View source for Chemistry:Phenols

{{Short description|Chemical compounds in which hydroxyl group is attached directly to an aromatic ring}}
In [[Chemistry:Organic chemistry|organic chemistry]], '''phenols''', sometimes called '''phenolics''', are a class of chemical compounds consisting of one or more hydroxyl [[Chemistry:Functional group|group]]s (−[[Chemistry:Oxygen|O]][[Chemistry:Hydrogen|H]]) [[Chemistry:Chemical bond|bonded]] directly to an [[Chemistry:Aromatic hydrocarbon|aromatic hydrocarbon]] group.<ref>{{GoldBookRef |title=phenols |file=P04539}}</ref> The simplest is [[Chemistry:Phenol|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 [[Chemistry:Salicylic acid|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}}</ref>

==Properties==
===Acidity===
Phenols are more [[Chemistry:Acid|acid]]ic than typical alcohols. The acidity of the hydroxyl group in phenols is commonly intermediate between that of aliphatic alcohols and [[Chemistry:Carboxylic acid|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 [[Chemistry:Salt|salt]]s are called '''phenolates''' or '''phenoxides''' ('''aryloxides''' according to the IUPAC Gold Book).

===Condensation with aldehydes and ketones===
Phenols are susceptible to [[Chemistry:Electrophilic aromatic substitution|Electrophilic aromatic substitution]]s. Condensation with [[Physics:Formaldehyde|formaldehyde]] gives resinous materials, famously [[Chemistry:Bakelite|Bakelite]].

Another industrial-scale electrophilic aromatic substitution is the production of [[Chemistry:Bisphenol A|bisphenol A]], which is produced by the [[Chemistry:Condensation reaction|condensation]] with [[Chemistry:Acetone|acetone]].<ref name="Fiege">{{Ullmann|author1=Fiege H |work=Ullmann's Encyclopedia of Industrial Chemistry |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 |doi=10.1002/14356007.a19_313|title=Phenol Derivatives }}</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:
: 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 [[Chemistry:Isobutylene|isobutylene]] (CH<sub>2</sub>=CMe<sub>2</sub>) as the alkylating agent. Especially important is [[Chemistry:2,6-Di-tert-butylphenol|2,6-ditert-butylphenol]], a versatile [[Biology:Antioxidant|antioxidant]].<ref name="Fiege"/>

===Other reactions===<!-- This section is linked from [[Chemistry:Organic reaction|Organic reaction]] -->
Phenols undergo [[Chemistry:Esterification|esterification]]. Phenol esters are [[Chemistry:Active ester|active ester]]s, being prone to hydrolysis. Phenols are [[Chemistry:Reactivity|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)- [[Chemistry:Organic Syntheses|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 [[Chemistry:Quinone|quinone]]s also known as the Teuber reaction.<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 [[Chemistry:Singlet oxygen|singlet oxygen]] generated from oxone/[[Chemistry:Sodium carbonate|sodium carbonate]] in an [[Chemistry:Acetonitrile|acetonitrile]]/water mixture to a para-peroxyquinole. This [[Chemistry:Hydroperoxide|hydroperoxide]] is reduced to the quinole with [[Chemistry:Sodium thiosulfate|sodium thiosulfate]].
:[[Image:OxonePhenolDearomatization.png|600px|Oxone phenol dearomatization]]
Phenols are oxidized to [[Chemistry:Hydroquinone|hydroquinone]]s in the [[Chemistry:Elbs persulfate oxidation|Elbs persulfate oxidation]].

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

==Synthesis==<!-- This section is linked from [[Chemistry:Organic reaction|Organic reaction]] -->
Many phenols of commercial interest are prepared by elaboration of [[Chemistry:Phenol|phenol]] or [[Chemistry:Cresol|cresol]]s. They are typically produced by the alkylation of [[Chemistry:Benzene|benzene]]/[[Chemistry:Toluene|toluene]] with [[Chemistry:Propylene|propylene]] to form [[Chemistry:Cumene|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 [[Chemistry:Fries rearrangement|Fries rearrangement]]<ref>{{cite journal |title=Über Homologe des Cumaranons und ihre Abkömmlinge |author1=Fries, K. |author2=Finck, G. |journal=[[Chemistry:Chemische Berichte|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=[[Chemistry:Chemische Berichte|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 [[Chemistry:Bamberger rearrangement|Bamberger rearrangement]]<ref>{{cite journal |last=Bamberger |first=E. |journal=[[Chemistry:Chemische Berichte|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 [[Chemistry:Quinone|quinone]]s
* replacement of an aromatic amine by an hydroxyl group with water and sodium bisulfide in the [[Chemistry:Bucherer reaction|Bucherer reaction]]<ref>{{cite journal |author=H. 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 [[Chemistry: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 [[Chemistry:Nitrous oxide|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. is Acetaminophen, also known as Paracetamol is a phenol.]]
There are various [[Chemistry: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;"
|[[Chemistry:Phenol|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 [[Chemistry:Chemical synthesis|chemical synthesis]]
|-
|[[Chemistry:Bisphenol A|Bisphenol A]]||and other bisphenols produced from ketones and phenol / cresol
|-
|[[Chemistry:Butylated hydroxytoluene|BHT]]||(butylated hydroxytoluene) - a fat-soluble [[Biology:Antioxidant|antioxidant]] and [[Chemistry:Food additive|food additive]]
|-
|4-Nonylphenol||a breakdown product of detergents and [[Chemistry:Nonoxynol-9|nonoxynol-9]]
|-
|Orthophenyl phenol||a [[Biology:Fungicide|fungicide]] used for waxing citrus fruits
|-
|[[Chemistry:Picric acid|Picric acid]]||(trinitrophenol) - an explosive material
|-
|[[Chemistry:Phenolphthalein|Phenolphthalein]]||[[Chemistry:PH indicator|pH indicator]]
|-
|[[Chemistry:Xylenol|Xylenol]]|| |used in antiseptics & disinfectants
|}

===Drugs and bioactive natural products===
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;"
|[[Chemistry:Tyrosine|tyrosine]]|| one of the 20 standard amino acids
|-
|L-DOPA||[[Biology:Dopamine|dopamine]] prodrug used to treat [[Medicine:Parkinson's disease|Parkinson's disease]]
|-
|[[Chemistry:Propofol|propofol]]||short-acting intravenous [[Medicine:Anesthesia|anesthetic]] agent
|-
|[[Chemistry:Vitamin K|vitamin K]] hydroquinone||blood-clotting agent that converts
|-
| [[Biology:Levothyroxine|levothyroxine]] (L-thyroxine)|| Top-selling drug to treat thyroid hormone deficiency.
|-
|[[Chemistry:Amoxicillin|amoxicillin]]||Top-selling antibiotic
|-
|[[Chemistry:Estradiol|estradiol]]|| the major female sex hormone
|}

==References==
<references />


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

{{Sourceattribution|Phenols}}