Origins of N-formylmethamphetamine and N-acetylmethamphetamine in methamphetamine produced by the hydriodic acid and red phosphorus reduction of pseudoephedrine

Abstract

N-Formylmethamphetamine (FMA) and N-acetylmethamphetamine (AMA) are suspected to be trace by-products in methamphetamine (MA) produced from pseudoephedrine using the Nagai reaction. However, these amides are not rational by-products of the Nagai reaction.FMA is an intermediate in the synthesis of MA using the Leuckart reaction. However, as there is the possibility that FMA is a by-product of the Nagai reaction, the significance of FMA as an indicator of the Leuckart reaction has been debated. It is therefore important to establish whether AMA and especially FMA are by-products of the Nagai reaction and thus establish their significance as synthetic route markers.From the work presented here, FMA is a by-product of the Nagai reaction but the mechanism by which FMA arises could be not determined.AMA was also shown to be a by-product of the Nagai reaction, most likely due to reaction between MA and phenyl-2-propanone (P-2-P), itself a by-product of the Nagai reaction. Furthermore, during GC analysis of Nagai reaction products, MA has been shown to react with P-2-P or ethyl acetate in the injector to form AMA.Caution is recommended if the relative abundance of AMA and/or FMA are used as a basis for determining whether MA samples have a common source or not. Furthermore, it is clear that FMA cannot be considered to be a route-specific by-product for the Leuckart reaction – it is the abundance of FMA in a reaction mixture or profile, not simply its presence, that points to the involvement of the Leuckart reaction.