High-resolution solid state 13C nuclear magnetic resonance spectra of 3,4-methylenedioxyamphetamine hydrochloride and related compounds and their mixtures with lactose

Differences between solution and solid state ¹³C nuclear magnetic resonance spectra of some amphetamines namely, 3,4-methylenedioxyamphetamine·HCl, (R,S)-MDA·HCl, the methyl derivative 3,4-methylenedioxy-N-methylamphetamine·HCl, (R,S)-MDMA·HCl, the ethyl derivative, (R,S)-MDEA·HCl, and the analogues (R,S)-methamphetamine·HCl, (?)-ephedrine·HCl (the 3R,2S enantiomer as numbered here), and (+)-pseudo-ephedrine·HCl (the 3S,2S enantiomer as numbered here) have been studied and related to their crystal structure. For (R,S)-MDMA·HCl, an interesting new finding is that the observed solid state chemical shifts changed when lactose monohydrate was added as a dry powder and thoroughly mixed at room temperature. This experiment mimicked the illicit production of “Ecstasy” tablets. The mixing phenomena with lactose observed for (R,S)-MDMA·HCl was not seen for the other compounds studied. The results are discussed in terms of hydrogen bonding and possible polymorphs. It appears that lactose affects crystal packing by reducing conformational rigidity so that the molecule more closely resembles that in solution.