title: Forensic analysis of P2P derived amphetamine synthesis impurities: identification and characterization of indene by-products.
abstract: 1-Phenyl-2-propanone (P2P) is an internationally monitored precursor that has become increasingly difficult for illicit amphetamine producers to source, which means that alternative routes to its preparation have become increasingly important. One such approach includes the hydrolysis of alpha-phenylacetoacetonitrile (APAAN) with sulfuric acid. Previously, we reported the identification of 4,6-dimethyl-3,5-diphenylpryid-2-one following implementation of hydrolysis conditions and it was proposed that this compound might serve as one route specific by-product in the APAAN to P2P conversion. This study continued to explore the presence of impurities formed during this conversion and expanded also into a second route of P2P synthesis starting from alpha-methylstyrene (AMS). All P2P products underwent the Leuckart procedure to probe the presence of P2P-related impurities that might have carried through to the final product. Two by-products associated with the APAAN hydrolysis route to P2P were identified as 2,3-diacetyl-2,3-diphenylsuccinonitrile (1) and 2-methyl-1-phenyl-1,3-dicarbonitrile-1H-indene (2), respectively. Two by-products associated with the AMS route to P2P and subsequent Leuckart reaction were 1,1,3-trimethyl-3-phenyl-2,3-dihydro-1H-indene (3) and 1-phenyl-N-(phenylethyl)propan-2-amine (4), respectively. The two indenes (2 and 3) identified in synthesized amphetamine originating from P2P suggested that it might be possible to differentiate between the two synthetic routes regarding the use of APAAN and AMS. Furthermore, the association of these compounds with amphetamine production appears to have been reported for the first time. The presence of compounds 1 - 4 in seized amphetamine samples and waste products could facilitate the suggestion whether APAAN or AMS were employed in the synthesis route to the P2P. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.|Forensic Science Ireland, Garda HQ, Phoenix Park, Dublin 8, Ireland.
authors.forename: John D
authors.initials: JD
authors.lastname: Power
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.
authors.forename: Pierce
authors.initials: P
authors.lastname: Kavanagh
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.
authors.forename: Gavin
authors.initials: G
authors.lastname: McLaughlin
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dowling
authors.forename: Michael
authors.initials: M
authors.lastname: Barry
authors.affiliation: School of Chemistry, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Talbot
authors.affiliation: TCD Small Molecule X-Ray Facility, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Twamley
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, L3 3AF, Liverpool, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000661:Amphetamine / Q000138:chemical synthesis* / Q000737:chemistry; D000697:Central Nervous System Stimulants / Q000138:chemical synthesis* / Q000737:chemistry; D002853:Chromatography, Liquid; D018360:Crystallography, X-Ray; D004340:Drug Contamination; D008401:Gas Chromatography-Mass Spectrometry; D013287:Illicit Drugs / Q000138:chemical synthesis / Q000737:chemistry; D007192:Indenes / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D007192:Indenes; D013343:Styrenes; D000096:Acetone; D000661:Amphetamine; C017915:alpha-methylstyrol; C008863:1-phenyl-2-propanone
keywords: APAAN; P2P; alpha-methylstyrene; cyclic indene; impurities