Chiral analysis of chloro intermediates of methylamphetamine by one-dimensional and multidimentional NMR and GC/MS.
Impurity profiling and classification of abused drugs using chiral analytical techniques is of particular interest and importance because of the additional information obtained from this approach. When these methods are applied to the synthesis of illicitly used substances, they can supply valuable information about the conditions/chemicals used in the synthesis. We have applied GC and NMR methods to the study of intermediates found in methylamphetamine manufacture with the aim of linking the intermediates to the ephedrine/pseudoephedrine starting materials. Therefore, determination of the stereochemical makeup within samples of forensic interest is important giving further specific information to the analyst. This study investigates the stereochemical course of the Emde synthesis of methylamphetamine with particular focus on intermediate formation via the chlorination of ephedrine and pseudoephedrine enantiomers. The configurations of these chloro-phenethylamines were determined by 1D and 2D NMR analysis, and thereafter, the GC/MS analysis was carried out. We have shown here that chlorination of the ephedrine/pseudoephedrine compounds occurs via inversion (S(N)2) and retention (S(N)i) of configuration around the α carbon and mixture of diastereoisomers (chloroephedrine and chloropseudoephedrine) were formed, with the ratio of the resulting compounds dependent on the precursors used. The preparation and analytical properties of these intermediate standards provide data for laboratories interested in the stereochemical analysis of methylamphetamine intermediates such as forensic/law enforcement, and illustrate the value of using a combination of analytical methodology.
Department of Analytical Chemistry, Chemical Faculty, Gdańsk University of Technology, Gdańsk, Poland. plotkajustyna@gmail.com
Justyna M
JM
Płotka
Calum
C
Morrison
David
D
Adam
Marek
M
Biziuk
D000697:Central Nervous System Stimulants / Q000138:chemical synthesis / Q000737:chemistry*; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008694:Methamphetamine / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000697:Central Nervous System Stimulants; C420125:chloroephedrine; D008694:Methamphetamine; D004809:Ephedrine