1-Tetralone

{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 361749842 | Reference = | ImageFile =1-tetralone.png | ImageSize = 120 | ImageAlt = Structural formula of 1-tetralone | ImageFile1 = 1-Tetralone 3D ball.png | ImageSize1 = 155 | ImageAlt1 = Ball-and-stick model of the 1-tetralone molecule | PIN = 3,4-Dihydronaphthalen-1(2''H'')-one | OtherNames = α-Tetralone; 1-Tetralone |Section1={{Chembox Identifiers | CASNo_Ref = {{cascite|correct|CAS}} | CASNo =529-34-0 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 6VT52A15HY | PubChem =10724 | SMILES =C1CC2=CC=CC=C2C(=O)C1 | ChEMBL = 193373 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 10273 | EC_number = 208-460-6 | InChI = 1/C10H10O/c11-10-7-3-5-8-4-1-2-6-9(8)10/h1-2,4,6H,3,5,7H2 | InChIKey = XHLHPRDBBAGVEG-UHFFFAOYAD | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C10H10O/c11-10-7-3-5-8-4-1-2-6-9(8)10/h1-2,4,6H,3,5,7H2 | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = XHLHPRDBBAGVEG-UHFFFAOYSA-N }} |Section2={{Chembox Properties | C=10 | H=10 | O=1 | Appearance = colorless liquid | Density = 1.099 g·cm⁻³ (25 °C)<ref name="Sigma" >{{Sigma-Aldrich|id=T19003|name=α-Tetralon |accessdate=25. November 2017}}</ref> | MeltingPt = 2–7&nbsp;°C<ref name="Sigma" /> | BoilingPt = 255–257&nbsp;°C<ref name="CRC" >{{citation|surname1=William M. Haynes|title=CRC Handbook of Chemistry and Physics, 97th Edition|publisher=CRC Press|location=Boca Raton, FL, U.S.A.|pages=3–504|isbn=978-1-4987-5429-3|date= 2016 }}</ref><br />113–116&nbsp;°C (8 hPa)<ref name="Sigma" /> | Solubility = insoluble<ref name="TCI" >{{Cite web|url=http://www.tcichemicals.com/eshop/de/de/commodity/T0134|title=alpha-Tetralone 529-34-0 {{!}} TCI Deutschland GmbH|website=www.tcichemicals.com|language=de|access-date=2017-12-17}}</ref> | SolubleOther = soluble in organic solvents | Solvent = | VaporPressure = 2.7 Pa (20&nbsp;°C)<ref name="TCI" /> | RefractIndex = 1.5672 }} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = | GHS_ref=<ref>{{cite web |title=1-Tetralone |url=https://pubchem.ncbi.nlm.nih.gov/compound/10724#section=Safety-and-Hazards |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref> | GHSPictograms = {{GHS07}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|302}} | PPhrases = {{P-phrases|264|270|301+317|330|501}} }} }}

'''1-Tetralone''' is a bicyclic aromatic hydrocarbon and a ketone. In terms of its structure, it can also be regarded as benzo-fused cyclohexanone. It is a colorless oil with a faint odor.<ref name="Snyder"/> It is used as starting material for agricultural and pharmaceutical agents. The carbon skeleton of 1-tetralone is found in natural products such as Aristelegone A (4,7-dimethyl-6-methoxy-1-tetralone) from the family of Aristolochiaceae used in traditional Chinese medicine.<ref>{{citation|author1=P.-C. Kuo|author2= Y.-C. Li|author3= T.-S. Wu|periodical=EJTCM|title=Chemical constituents and pharmacology of the Aristolochia species|volume=2|issue=4|pages=249–266|date= 2012|doi=10.1016/S2225-4110(16)30111-0 |pmid= 24716140|pmc= 3942903|doi-access=free}}</ref>

== Preparation == ===By oxidation of 1,2,3,4-tetrahydronaphthalene=== As already described in 1933 by Heinrich Hock, 1,2,3,4-tetrahydronaphthalene tends to autoxidize and gradually forms the 1-hydroperoxide with atmospheric oxygen.<ref>{{citation|author1=H. Hock|author2= W. Susemihl|periodical=Ber. Dtsch. Chem. Ges.|title=Autoxydation von Kohlenwasserstoffen: Über ein durch Autoxydation erhaltenes Tetrahydro-naphthalin-peroxyd (I. Mitteil.)|volume=66|issue=1|pages=61–68|date= 1933|language=German|doi=10.1002/cber.19330660113 }}</ref> The heavy metal ion catalyzed air oxidation of 1,2,3,4-tetrahydronaphthalene with Cr³⁺<ref>{{citation|author1=S. Bhattacharjee|author2= Y.-R. Lee|author3= W.-S. Ahn|periodical=Korean J. Chem. Eng.|title=Oxidation of tetraline to 1-tetralone over CrAPO-5|volume=34|issue=3|pages=701–705|date= 2017|language=German|doi=10.1007/s11814-016-0310-4 |s2cid= 100124813}}</ref> or Cu²⁺ in the liquid phase leads via the hydroperoxide to a mixture of the intermediate 1-tetralol and the final product 1-tetralone.<ref>{{Cite patent|country = US|number =4473711 |title=Liquid-phase process for oxidation of tetralin |pubdate =1984-09-25 |fdate =1981-08-06 |invent1 =R.W. Coon | assign=Union Carbide Corp.}}</ref>

