Editing Benzophenone

{{about|the parent chemical|the sunscreening-agent derivatives|benzophenone-n}}
{{use dmy dates|date=August 2024}}
{{chembox
|Watchedfields = changed
|verifiedrevid = 443416927
|ImageFile = Benzophenon.svg
|ImageClass = skin-invert
|ImageFile1 = Benzophenone-from-xtal-stable-phase-1968-3D-balls.png
|ImageFile2 = Benzophenone-from-xtal-stable-phase-1968-3D-vdW.png
|ImageFile3 = Benzophenone vial.jpg
|ImageSize3 = 220px
|PIN = Diphenylmethanone<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 = 723–724, 726 | doi = 10.1039/9781849733069-FP001 | isbn = 978-0-85404-182-4| chapter = Front Matter }}</ref>
|OtherNames = Benzophenone<ref name=iupac2013 />
<br />Diphenyl ketone<br />Benzoylbenzene<br />Benzoylphenyl
|Section1={{Chembox Identifiers
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 701M4TTV9O
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C06354
|Beilstein = 1238185
|Gmelin = 4256
|EC_number = 204-337-6
|RTECS = DI9950000
|UNNumber = 1224
|InChIKey = RWCCWEUUXYIKHB-UHFFFAOYAX
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 90039
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C13H10O/c14-13(11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = RWCCWEUUXYIKHB-UHFFFAOYSA-N
|CASNo_Ref = {{cascite|correct|CAS}}
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID=2991
|CASNo = 119-61-9
|PubChem = 3102
|DrugBank_Ref = {{drugbankcite|correct|drugbank}}
|DrugBank = DB01878
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 41308
|SMILES = O=C(c1ccccc1)c2ccccc2
|InChI = 1/C13H10O/c14-13(11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H
}}
|Section2={{Chembox Properties
|C=13 | H=10 | O=1
|Appearance = White solid
|Odor = [[Geranium]]-like<ref name=Merck>{{cite book|title=Merck Index|edition=11th|page=1108|title-link=Merck Index}}</ref>
|Density = 1.11 g/cm<sup>3</sup><ref name=Merck/>
|MeltingPtC = 48.5
|MeltingPt_ref = <ref name=Merck/>
|MagSus = −109.6·10<sup>−6</sup> cm<sup>3</sup>/mol
|BoilingPtC = 305.4
|BoilingPt_ref = <ref name=Merck/>
|Solubility = Insoluble<ref name=Merck/>
|Solubility1 = 1 g/7.5 mL in [[ethanol]]<ref name=Merck/><br/>1 g/6 mL in [[diethyl ether]].<ref name=Merck/> Alkanes + [[tetrachloromethane]]: better with increasing tetrachloromethane content<ref>{{cite journal|last1=Azizian|first1=Saeid|last2=Haydarpour|first2=Afshin|title=Solubility of Benzophenone in Binary Alkane + Carbon Tetrachloride Solvent Mixtures|journal=Journal of Chemical & Engineering Data|date=November 2003|volume=48|issue=6|pages=1476–1478|doi=10.1021/je0340497}}</ref>
|Solvent1 = organic solvents
}}
|Section3={{Chembox Hazards
|MainHazards = Harmful (XN)
|FlashPtC = 110
|NFPA-H = 1
|NFPA-F = 1
|NFPA-R = 0
|ExternalSDS = [https://www.sigmaaldrich.com/US/en/sds/mm/8.01801?userType=anonymous External MSDS by Sigma-Aldritch]
|GHSPictograms = {{GHS08}}{{GHS09}}
|GHSSignalWord = Warning
|HPhrases = {{H-phrases|373|411}}
|PPhrases = {{P-phrases|260|273|314|391|501}}
}}
}}

