Identification and characterization of an imidazolium by‐product formed during the synthesis of 4‐methylmethcathinone (mephedrone)

Abstract

Abstract: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 toward thermal instability under GC conditions. An 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 http://mc.manuscriptcentral.com/dta Drug Testing and AnalysisAccepted but uncorrected F o r P e e r R e v i e w 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 was 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. When TMMPI was subjected to analysis by gas chromatography-mass spectrometry (GC-MS), isomerization and degradation into two distinct compounds were observed, which pointed toward thermal instability under GC conditions. An 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 was 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.

Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N‐methoxy positional isomer, N‐methoxymephedrone

“…[38] The cathinone molecular scaffold gives rise to a large range of biologically active compounds. Synthetic cathinones remain a popular choice amongst drug users and are the second largest family of compounds monitored by the EMCDDA Early Warning Network.…”

“…Both the analytical and pharmacological characterization of mephedrone has been well documented in the scientific literature [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and studies focusing specifically on synthesis related by-products have also been conducted. [38] The cathinone molecular scaffold gives rise to a large range of biologically active compounds. Synthetic cathinones remain a popular choice amongst drug users and are the second largest family of compounds monitored by the EMCDDA Early Warning Network.…”

Organic impurity profiling of methylone and intermediate compounds synthesized from catechol

“…3,4-Methylenedioxyphenyl-1,2propanedione may form by decomposition of methylone under a variety of conditions. The reaction of two cathinone molecules during synthesis and/or storage may form an imidazolium compound [14] which, similarly, might not offer unambiguous insights into the precursors used during synthesis. The reaction of two cathinone molecules during synthesis and/or storage may form an imidazolium compound [14] which, similarly, might not offer unambiguous insights into the precursors used during synthesis.…”

“…[7] The vast majority of chemical analysis for synthetic cathinones has focused on characterization and structural elucidation, including the analysis of methylone. [8][9][10][11][12][13] There have been few reports of the organic impurity profiling of synthetic cathinones, [14][15][16][17][18][19] presumably as these psychoactive substances (NPS) are relatively new to the recreational drug market. Organic impurities are typically identified by gas chromatographymass spectrometry (GC-MS), [20] however, structural elucidation can also be aided via nuclear magnetic resonance (NMR) spectroscopy.…”

“…[2,23,24] These ring-substituted propiophenones can be synthesized using the Grignard reaction with the corresponding ring-substituted benzaldehyde or through the Friedel-Crafts acylation of the appropriately ringsubstituted benzene. [2,14] The respective precursors for methylone synthesis are piperonal, which is controlled under the Convention against Illicit Traffic in Narcotic and Psychotropic Substances 1988, [25] and 1,3-benzodioxole, which is monitored under Category II of the Code of Practice for the Supply Diversion into Illicit Drug Manufacture. [26] Interestingly, the unmonitored chemical catechol can be converted into 1,3-benzodioxole, the preferential methylone precursor, [2] in one step.…”