Methamphetamine and MDMA - Structural Similarity in NMR Spectroscopy

Methamphetamine and Ecstasy (or MDMA, 3,4-Methylenedioxymethamphetamine) are prominent recreational ‘club’ drugs. Both phenylethylamine derivatives, just as their hydrochloride salt forms, differ structurally only in the 3,4-dioxol fragment as depicted in Figure 1. Despite their similarity, the physiological activity of the drugs differs to an extent that users should be aware when mixing these.[1]

NMR spectra visualize the change in the Larmor frequency of each hydrogen atom in the analyte. This change is what we call the chemical shift of the signal which is dependent on electronic effects (see an interesting blog post about the role of electronegativity here). Well, similar molecules show similar NMR spectra and this is another advantage of NMR spectroscopy compared to other analytical methods: Derivatives or in this case new psychological active substances or ‘designer drugs’ can be recognized as a potential illicit compound, which is what we are currently working on with police authorities in Germany.

Figure 1. ¹H NMR spectra of Methamphetamine*HCl (left) and MDMA*HCl (right).

In the NMR spectra, the aliphatic signal sets (between 1 and 4 ppm) look pretty much the same for both compounds. It seems like the oxygen atoms of the dioxol group do not affect the electronic environment of the other aliphatic hydrogen atoms significantly. It has to be noted that the residual solvent signal of DMSO-d6 and the water impurity of the solvent overlap with the NCH₃, NCH, and NCHCH₂ signals. This causes the deviation of the integration areas for these signals, but they still fit quite well. NMR spectroscopy is also great to point out structural differences. We can see that in the MDMA spectrum there is an additional methylene signal at 5.99 ppm and the splitting pattern of the aromatic signals differs a lot from the methamphetamine spectrum due to the benzene substitution. As you see, NMR spectroscopy can prove structural similarity and also point out structural differences.

[1] K. J. Clemens, I. S. McGregor, G. E. Hunt, J. L. Cornish, Drug and Alcohol Review 2007, 26, 9 – 15.