GC–MS analysis of N-(bromodimethoxybenzyl)-2-, 3-, and 4-methoxyphenethylamines: Inverse analogues of the psychoactive 25B-NBOMe drug

Abstract

The substituted phenethylamine analogues in this study are derivatives of N-(2-methoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine (25B-NBOMe) having the reverse substitution pattern for the two aromatic rings. These compounds contain only a single methoxy substituent in the phenethylamine part, and a bromodimethoxy substitution pattern in the benzyl portion. The regioisomers were prepared with variations in the substitution pattern in both the bromodimethoxy substitution pattern of the benzyl part as well as the methoxy substitution pattern in the phenethylamine part. The nine regioisomeric compounds were prepared from the regioisomeric 2-, 3-, and 4- methoxyphenethylamines via N-reductive alkylation with the three regioisomeric 2,4,5-substituted bromodimethoxybenzaldehydes.The EI-MS spectra of these regioisomers gave two major bromine containing ions at m/z 229/231 (base peak) and 258/260 and two non-brominated fragments at m/z 91 and 121. The relative abundance of the m/z 91 was higher for the 2-methoxyphenethylamine substituted isomers and the relative abundance of the m/z 121 fragment was higher in the 4-methoxy substituted isomers. The gas chromatographic separation for the regioisomeric methoxyphenethylamines of each bromodimethoxybenzyl aromatic ring substitution pattern showed the 2-methoxyphenethylamine substituted isomer eluted first followed by the 3-substituted isomer and the 4-methoxyphenethylamine substituted isomer was the last to elute and the three bromodimethoxybenzyl regioisomers for the 2-methoxyphenethylamine subseries were resolved as the trifluoroacetamides. The EI-MS for the TFA derivatives of the 2-bromo-4,5-dimethoxybenzyl substituted isomer gave unique fragment ions resulting from displacement of bromine from the molecular ion. This fragmentation pathway was confirmed using the model compounds N-(2-, 3- and 4-bromobenzyl)phenethylamine trifluoroacetamides.