Profiling ephedrine prepared from N‐methylalanine via the Akabori‐Momotani reaction

Abstract

Novel methods for synthesising methylamphetamine precursors are appearing in clandestine laboratories within Australia. One such laboratory involved the synthesis of ephedrine from N-methylalanine and benzaldehyde via the Akabori-Momotani reaction. This article presents chiral and stable isotope ratios of ephedrine synthesised via this method, along with a chemical profile of methylamphetamine produced from this ephedrine. Based on the chiral results and the δ C, δ N, and δ H values, it is possible to distinguish ephedrine made via the Akabori-Momotani reaction from ephedrine of a "natural", "semi-synthetic", or "fully-synthetic" origin. Methylamphetamine and ephedrine samples synthesised from benzaldehyde having an enriched δ H value (ie, > 0‰), via the Akabori-Momotani reaction, had an isotopic profile which set them apart from all other methylamphetamine samples. It was noted, however, that using stable isotope ratios alone to determine the precursor of methylamphetamine is limited; they could not with confidence differentiate between methylamphetamine and ephedrine synthesised from benzaldehyde having a depleted δ H value (ie, <0‰) from other ephedrine sources and phenyl-2-propanone based methylamphetamine samples profiled.

Detailed investigations into the Akabori–Momotani reaction for the synthesis of amphetamine type stimulants: Part 2

“…The activation energy for the 1,3-dipolar cycloaddition calculated in this study is approximately 80 kJmol -1 , which is comparable to literature barriers for 1,3-dipolar cycloadditions [17][18][19]. The possibility of the reaction occurring via stepwise mechanisms [20] was also examined theoretically but the barriers calculated were unreasonable 3 .…”

“…One of these novel methods is the Akabori-Momotani reaction and we have recently reported [1,2] the importance of this pathway in ATS production. Further, isotope and stereochemical profiling of ephedrine synthesised via this method has recently been reported [3]. The reaction was established in 1943 by Japanese chemists Akabori and Momotani [4], where N-methylalanine 1 was allowed to react with benzaldehyde 2a and produced a mixture of pseudoephedrine and ephedrine 5a in 16% yield.…”

Investigations into the stable isotope ratios of 1‐phenyl‐2‐propanone

“…The identity of all products was verified using gas chromatography/ mass spectrometry using the method of Anderson et al 15 The methylamphetamine purity was determined using gas chromatography with flame ionisation detection as outlined in our previous work or using qNMR procedure. 16,17…”

Characterization of Ephedrine as Illegal Methamphetamine Precursors Based on δ15N, δ13C, and δ2H Isotopes: Their Application for Methamphetamine Profiling in Indonesia

“…The natural, semi-synthetic, and fully-synthetic cluster had unique fingerprints for nitrogen and carbon isotope ratios. 14 The δ 15 N values of the synthetic cluster were more negative in the value range of -9.11‰ to -0.17‰ than the other clusters. On the other hand, for the natural and semi-synthetic clusters, fingerprints were in δ 13 C profile.…”