-00460-5.pdf |title=Molecular representations in AI-driven drug discovery: A review and practical guide |year=2020 |last1=David |first1=Laurianne |last2=Thakkar |first2=Amol |last3=Mercado |first3=Rocío |last4=Engkvist |first4=Ola |journal=Journal of Cheminformatics |volume=12 |issue=1 |page=56 |pmid=33431035 |pmc=7495975 }}</ref> Thus the [[International_Chemical_Identifier#InChIKey|standard InChI]] for either tautomer is <code>
InChI=1S/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7)</code>.<ref>{{cite web |url=https://www.chemspider.com/Chemical-Structure.8537.html |title=2-pyridone |publisher=ChemSpider |access-date=2022-08-10}}</ref>

== See also ==
* [[Fluxional molecule]]

==References==
{{reflist}}

==External links==
*{{Commonscatinline|Tautomerism}}

[[Category:Isomerism]]