Editing Phenols

{{Short description|Chemical compounds in which hydroxyl group is attached directly to an aromatic ring}}
{{about|the class of chemicals containing a phenol group|the molecule alone|Phenol}}
In [[organic chemistry]], '''phenols''', sometimes called '''phenolics''', are a class of [[chemical compounds]] consisting of one or more [[hydroxyl]] [[Functional group|group]]s (−[[Oxygen|O]] [[Hydrogen|H]]) [[Chemical bond|bonded]] directly to an [[aromatic hydrocarbon]] group.<ref>{{GoldBookRef |title=phenols |file=P04539}}</ref> The simplest is [[phenol]], {{chem|C|6|H|5|OH}}. Phenolic compounds are classified as simple phenols or [[polyphenols]] based on the number of phenol units in the molecule.
[[Image:Phenol chemical structure.svg|thumb|right|Phenol{{snd}} the simplest of the phenols]]
[[File:Salicylic-acid-skeletal.svg|thumb|right|144px|Chemical structure of [[salicylic acid]], the [[active metabolite]] of [[aspirin]]]]

Phenols are both synthesized industrially and produced by plants and microorganisms.<ref name=Hattenschwiler>{{cite journal |doi=10.1016/S0169-5347(00)01861-9 |title=The role of polyphenols in terrestrial ecosystem nutrient cycling |year=2000 |last1=Hättenschwiler |first1=Stephan |last2=Vitousek |first2=Peter M. |journal=Trends in Ecology & Evolution |volume=15 |issue=6 |pages=238–243 |pmid=10802549|doi-access=free }}</ref>

==Properties==
===Acidity===
Phenols are more [[acid]]ic than typical alcohols. The acidity of the hydroxyl group in phenols is commonly intermediate between that of [[aliphatic]] alcohols and [[carboxylic acid]]s (their pK<sub>a</sub> is usually between 10 and 12). Deprotonation of a phenol forms a corresponding negative phenolate ion or phenoxide ion, and the corresponding [[Salt (chemistry)|salt]]s are called phenolates or phenoxides (aryloxides, according to the IUPAC Gold Book).{{cn|date=July 2024}}

===Condensation with aldehydes and ketones===
Phenols are susceptible to [[electrophilic aromatic substitution]]s. Condensation with [[formaldehyde]] gives resinous materials, famously [[Bakelite]].{{cn|date=July 2024}}

Another industrial-scale electrophilic aromatic substitution is the production of [[bisphenol A]], which is produced by the [[condensation reaction|condensation]] with [[acetone]].<ref name="Fiege">{{Ullmann |author1=Fiege H |author2=Voges H-W |author3=Hamamoto T |author4=Umemura S |author5=Iwata T |author6=Miki H |author7=Fujita Y |author8=Buysch H-J |author9=Garbe D |author10=Paulus W |year=2000 |title=Phenol Derivatives |doi=10.1002/14356007.a19_313}}</ref>
:[[File:Synthesis Bisphenol A.svg|frameless|upright=2.5]]

===C-Alkylation with alkenes===
Phenol is readily alkylated at the ortho positions using alkenes in the presence of a Lewis acid such as [[aluminium phenoxide]]:{{citation needed|date=April 2024}}
: CH<sub>2</sub>=CR<sub>2</sub>  +  C<sub>6</sub>H<sub>5</sub>OH  →  R<sub>2</sub>CHCH<sub>2</sub>-2-C<sub>6</sub>H<sub>4</sub>OH
More than 100,000 tons of [[tert-butyl]] phenols are produced annually (year: 2000) in this way, using [[isobutylene]] (CH<sub>2</sub>=CMe<sub>2</sub>) as the alkylating agent. Especially important is [[2,6-Di-tert-butylphenol|2,6-ditert-butylphenol]], a versatile [[antioxidant]].<ref name="Fiege"/>

===Other reactions===<!-- This section is linked from [[Organic reaction]] -->
Phenols undergo [[esterification]]. Phenol esters are [[active ester]]s, being prone to [[hydrolysis]]. Phenols are [[Reactivity (chemistry)|reactive]] species toward [[oxidation]]. Oxidative cleavage, for instance cleavage of [[1,2-dihydroxybenzene]] to the monomethylester of 2,4-hexadienedioic acid with oxygen, [[copper chloride]] in [[pyridine]].<ref>2,4-Hexadienedioic acid, monomethyl ester, (Z,Z)- [[Organic Syntheses]], Coll. Vol. 8, p. 490 (1993); Vol. 66, p. 180 (1988) [http://www.orgsynth.org/orgsyn/prep.asp?prep=cv8p0490 Article].</ref> Oxidative de-aromatization to [[quinone]]s also known as the [[Teuber reaction]]. Oxidizing reagents are [[Fremy's salt]]<ref>{{cite journal |year=1972 |title=2,5-Cyclohexadiene-1,4-dione, 2,3,5-trimethyl |journal=Organic Syntheses |volume=52 |page=83}}</ref> and [[oxone]].<ref>{{cite journal |last1=Carreño |first1=M. Carmen |last2=González-López |first2=Marcos |last3=Urbano |first3=Antonio |year=2006 |title=Oxidative De-aromatization of para-Alkyl Phenols into para-Peroxyquinols and para-Quinols Mediated by Oxone as a Source of Singlet Oxygen |journal=[[Angewandte Chemie International Edition]] |volume=45 |issue=17 |pages=2737–2741 |doi=10.1002/anie.200504605 |pmid=16548026}}</ref> In reaction depicted below 3,4,5-trimethylphenol reacts with [[singlet oxygen]] generated from [[oxone]]/[[sodium carbonate]] in an [[acetonitrile]]/water mixture to a para-peroxyquinole. This [[hydroperoxide]] is reduced to the quinole with [[sodium thiosulfate]].
:[[Image:OxonePhenolDearomatization.png|600px|Oxone phenol dearomatization]]
Phenols are oxidized to [[hydroquinone]]s in the [[Elbs persulfate oxidation]].

