View source for Enol

{{Short description|1=Organic compound with a C=C–OH group}}
<div class="skin-invert-image">
{{multiple image|caption_align=left|header_align=center
| align = right
| direction = vertical
| width = 250
| header = Examples of keto-enol [[tautomerism]]
| image1 = enol.png
| alt1 = TBD
| caption1 =Ketone
[[tautomerization]], keto-form at left, enol at right. Ex. is [[3-pentanone]], a less stabilized enol.{{citation needed|date=March 2023}}
| image2 = Enolate Resonance.svg
| alt2 = TBD
| caption2  = Enolate [[resonance structures]], schematic representation of forms (see text regarding [[molecular orbital]]s); [[carbanion]] form at left, [[enolate]] at right; Ex. is [[2-butanone]], also a less stabilized enol.{{citation needed|date=March 2023}}
| image4 =AcacH.svg
| alt4 = TBD
| caption4 = Ketone [[tautomerization]], enol-form at left, keto at right. Ex. is [[2,4-pentanedione]], a [[hydrogen bond]] (---) stabilized enol.{{citation needed|date=March 2023}}
| image5 = Tartronaldehyde.svg
| alt5 = TBD
| caption5  = Aldehyde [[tautomerization]], enol-form at left, "keto" at right; Ex. is [[tartronaldehyde]] (reductone), an [[enediol]]-type of enol.{{citation needed|date=March 2023}}
}}
</div>
In [[organic chemistry]], '''enols''' are a type of [[Functional group]] or [[chemical intermediate|intermediate]] in [[organic chemistry]] containing a group with the formula {{chem2|C\dC(OH)}} (R = many substituents). The term ''enol'' is an abbreviation of ''alkenol'', a [[portmanteau]] deriving from "-ene"/"alkene" and the "-ol".  Many kinds of enols are known.<ref name=March/>
'''Keto–enol tautomerism''' refers to a [[chemical equilibrium]] between a "keto" form (a [[carbonyl]], named for the common [[ketone]] case) and an enol. The interconversion of the two forms involves the transfer of an alpha hydrogen atom and the reorganisation of bonding [[electron]]s. The keto and enol forms are [[tautomerism|tautomers]] of each other.<ref name="Clayden-2012">{{cite book |last1=Clayden |first1=Jonathan |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart |title=Organic chemistry |date=2012 |publisher=Oxford University Press |location=New York |isbn=978-0-19-927029-3 |pages=450–451 |edition=2nd}}</ref>
==Enolization==
[[organic compound|Organic]] [[ester]]s, [[ketones]], and [[aldehydes]] with an [[α-hydrogen]] ({{chem2|C\sH}} bond adjacent to the [[carbonyl group]]) often form enols. The reaction involves migration of a proton ({{red|H}}) from carbon to oxygen:<ref name=March>{{cite book |author=Smith MB, March J |title=Advanced Organic Chemistry |edition=5th |publisher=[[Wiley Interscience]] |location=New York |year=2001 |pages=1218–1223 |isbn=0-471-58589-0}}</ref>
:{{chem2 | RC(\dO)C{{red|H}}R′R′′ <-> RC(O{{red|H}})\dCR′R′′ }}
In the case of ketones, the conversion is called a keto-enol tautomerism, although this name is often more generally applied to all such tautomerizations.  Usually the equilibrium constant is so small that the enol is undetectable spectroscopically.
