Synthesis and characterization of 5‐methoxy‐2‐methyl‐N,N‐dialkylated tryptamines

Summary

Thirteen new tryptamine derivatives were synthesized and analyzed to provide reference data for forensic and clinical identification. Using NMR and mass spectrometry, the compounds were characterized and distinguished from each other and from related substances. Key mass spectral fragments were identified, including an iminium ion and indole-related ions at specific mass-to-charge ratios. The work extends earlier research on similar compounds and supplies analytical standards that can help professionals identify these substances before they cause adverse health effects.

Study at a glance

Abstract

The absence of reference material is a commonly experienced difficulty among medical and forensic professionals tasked with identifying new psychoactive substances that are encountered for the first time. The identification of newly emerging substances lies at the heart of forensic and clinical analysis, and a proactive public health policy calls for a thorough analysis of the properties of new psychoactive substances before they appear in the emergency clinic, where they may be noticed because of adverse reactions or toxicity. For example, a wide range of N,N-dialkyltryptamines show psychoactive properties in humans and these tryptamines are sometimes encountered as intoxicants. However, most of the existing reference data on new psychoactive tryptamines have been obtained retrospectively, after reports of acute toxicities. To address the need for reference standards for new tryptamines, thirteen 5-methoxy-2-methyl-N,N-dialkyltryptamines were prepared. Analytical characterization was based on ¹H and ¹³C nuclear magnetic resonance (NMR), gas chromatography-electron ionization ion-trap mass spectrometry (GC-EI-IT-MS) and chemical ionization-ion-trap tandem mass spectrometry (CI-IT-MS/MS), respectively. Differentiation among isomers was feasible by NMR and MS. In addition to the expected iminium ion base peak, indole-related key ions were detected under EI-IT-MS conditions at m/z 174, 159, 131, 130, and 103. CI-IT-MS/MS analysis of the 5-methoxy-2-methyl derivatives revealed the presence of m/z 188 in addition to [M+H]+ and the iminium species. This study served as an extension from previous work on isomeric 5-ethoxylated counterparts and confirmed the ability to differentiate between the two groups. The data provided here add to the existing body of literature and aim to serve both forensic and clinical communities.