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{{cite book | title = Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 (Blue Book) | publisher = 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).}}

| OtherNames = Methyl phenyl ether
Phenoxymethane

| SystematicName = Methoxybenzene

| 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/cm³

| MeltingPtC = −37

| BoilingPtC = 154

| SolubleOther = Insoluble

| MagSus = {{val|-72.79e-6|u=cm³/mol}}

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| 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)

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| Section6 =

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Anisole, or methoxybenzene, is an organic compound with the formula {{chem2|CH3OC6H5}}. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is mainly made synthetically and is a 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.{{March6th}}

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 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 cloud of the ring as a mesomeric electron donor, more so than as an inductive electron withdrawing group despite the electronegativity of the oxygen. Stated more quantitatively, the 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}}.{{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}}

Also indicating an electron-rich ring, anisole readily forms π-complexes with metal carbonyls, e.g. {{chem2|Cr(\h{6}anisole)(CO)3}}.{{cite journal|journal=Topics Organomet Chem.|year=2004| volume=7|pages=3–20|doi=10.1007/b94489|title=Synthesis of Transition Metal η⁶-Arene Complexes|author=E. Peter Kündig|series=Topics in Organometallic Chemistry|isbn=978-3-540-01604-5}}

The ether linkage is highly stable, but the methyl group can be removed with strong acids, such as hydroiodic acid or boron trichloride:{{rp|pp=565-566}}

:{{chem2|CH3OC6H5 + HI -> HOC6H5 + CH3I}}

Birch reduction of anisole gives 1-methoxycyclohexa-1,4-diene.{{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}}

Synthesis

Anisole was first synthesized in 1841 by Auguste Cahours by barium anisate decarboxylation while heating p-anisic acid he made earlier from the anise essence with barium oxide:{{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 }}{{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}}

It can be prepared by the Williamson ether synthesis from sodium phenoxide and dimethyl sulfate or methyl chloride:{{OrgSynth | author = G. S. Hiers and F. D. Hager | volume = 9 | page = 12 | title = Anisole | year = 1929|doi=10.15227/orgsyn.009.0012}}

: {{chem2|2 C6H5O- Na+ + (CH3O)2SO2 -> 2 C6H5OCH3 + Na2SO4}}

Applications

Anisole is a precursor to perfumes, insect pheromones, and pharmaceuticals.{{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}} For example, synthetic anethole is prepared from anisole.

Safety

Anisole is relatively nontoxic with an {{LD50}} of 3700 mg/kg in rats.[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 }} Its main hazard is its flammability.

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.{{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}}