Lead
editPhenylacetone, also known as phenyl-2-propanone (P2P), 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 the most popular precursor in the manufacture of methamphetamine and amphetamine.[1][2] Due to illicit drug labs using phenylacetone to make amphetamines, phenylacetone was declared a schedule II controlled substance in the United States in 1980. In humans, phenylacetone occurs as a metabolite of amphetamine and methamphetamine via FMO3-mediated oxidative deamination.[3]
Synthesis
editThere are many possible routes to synthesize phenylacetone. However, many of these synthetic pathways are not used as the precursor materials are subjected to regulations in the United States under the Chemical Diversion and Trafficking Act. One of the earliest routes used phenylacetic acid and sodium acetate to synthesize phenylacetone.[4] American chemists, Charles Hurd and Charles Thomas first reported this synthesis pathway in 1936.[4]
Phenylacetone can also be prepared by Friedel-Crafts alkylation reaction of chloroacetone with benzene in the presence of an aluminum chloride catalyst.[5]
Amphetamine metabolism
editIn the human body, flavin-containing monooxygenase 3 (FMO3) deaminates amphetamines in the liver into phenylacetone, which is non-toxic to humans.[6] Phenylacetone gets oxidized to benzoic acid and glycine N-acyltransferase (GLYAT) enzymes further convert benzoic acid to hippuric acid, which can then be excreted in urine.
Furthermore, phenylacetone can undergo para-hydroxylation to 4-hydroxyphenylacetone, which occurs as a metabolite of amphetamine in the human body.
In popular culture
editIn the TV series, Breaking Bad, Walter White synthesized methamphetamine using phenylacetone and methylamine through a reductive amination reaction. White produced phenylacetone in a tube furnace using phenylacetic acid and acetic acid.
References
edit- ^ Toske, Steven G.; Brown, Jaclyn L.; Miller, Erin E.; Phillips, Monica Z.; Kerr, Susan C.; Hays, Patrick A. (2019-05-01). "Recent methamphetamine profiling trends: Tracking the nitrostyrene method used for P2P production". Forensic Chemistry. 13: 100140. doi:10.1016/j.forc.2018.12.003. ISSN 2468-1709.
- ^ "Synthesis of Phenyl-2-Propanone (P2P) - [www.rhodium.ws]". erowid.org. Retrieved 2023-04-14.
- ^ Cashman, J. R.; Xiong, Y. N.; Xu, L.; Janowsky, A. (1999-03). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication". The Journal of Pharmacology and Experimental Therapeutics. 288 (3): 1251–1260. ISSN 0022-3565. PMID 10027866.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Hurd, Charles D.; Thomas, Charles L. (1936-07). "Preparation of Dibenzyl Ketone and Phenylacetone". Journal of the American Chemical Society. 58 (7): 1240–1240. doi:10.1021/ja01298a043. ISSN 0002-7863.
{{cite journal}}: Check date values in:|date=(help) - ^ Mason, J. Philip; Terry, Lewis I. (1940-06). "Preparation of Phenylacetone". Journal of the American Chemical Society. 62 (6): 1622–1622. doi:10.1021/ja01863a506. ISSN 0002-7863.
{{cite journal}}: Check date values in:|date=(help) - ^ Krueger, Sharon K.; Williams, David E. (2005-06-01). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacology & Therapeutics. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. ISSN 0163-7258.