'''Benzophenone''' is a naturally occurring [[organic compound]] with the formula (C<sub>6</sub>H<sub>5</sub>)<sub>2</sub>CO, generally abbreviated [[phenyl|Ph]]<sub>2</sub>CO. Benzophenone has been found in some fungi, fruits and plants, including grapes.<ref>{{cite journal |last1=Surana |first1=Khemchand |last2=Chaudhary |first2=Bharatkumar |last3=Diwaker |first3=Monika |last4=Sharma |first4=Satyasheel |title=Benzophenone: a ubiquitous scaffold in medicinal chemistry |journal=MedChemComm |date=2018 |volume=9 |issue=11 |pages=1803–1817 |doi=10.1039/C8MD00300A |pmid=30542530 |language=en |issn=2040-2503|pmc=6238883 }}</ref> It is a white solid with a low melting point and rose-like odor<ref name="acs">{{cite web |title=Molecule of the Week Archive: Benzophenone |url=https://www.acs.org/molecule-of-the-week/archive/b/benzophenone.html?cid=home_motw |publisher=American Chemical Society |access-date=20 May 2024 |date=March 11, 2024}}</ref> that is soluble in organic solvents. Benzophenone is the simplest diaromatic [[ketone]]. It is a widely used [[Building block (chemistry)|building block]] in organic chemistry, being the parent diarylketone.{{cn|date=August 2024}}

==History==
[[Carl Graebe]] of the [[University of Königsberg]], in an early literature report from 1874, described working with benzophenone.<ref name="acs"/>
==Uses==
Benzophenone can be used as a [[Photoinitiator|photo initiator]] in [[ultraviolet]] (UV)-curing applications<ref>{{cite journal|title=Patterning dewetting in thin polymer films by spatially directed photocrosslinking|author1=Carroll, G.T. |author2=Turro, N.J. |author3=Koberstein, J.T. |journal=Journal of Colloid and Interface Science|year=2010|volume=351|issue=2|pages=556–560|doi=10.1016/j.jcis.2010.07.070|pmid=20728089 |bibcode=2010JCIS..351..556C }}</ref> such as inks, imaging, and clear coatings in the [[printing]] industry. Benzophenone prevents UV light from damaging scents and colors in products such as perfumes and soaps.

Benzophenone can also be added to plastic packaging as a UV blocker to prevent photo-degradation of the packaging polymers or its contents. Its use allows manufacturers to package the product in clear glass or plastic (such as a [[PETE]] water bottle).<ref>{{cite web|last1=Dornath |first1=Paul John |title=Analysis of Chemical Leaching from Common Consumer Plastic Bottles Under High Stress Conditions |url=https://ir.library.oregonstate.edu/xmlui/bitstream/handle/1957/17627/Dornath%20thesis.pdf?sequence=1 |access-date=26 February 2015 |page=32 |date=2010 |url-status=dead |archive-url=https://web.archive.org/web/20150226053029/https://ir.library.oregonstate.edu/xmlui/bitstream/handle/1957/17627/Dornath%20thesis.pdf?sequence=1 |archive-date=26 February 2015}}</ref> Without it, opaque or dark packaging would be required.

In biological applications, benzophenones have been used extensively as photophysical probes to identify and map peptide–protein interactions.<ref>{{cite journal|last=Dorman|first=Gyorgy|author2=Prestwich, Glenn D.|title=Benzophenone Photophores in Biochemistry|journal=Biochemistry|date=1 May 1994|volume=33|issue=19|pages=5661–5673|doi=10.1021/bi00185a001|pmid=8180191}}</ref>

Benzophenone is used as an additive in flavorings or perfumes for "sweet-woody-geranium-like notes".<ref>{{Cite book|title=Perfume And Flavor Chemicals: (Aroma Chemicals)|last=Arctander|first=Steffen}}</ref>

==Synthesis==
Benzophenone is produced by the copper-catalyzed oxidation of [[diphenylmethane]] with air.<ref name="Ull">{{Ullmann|first1=Hardo |last1=Siegel |first2=Manfred |last2=Eggersdorfer |title=Ketones |doi=10.1002/14356007.a15_077}}</ref>

A laboratory route involves the reaction of benzene with [[carbon tetrachloride]] followed by hydrolysis of the resulting [[diphenyldichloromethane]].<ref>{{OrgSynth | author = Marvel, C. S. |author2=Sperry, W. M. | title = Benzophenone | prep = cv1p0095 | collvol = 1 | collvolpages = 95 | year = 1941}}</ref> It can also be prepared by [[Friedel–Crafts acylation]] of [[benzene]] with [[benzoyl chloride]] in the presence of a [[Lewis acid]] (e.g. [[aluminium chloride]]) catalyst: since benzoyl chloride can itself be produced by the reaction of benzene with [[phosgene]] the first synthesis proceeded directly from those materials.<ref>{{cite journal |doi=10.1039/CA8783400019 |doi-access=free |title=Synthesis of benzoic acid and benzophenone |journal=Journal of the Chemical Society, Abstracts |year=1878 |volume=34 |pages=69–70 }}</ref>

