acetophenone

{{chembox

|Watchedfields = changed

|verifiedrevid = 477239601

|Name = Acetophenone

|ImageFile1 = File:Acetophenone-2D-skeletal.svg

|ImageName1 = Skeletal formula of the acetophenone molecule

|ImageSize1 = 150px

|ImageFileL2 = Acetophenone-from-xtal-Mercury-3D-bs.png

|ImageNameL2 = Ball-and-stick model of the acetophenone molecule

|ImageSizeL2 = 150px

|ImageFileR2 = Acetophenone-from-xtal-Mercury-3D-sf.png

|ImageNameR2 = Space-filling model of the acetophenone molecule

|ImageSizeR2 = 150px

|ImageFile3 = Ацетофенон.jpg

|ImageName3 = sample of acetophenone

|PIN = 1-Phenylethanone{{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 | page = 723 | doi = 10.1039/9781849733069-00648 | isbn = 978-0-85404-182-4 | quote=The names acetophenone and benzophenone are retained only for general nomenclature, but no substitution is allowed.}}

|OtherNames = Acetophenone
Phenylethanone
Methyl phenyl ketone

|Section1={{Chembox Identifiers

|Abbreviations = ACP

|UNII_Ref = {{fdacite|correct|FDA}}

|UNII = RK493WHV10

|KEGG_Ref = {{keggcite|correct|kegg}}

|KEGG = C07113

|EC_number = 202-708-7

|RTECS = AM5250000

|UNNumber = 1993

|InChIKey = KWOLFJPFCHCOCG-UHFFFAOYAT

|PubChem = 7410

|SMILES1 = CC(=O)c1ccccc1

|ChEMBL_Ref = {{ebicite|correct|EBI}}

|ChEMBL = 274467

|StdInChI_Ref = {{stdinchicite|correct|chemspider}}

|StdInChI = 1S/C8H8O/c1-7(9)8-5-3-2-4-6-8/h2-6H,1H3

|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

|StdInChIKey = KWOLFJPFCHCOCG-UHFFFAOYSA-N

|CASNo_Ref = {{cascite|correct|CAS}}

|CASNo = 98-86-2

|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

|ChemSpiderID = 7132

|ChEBI_Ref = {{ebicite|correct|EBI}}

|ChEBI = 27632

|DrugBank_Ref = {{drugbankcite|correct|drugbank}}

|DrugBank = DB04619

|SMILES = O=C(c1ccccc1)C

|InChI = 1/C8H8O/c1-7(9)8-5-3-2-4-6-8/h2-6H,1H3

}}

|Section2={{Chembox Properties

|C=8 | H=8 | O=1

|Density = 1.028 g/cm3

|MeltingPtC = 19–20

|BoilingPtC = 202

|Solubility = 5.5 g/L at 25 °C
12.2 g/L at 80 °C

|MagSus = −72.05·10−6 cm3/mol

}}

|Section3={{Chembox Hazards

|ExternalSDS = [https://fscimage.fishersci.com/msds/00002.htm MSDS]

|FlashPtC = 77

|NFPA-H = 1

|NFPA-F = 2

|NFPA-R = 0

|GHSPictograms = {{GHS07}}

|GHSSignalWord = Warning

|HPhrases = {{H-phrases|302|319}}

|PPhrases = {{P-phrases|264|270|280|301+312|305+351+338|330|337+313|501}}

}}

}}

Acetophenone is the organic compound with the formula C6H5C(O)CH3. It is the simplest aromatic ketone. This colorless, viscous liquid is a precursor to useful resins and fragrances.{{Ullmann|first1=Hardo|last1=Siegel|first2=Manfred|last2=Eggersdorfer|title=Ketones|doi=10.1002/14356007.a15_077}}

Production

Acetophenone is formed as a byproduct of the cumene process, the industrial route for the synthesis of phenol and acetone. In the Hock rearrangement of isopropylbenzene hydroperoxide, migration of a methyl group rather than the phenyl group gives acetophenone and methanol as a result of an alternate rearrangement of the intermediate:

:{{chem2 | C6H5C(CH3)2O2H -> C6H5C(O)CH3 + CH3OH }}

The cumene process is conducted on such a large scale that even the small amount of acetophenone by-product can be recovered in commercially useful quantities.

Acetophenone is also generated from ethylbenzene hydroperoxide. Ethylbenzene hydroperoxide is primarily converted to 1-phenylethanol (α-methylbenzyl alcohol) in the process with a small amount of by-product acetophenone. Acetophenone is recovered or hydrogenated to 1-phenylethanol which is then dehydrated to produce styrene.

Uses

=Precursor to resins=

Commercially significant resins are produced from treatment of acetophenone with formaldehyde and a base. The resulting copolymers are conventionally described with the formula {{chem2|[(C6H5COCH)_{x}(CH2)_{x}]_{n} }}, resulting from aldol condensation. These substances are components of coatings and inks. Modified acetophenone-formaldehyde resins are produced by the hydrogenation of the aforementioned ketone-containing resins. The resulting polyol can be further crosslinked with diisocyanates. The modified resins are found in coatings, inks and adhesives.