In some compounds with two (or more) carbonyls, the enol form becomes dominant. The behavior of [[2,4-pentanedione]] illustrates this effect:<ref>{{cite journal
|title=Substituent Effects on Keto–Enol Equilibria Using NMR Spectroscopy
|first1=Kimberly A.|last1=Manbeck|first2=Nicholas C.|last2=Boaz|first3=Nathaniel C.|last3=Bair|first4=Allix M. S.|last4=Sanders|first5=Anderson L.|last5=Marsh|year=2011
|journal=[[Journal of Chemical Education|J. Chem. Educ.]]|volume=88|issue=10|pages=1444–1445|doi=10.1021/ed1010932
|bibcode=2011JChEd..88.1444M}}</ref>
:[[File:AcacH.svg|200px|left|class=skin-invert-image]]{{clear-left}}
{| class="wikitable"
|+ Selected enolization constants<ref>{{cite journal |doi=10.1002/poc.3168|title=Equilibrium constants for enolization in solution by computation alone|year=2013|last1=Guthrie|first1=J. Peter|last2=Povar|first2=Igor|journal=Journal of Physical Organic Chemistry|volume=26|issue=12|pages=1077–1083}}</ref>
!carbonyl
!enol
!K<sub>enolization</sub>
|-
|[[Acetaldehyde]]<br />{{chem2|CH3CHO}}
|{{chem2|CH2\dCHOH}}
|5.8{{x10^|-7}}
|-
|[[Acetone]]<br />{{chem2|CH3C(O)CH3}}
|{{chem2|CH3C(OH)\dCH2}}
|5.12{{x10^|-7}}
|-
|[[Methyl acetate]]<br />{{chem2|CH3CO2CH3}}
|{{chem2|CH2\dCH(OH)OCH3}}
|4{{x10^|-20}}
|-
|[[Acetophenone]]<br />{{chem2|C6H5C(O)CH3}}
|{{chem2|C6H5C(OH)\dCH2}}
|1{{x10^|-8}}
|-
|[[Acetylacetone]]<br />{{chem2|CH3C(O)CH2C(O)CH3}}
|{{chem2|CH3C(O)CH\dC(OH)CH3}}
|0.27
|-
|[[1,1,1-Trifluoroacetylacetone|Trifluoroacetylacetone]]<br />{{chem2|CH3C(O)CH2C(O)CF3}}
|{{chem2|CH3C(O)CH\dC(OH)CF3}}
|32
|-
|[[Hexafluoroacetylacetone]]<br />{{chem2|CF3C(O)CH2C(O)CF3}}
|{{chem2|CF3C(O)CH\dC(OH)CF3}}
|~10<sup>4</sup>
|-
|Cyclohexa-2,4-dienone
|[[Phenol]]<br />{{chem2|C6H5OH}}
|>10<sup>12</sup>
|}
Enols are derivatives of [[vinyl alcohol]], with a {{chem2|C\dC\sOH}} connectivity. Deprotonation of organic carbonyls gives the [[enolate anion]], which are a strong [[nucleophile]]. A classic example for favoring the keto form can be seen in the equilibrium between [[vinyl alcohol]] and [[acetaldehyde]] (K&nbsp;=&nbsp;[enol]/[keto]&nbsp;≈&nbsp;3{{x10^|-7}}). In [[diketone#1,3-Diketones|1,3-diketones]], such as [[acetylacetone]] (2,4-pentanedione), the enol form is favored.
The acid-catalyzed conversion of an enol to the keto form proceeds by proton transfer from O to carbon.  The process does not occur intramolecularly, but requires participation of solvent or other mediators.
==Stereochemistry of ketonization==
If R<sup>1</sup> and R<sup>2</sup> (note equation at top of page) are different substituents, there is a new stereocenter formed at the alpha position when an enol converts to its keto form. Depending on the nature of the three R groups, the resulting products in this situation would be [[diastereomer]]s or [[enantiomer]]s.{{cn|date=February 2024}}
== Enediols ==
Enediols are alkenes with a hydroxyl group on each carbon of the C=C double bond. Normally such compounds are disfavored components in equilibria with [[acyloin]]s.  One special case is [[catechol]], where the C=C subunit is part of an aromatic ring.  In some other cases however, enediols are stabilized by flanking carbonyl groups. These stabilized enediols are called [[reductone]]s.  Such species are important in glycochemistry, e.g., the [[Lobry de Bruyn-van Ekenstein transformation]].<ref>{{cite journal|title=Reductones |author=Schank, Kurt|journal=Synthesis|year=1972|volume=1972|issue=4|pages=176–90|doi=10.1055/s-1972-21845|s2cid=260331550 }}</ref>
:[[File:Keto-Endiol-Tautomerie.svg|thumb|center|350 px|class=skin-invert-image|'''Keto-enediol tautomerizations.''' Enediol in the center; [[acyloin]] isomers at left and right. Ex. is [[hydroxyacetone]], shown at right.]]