Another route of synthesis is through a palladium(II)/oxometalate catalyst. This converts an alcohol to a ketone with two groups on each side.<ref>{{cite journal|last1=Dornan |first1=L. |last2=Muldoon |first2=M. |title=A highly efficient palladium(II)/polyoxometalate catalyst system for aerobic oxidation of alcohols |journal=Catalysis Science & Technology |date=2015 |volume=5 |issue=3 |pages=1428–1432 |doi=10.1039/c4cy01632g}}</ref>

Another, less well-known reaction to produce benzophenone is the [[pyrolysis]] of anhydrous calcium benzoate.<ref>{{cite journal|doi=10.1021/jo50015a003 | volume=18 | issue=9 | title=The Mechanism of the Ketonic Pyrolysis of Calcium Carboxylates | journal=The Journal of Organic Chemistry | pages=1079–1086 | last1 = Lee | first1 = C. C.| year=1953}}</ref>

==Organic chemistry==
[[File:Haller-Bauer reaction.png|class=skin-invert-image|thumb|500px|left|The Haller–Bauer reaction occurs between a ''non-enolizable'' ketone and a strong amide base. In this prototypical example involving benzophenone, the tetrahedral intermediate expels phenyl anion to give benzamide and benzene as the organic products.]]
Benzophenone is a common [[photosensitizer]] in [[photochemistry]]. It [[Intersystem crossing|crosses]] from the S<sub>1</sub> state into the [[Spin triplet|triplet]] state with nearly 100% yield. The resulting diradical will abstract a hydrogen atom from a suitable [[hydrogen donor]] to form a [[ketyl]] [[Radical (chemistry)|radical]].

===Radical anion<span class="anchor" id="Benzophenone radical anion"></span>===
{{See also|Air-free technique}}
[[File:Making benzophenone radical anion.webm|left|thumb|Addition of a solution of benzophenone in [[Tetrahydrofuran|THF]] to a vial containing THF, sodium metal, and a stir bar, yielding the deep blue benzophenone anion radical. Playback speed 4x original recording. Notice that the stirbar is not Teflon-coated, which would be attacked by the ketyl.]]
[[File:Solvent pot.JPG|thumb|left|upright|A solvent pot containing [[dibutyl ether]] solution of sodium benzophenone ketyl, which gives it its purple color.]]

Alkali metals reduce benzophenone to the deeply blue colored [[Radical ion|radical anion]], diphenylketyl:<ref name=":0">{{Cite journal|title = Chemical Redox Agents for Organometallic Chemistry|last1 = Connelly|first1 = Neil|date = March 28, 1996|journal = Chemical Reviews|doi = 10.1021/cr940053x|last2 = Geiger|first2 = William|pmid=11848774|volume=96|issue=2|pages=877–910}}</ref>
:M + Ph<sub>2</sub>CO → M<sup>+</sup>Ph<sub>2</sub>CO<sup>•−</sup>

