Phenylacetone

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. A related laboratory-scale reaction has been described.

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.

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.

As a metabolite of amphetamine

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. 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.

Notes

References

References

1. Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. (2019-05-01). "Recent methamphetamine profiling trends: Tracking the nitrostyrene method used for P2P production". Forensic Chemistry.
3. "Synthesis of Phenyl-2-Propanone (P2P) - [www.rhodium.ws]".
4. (February 11, 1980). "Schedules of Controlled Substances; Schedule II Placement of Phenylacetone; (Phenyl-2-propanone, P2P, methyl benzyl ketone, benzyl methyl ketone)". [[Drug Enforcement Administration]].
5. (1999-03-01). "N-Oxygenation of Amphetamine and Methamphetamine by the Human Flavin-Containing Monooxygenase (Form 3): Role in Bioactivation and Detoxication". Journal of Pharmacology and Experimental Therapeutics.
6. (2000). "Ullmann's Encyclopedia of Industrial Chemistry".
7. (July 1936). "Preparation of Dibenzyl Ketone and Phenylacetone". Journal of the American Chemical Society.
8. (June 1, 1940). "Preparation of Phenylacetone". J. Am. Chem. Soc..
9. (2005-06-01). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacology & Therapeutics.