300px|center|Oxidation von Tetraloin zu 1-Tetralon

The boiling points of the main component 1-tetralone (255-257&nbsp;°C) and the minor component 1-tetralol (255&nbsp;°C)<ref name="CRC" /> are virtually identical, the latter is therefore removed by a chemical reaction.<ref name="Bader" >{{cite journal|author=C.E. Olson, A.R. Bader |title=α-Tetralone |year=1955 |volume=35 |page=95 |journal=Org. Synth. |doi=10.15227/orgsyn.035.0095}}</ref>

===By Friedel-Crafts reactions=== The starting compound 4-phenylbutanoic acid is accessible from 3-benzoylpropanoic acid via catalytic hydrogenation, using a palladium contact catalyst.<ref name="Snyder">{{cite journal|doi=10.15227/orgsyn.020.0094|author=H.R. Snyder, F.X. Werber |title=α-Tetralone |year=1940 |volume=20 |page=94|journal=Org. Synth.}}</ref> 3-Benzoylpropanoic acid<ref>{{cite journal|author=L. F. Somerville, C. F. H. Allen |journal=Org. Synth.|title=β-Benzoylpropionic acid |year=1933 |volume=13 |page=12 |doi=10.15227/orgsyn.013.0012}}</ref> itself can be obtained by a Haworth reaction (a variant of the Friedel-Crafts reaction) from benzene and succinic anhydride.

The intramolecular cyclization of 4-phenylbutanoic acid to 1-tetralone is catalyzed by polyphosphoric acid<ref name="Snyder" /> and methanesulfonic acid.<ref>{{citation|author1=V. Premasagar|author2= V.A. Palaniswamy|author3= E.J. Eisenbraun|periodical=J. Org. Chem.|title=Methanesulfonic acid catalyzed cyclization of 3-arylpropanoic and 4-arylbutanoic acids to 1-indanones and 1-tetralones|volume=46|issue=14|pages=2974–2976|date= 1981|doi=10.1021/jo00325a028 }}</ref>350px|center|Cyclisierung von 4-Phenylbuttersäure zu 1-Tetralon

It has been described as a teaching experiment for chemistry lessons.<ref>{{citation|author1=M.S. Holden|author2= R.D. Crouch|author3= K.A. Barker|periodical=J. Chem. Educ.|title=Formation of α-tetralone by intramolecular Friedel-Crafts acylation|volume=82|issue=6|pages=934–935|date= 2005|doi=10.1021/ed082p934|bibcode= 2005JChEd..82..934H}}</ref> 4-Phenylbutanoic acid can also be quantitatively converted into 1-tetralone by heating in the presence of a strong Lewis acid catalyst such as bismuth(III)bis(trifluoromethanesulfonyl)amide<ref>{{citation|author1=S. Antoniotti|author2= E. Dunach|periodical=Chem. Commun.|title=Facile preparation of metallic triflates and triflimidates by oxidative dissolution of metal powders|volume=8|issue= 8|pages=993–995|date= 2008|doi=10.1039/B717689A |pmid= 18283360}}</ref> [Bi(NTf₂)₃], which is relatively easily accessible.<ref name="Cui">{{citation|author1=D.-M. Cui|author2= M. Kawamura|author3= S. Shimada|author4= T. Hayashi|author5= M. Tanaka|periodical=Tetrahedron Lett.|title=Synthesis of 1-tetralones by intramolecular Friedel-Crafts reaction of 4-arylbutyric acids using Lewis acid catalysts|volume=44|issue=21|pages=4007–4010|date= 2003|doi=10.1016/S0040-4039(03)00855-4 }}</ref>

The use of the acid chloride and tin(IV) chloride (SnCl₄) allows significantly shorter reaction times than the Friedel-Crafts acylation with 4-phenylbutanoic acid.<ref name="Bader" />

