Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA) synthesised from catechol and eugenol via 4-allylcatechol.

This work examines organic impurity profiles of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from the "pre-precursors" catechol (1,2-dihydroxybenzene) and eugenol, via a safrole intermediate. MDMA was synthesised from the catechol- and eugenol-derived safrole intermediate via two routes, which resulted in the synthesis of MDMA from catechol via two routes (Route 1A and 1B) and from eugenol via two routes (Route 2A and 2B). Twelve organic impurities were identified in MDMA synthesised via Routes 1A and 1B, and eleven organic impurities were identified in MDMA synthesised via Routes 2A and 2B. Route specific organic impurities were identified in MDMA that indicated the "pre-precursors" catechol and eugenol were used in the respective synthetic routes. Route specific organic impurities were also identified in MDMA that indicated the route used to synthesise safrole from the "pre-precursor" and the route used to synthesise MDMA from safrole. Thus, the use of the "pre-precursors" catechol and eugenol and the synthetic route utilised could be ascertained by the organic impurity profiling of MDMA under the conditions used here.

Synthesis and organic impurity profiling of 4-methoxymethamphetamine hydrochloride and its precursors.

4-Methoxymethamphetamine (PMMA) was synthesised from star anise and from 4-methoxytoluene and the organic impurity profiles examined. These two starting materials are unrestricted chemicals in many jurisdictions and contain the requisite functional groups and are thus well suited for clandestine manufacturers. trans-Anethole was extracted from star anise and oxidised to 4-methoxyphenyl-2-propanone (PMP2P). 4-Methoxytoluene was oxidised to anisaldehyde, converted to 4-methoxyphenyl-2-nitropropene, and then reduced to PMP2P. The PMP2P obtained by both methods was then converted to PMMA via the Leuckart reaction. 4-Methoxymethamphetamine hydrochloride (PMMA·HCl) was synthesised from PMMA using hydrogen chloride gas. Both of the examined synthetic methods were found to be feasible routes into PMMA·HCl. The products of each step were analysed by gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance spectroscopy (1H NMR). Impurities were examined in an attempt to identify route specific compounds, which may provide valuable information about the synthetic pathway and precursors.

Organic impurity profiling of methylone and intermediate compounds synthesized from catechol.

This work examined the synthesis and organic impurity profile of methylone prepared from catechol. The primary aim of this work was to determine whether the synthetic pathway used to prepare 3,4-methylenedioxypropiophenone could be ascertained through analysis of the synthesized methylone. The secondary aim was the structural elucidation and origin determination of the organic impurities detected in methylone and the intermediate compounds. The organic impurities present in the reaction products were identified using GC-MS and NMR spectroscopy. Six organic impurities were detected in 1,3-benzodioxole and identified as the 1,3-benzodioxole dimer, 1,3-benzodioxole trimer, [1,3] dioxolo[4,5-b]oxanthrene, 4,4'-, 4,5'-, and 5,5'-methylenebis-1,3-benzodioxole. Six organic impurities were detected in 3,4-methylenedioxypropiophenone and identified as (2-hydroxyphenyl) propanoate, [2-(chloromethoxy) phenyl] propanoate, (2-propanoyloxyphenyl)propanoate, 5-[1-(1,3-benzodioxol-5-yl)prop-1-enyl]-1,3-benzodioxole, (5E)- and (5Z)-7-(1,3-benzodioxol-5-yl)-5-ethylidene-6-methyl-cyclopenta[f][1,3]benzodioxole). Exploratory synthetic experiments were also conducted to unambiguously identify the organic impurities detected in 3,4-methylenedioxypropiophenone. Two organic impurities were detected in 5-bromo-3,4-methylenedioxypropiophenone and identified as [2-(chloromethoxy)phenyl] propanoate and 3,4-methylenedioxypropiophenone. Five organic impurities were detected in methylone and identified as 3,4-methylenedioxypropiophenone, 1-(1,3-benzodioxol-5-yl)-N-methyl-propan-1-imine, 1-(1,3-benzodioxol-5-yl)-2-methylimino-propan-1-one, 1-(1,3-benzodioxol-5-yl)-N1,N2-dimethyl-propane-1,2-diimine and butylated hydroxytoluene. The origin of these organic impurities was also ascertained, providing valuable insight into the chemical profiles of methylone and the intermediate compounds. However, neither the catechol precursor nor the 1,3-benzodioxole intermediate could be identified based on the organic impurities detected in the synthesized methylone using standard techniques. This demonstrated that the organic impurity profiling of methylone had limitations in the determination of precursor chemical and synthetic pathways used. Copyright © 2017 John Wiley & Sons, Ltd.

Organic impurity profiling of 3,4-methylenedioxymethamphetamine (MDMA) synthesised from catechol.

This work examines the organic impurity profile of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from catechol (1,2-dihydroxybenzene), a common chemical reagent available in industrial quantities. The synthesis of MDMA from catechol proceeded via the common MDMA precursor safrole. Methylenation of catechol yielded 1,3-benzodioxole, which was brominated and then reacted with magnesium allyl bromide to form safrole. Eight organic impurities were identified in the synthetic safrole. Safrole was then converted to 3,4-methylenedioxyphenyl-2-propanone (MDP2P) using two synthetic methods: Wacker oxidation (Route 1) and an isomerisation/peracid oxidation/acid dehydration method (Route 2). MDMA was then synthesised by reductive amination of MDP2P. Thirteen organic impurities were identified in MDMA synthesised via Route 1 and eleven organic impurities were identified in MDMA synthesised via Route 2. Overall, organic impurities in MDMA prepared from catechol indicated that synthetic safrole was used in the synthesis. The impurities also indicated which of the two synthetic routes was utilised.