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

NCJ Number
300993
Journal
Rapid Communications in Mass Spectrometry Volume: 34 Issue: 4 Dated: 2020
Author(s)
A. J. Almalki; et al
Date Published
2020
Annotation

Since the halogenated derivatives of N-(2-methoxy)benzyl-2,5-dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs, the current study sought 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.

Abstract

The systematic removal of substituents from the 4-halogenated 2,5-dimethoxyphenethylamine portion of the N-dimethoxybenzyl NBOMe analogues enabled an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzyl-substituted 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. The analogues yielded 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 12 isomers. Only one isomer in the phenethylamine series yields the corresponding unsubstituted phenylethene radical cation at m/z 104. The study concluded that 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 electron-donating 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. (publisher abstract modified)