Phenylacetone

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.

Phenylacetone

Skeletal formula
Ball-and-stick model
Names
Preferred IUPAC name 1-Phenylpropan-2-one
Other names Benzyl methyl ketone; Methyl benzyl ketone; Phenyl-2-propanone
Identifiers
CAS Number	103-79-7 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:52052 Y
ChemSpider	21106366 Y
ECHA InfoCard	100.002.859
KEGG	C15512 Y
PubChem CID	7678
UNII	O7IZH10V9Y Y
CompTox Dashboard (EPA)	DTXSID1059280
InChI InChI=1S/C9H10O/c1-8(10)7-9-5-3-2-4-6-9/h2-6H,7H2,1H3 Y Key: QCCDLTOVEPVEJK-UHFFFAOYSA-N Y InChI=1/C9H10O/c1-8(10)7-9-5-3-2-4-6-9/h2-6H,7H2,1H3 Key: QCCDLTOVEPVEJK-UHFFFAOYAG
SMILES O=C(C)Cc1ccccc1
Properties
Chemical formula	C9H10O
Molar mass	134.178 g·mol−1
Appearance	Colorless
Odor	pleasant
Density	1.006 g/mL
Melting point	−15 °C (5 °F; 258 K)
Boiling point	214 to 216 °C (417 to 421 °F; 487 to 489 K)
Magnetic susceptibility (χ)	−83.44·10−6 cm3/mol
Legal status	BR: Class D1 (Drug precursors)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

This substance is used in the manufacture of methamphetamine and amphetamine, where it is commonly known as P2P.^[2][3] Due to illicit drug labs using phenylacetone to make amphetamines, phenylacetone was declared a schedule II controlled substance in the United States in 1980.^[4] In humans, phenylacetone occurs as a metabolite of amphetamine and methamphetamine via FMO3-mediated oxidative deamination.^[5]

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.^[6] A related laboratory-scale reaction has been described.^[7]

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.^[8]

Regulation

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

Culture

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. ^{[citation needed]}

Synthesis of methamphetamine in Breaking Bad

As a metabolite of amphetamine

Metabolic pathways of amphetamine in humans[sources 1] 4-Hydroxyphenylacetone Phenylacetone Benzoic acid Hippuric acid Amphetamine Norephedrine 4-Hydroxyamphetamine 4-Hydroxynorephedrine Para- Hydroxylation Para- Hydroxylation Para- Hydroxylation CYP2D6 CYP2D6 unidentified Beta- Hydroxylation Beta- Hydroxylation DBH DBH [note 1] Oxidative Deamination FMO3 Oxidation unidentified Glycine Conjugation XM-ligase GLYAT

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.^[20] 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.

See also

• MDP2P – related compound with a methylenedioxy group, and a precursor to MDMA.
• Cyclohexylacetone – the cyclohexane derivative of phenylacetone
• Phenylacetones
• Methamphetamine
• Controlled Substances Act

Notes

1. 4-Hydroxyamphetamine has been shown to be metabolized into 4-hydroxynorephedrine by dopamine beta-hydroxylase (DBH) in vitro and it is presumed to be metabolized similarly in vivo.^[10][15] Evidence from studies that measured the effect of serum DBH concentrations on 4-hydroxyamphetamine metabolism in humans suggests that a different enzyme may mediate the conversion of 4-hydroxyamphetamine to 4-hydroxynorephedrine;^[15][17] however, other evidence from animal studies suggests that this reaction is catalyzed by DBH in synaptic vesicles within noradrenergic neurons in the brain.^[18][19]

1. ^{[9][10][11][12][13][14][15][16]}