=Niche uses=

Acetophenone is an ingredient in fragrances that resemble almond, cherry, honeysuckle, jasmine, and strawberry. It is used in chewing gum.{{Citation| last =Burdock| first =George A.| title =Fenaroli's Handbook of Flavor Ingredients| publisher =CRC Press| year =2005| edition =5th| page =15| url =https://books.google.com/books?id=A8OyTzGGJhYC&q=Fenaroli's%20handbook%20of%20flavor%20ingredients&pg=PP1| archive-url =https://web.archive.org/web/20140925024441/http://books.google.com/books?id=A8OyTzGGJhYC&lpg=PP1&dq=Fenaroli's%20handbook%20of%20flavor%20ingredients&pg=PP1| archive-date =2014-09-25| isbn =0-8493-3034-3| url-status =live}}

It is also listed as an approved excipient by the U.S. FDA.{{cite web|url=https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm|title=Inactive Ingredient Search for Approved Drug Products|url-status=live|archive-url=https://web.archive.org/web/20130504122045/http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm|archive-date=2013-05-04}}

=Laboratory reagent=

In instructional laboratories,{{cite journal |title= Polystyrene—A multistep synthesis: For the undergraduate organic chemistry laboratory |first1= Samuel H. |last1= Wilen |first2= Chester B. |last2= Kremer |first3= Irving |last3= Waltcher |journal= J. Chem. Educ. |year= 1961 |volume= 38 |issue= 6 |pages= 304–305 |doi= 10.1021/ed038p304 |bibcode= 1961JChEd..38..304W }} acetophenone is converted to styrene in a two-step process that illustrates the reduction of carbonyls using sodium borohydride and the dehydration of alcohols:

:{{chem2 | 4 C6H5C(O)CH3 + NaBH4 + 4 H2O -> 4 C6H5CH(OH)CH3 + NaOH + B(OH)3}}

:{{chem2 | C6H5CH(OH)CH3 -> C6H5CH\dCH2 + H2O}}

A similar two-step process is used industrially, but reduction step is performed by hydrogenation over a copper chromite catalyst:

:{{chem2 | C6H5C(O)CH3 + H2 -> C6H5CH(OH)CH3 }}

Being prochiral, acetophenone is also a popular test substrate for asymmetric hydrogenation experiments.

=Drugs=

Acetophenone is used for the synthesis of many pharmaceuticals.

{{cite book

| isbn = 978-0-8155-1144-1

| pages = [https://archive.org/details/pharmaceuticalma02sitt/page/n65 39], 177

| last = Sittig

| first = Marshall

| title = Pharmaceutical Manufacturing Encyclopedia

| url = https://archive.org/details/pharmaceuticalma02sitt

| url-access = limited

| year = 1988

}}

{{cite book

| isbn =978-0-8493-9051-7

| pages = 142–145

| last1 = Gadamasetti

| first1 = Kumar

| last2= Tamim Braish

| title = Process Chemistry in the Pharmaceutical Industry, Volume 2

| year = 2007

| publisher = Taylor & Francis

}}

Natural occurrence

Acetophenone occurs naturally in many foods including apple, cheese, apricot, banana, beef, and cauliflower. It is also a component of castoreum, the exudate from the castor sacs of the mature beaver.{{cite journal | title = Pheromonal activity of single castoreum constituents in beaver, Castor canadensis |last1=Müller-Schwarze|first1= D. |last2=Houlihan|first2= P. W. | journal = Journal of Chemical Ecology | date = April 1991 | volume = 17 | issue = 4 | doi = 10.1007/BF00994195 | pmid=24258917 | pages=715–34|bibcode=1991JCEco..17..715M |s2cid=29937875}}

Pharmacology

In the late 19th and early 20th centuries, acetophenone was used in medicine.{{Merck12th}} It was marketed as a hypnotic and anticonvulsant under brand name Hypnone. The typical dosage was 0.12 to 0.3 milliliters.{{cite book | last= Bartholow|first= Roberts | title = A Practical Treatise on Materia Medica and Therapeutics | publisher = Appleton & Co | date = 1908}} It was considered to have superior sedative effects to both paraldehyde and chloral hydrate.{{cite journal|last=Norman|first=Conolly|title=Cases illustrating the sedative effects of aceto-phenone|journal=Journal of Mental Science|volume=32|page=519|date=1887|doi=10.1192/bjp.32.140.519}} In humans, acetophenone is metabolized to benzoic acid, carbonic acid, and acetone.{{cite journal | title = Hypnone – The new hypnotic | journal = Journal of the American Medical Association | volume = 5 | page = 632 | date = 1885 | issue = 23 | doi = 10.1001/jama.1885.02391220016006}} Hippuric acid occurs as an indirect metabolite and its quantity in urine may be used to confirm acetophenone exposure,{{PubChem|7410}} although other substances, like toluene, also induce hippuric acid in urine.{{cite web|url=http://www.beroepsziekten.nl/datafiles/A044.pdf|title=The Netherlands Center for Occupational Diseases (NCvB): toluene (Dutch)|website=beroepsziekten.nl|access-date=19 April 2018}}

Toxicity

The {{LD50}} is 815 mg/kg (oral, rats). Acetophenone is currently listed as a Group D carcinogen indicating that there is no evidence at present that it causes cancer in humans.

References