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 groups (−O H) 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. 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 acidic than typical alcohols. The acidity of the hydroxyl group in phenols is commonly intermediate between that of aliphatic alcohols and carboxylic acids (their pK_a is usually between 10 and 12). Deprotonation of a phenol forms a corresponding negative phenolate ion or phenoxide ion, and the corresponding salts 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 substitutions. 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 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> :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}} : CH₂=CR₂ + C₆H₅OH → R₂CHCH₂-2-C₆H₄OH More than 100,000 tons of tert-butyl phenols are produced annually (year: 2000) in this way, using isobutylene (CH₂=CMe₂) as the alkylating agent. Especially important is 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 esters, being prone to hydrolysis. Phenols are 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 quinones 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. :600px|Oxone phenol dearomatization Phenols are oxidized to hydroquinones 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 cresols. 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 quinones * 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 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|doi-access=free }}</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 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 |- |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 fruits |- |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|url-access=subscription }}</ref> {|align="center" class="wikitable" style="background-color:white;" |tyrosine|| one of the 20 standard amino acids |- |L-DOPA||dopamine prodrug used to treat Parkinson's disease |- |propofol||short-acting intravenous 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.<ref>{{Cite journal |last1=Ettinger |first1=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 |bibcode=1948AnaCh..20.1191E |issn=0003-2700|url-access=subscription }}</ref> It reacts with phenols to form indophenols, resulting in a color change.<ref>{{Cite journal |last=Gibbs |first=H.D. |date=1 April 1927 |title=PHENOL TESTS |journal=Journal of Biological Chemistry |language=en |volume=72 |issue=2 |pages=649–664 |doi=10.1016/S0021-9258(18)84338-1|bibcode=1927JBiCh..72..649G |doi-access=free }}</ref>

==References== <references />

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Category:Phenols Category:Functional groups Category:Disinfectants