Reaction of naphtols and hydrazines and sodium bisulfite in the [[Bucherer carbazole synthesis]].

==Synthesis==<!-- This section is linked from [[Organic reaction]] -->
Many phenols of commercial interest are prepared by elaboration of [[phenol]] or [[cresol]]s. They are typically produced by the alkylation of [[benzene]]/[[toluene]] with [[propylene]] to form [[cumene]] then {{chem|O|2}} is added with {{chem|H|2|SO|4}} to form phenol ([[Hock process]]). In addition to the reactions above, many other more specialized reactions produce phenols:
* rearrangement of esters in the [[Fries rearrangement]]<ref>{{cite journal |title=Über Homologe des Cumaranons und ihre Abkömmlinge |author1=Fries, K. |author2=Finck, G. |journal=[[Chemische Berichte]] |volume=41 |issue=3 |pages=4271–4284 |year=1908 |url=https://zenodo.org/record/1426311 |doi=10.1002/cber.190804103146 |author1-link= Karl Theophil Fries}}</ref><ref>{{cite journal |title=Über ein Kondensationsprodukt des Cumaranons und seine Umwandlung in Oxindirubin |author1=Fries, K. |author2=Pfaffendorf, W. |journal=[[Chemische Berichte]] |volume=43 |issue=1 |pages=212–219 |year=1910 |url=https://zenodo.org/record/1426389 |doi=10.1002/cber.19100430131}}</ref>
* rearrangement of ''N''-phenylhydroxylamines in the [[Bamberger rearrangement]]<ref>{{cite journal |last=Bamberger |first=E. |journal=[[Chemische Berichte]] |year=1894 |volume=27 |issue=2 |pages=1347–1350 |title=Ueber die Reduction der Nitroverbindungen |doi=10.1002/cber.18940270229 |url=http://gallica.bnf.fr/ark:/12148/bpt6k907342/f163}}</ref><ref>{{cite journal |last=Bamberger |first=E. |journal=Chemische Berichte |year=1894 |volume=27 |issue=2 |pages=1548–1557 |title=Über das Phenylhydroxylamin |doi=10.1002/cber.18940270276 |url=http://gallica.bnf.fr/ark:/12148/bpt6k907342/f376.table}}</ref>
* [[dealkylation]] of phenolic [[ethers]]
* reduction of [[quinone]]s
* replacement of an aromatic amine by an hydroxyl group with water and sodium bisulfide in the [[Bucherer reaction]]<ref>{{cite journal |author=H. Bucherer |authorlink=Hans Theodor Bucherer |title=Über die Einwirkung schwefligsaurer Salze auf aromatische Amido- und Hydroxylverbindungen |language=German |journal=[[J. Prakt. Chem.]] |year=1904 |pages=49–91 |volume=69 |doi=10.1002/prac.19040690105 |issue=1 |url=https://zenodo.org/record/1428014}}</ref>
* thermal decomposition of aryl [[Diazonium compound|diazonium]] salts, the salts are converted to phenol<ref>{{cite journal |author=H. E. Ungnade, E. F. Orwoll |doi=10.15227/orgsyn.023.0011 |title=3-Bromo-4-hydroxytoluene |journal=Organic Syntheses |volume=23 |pages=11 |year=1943}}</ref>
* by the oxidation of aryl silanes—an aromatic variation of the [[Fleming-Tamao oxidation]]<ref>{{cite journal |last1=Bracegirdle |first1=Sonia |last2=Anderson |first2=Edward A. |title=Arylsilane oxidation—new routes to hydroxylated aromatics |journal=Chem. Comm. |volume=46 |issue=20 |pages=3454–6 |doi=10.1039/b924135c |pmid=20582346 |year=2010 |s2cid=31736757}}</ref>
* catalytic synthesis from aryl bromides and iodides using [[nitrous oxide]]<ref>{{cite journal |last1=Le Valliant |first1=Franck |last2=Mateos Calbet |first2=Ana |last3=González-Pelayo |first3=Silvia |last4=Reijerse |first4=Edward J. |last5=Ni |first5=Shengyang |last6=Busch |first6=Julia |last7=Cornella |first7=Josep |title=Catalytic synthesis of phenols with nitrous oxide |journal=Nature |year=2022 |volume=604 |issue=7907 |pages=677–683 |doi=10.1038/s41586-022-04516-4|pmid=35478236 |pmc=9046086 |bibcode=2022Natur.604..677L}}</ref>

