Syntheses and analytical characterizations of N‐alkyl‐arylcyclohexylamines

Abstract

Abstract:The rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continued to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances the syntheses of fifteen Nalkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, N-ethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3-and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from a 3-methylphenyl and 2-thienyl moiety. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxyl-substituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions. Running title: Characterization of N-alkyl-arylcyclohexylamines AbstractThe rise in new psychoactive substances that are available as 'research chemicals' (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continued to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances the syntheses of fifteen N-alkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, Nethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3-and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from a 3-methylphenyl and 2-thienyl moiety. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxylsubstituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions.

Syntheses, analytical and pharmacological characterizations of the ‘legal high’ 4‐[1‐(3‐methoxyphenyl)cyclohexyl]morpholine (3‐MeO‐PCMo) and analogues

“…The six morpholine analogues investigated in this study (Figure B) were synthesized using the modified Geneste route as reported previously for the preparation of PCP and PCPy analogues . The conversion from the primary amine (PCA) to the morpholine ring was performed using an S N 2 cyclization reaction between the substituted PCA material and bis(2‐bromoethylether) (Figure ) and gave ~ 45% yields following purification by column chromatography and recrystallization.…”

“…The syntheses of the primary amine intermediates were performed using a modified Geneste route (Figure ) as described previously . Reactions starting from the primary amine intermediate to yield the morpholine ring products were carried out in a CEM Discover SP microwave synthesizer.…”

“…Reactions starting from the primary amine intermediate to yield the morpholine ring products were carried out in a CEM Discover SP microwave synthesizer. The primary amine (PCA) intermediates were available from previous studies …”

“…Synthetic scheme used for the preparation of the investigated PCMo series via the modified Geneste route . TFA: trifluoroacetic acid; TEA: triethylamine.…”

“…Substances that target the NMDAR are of interest for the development of treatment options for conditions such as depression, neuropathic pain and a variety of neurodegenerative disorders and dementias . At the same time, a number of these substances are used recreationally, outside of a medical setting, and include compounds that have not undergone any substantial pharmacological and toxicological evaluations.…”