500px|center|Synthese von 1-Tetralon über 4-Phenylbuttersäurechlorid

4-Phenylbutanoic acid chlorides with electron-donating groups can be cyclized to 1-tetralones under mild reaction conditions in yields greater than 90% using the strong hydrogen-bonding solvent hexafluoroisopropanol (HFIP).<ref>{{citation|author1=H. Motiwala|author2= R.H. Vekariya|author3= J. Aubé|periodical=Org. Lett.|title=Intramolecular Friedel-Crafts acylation reaction promoted by 1,1,1,3,3,3-hexafluoro-2-propanol|volume=17|issue= 21|pages=5484–5487|date= 2015|language=German|doi=10.1021/acs.orglett.5b02851 |pmid= 26496158}}</ref>

The AlCl₃-catalyzed acylation of benzene with γ-butyrolactone produces 1-tetralone.<ref name="Bader" />350px|center|Synthesis of 1-tetralone using butyrolactone.

==Reactions== 1-Tetralone can be reduced via a Birch reduction with lithium in liquid ammonia to 1,2,3,4-tetrahydronaphthalene.<ref>{{citation|author1=S.S. Hall|author2= S.D. Lipsky|author3= F.J. McEnroe|author4= A.P. Bartels|periodical=J. Org. Chem.|title=Lithium-ammonia Reduction of Aromatic Ketones to Aromatic Hydrocarbons|volume=38|issue=18|pages=2588–2591|date= 1971|doi=10.1021/jo00817a004 }}</ref> The keto group can also be reduced to a secondary alcohol giving 1-tetralol, when a modified process is applied, using the addition of aqueous ammonium chloride solution after evaporation of the ammonia.<ref>{{citation|author1=Z. Marcinow|author2= P.W. Rabideau|periodical=J. Org. Chem.|title=Metal-Ammonia Reduction of α-Tetralone. Competition Between Ring Reduction, Carbonyl Reduction, and Dimer Formation|volume=53|issue=9|pages=2117–2119|date= 1988|doi=10.1021/jo00244a054 }}</ref>

500px|center|Reaktionen von 1-Tetralon mit Li in Ammoniak

With calcium in liquid ammonia, 1-tetralone is reduced to 1-tetralol at −33&nbsp;°C in 81% yield.<ref>{{citation|author1=J.R. Hwu|author2= Y.S. Wein|author3= Y.-J. Leu|periodical=J. Org. Chem.|title=Calcium metal in liquid ammonia for selective reduction of organic compounds|volume=61|issue=4|pages=1493–1499|date= 1996|language=German|doi=10.1021/jo951219c }}</ref>

The methylene group in α-position to the keto group is particularly reactive and can be converted with formaldehyde (in the form of the trimeric trioxane) to 2-methylene-1-tetralone in the presence of the trifluoroacetic acid salt of ''N''-methylaniline with yields up to 91% .

500px|center|Synthese von 2-Methylen-1-tetralon aus 1-Tetralon

The 2-methylene ketone is stable at temperatures below −5&nbsp;°C, but fully polymerizes at room temperature within 12 hours.<ref>{{OrgSynth|Kurzcode=CV7P0332 |Autor=J.-L. Gras |title=Methylene ketones and aldehydes by simple, direct methylene transfer: 2-Methylene-1-oxo-1,2,3,4-tetrahydronaphthalene |Jahrgang=1981 |Volume=60 |Seiten=88 |ColVol=7 |ColVolSeiten=332 |doi=10.15227/orgsyn.060.0088}}</ref>

In the Pfitzinger reaction of 1-tetralone with isatin, a compound called tetrofan (3,4-dihydro-1,2-benzacridine-5-carboxylic acid) is formed.450px|center|Synthese von Tetrophan

The reactivity of the α-methylene group is also exploited in the reaction of 1-tetralone with methanol at 270-290&nbsp;°C, which produces via dehydrogenation and formation of the aromatic naphthalene ring system 2-methyl-1-naphthol in 66% yield.<ref>{{citation|author1=I. Yuranov|author2= L. Kiwi-Minsker|author3= A. Renken|periodical=Appl. Catal. A|title=One-step vapour-phase synthesis of 2-methyl-1-naphthol from 1-tetralone|volume=226|issue=1–2|pages=193–198|date= 2002|language=German|doi=10.1016/S0926-860X(01)00902-4 |url= http://infoscience.epfl.ch/record/84417}}</ref>

450px|center|Synthese von 2-Methyl-1-naphthol

The oxime of 1-tetralone reacts with acetic anhydride leading to aromatization of the cycloalkanone ring. The resulting N-(1-naphthyl)acetamide<ref>{{citation|author1=M.S. Newman|author2= W.M. Hung|periodical=J. Org. Chem.|title=An improved aromatization of α-tetralone oximes to N-(1-naphthyl)acetamides|volume=38|issue=23|pages=4073–4074|date= 1973|language=German|doi=10.1021/jo00987a029 }}</ref> has biological properties akin to those of 2-(1-Naphthyl)acetic acid as a synthetic auxin.

