Enol

Organic esters, 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:{{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}}

:{{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:{{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=J. Chem. Educ.|volume=88|issue=10|pages=1444–1445|doi=10.1021/ed1010932

|bibcode=2011JChEd..88.1444M}}

:File:AcacH.svg{{clear-left}}

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 = [enol]/[keto] ≈ 3{{x10^|-7}}). In 1,3-diketones, such as acetylacetone (2,4-pentanedione), the enol form is more 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.

If R¹ and R² (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 diastereomers or enantiomers.{{cn|date=February 2024}}

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 acyloins. 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 reductones. Such species are important in glycochemistry, e.g., the Lobry de Bruyn–Van Ekenstein transformation.{{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 }}

:File:Keto-Endiol-Tautomerie.svg isomers at left and right. Ex. is hydroxyacetone, shown at right.]]

Image:Ascorbic acidity3.png (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 (O₂) in the (undesirable) process called photorespiration.

File:EnediolPhotoResp.svg.]]

Phenols 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.{{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}}

:File:Tetrahydronaphthalenedione.png

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.{{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 }}

{{See also|Carbonyl α-substitution reactions}}

The terminus of the double bond in enols is nucleophilic. Its reactions with electrophilic organic compounds is important in biochemistry as well as synthetic organic chemistry. In the former area, the fixation of carbon dioxide involves addition of CO₂ to an enol.{{cn|date=February 2024}}

{{main|enolate}}

Deprotonation of enolizable ketones, aldehydes, and esters gives enolates.{{March6th}}{{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}} Enolates can be trapped by the addition of electrophiles at oxygen. Silylation gives silyl enol ether.Mukaiyama, T.; Kobayashi, S. Org. React. 1994, 46, 1. {{doi|10.1002/0471264180.or046.01}} Acylation gives

esters such as vinyl acetate.{{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 }}

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

Delocalization can stabilize the enol tautomer. Thus, very stable enols are phenols.{{Cite book|last=Clayden|first=Jonathan|title=Organic Chemistry|publisher=Oxford University Press|year=2012|pages=456–459}} Another stabilizing factor in 1,3-dicarbonyls is intramolecular hydrogen bonding.{{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}} Both of these factors influence the enol-dione equilibrium in acetylacetone.

• Alkenal
• Enolase
• Ketone
• Ynol
• Geminal diol, another form of ketones and aldehydes in water solutions
• Regioselectivity

{{reflist}}

{{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]

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{{DEFAULTSORT:Keto-Enol Tautomerism}}

Category:Functional groups

Category:Metabolism

Category:Reactive intermediates

Category:Alcohols

Category:Alkene derivatives

Category:Organic reactions