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| Names | |
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| Preferred IUPAC name 1-Phenylpropan-2-one | |
| Other names Benzyl methyl ketone; Methyl benzyl ketone; Phenyl-2-propanone | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
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| ECHA InfoCard | 100.002.859 |
| KEGG |
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| UNII | |
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| Properties | |
| 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) |
| −83.44·10−6 cm3/mol | |
| Legal status | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Phenylacetone, also known asphenyl-2-propanone, is anorganic compound with thechemical formula C6H5CH2COCH3. It is a colorless oil that is soluble inorganic solvents. It is a mono-substituted benzene derivative, consisting of anacetone attached to aphenyl group. As such, its systematic IUPAC name is1-phenyl-2-propanone.
Thissubstance is used in the manufacture ofmethamphetamine andamphetamine, where it is commonly known asP2P.[2][3] Due toillicit drug labs using phenylacetone to make amphetamines, phenylacetone was declared aschedule II controlled substance in theUnited States in 1980.[4] In humans, phenylacetone occurs as a metabolite ofamphetamine andmethamphetamine viaFMO3-mediatedoxidative deamination.[5]
There are many routes to synthesize phenylacetone. Industry uses the gas-phaseketonic decarboxylation ofphenylacetic acid usingacetic acid over aceria-aluminasolid acid catalyst.[6] A related laboratory-scale reaction has been described.[7]
An alternative route iszeolite-catalyzed isomerization of phenylpropylene oxide. Another laboratory synthesis involves conventional routes including theFriedel-Crafts alkylation reaction ofchloroacetone withbenzene in the presence ofaluminum chloridecatalyst.[8]
To prevent illicit synthesis of amphetamine and methamphetamine, phenylacetone itself and the precursor phenylacetic acid is subject to regulation in the United States under theChemical Diversion and Trafficking Act.
In the TV seriesBreaking Bad, Walter White manufactures methamphetamine using phenylacetone and methylamine through areductive amination reaction. Whiteproduced phenylacetone in atube furnace using phenylacetic acid and acetic acid.[citation needed]
Metabolic pathways of amphetamine in humans[sources 1]  Para- Hydroxylation Para- Hydroxylation Para- Hydroxylation unidentified Beta- Hydroxylation Beta- Hydroxylation Oxidative Deamination Oxidation unidentified Glycine Conjugation |
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 tobenzoic acid, which is converted tohippuric acid byglycine N-acyltransferase (GLYAT) enzymes prior to excretion.
Phenylacetone can undergo para-hydroxylation to4-hydroxyphenylacetone, which occurs as a metabolite of amphetamine in the human body.
The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. ... Amphetamine can also undergo aromatic hydroxylation top-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affordsp-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.
Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, fromd-amphetamine.
Hydroxyamphetamine was administered orally to five human subjects ... Since conversion of hydroxyamphetamine to hydroxynorephedrine occurs in vitro by the action of dopamine-β-oxidase, a simple method is suggested for measuring the activity of this enzyme and the effect of its inhibitors in man. ... The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues. ... a major portion of the β-hydroxylation of hydroxyamphetamine occurs in non-adrenal tissue. Unfortunately, at the present time one cannot be completely certain that the hydroxylation of hydroxyamphetamine in vivo is accomplished by the same enzyme which converts dopamine to noradrenaline.
Figure 1. Glycine conjugation of benzoic acid. The glycine conjugation pathway consists of two steps. First benzoate is ligated to CoASH to form the high-energy benzoyl-CoA thioester. This reaction is catalyzed by the HXM-A and HXM-B medium-chain acid:CoA ligases and requires energy in the form of ATP. ... The benzoyl-CoA is then conjugated to glycine by GLYAT to form hippuric acid, releasing CoASH. In addition to the factors listed in the boxes, the levels of ATP, CoASH, and glycine may influence the overall rate of the glycine conjugation pathway.
The biologic significance of the different levels of serum DβH activity was studied in two ways. First, in vivo ability to β-hydroxylate the synthetic substrate hydroxyamphetamine was compared in two subjects with low serum DβH activity and two subjects with average activity. ... In one study, hydroxyamphetamine (Paredrine), a synthetic substrate for DβH, was administered to subjects with either low or average levels of serum DβH activity. The percent of the drug hydroxylated to hydroxynorephedrine was comparable in all subjects (6.5-9.62) (Table 3).
In species where aromatic hydroxylation of amphetamine is the major metabolic pathway,p-hydroxyamphetamine (POH) andp-hydroxynorephedrine (PHN) may contribute to the pharmacological profile of the parent drug. ... The location of thep-hydroxylation and β-hydroxylation reactions is important in species where aromatic hydroxylation of amphetamine is the predominant pathway of metabolism. Following systemic administration of amphetamine to rats, POH has been found in urine and in plasma.
The observed lack of a significant accumulation of PHN in brain following the intraventricular administration of (+)-amphetamine and the formation of appreciable amounts of PHN from (+)-POH in brain tissue in vivo supports the view that the aromatic hydroxylation of amphetamine following its systemic administration occurs predominantly in the periphery, and that POH is then transported through the blood-brain barrier, taken up by noradrenergic neurones in brain where (+)-POH is converted in the storage vesicles by dopamine β-hydroxylase to PHN.
The metabolism ofp-OHA top-OHNor is well documented and dopamine-β hydroxylase present in noradrenergic neurons could easily convertp-OHA top-OHNor after intraventricular administration.
