title: The identification of an impurity product, 4,6-dimethyl-3,5-diphenylpyridin-2-one in an amphetamine importation seizure, a potential route specific by-product for amphetamine synthesized by the APAAN to P2P, Leuckart route.
abstract: During the analysis of a Customs' importation case for the suspected presence of controlled drugs, amphetamine was found to be present. The samples were also found to contain by-products from the amphetamine synthesis and these included benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, a pair of naphthalene derivatives and amphetamine dimers. During the experimental investigation of the naphthalenes formation, a series of syntheses involved the acid hydrolysis of α-phenylacetoacetonitrile (APAAN). In one such experiment with sulfuric acid, a white substance was visibly deposited on the glassware and this was identified as the pyridone derivative, 4,6-dimethyl-3,5-diphenylpyridin-2-one. This compound was subsequently found to be present in the amphetamine product seized by the Customs and also in the final product of our own laboratory synthesized amphetamine (APAAN hydrolyzed to P2P/Leuckart reaction). Interestingly, the, 4,6-dimethyl-3,5-diphenylpyridin-2-one was not found when commercially supplied P2P underwent the Leuckart reaction to yield amphetamine. This suggests that 4,6-dimethyl-3,5-diphenylpyridin-2-one may be a route specific marker to the use of APAAN as a starting material in the synthesis of P2P and subsequent Leuckart reaction to yield amphetamine.
authors.affiliation: Forensic Science Laboratory, Garda HQ, Dublin 8, Ireland; Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland. Electronic address: jdpower@tcd.ie.
authors.forename: John D
authors.initials: JD
authors.lastname: Power
authors.affiliation: School of Chemistry, Trinity College, Dublin 2, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College, Dublin 2, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Talbot
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Barry
authors.affiliation: Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, St. James Hospital, Dublin 8, Ireland.
authors.forename: Pierce
authors.initials: P
authors.lastname: Kavanagh
keywords: Amphetamine; Drug impurity profile; Forensic; Leuckart; Route specific and 4,6-dimethyl-3,5-diphenylpyridin-2-one; Synthesis by-products