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

- 4-Methoxymethamphetamine (PMMA) was synthesised from star anise and from 4-methoxytoluene.
- Organic impurity profiles of PMMA have been examined.
- The organic impurities of the intermediate 4-methoxyphenyl-2-propanone have been examined.
- The organic impurities in PMMA did not allow discrimination of the pathways or starting materials.

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.