Structure fragmentation studies of ring‐substituted N‐trifluoroacetyl‐N‐benzylphenethylamines related to the NBOMe drugs

Abstract

Rationale: The halogenated derivatives of N-(2-methoxy)benzyl-2,5dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was to determine the role of the electron-donating groups (halogen and dimethoxy) in the pathway of decomposition for the distonic molecular radical cation in the electron ionization mass spectrometry (EI-MS) process of the trifluoroacetamide (TFA) derivatives. Methods: The systematic removal of substituents from the 4-halogenated 2,5dimethoxyphenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzylsubstituted analogues (2,3-, 2,4-, 2,5-, 2,6-, 3,4-and 3,5-dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared, derivatized and analyzed via gas chromatography coupled with EI-MS. Results: The analogues yield two unique radical cation fragments from the decomposition of the common distonic molecular radical cation. The substituted phenylethene radical cation (m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation (m/z 263) is the base peak or second most abundant ion in the 2-and 3-monomethoxyphenethylamine isomers. However, the 2-and 3-methoxyphenylethene radical cation (m/z 134) is among the five most abundant ions for each of these twelve isomers. Only one isomer in the phenethylamine series yields the corresponding unsubstituted phenylethene radical cation at m/z 104. Conclusions: The decomposition of the hydrogen-rearranged distonic molecular radical cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the less electron-rich phenethyl aromatic rings. The addition of electrondonating groups to the aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the decomposition of the common distonic molecular radical cation to favor the formation of the electron-rich substituted phenylethene radical cation.

Electron ionization fragmentation studies for a series of 4‐methoxymethylene benzoate esters

“…Observed mass shifts for deuterated compounds often provide key insights into the process and structure of fragment ions. Stable isotope and homolog labeling has been applied to numerous MS studies 1,[16][17][18][19][20] and this technique has been a staple method for EI-MS fragmentation studies across many categories of compounds.…”

“…Comparative evaluation of the electron ionization (EI) mass spectra for regioisomeric and homologous substances provides unique insight into the details of molecular fragmentation mechanisms and pathways. [1][2][3][4][5] This study evaluated EI-mass spectroscopy (MS), MS/MS and chemical ionization (CI)-MS for a series of 1,4-disubstituted benzene derivatives containing small ether and ester groups and their stable isotope deuterated analogs. The target compounds were prepared as precursor substrates for the synthesis of phenethylamines having a regioisomeric relationship to many novel psychoactive substances (NPS).…”

Potential of chromatography and mass spectrometry for the differentiation of three series of positional isomers of 2‐(dimethoxyphenyl)‐N‐(2‐halogenobenzyl)ethanamines

“…A behavioral activity study was published only for regioisomers of 25I-NBBr. 40,41 A number of recent studies were focused on the differentiation of isomers of the NBOMe series of compounds by GC-MS and GC-FT-IR (for regioisomers), [42][43][44][45] and by GC-MS and UHPLC-HRMS 2 (for positional isomers). 17 On the contrary, information analysis presented in the scientific literature showed the complete absence of any analytical data on the differentiation of positional isomers of NBF, NBCl, and NBBr series.…”