Methamphetamine, a drug frequently abused in the United States, is often manufactured illicitly. One method commonly employed for this purpose is the Leuckart reaction, which is initiated with methyl benzyl ketone (IV) and either methylamine (I) and formic acid (II) or N-methylformamide (III), producing N-formylmethamphetamine (IX) as an intermediate [1]. Hydrolysis of IX with a strong acid such as hydrochloric acid produces methamphetamine (VI). (See Table 1 for a list of abbreviations and Fig. 1 for corresponding structures.) As the synthesis proceeds, various impurities are accumulated: reactants, byproducts, and intermediates, as well as contaminants arising from within the reagents themselves. The identification of such impurities thus far encountered in this laboratory by gas chromatography/mass spectrometry (GC/MS) and nuclear magnetic resonance (NMR) spectroscopy will be the subject of this discussion.
Three impurities have been identified in illicit methamphetamine samples. One of these, N-formylmethamphetamine (N-methyl-N-(α-methylphenethyl) formamide), is an intermediate in the synthesis of methamphetamine by the Leuckart reaction. The remaining 2, ,α,α’-trimethyldiphenethylamine and α-benzyl-N-methylphenethylamine, are by-products of methamphetamine synthesis. Ultraviolet, infrared, nuclear magnetic resonance, and gas chromatographic- mass spectral techniques were used to identify these compounds. The data obtained are discussed and synthetic pathways are postulated to explain the presence of each compound in samples of methamphetamine.
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