Phenylacetone

{{chembox

| Watchedfields = changed

| verifiedrevid = 464396258

| ImageFile = 1-phenylpropan-2-one 200.svg

| ImageSize = 170

| ImageName = Skeletal formula

| ImageClass = skin-invert

| ImageFile1 = Phenylacetone-3D-balls.png

| ImageSize1 = 190

| ImageName1 = Ball-and-stick model

| PIN = 1-Phenylpropan-2-one

| OtherNames = Benzyl methyl ketone; Methyl benzyl ketone; Phenyl-2-propanone

|Section1={{Chembox Identifiers

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

| UNII = O7IZH10V9Y

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

| KEGG = C15512

| InChI = 1/C9H10O/c1-8(10)7-9-5-3-2-4-6-9/h2-6H,7H2,1H3

| InChIKey = QCCDLTOVEPVEJK-UHFFFAOYAG

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

| StdInChI = 1S/C9H10O/c1-8(10)7-9-5-3-2-4-6-9/h2-6H,7H2,1H3

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

| StdInChIKey = QCCDLTOVEPVEJK-UHFFFAOYSA-N

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

| CASNo = 103-79-7

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

| ChemSpiderID=21106366

| PubChem = 7678

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

| ChEBI = 52052

| SMILES = O=C(C)Cc1ccccc1

}}

|Section2={{Chembox Properties

| C = 9 | H = 10 | O =1

| Appearance = Colorless, pleasant odor

| Density = 1.006 g/mL

| MeltingPtC = -15

| BoilingPtC = 214 to 216

| Solubility =

| MagSus = −83.44·10⁻⁶ cm³/mol

}}

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

|Section4={{Chembox Legal status

| legal_AU =

| legal_BR = D1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

| legal_US =

| legal_UK =

| legal_UN =

}}

Phenylacetone, also known as phenyl-2-propanone, is an organic compound with the chemical formula C₆H₅CH₂COCH₃. It is a colorless oil that is soluble in organic solvents. It is a mono-substituted benzene derivative, consisting of an acetone attached to a phenyl group. As such, its systematic IUPAC name is 1-phenyl-2-propanone.

This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known as P2P.{{Cite journal |last1=Toske |first1=Steven G. |last2=Brown |first2=Jaclyn L. |last3=Miller |first3=Erin E. |last4=Phillips |first4=Monica Z. |last5=Kerr |first5=Susan C. |last6=Hays |first6=Patrick A. |date=2019-05-01 |title=Recent methamphetamine profiling trends: Tracking the nitrostyrene method used for P2P production |url=https://www.sciencedirect.com/science/article/pii/S2468170918301061 |journal=Forensic Chemistry |language=en |volume=13 |pages=100140 |doi=10.1016/j.forc.2018.12.003 |s2cid=104413528 |issn=2468-1709}}{{Cite web |title=Synthesis of Phenyl-2-Propanone (P2P) - [www.rhodium.ws] |url=https://erowid.org/archive/rhodium/chemistry/phenylacetone.html |access-date=2023-04-15 |website=erowid.org}} Due to illicit drug labs using phenylacetone to make amphetamines, phenylacetone was declared a schedule II controlled substance in the United States in 1980.{{Cite web |date=February 11, 1980 |title=Schedules of Controlled Substances; Schedule II Placement of Phenylacetone; (Phenyl-2-propanone, P2P, methyl benzyl ketone, benzyl methyl ketone) |url=http://isomerdesign.com/Cdsa/FR/44FR71822.pdf |url-status=live |archive-url=https://web.archive.org/web/20220303023127/http://isomerdesign.com/Cdsa/FR/44FR71822.pdf |archive-date=March 3, 2022 |access-date=January 16, 2023 |website=Isomer Design |publisher=Drug Enforcement Administration}} In humans, phenylacetone occurs as a metabolite of amphetamine and methamphetamine via FMO3-mediated oxidative deamination.{{Cite journal |last1=Cashman |first1=John R. |last2=Xiong |first2=Yeng N. |last3=Xu |first3=Lifen |last4=Janowsky |first4=Aaron |date=1999-03-01 |title=N-Oxygenation of Amphetamine and Methamphetamine by the Human Flavin-Containing Monooxygenase (Form 3): Role in Bioactivation and Detoxication |url=https://jpet.aspetjournals.org/content/288/3/1251 |journal=Journal of Pharmacology and Experimental Therapeutics |language=en |volume=288 |issue=3 |pages=1251–1260 |issn=0022-3565 |pmid=10027866}}

Synthesis

There are many routes to synthesize phenylacetone. Industry uses the gas-phase ketonic decarboxylation of phenylacetic acid using acetic acid over a ceria-alumina solid acid catalyst.{{cite book |doi=10.1002/14356007.a15_077 |chapter=Ketones |title=Ullmann's Encyclopedia of Industrial Chemistry |year=2000 |last1=Siegel |first1=Hardo |last2=Eggersdorfer |first2=Manfred |isbn=9783527306732 }} A related laboratory-scale reaction has been described.{{Cite journal |last1=Hurd |first1=Charles D. |last2=Thomas |first2=Charles L. |date=July 1936 |title=Preparation of Dibenzyl Ketone and Phenylacetone |url=https://pubs.acs.org/doi/abs/10.1021/ja01298a043 |journal=Journal of the American Chemical Society |language=en |volume=58 |issue=7 |pages=1240 |doi=10.1021/ja01298a043 |issn=0002-7863}}

An alternative route is zeolite-catalyzed isomerization of phenylpropylene oxide. Another laboratory synthesis involves conventional routes including the Friedel-Crafts alkylation reaction of chloroacetone with benzene in the presence of aluminum chloride catalyst.{{cite journal |doi=10.1021/ja01863a506|date=June 1, 1940 |title=Preparation of Phenylacetone |author1=J. Philip Mason |author2=Lewis I. Terry |journal=J. Am. Chem. Soc.|volume=62 |issue=6 |page=1622 |s2cid=101303942 |hdl=2144/16978 |hdl-access=free }}

Amphetamine metabolism

Phenylacetone is an intermediate in the biodegradation of amphetamine. In the human liver, flavin-containing monooxygenase 3 (FMO3) deaminates amphetamines into phenylacetone, which is non-toxic to humans.{{Cite journal |last1=Krueger |first1=Sharon K. |last2=Williams |first2=David E. |date=2005-06-01 |title=Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism |journal=Pharmacology & Therapeutics |language=en |volume=106 |issue=3 |pages=357–387 |doi=10.1016/j.pharmthera.2005.01.001 |pmid=15922018 |pmc=1828602 |issn=0163-7258}} Phenylacetone is oxidized to benzoic acid, which is converted to hippuric acid by glycine N-acyltransferase (GLYAT) enzymes prior to excretion.

Phenylacetone can undergo para-hydroxylation to 4-hydroxyphenylacetone, which occurs as a metabolite of amphetamine in the human body. {{clear}}

Regulation and culture

To prevent illicit synthesis of amphetamines from phenylacetone, the precursor phenylacetic acid is subject to regulation in the United States under the Chemical Diversion and Trafficking Act.

In the TV series Breaking Bad, Walter White manufactures methamphetamine using phenylacetone and methylamine through a reductive amination reaction. White produced phenylacetone in a tube furnace using phenylacetic acid and acetic acid. {{cn|date=March 2024}}

File:Breaking Bad Meth Synthesis.svg