[[Image:Ascorbic acidity3.png|thumb|center|350 px|class=skin-invert-image|Conversion of [[ascorbic acid]] (vitamin C) to an enolate. Enediol at left, enolate at right, showing movement of electron pairs resulting in deprotonation of the stable parent enediol. A distinct, more complex chemical system, exhibiting the characteristic of [[vinylogy]].]]
[[Ribulose-1,5-bisphosphate]] is a key substrate in the [[Calvin cycle]] of [[photosynthesis]].  In the Calvin cycle, the ribulose equilibrates with the enediol, which then binds [[carbon dioxide]].  The same enediol is also susceptible to attack by oxygen (O<sub>2</sub>) in the (undesirable) process called [[photorespiration]].
[[File:EnediolPhotoResp.svg|thumb|center|class=skin-invert-image|Keto-enediol equilibrium for [[ribulose-1,5-bisphosphate]].]]
==Phenols==
[[Phenol]]s represent a kind of enol.  For some phenols and related compounds, the keto tautomer plays an important role.  Many of the reactions of [[resorcinol]] involve the keto tautomer, for example. Naphthalene-1,4-diol exists in observable equilibrium with the diketone tetrahydronaphthalene-1,4-dione.<ref>{{cite journal|doi=10.1002/anie.200502588|title=Rediscovery, Isolation, and Asymmetric Reduction of 1,2,3,4-Tetrahydronaphthalene-1,4-dione and Studies of Its [Cr(CO)3] Complex|year=2006|last1=Kündig|first1=E. Peter|last2=Enríquez García|first2=Alvaro|last3=Lomberget|first3=Thierry|last4=Bernardinelli|first4=Gérald|journal=Angewandte Chemie International Edition|volume=45|issue=1|pages=98–101|pmid=16304647}}</ref>
:[[File:Tetrahydronaphthalenedione.png|220px|class=skin-invert-image]]
==Biochemistry==
Keto–enol tautomerism is important in several areas of [[biochemistry]].{{cn|date=February 2024}}
The high phosphate-transfer potential of [[phosphoenolpyruvate]] results from the fact that the phosphorylated compound is "trapped" in the less thermodynamically favorable enol form, whereas after dephosphorylation it can assume the keto form.{{cn|date=February 2024}}
The [[enzyme]] [[enolase]] catalyzes the dehydration of [[2-phosphoglyceric acid]] to the enol phosphate ester.  Metabolism of PEP to [[pyruvic acid]] by [[pyruvate kinase]] (PK) generates [[adenosine triphosphate]] (ATP) via [[substrate-level phosphorylation]].<ref>{{cite book |last=Berg |first=Jeremy M. |author2=Tymoczko, Stryer |title=Biochemistry |year=2002 |edition=5th |publisher=[[W.H. Freeman and Company]] |location=New York |isbn=0-7167-3051-0 |url=https://archive.org/details/biochemistrychap00jere |url-access=registration }}</ref>
{| style="background: white; text-align:center;"
|-
| rowspan="5" | [[image:2-phospho-D-glycerate wpmp.png|class=skin-invert-image]]
| colspan="2" style="width:75px" |
| rowspan="5" | [[image:phosphoenolpyruvate wpmp.png|class=skin-invert-image]]
| colspan="2" style="width:75px" |
| rowspan="5" | [[image:pyruvate wpmp.png|class=skin-invert-image]]
|-
|
| H<sub>2</sub>O
| [[Adenosine diphosphate|ADP]]
| [[adenosine triphosphate|ATP]]
|-
| colspan="2" style="width:75px" | [[image:Biochem reaction arrow reversible NYYN horiz med.svg|75px|class=skin-invert-image]]
| colspan="2" style="width:75px" | [[image:Biochem reaction arrow reversible YYNN horiz med.svg|75px|class=skin-invert-image]]
|-
|
| H<sub>2</sub>O
|
|
|-
| colspan="2" style="width:75px" |
| colspan="2" style="width:75px" |
|-
|}
==Reactivity==
{{See also|Carbonyl α-substitution reactions}}
===Addition of electrophiles===
