Identification and characterization of N‐tert‐butoxycarbonyl‐MDMA: a new MDMA precursor

Abstract

In September 2015, 80 litres of a viscous, light-red liquid, described as hair product, was seized by the Australian Border Force (ABF). Initial testing by ABF indicated that the liquid was the 3,4-methylenedioxymethamphetamine (MDMA) precursor chemical safrole and custody of the material was transferred to the Australian Federal Police (AFP) who coordinated all subsequent investigations. Initial gas chromatography-mass spectrometry (GC-MS) analysis by the AFP indicated that the material was not safrole and samples of the liquid were transferred to the National Measurement Institute Australia (NMIA) for identification. Using a combination of nuclear magnetic resonance spectroscopy (NMR), GC-MS, infrared spectroscopy, and synthesis, the unknown substance was identified as N-tert.-butoxycarbonyl-MDMA (t-BOC-MDMA). The substance was also converted in high yield to MDMA (aqueous HCl, 80 °C, 30 min). The possibility that the t-BOC-MDMA may act as a pro-drug following ingestion was explored by exposure to simulated gastric juice (pH 1.5) and monitored by NMR (37 °C) at various intervals. The majority of t-BOC-MDMA was converted to MDMA after 305 min, which suggested that this derivatized form might serve as a pro-drug in vivo. An investigation into the chemistry of potential pro-drugs showed that t-BOC derivatives of methamphetamine, pseudoephedrine and 4-methylmethcahtinone (mephedrone) could also be prepared using di-tert.-butyl dicarbonate. The appearance of t-BOC-derivatives on the drug market requires further monitoring. © 2016 Commonwealth of Australia. Drug Testing and Analysis © 2016 John Wiley & Sons, Ltd.

Identification and characterization of chemically masked derivatives of pseudoephedrine, ephedrine, methamphetamine, and MDMA

“…While it is common to find ions one mass unit apart, as a result of hydrogen atom loss/gain from internal rearrangement, it is likely that the fragments at m/z 57 and 58 are independent, as m/z 57 is a common ion observed in the EI mass spectra of t ‐Boc‐protected compounds. An alternative pathway for the formation of the fragment ion at m/z 102 was proposed by Collins et al (2016), producing the fragment ion directly from the molecular ion (Pathway 2, Figure ) . The EI mass spectra of t‐ Boc methamphetamine and t ‐Boc MDMA displayed the same fragment ions as those generated by N‐t ‐Boc pseudoephedrine, with the exception of ions at m/z 91 and 135 forming instead of the ion at m/z 107, respectively, due to the difference in structure of the core compound (Figure ).…”

“…Altering the chemical structure of a drug is used widely to evade the traditional detection techniques and legislative control . A novel method of drug concealment has recently been encountered where the chemical structure of the drug, or precursor, is altered by way of appending protecting groups to mask the functional group reactivity, thereby changing the drug's chemical signature . The identity of these new substances is difficult for authorities to determine as traditional techniques rely on reference spectra in databases or published in the literature, which are typically limited for novel compounds.…”

“…Since 2015, instances of such chemical concealment have been reported in Australia, New Zealand, and the Netherlands, with tert ‐butoxycarbonyl ( t ‐Boc) 3,4‐methylenedioxymethamphetamine (MDMA) being the first masked compound to be detected. Di‐ tert ‐butyl dicarbonate is one of the most common amine protecting group reagents, widely used in synthetic chemistry due to its stability in alkaline environments and the little chemical expertise required to both affix and remove the group from the compound of interest .…”

‘APAAN in the neck’ – A reflection on some novel impurities found in seized materials containing amphetamine in Ireland during routine forensic analysis

“…[14,42] Obtaining product and remaining 'legal' (and thus beyond control mechanisms) may provide information about what appears to be the possible start of a new trend in the supply of precursors for illicit production facilities. [46,47] The illicit precursor suppliers exploit the fact that in many countries (including Ireland), no legal sanctions apply to substances that are not specifically listed either internationally or in their respective national legislation as precursors. Alternatively, some moiety may be added to the desired synthesized substance that can subsequently be easily removed.…”

“…[42] Worldwide seizures of P2P derivatives, phenylacetic acid and benzaldehyde have increased in recent years, indicating a shift to P2P as the main precursor used in both North and Central America, as well as in Europe, in the production of both amphetamine and methamphetamine. [46,47] APAAN hydrolysis experiments APAAN, when subjected to acidic medium forms P2P and benzaldehyde along with other by-products. The provision of information about new impurities arising from new methods of production is important for clandestine laboratory investigators.…”