Generally sodium is used as the alkali metal. Sodium-benzophenone ketyl is used in the purification of organic solvents, particularly ethers, because it reacts with water and oxygen to give non-volatile products.<ref>{{cite book |last1=Armarego |first1=W. L. F. |title=Purification of laboratory chemicals |last2=Chai |first2=C. |publisher=Butterworth-Heinemann |year=2003 |isbn=978-0-7506-7571-0 |location=Oxford}}</ref><ref>{{cite book |last1=Harwood |first1=L. M. |url=https://archive.org/details/experimentalorga0002harw |title=Experimental Organic Chemistry: Standard and Microscale |last2=Moody |first2=C. J. |last3=Percy |first3=J. M. |publisher=Blackwell Science |year=1999 |isbn=978-0-632-04819-9 |location=Oxford |url-access=registration}}</ref> Adsorbents such as alumina, silica gel, and especially [[molecular sieves]] are superior and far safer.<ref>{{cite journal|last1=Williams |first1=D. B. G. |last2=Lawton |first2=M. |title=Drying of Organic Solvents: Quantitative Evaluation of the Efficiency of Several Desiccants |journal=The Journal of Organic Chemistry |date=2010 |volume=75 |issue=24 |pages=8351–4 |doi= 10.1021/jo101589h |pmid=20945830|s2cid=17801540 }}</ref> The sodium-benzophenone method is common since it gives a visual indication that water, oxygen, and peroxides are absent from the solvent. Large scale purification may be more economical using devices which utilize adsorbents such as the aforementioned alumina or molecular sieves.<ref>{{Cite journal |last1=Simas |first1=Alessandro B. C. |last2=Pereira |first2=Vera L. P. |last3=Barreto Jr. |first3=Cleber B. |last4=Sales |first4=Daniel L. de |last5=Carvalho |first5=Leandro L. de |date=2009 |title=An expeditious and consistent procedure for tetrahydrofuran (THF) drying and deoxygenation by the still apparatus |journal=Química Nova |language=en |volume=32 |issue=9 |pages=2473–2475 |doi=10.1590/S0100-40422009000900042 |issn=0100-4042|doi-access=free }}</ref> The ketyl is soluble in the organic solvent being dried, which leads to faster purification. In comparison, sodium is insoluble, and its heterogeneous reaction is much slower. When excess alkali metal is present a second reduction may occur, resulting in a color transformation from deep blue to purple:<ref name=":0" />
:M  +  M<sup>+</sup>Ph<sub>2</sub>CO<sup>•−</sup>   →   (M<sup>+</sup>)<sub>2</sub>(Ph<sub>2</sub>CO)<sup>2−</sup>

==Commercially significant derivatives and analogues==
There are over 300 natural benzophenones, with great structural diversity and biological activities. They are being investigated as potential sources of new drugs. <ref>{{Cite journal|last1=Wu|first1=Shi-Biao|last2=Long|first2=Chunlin|last3=Kennelly|first3=Edward J.|date=2014|title=Structural diversity and bioactivities of natural benzophenones|url=http://xlink.rsc.org/?DOI=C4NP00027G|journal=Nat. Prod. Rep.|language=en|volume=31|issue=9|pages=1158–1174|doi=10.1039/C4NP00027G|pmid=24972079|issn=0265-0568|url-access=subscription}}</ref>   [[Substitution (chemistry)|Substituted]] benzophenones such as [[oxybenzone]] and [[dioxybenzone]] are used in many [[sunscreen]]s. The use of benzophenone-derivatives which structurally resemble a strong [[photosensitizer]] has been criticized (see [[sunscreen controversy]]).

[[Michler's ketone]] has [[aniline|dimethylamino]] [[substituent]]s at each [[aromatic para position|''para'' position]]. The high-strength polymer [[PEEK]] is prepared from derivatives of benzophenone.

[[2-Amino-5-chlorobenzophenone]] is used in the synthesis of [[Benzodiazepine|benzodiazepines]].<ref>{{Cite journal |last1=Massah |first1=Ahmad R. |last2=Gharaghani |first2=Sajjad |last3=Lordejani |first3=Hamid Ardeshiri |last4=Asakere |first4=Nahad |date=2016-08-01 |title=New and mild method for the synthesis of alprazolam and diazepam and computational study of their binding mode to GABAA receptor |url=https://doi.org/10.1007/s00044-016-1585-z |journal=Medicinal Chemistry Research |language=en |volume=25 |issue=8 |pages=1538–1550 |doi=10.1007/s00044-016-1585-z |issn=1554-8120|url-access=subscription }}</ref>

==Safety==
It is considered "essentially nontoxic".<ref name=Ull/> Benzophenone is however banned as a food additive by the US [[Food and Drug Administration]], despite the FDA's continuing stance that this chemical does not pose a risk to public health under the conditions of its intended use.<ref>{{Cite news|url=https://www.npr.org/sections/thesalt/2018/10/06/655135633/fda-bans-use-of-7-synthetic-food-additives-after-environmental-groups-sue|title=FDA Bans Use of 7 Synthetic Food Additives After Environmental Groups Sue|work=NPR.org|access-date=2018-10-09|language=en}}</ref><ref>{{Federal Register|83|50490}}</ref> 