The terminus of the double bond in enols is [[nucleophile|nucleophilic]].  Its reactions with [[electrophile|electrophilic]] organic compounds is important in [[biochemistry]] as well as [[organic synthesis|synthetic organic chemistry]].  In the former area, the fixation of carbon dioxide involves addition of CO<sub>2</sub> to an enol.{{cn|date=February 2024}}
===Deprotonation: enolates===
{{main|enolate}}
Deprotonation of enolizable ketones, aldehydes, and esters gives [[enolate]]s.<ref>{{March6th}}</ref><ref name=enolate>{{cite book|title=Modern Enolate Chemistry: From Preparation to Applications in Asymmetric Synthesis|author=Manfred Braun|year=2015|isbn=9783527671069 |doi=10.1002/9783527671069
|publisher=Wiley-VCH}}</ref>  Enolates can  be trapped by the addition of electrophiles at oxygen.  Silylation gives [[silyl enol ether]].<ref>Mukaiyama, T.; Kobayashi, S. ''[[Org. React.]]'' '''1994''', ''46'', 1. {{doi|10.1002/0471264180.or046.01}}</ref> Acylation gives
esters such as [[vinyl acetate]].<ref name=Ullmann>{{cite encyclopedia|author=G. Roscher|title=Vinyl Esters|encyclopedia=Ullmann's Encyclopedia of Chemical Technology|year=2007|publisher=Wiley-VCH|location=Weinheim|doi=10.1002/14356007.a27_419|isbn=978-3527306732|s2cid=241676899 }}</ref>
== Stable enols ==
In general, enols are less stable than their keto equivalents because of the favorability of the C=O double bond over C=C double bond. However, enols can be stabilized kinetically or thermodynamically.{{cn|date=February 2024}}
Some enols are sufficiently stabilized kinetically so that they can be characterized.{{cn|date=February 2024}}
[[File:Hindrance.png|thumb|class=skin-invert-image|Diaryl-substitution stabilizes some enols.<ref>{{cite journal |title=Stable simple enols |journal=Journal of the American Chemical Society |year=1989 |doi=10.1021/ja00203a019}}</ref>]]
Delocalization can stabilize the enol tautomer. Thus, very stable enols are [[phenol]]s.<ref name=":0">{{Cite book|last=Clayden|first=Jonathan|title=Organic Chemistry|publisher=Oxford University Press|year=2012|pages=456–459}}</ref> Another stabilizing factor in 1,3-dicarbonyls is intramolecular hydrogen bonding.<ref>{{Cite journal|last1=Zhou|first1=Yu-Qiang|last2=Wang|first2=Nai-Xing|last3=Xing|first3=Yalan|last4=Wang|first4=Yan-Jing|last5=Hong|first5=Xiao-Wei|last6=Zhang|first6=Jia-Xiang|last7=Chen|first7=Dong-Dong|last8=Geng|first8=Jing-Bo|last9=Dang|first9=Yanfeng|last10=Wang|first10=Zhi-Xiang|date=2013-01-14|title=Stable acyclic aliphatic solid enols: synthesis, characterization, X-ray structure analysis and calculations|journal=Scientific Reports|language=en|volume=3|issue =1|pages=1058|doi=10.1038/srep01058|pmid=23320139|pmc=3544012|bibcode=2013NatSR...3E1058Z|issn=2045-2322|doi-access=free}}</ref> Both of these factors influence the enol-dione equilibrium in acetylacetone.
== See also ==
* [[Alkenal]]
* [[Enolase]]
* [[Ketone]]
* [[Ynol]]
* [[Geminal diol]], another form of ketones and aldehydes in water solutions
* [[Regioselectivity]]
== References ==
{{reflist}}
==External links==
{{wikiquote}}
* [http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_13%3a_Reactions_with_stabilized_carbanion_intermediates_I/Section_13.1%3a_Tautomers Enols and enolates in biological reactions]
{{Authority control}}
{{DEFAULTSORT:Keto-Enol Tautomerism}}
[[Category:Functional groups]]
[[Category:Metabolism]]
[[Category:Reactive intermediates]]
[[Category:Alcohols]]
[[Category:Alkene derivatives]]
[[Category:Enols| ]]
[[Category:Organic reactions]]