title: Identification and characterization of an imidazolium by-product formed during the synthesis of 4-methylmethcathinone (mephedrone).
abstract: 4-Methylmethcathinone (2-methylamino-1-(4-methylphenyl)propan-1-one, mephedrone) is a psychoactive substance that has been associated with recreational use worldwide. Analytical data related to mephedrone are abundantly available but the characterization of by-products obtained during organic synthesis remains to be explored. This study presents the identification of a 1,2,3,5-tetramethyl-4-(4-methylphenyl)-1H-imidazol-3-ium salt (TMMPI), which was formed during the synthesis of mephedrone. When diethyl ether was added to the crude reaction product, solid material precipitated from the solution. Analytical characterization of TMMPI employed a range of analytical techniques including chromatographic analysis in combination with various mass spectrometric detection methods, nuclear magnetic resonance spectroscopy, and crystal structure analysis. Additional confirmation was obtained from organic synthesis of the imidazolium by-product. When TMMPI was subjected to analysis by gas chromatography-mass spectrometry (GC-MS), isomerization and degradation into two distinct compounds were observed, which pointed towards thermal instability under GC conditions. A liquid chromatography-mass spectrometry (LC-MS) based investigation into a micro-scale synthesis of mephedrone and three additional analogues revealed that the corresponding TMMPI analogue was formed. Interestingly, storage of mephedrone freebase in a number of organic solvents also gave rise to TMMPI and it appeared that its formation during storage was significantly reduced in the absence of air. The present study aimed to support clandestine forensic investigations by employing analytical strategies that are applicable to manufacturing sites. The imidazolium salts will most likely be found amongst the waste products of any clandestine lab site under investigation rather than with the desired product.
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, 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: 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's Hospital, Dublin 8, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Barry
authors.affiliation: School of Chemistry, Trinity College, Dublin 2, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Twamley
authors.affiliation: State Laboratory, Backweston Campus, Stacummy Lane, Celbridge, Co. Kildare, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dowling
authors.affiliation: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Brandt
mesh_terms: D002853:Chromatography, Liquid; D018360:Crystallography, X-Ray; D015198:Designer Drugs / Q000138:chemical synthesis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D007093:Imidazoles / Q000032:analysis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D015198:Designer Drugs; D007093:Imidazoles; D011619:Psychotropic Drugs; D008694:Methamphetamine; C029899:imidazole; C548233:mephedrone
keywords: cathinones; forensic; imidazolium; mephedrone; synthesis