Identification of common impurities present in the synthetic routes leading to 4-methylthioamphetamine (4-MTA). Part II: Reductive amination and nitropropene route

In this paper the by-products arising during the synthesis of 4-methylthioamphetamine (4-MTA) by LiAlH4 reduction of 1-(4-methylthiophenyl)-2-nitropropene (nitropropene route) and reductive amination of 4-methylthiophenyl-2-propanone in the presence of NaCNBH4 are investigated. The identification of 4-methylthio derivatives of N-(β-phenylisopropyl)benzaldimine, 4-methylthio derivative of N-(β-phenylisopropyl)benzyl methyl ketimine, 1-(4-methylthiophenyl)-N-(4-methylthiobenzyl)-2-propanamine, (RS) and (SS/RR)-N,N-di-[β-(4-methylthiophenyl)isopropyl]amine, 4-methylthiobenzyl ether and methylthiobenzoic acid methyl ester as most prominent impurities in crude 4-MTA synthesised by reductive amination of 4-methylthiophenyl-2-propanone, is reported. Methylthio derivatives of 2-methyl-3-phenylaziridine, 2-benzylaziridine, and 4-methylthio derivative of BMK oxime as route-specific markers of nitropropene route leading to 4-MTA, were also characterized. The identity of these compounds was confirmed by their independent synthesis.