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Structure fragmentation studies of ring‐substituted N ‐trifluoroacetyl‐ N ‐benzylphenethylamines related to the NBOMe drugs
Author(s) -
Almalki Ahmad J.,
Clark C. Randall,
DeRuiter Jack
Publication year - 2020
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8593
Subject(s) - chemistry , electron ionization , radical ion , ring (chemistry) , medicinal chemistry , structural isomer , fragmentation (computing) , halogen , stereochemistry , ion , ionization , organic chemistry , alkyl , computer science , operating system
Rationale 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 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 2,5‐dimethoxyphenethylamine 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 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. 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 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.