== Classification ==
[[File:Paracetamol-skeletal.svg|thumb|144px|The best-selling drug in the U.S., [[Acetaminophen]], also known as Paracetamol, is a phenol.]]
There are various [[Chemical classification|classification]] schemes.<ref name=Vermerris>Wilfred Vermerris and Ralph Nicholson. [https://books.google.com/books?id=uLzdv8fsRxYC&dq Phenolic Compound Biochemistry] Springer, 2008.</ref>{{rp|2}} A commonly used scheme is based on the number of carbons and was devised by [[Jeffrey Harborne]] and Simmonds in 1964 and published in 1980:<ref name=Vermerris/>{{rp|2}}<ref name=Harborne>{{cite book |last1=Harborne |first1=J. B. |year=1980 |chapter=Plant phenolics |editor1-last=Bell |editor1-first=E. A. |editor2-last=Charlwood |editor2-first=B. V. |title=Encyclopedia of Plant Physiology, volume 8 Secondary Plant Products |publisher=Springer-Verlag |location=Berlin Heidelberg New York |pages=329–395}}</ref>

{|align="center"  class="wikitable" style="background-color:white;"
|[[Phenol]]||the parent compound, used as a [https://web.archive.org/web/20091020104225/http://www.pedicure-tips.com/Pedicure-Disinfectant-Phenolics.html disinfectant] and for [[chemical synthesis]]
|-
|[[Bisphenol A]]||and other bisphenols produced from ketones and phenol / cresol
|-
|[[Butylated hydroxytoluene|BHT]]||(butylated hydroxytoluene) - a fat-soluble [[antioxidant]] and [[food additive]]
|-
|[[4-Nonylphenol]]||a breakdown product of [[detergents]] and [[nonoxynol-9]]
|-
|[[Orthophenyl phenol]]||a [[fungicide]] used for waxing [[citrus fruit]]s
|-
|[[Picric acid]]||(trinitrophenol) - an [[explosive material]]
|-
|[[Phenolphthalein]]||[[pH indicator]]
|-
|[[Xylenol]]|| |used in antiseptics & disinfectants
|}

===Drugs and bioactive natural products===
{{main|Naturally occurring phenols}}
More than 371 drugs approved by the FDA between the years of 1951 and 2020 contain either a phenol or a phenolic ether (a phenol with an alkyl), with nearly every class of small molecule drugs being represented, and natural products making up a large portion of this list.<ref>{{Cite journal |last1=Scott |first1=Kevin A. |last2=Cox |first2=Philip B. |last3=Njardarson |first3=Jon T. |date=2022-05-26 |title=Phenols in Pharmaceuticals: Analysis of a Recurring Motif |url=https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00223 |journal=Journal of Medicinal Chemistry |language=en |volume=65 |issue=10 |pages=7044–7072 |doi=10.1021/acs.jmedchem.2c00223 |pmid=35533692 |s2cid=248667453 |issn=0022-2623}}</ref>
{|align="center"  class="wikitable" style="background-color:white;"
|[[tyrosine]]|| one of the 20 standard amino acids
|-
|[[levodopa|L-DOPA]]||[[dopamine]] prodrug used to treat [[Parkinson's disease]]
|-
|[[propofol]]||short-acting intravenous [[Anesthesia|anesthetic]] agent
|-
|[[vitamin K]] hydroquinone||blood-clotting agent that converts
|-
| [[levothyroxine]] (L-thyroxine)|| Top-selling drug to treat thyroid hormone deficiency.
|-
|[[amoxicillin]]||Top-selling antibiotic
|-
|[[estradiol]]|| the major female sex hormone
|}

== Analysis ==
In [[chemical analysis]], phenols can be detected using [[2,6-Dibromoquinonechlorimide|2,6‑dibromoquinonechlorimide]].<ref>{{Cite journal |last=Ettinger |first=M. B. |last2=Ruchhoft |first2=C. C. |date=1948-12-01 |title=Determination of Phenol and Structurally Related Compounds by Gibbs Method |url=https://doi.org/10.1021/ac60024a018 |journal=Analytical Chemistry |volume=20 |issue=12 |pages=1191–1196 |doi=10.1021/ac60024a018 |issn=0003-2700}}</ref> It reacts with phenols to form [[Indophenol|indophenols]], resulting in a color change.<ref>{{Cite journal |last=Gibbs |first=H.D. |date=1 April 1927 |title=PHENOL TESTS |url=https://linkinghub.elsevier.com/retrieve/pii/S0021925818843381 |journal=Journal of Biological Chemistry |language=en |volume=72 |issue=2 |pages=649–664 |doi=10.1016/S0021-9258(18)84338-1|doi-access=free }}</ref>

==References==
<references />

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[[Category:Phenols| ]]
[[Category:Functional groups]]
[[Category:Disinfectants]]