450px|center|Synthese von N-(1-Naphthyl)acetamid

The tertiary alcohol formed in the Grignard reaction of 1-tetralone with phenylmagnesium bromide reacts with acetic anhydride upon elimination of water to 1-phenyl-3,4-dihydronaphthalene, which is dehydrated with elemental sulfur in an overall yield of about 45% to 1-phenylnaphthalene.<ref>{{OrgSynth|Kurzcode=CV3P0729 |Autor=R. Weiss |title=1-Phenylnaphthalene |Jahrgang=1944 |Volume=24 |Seiten=84 |ColVol=3 |ColVolSeiten=729 |doi=10.15227/orgsyn.024.0084}}</ref>

350px|center|Synthese von 1-Phenylnaphthalin aus 1-Tetralon

The ruthenium(II)-catalyzed arylation of 1-tetralone using phenyl boronic acid neopentyl glycol ester gives 8-phenyl-1-tetralone in up to 86% yield.<ref>{{OrgSynth|Kurzcode=V87P0209 |Autor=K. Kitazawa, T. Kochi, F. Kakiuchi |title=Ruthenium-catalyzed arylation of ortho C-H bond in an aromatic with an arylboronate: 8-Phenyl-1-tetralone |Jahrgang=2009 |Volume=87 |Seiten=209–217 |ColVol=11 |ColVolSeiten=1210–1216 |doi=10.15227/orgsyn.087.0209}}</ref>

550px|center|Synthese von 8-Phenyl-1-tetralon aus 1-Tetralon

With 5-aminotetrazole and an aromatic aldehyde, 1-tetralone reacts in a multi-component reaction under microwave irradiation to form a four-membered heterocyclic ring system.<ref>{{citation|author1=G.P. Kantin|author2= M. Krasavin|periodical=Chem. Heterocycl. Compd.|title=Reaction of α-tetralone, 1''H''-tetrazol-5-amine, and aromatic aldehydes upon microwave irradiation – a convenient method for the synthesis of 5,6,7,12-tetrahydrobenzo[h]tetrazolo[5,1-b]quinazolines|volume=52|issue=11|pages=918–922|date= 2016|language=German|doi=10.1007/s10593-017-1985-0 |s2cid= 99144245}}</ref>

550px|center|Multikomponentenreaktion von 1-Tetralon mit Aminotetrazol und aromatischem Aldehyd

==Applications== By far the most important application of 1-tetralone is in the synthesis of 1-naphthol by aromatization, e.g. upon contact with platinum catalysts at 200 to 450&nbsp;°C.<ref>{{Cite patent|country = DE|number =2421745 |title=Verfahren zur Herstellung von α-Naphthol durch katalytische Dehydrierung von α-Tetralon |pubdate =1975-11-20 |fdate =1974-05-06 |invent1 =K. Kudo, T. Ohmae, A. Uno | assign =Sumitomo Chemical Co., Ltd.}}</ref>

300px|center|Synthese von 1-Naphthol aus 1-Tetralon

1-Naphthol is the starting material for the insecticides carbaryl and the beta-blockers propranolol.

A known application of 1-tetralone is in the synthesis of RAC-109 [17592-97-1] & RAC-421 [139085-58-8].<ref>{{cite journal | vauthors=((Castañer, J.)), ((Kolwas, J.)) | journal=Drugs of the Future | title=RAC-109 and RAC-421 | volume=7 | issue=7 | pages=489 | date= 1982 | url=http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1000241&p_IsPs=N | issn=0377-8282 | doi=10.1358/dof.1982.007.07.1000241| url-access=subscription }}</ref><ref name="pmid7205874">{{cite journal | vauthors = Tenthorey PA, Ronfeld RA, Feldman HS, Sandberg RV, McMaster PD, Smith ER | title = New antiarrhythmic agents. 4. 1'-(Aminoalkyl)-1,2,3,4-tetrahydronaphthalene-1-spiro-3'-pyrrolidine-2',5'-dione derivatives | journal = Journal of Medicinal Chemistry | volume = 24 | issue = 1 | pages = 47–53 | date = January 1981 | pmid = 7205874 | doi = 10.1021/jm00133a011 | url = }}</ref>

==Safety== Toxicological studies were dermally performed with rabbits, with an LD50 of 2192&nbsp;mg·kg⁻¹ body weight being observed.<ref name="Sigma" />

==References== {{Reflist}}

{{DEFAULTSORT:Tetralone, 1-}} Category:Tetralones