View source for Anisole

{{Short description|Organic compound (CH3OC6H5) also named methoxybenzene}}
{{chembox
| Watchedfields  = changed
| verifiedrevid  = 443391776
| Name           = 
| ImageFile      = 
| ImageFileL1    = Anisol.svg
| ImageSizeL1    = 80px
| ImageFileR1    = Anisole-3D-balls.png
| ImageSizeR1    = 100px
| ImageFile2     = Anisole.jpg
| ImageSize2     = 220px
| PIN            = Anisole<ref name=iupac2013>{{cite book | title =  Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = [[Royal Society of Chemistry|The Royal Society of Chemistry]] | date = 2014 | location = Cambridge | pages = 702–703 | doi = 10.1039/9781849733069-00648 | isbn = 978-0-85404-182-4 | quote = Anisole, {{chem2|C6H5\sO\sCH3}}, is the only name in the class of ethers which is retained both as a preferred IUPAC name and for use in general nomenclature. For preferred IUPAC names, no substitution is allowed; for general nomenclature substitution is allowed on the ring and on the side chain under certain conditions (see P-34.1.1.4).}}</ref>
| OtherNames     = Methyl phenyl ether<ref name=iupac2013/><br />Phenoxymethane
| SystematicName      = Methoxybenzene<ref name=iupac2013/>
| Section1       = {{Chembox Identifiers
|   ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 7238
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = B3W693GAZH
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C01403
| InChI = 1/C7H8O/c1-8-7-5-3-2-4-6-7/h2-6H,1H3
| InChIKey = RDOXTESZEPMUJZ-UHFFFAOYAP
| SMILES = COc1ccccc1
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 278024
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H8O/c1-8-7-5-3-2-4-6-7/h2-6H,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RDOXTESZEPMUJZ-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 100-66-3
|   ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16579
| PubChem = 7519
| EC_number = 202-876-1
| RTECS = BZ8050000
| UNNumber = 2222
| Gmelin = 2964
| Beilstein = 506892
}}
| Section2       = {{Chembox Properties
|   C=7|H=8|O=1
|   Appearance = Colorless liquid
|   Density = 0.995 g/cm<sup>3</sup>
|   MeltingPtC = −37
|   BoilingPtC = 154
|   SolubleOther = Insoluble
| MagSus = {{val|-72.79e-6|u=cm<sup>3</sup>/mol}}
  }}
| Section3       = 
| Section4       = 
| Section5       = {{Chembox Hazards
| NFPA-H = 1
| NFPA-F = 2
| NFPA-R =0
| GHSPictograms = {{GHS02}}{{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|226|315|319}}
| PPhrases = {{P-phrases|210|233|240|241|242|243|264|280|302+352|303+361+353|305+351+338|321|332+313|337+313|362|370+378|403+235|501}}
|  LD50 = 3700 mg/kg (rat, oral)
  }}
| Section6       = 
}}

'''Anisole''', or '''methoxybenzene''', is an [[organic compound]] with the [[chemical formula|formula]] {{chem2|CH3OC6H5}}.  It is a colorless [[liquid]] with a [[odor|smell]] reminiscent of [[anise]] seed, and in fact many of its derivatives are found in natural and artificial [[fragrance]]s. The compound is mainly made synthetically and is a [[organic synthesis|precursor]] to other synthetic compounds. Structurally, it is an [[ether]] ({{chem2|\sO\s}}) with a [[methyl]] ({{chem2|\sCH3}}) and [[phenyl]] ({{chem2|\sC6H5}}) group attached.  Anisole is a standard reagent of both practical and pedagogical value.<ref>{{March6th}}</ref>

==Reactivity==
Anisole undergoes [[electrophilic aromatic substitution]] reaction at a faster speed than [[benzene]], which in turn reacts more quickly than [[nitrobenzene]]. The methoxy group is an [[Arene substitution patterns|ortho/para]] directing group, which means that electrophilic substitution preferentially occurs at these three sites.  The enhanced [[nucleophilicity]] of anisole vs. [[benzene]] reflects the influence of the [[methoxy]] group, which renders the ring more electron-rich. The methoxy group strongly affects the [[pi bond|pi cloud]] of the ring as a [[mesomeric]] electron donor, more so than as an [[inductive effect|inductive]] electron withdrawing group despite the  [[electronegativity]] of the [[oxygen]].  Stated more quantitatively, the [[Hammett equation|Hammett constant]] for ''para''-substitution of anisole is –0.27.

Illustrative of its [[nucleophilicity]], anisole reacts with [[acetic anhydride]] to give {{nobr|[[4-methoxyacetophenone]]:}}
:{{chem2|CH3OC6H5  +  (CH3CO)2O   ->  CH3OC6H4C(O)CH3  +  CH3CO2H}}
Unlike most acetophenones, but reflecting the influence of the methoxy group, methoxyacetophenone undergoes a second [[acetylation]].  Many related reactions have been demonstrated.  For example, [[phosphorus pentasulfide]] ({{chem2|P4S10}}) converts anisole to [[Lawesson's reagent]], {{chem2|[(CH3OC6H4)PS2]2}}.<ref>{{cite journal |doi=10.15227/orgsyn.062.0158|title=Thiation with 2,4-Bis(4-Methoxyphenyl)-1,3,2,4-Dithiadiphosphetane 2,4-Disulfide: ''N''-Methylthiopyrrolidone|journal=Organic Syntheses|year=1984|volume=62|page=158 |author=I. Thomsen |author2=K. Clausen |author3=S. Scheibye |author4=S.-O. Lawesson}}</ref>