The European Union permits it as a flavouring substance,<ref>{{Cite report|url=https://www.canada.ca/en/environment-climate-change/services/evaluating-existing-substances/risk-management-approach-benzophenone.html#toc25|title=Risk management approach for benzophenone|date=Jan 2001|publisher=Health Canada|language=en}}</ref> having established a Total Dietary Intake of 0.3mg/kg of body weight per day.<ref>{{Cite journal|title=Safety of benzophenone to be used as flavouring|date=14 November 2017|journal=EFSA Journal|volume=15|issue=11|doi=10.2903/j.efsa.2017.5013|language=en|hdl=2164/9927|hdl-access=free |last1=Silano |first1=Vittorio |last2=Bolognesi |first2=Claudia |last3=Castle |first3=Laurence |last4=Chipman |first4=Kevin |last5=Cravedi |first5=Jean-Pierre |last6=Engel |first6=Karl-Heinz |last7=Fowler |first7=Paul |last8=Franz |first8=Roland |last9=Grob |first9=Konrad |last10=Gürtler |first10=Rainer |last11=Husøy |first11=Trine |last12=Kärenlampi |first12=Sirpa |last13=Milana |first13=Maria Rosaria |last14=Pfaff |first14=Karla |last15=Riviere |first15=Gilles |last16=Srinivasan |first16=Jannavi |last17=Tavares Poças |first17=Maria de Fátima |last18=Tlustos |first18=Christina |last19=Wölfle |first19=Detlef |last20=Zorn |first20=Holger |last21=Benigni |first21=Romualdo |last22=Binderup |first22=Mona-Lise |last23=Brimer |first23=Leon |last24=Marcon |first24=Francesca |last25=Marzin |first25=Daniel |last26=Mosesso |first26=Pasquale |last27=Mulder |first27=Gerard |last28=Oskarsson |first28=Agneta |last29=Svendsen |first29=Camilla |last30=Anastassiadou |first30=Maria |pages=e05013 |pmid=32625332 |pmc=7010149 |display-authors=1 }}</ref>

Benzophenone derivatives are known to be pharmacologically active. From a molecular chemistry point of view interaction of benzophenone with B-DNA has been demonstrated experimentally.<ref>{{cite journal |author1=Consuelo Cuquerella, M. |author2=Lhiaubet-Vallet, V. |author3=Cadet, J. |author4=Miranda, M. A. | journal = Acc. Chem. Res. | volume = 45 |issue=9 | pages = 1558–1570 | year = 2012 | doi=10.1021/ar300054e |pmid=22698517 | title = Benzophenone Photosensitized DNA Damage}}</ref> The interaction with DNA and the successive photo-induced energy transfer is at the base of the benzophenone activity as a DNA photosensitizer and may explain part of its therapeutic potentialities.

In 2014, benzophenones were named Contact [[Allergen of the Year]] by the American Contact Dermatitis Society.<ref>{{cite web |author=Doug Brunk |url=http://www.skinandallergynews.com/single-view/benzophenones-named-2014-contact-allergen-of-the-year/cb086f7e351cccbcfd9dbf5fa806762b.html |title=Benzophenones named 2014 Contact Allergen of the Year : Dermatology News |website=Skinandallergynews.com |date=2014-03-14 |access-date=2016-06-16 |archive-url=https://web.archive.org/web/20160322084615/http://www.edermatologynews.com/single-view/benzophenones-named-2014-contact-allergen-of-the-year/cb086f7e351cccbcfd9dbf5fa806762b.html |archive-date=2016-03-22}}</ref>

Benzophenone is an [[endocrine disruptor]] capable of binding to the [[pregnane X receptor]].<ref>{{cite journal | doi = 10.1016/j.taap.2003.08.001| pmid = 14613717| title = Endocrine disruptors induce cytochrome P450 by affecting transcriptional regulation via pregnane X receptor| journal = Toxicology and Applied Pharmacology| volume = 193| issue = 1| pages = 66–72| year = 2003| last1 = Mikamo| first1 = Eriko| last2 = Harada| first2 = Shingo| last3 = Nishikawa| first3 = Jun-Ichi| last4 = Nishihara| first4 = Tsutomu| bibcode = 2003ToxAP.193...66M}}</ref>
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==References==
{{Reflist}}

[[Category:Benzophenones]]
[[Category:Printing materials]]
[[Category:Endocrine disruptors]]
[[Category:Articles containing video clips]]