Isomeric Fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs)

An impressively large number of clandestinely produced controlled-substance analogues (designer drugs) of amphetamine with high structural variety have been encountered in forensic samples in recent years. The continuous designer drug exploration and their widespread consumption results in an increasing number of reports regarding abuse and intoxication. This study presents the analytical properties of a series of new fluoro-methoxy-substituted controlled-substance analogues of amphetamine. Three ring positional isomeric fluoroamphetamines, two isomeric fluoromethoxyamphetamines, two N-alkyl 4-fluoroamphetamines, and one 4-fluorophenylbutan-2-amine were identified and differentiated by gas chromatography-mass spectrometry (GC-MS), 1H- and 13C-nuclear magnetic resonance (NMR), and gas chromatography-infrared spectroscopy (GC-IR). The regioisomeric 2-, 3-, and 4-fluoroamphetamines and the regioisomeric fluoro-methoxyamphetamines show virtually identical mass spectra so that this method is insufficient to discriminate between these closely related compounds. The mass spectra of the acetylated compounds allowed a differentiation of the 4-fluoroamphetamine from its regioisomeric 2- and 3-fluoroamphetamines. The gas chromatographic properties of the three regioisomeric fluoroamphetamines and their acetylated and trifluoroacetylated derivatives are also so similar that a complete separation of these compounds could not be achieved under GC-MS conditions. The two isomeric compounds 5-fluoro-2-methoxyamphetamine and 3-fluoro-4-methoxyamphetamine on the other hand showed significant different gas chromatographic retention times so that a separation was uncomplicated. The trifluoroacetylation of these compounds proved to be an effective method for their mass spectral differentiation. Gas chromatography-infrared spectroscopy and 1H- and 13C-nuclear magnetic resonance allowed an unequivocal differentiation of all studied regioisomeric fluoroamphetamines and fluoro-methoxyamphetamines.