Also indicating an electron-rich ring, anisole readily forms π-complexes with [[metal carbonyl]]s, e.g. {{chem2|Cr(\h{6}anisole)(CO)3}}.<ref name=PK>{{cite journal|journal=Topics Organomet Chem.|year=2004| volume=7|pages=3–20|doi=10.1007/b94489|title=Synthesis of Transition Metal ''η''<sup>6</sup>-Arene Complexes|author=E. Peter Kündig|series=Topics in Organometallic Chemistry|isbn=978-3-540-01604-5}}</ref>

The ether linkage is highly stable, but the [[methyl group]] can be removed with strong acids, such as [[hydroiodic acid]] or [[boron trichloride]]:<ref name=Ullmann />{{rp|pp=565-566}}
:{{chem2|CH3OC6H5 + [[hydriodic acid|HI]] -> [[phenol|HOC6H5]] + [[iodomethane|CH3I]]}}

[[Birch reduction]] of anisole gives 1-methoxycyclohexa-1,4-diene.<ref>{{cite journal |doi=10.15227/orgsyn.057.0107|title=Tricarbonyl[(2,3,4,5-''η'')-2,4-Cyclohexadien-1-one]Iron and Tricarbonyl[(1,2,3,4,5-''η'')-2-Methoxy-2,4-Cyclohexadien-1-yl]Iron(1+) Hexafluorophosphate(1−) from Anisole|journal=Organic Syntheses|year=1977|volume=57|page=107|author=A. J. Birch and K. B. Chamberlain}}</ref>

==Synthesis==
Anisole was first synthesized in 1841 by [[Auguste André Thomas Cahours|Auguste Cahours]] by barium anisate [[decarboxylation]] while heating [[P-Anisic acid|p-anisic acid]] he made earlier from the [[anise]] [[essence]] with [[barium oxide]]:<ref>{{Cite journal |last=Wisniak |first=Jaime |date=2013-10-01 |title=Auguste André Thomas Cahours |url=https://www.sciencedirect.com/science/article/pii/S0187893X1372500X |journal=Educación Química |volume=24 |issue=4 |pages=451–460 |doi=10.1016/S0187-893X(13)72500-X |issn=0187-893X|doi-access=free }}</ref><ref>{{Cite book |last=Crochard (París) |url=https://books.google.com/books?id=hChCAAAAcAAJ&pg=PA294 |title=Annales de chimie et de physique |last2=Arago |first2=François |last3=Gay-Lussac |first3=Joseph Louis |date=1841 |publisher=Chez Crochard |language=fr}}</ref>

{{chem2|2 CH3OC6H4COOH + BaO → (CH3OC6H4COO)2Ba + H2O}}

{{chem2|(CH3OC6H4COO)2Ba → 2 CH3OC6H5 + BaCO3}} 

It can be prepared by the [[Williamson ether synthesis]] from [[sodium phenoxide]] and [[dimethyl sulfate]] or [[Chloromethane|methyl chloride]]:<ref>{{OrgSynth | author =  G. S. Hiers and F. D. Hager | volume = 9 | page = 12 | title = Anisole | year = 1929|doi=10.15227/orgsyn.009.0012}}</ref><ref name="Ullmann" />
: {{chem2|2 C6H5O- Na+  + (CH3O)2SO2 ->   2 C6H5OCH3  +  Na2SO4}}

==Applications==
Anisole is a precursor to [[perfume]]s, insect [[pheromone]]s, and [[pharmaceuticals]].<ref name=Ullmann>{{Ullmann |author=Helmut Fiege |author2=Heinz-Werner Voges |author3=Toshikazu Hamamoto |author4=Sumio Umemura |author5=Tadao Iwata |author6=Hisaya Miki |author7=Yasuhiro Fujita |author8=Hans-Josef Buysch |author9=Dorothea Garbe |author10=Wilfried Paulus |title=Phenol Derivatives|doi=10.1002/14356007.a19_313}}</ref> For example, synthetic [[anethole]] is prepared from anisole.

==Safety==
Anisole is relatively nontoxic with an {{LD50}} of 3700&nbsp;mg/kg in rats.<ref name=MSDS>[http://www.seas.upenn.edu/~nanofab/chemicals/MSDS_Solvent_Anisole.pdf MSDS] {{webarchive |url=https://web.archive.org/web/20100701184343/http://www.seas.upenn.edu/~nanofab/chemicals/MSDS_Solvent_Anisole.pdf |date=July 1, 2010 }}</ref>  Its main hazard is its flammability.<ref name=MSDS/>

== Popular culture ==
In the board game ''[[Scrabble]]'', the word "anisole" is the 39th-most-likely word (out of over 25,000 possibilities) for a "bingo"/"bonus", i.e. the deployment of all seven letters in one's own hand simultaneously.<ref>{{Cite web |title=Fun with analytics: Probabilities and Scrabble |url=https://www.illumine8.com/blog/fun-with-analytics-probabilities-and-scrabble |access-date=2023-12-08 |website=www.illumine8.com |language=en-us}}</ref>

== See also ==
* [[Anethole]]
* [[Bromoanisole]]
* [[Butylated hydroxyanisole]]
* [[Ether]]
* [[Ethyl phenyl ether]]
* [[Phenol]]
* [[2,4,6-Trichloroanisole]] (cork taint)

==References==
<references />

== External links ==
* {{ICSC|1014|10}}
* [http://www.pherobase.com/database/compound/compounds-detail-anisole.php Pherobase] pheromone database entry

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[[Category:Flavors]]
[[Category:Pheromones]]
[[Category:Methoxy compounds]]
[[Category:Phenyl compounds]]