Redetermination of (+)-methamphetamine hydrochloride at 90 K

The title crystal structure (systematic name: N-methyl-1-phenylpropan-2-aminium chloride), C10H16N+·Cl−, was orginally determined by Simon, Bocskei & Torok [Acta Pharm. Hung. (1992). 62, 225–230] and Yao, Kan & Wang [Huaxue Shijie (1999). 40, 568–570] at room temperature but no atomic coordinates are available for these determinations. The molecule has interest with respect to biological activity. In the crystal structure, intermolecular N—H⋯Cl hydrogen bonds form one-dimensional chains.


Comment
The compound, (+)-methamphetamine hydrochloride has been reinvestigated in this study by single-crystal x-ray diffraction to provide a complete determination of the atomic coordinates and lattice dimensions at 90 (2) K. Earlier structural studies on this compound by Simon et al. (1992) and by Yanhong et al. (1999) were performed at or near room temperature and did not include atomic coordinates. The determination of crystallographic data at cryogenic temperatures improves the precision of the atomic coordinates and also provides insight into temperature-induced lattice changes. This information is important in the complete understanding of the molecular solid and is particularly useful for validation of first-principles solid-state modeling.
The compound studied is a synthetic sympathomimetic drug and is specified as a controlled substance by the United States Federal government (O'Neil et al., 2001). The substance is a strong stimulant that affects the central nervous system (CNS) and contributes cardiactoxicity (Yu et al., 2003). The use of methamphetamine has increased substantially and is becoming a problem nation wide with its use increasing across all age groups (Cho & Melega, 2002). The compound has a more potent effect on the CNS than structurally similar amphetamine due to its increased penetration of the CNS (Davis & Swalwell,1994). The potency of methamphetamine is also dependent upon its chirality, as its dextrorotatory enantiomer exhibits an effect roughly fives times greater than that provided by the levorotatory enantiomer (Cho, 1990). The stimulant effects of methamphetamine can be compared to the effects brought on by the use of cocaine, however, the duration of the effects can be much greater for the methamphetamine than for cocaine (Cho, 1990).
The (+)-methamphetamine hydrochloride form of methamphetamine has become the primary form used (Cho & Melega, 2002). This highlights the importance of complete characterization of the substance. Knowledge of the solid-state Crystal Structure of this compound is imperative for its identification and detection via various spectroscopic methods, such as solid-state NMR and terahertz. The unit-cell dimensions determined by this study are slightly smaller than those published by Simon et al., (1992) leading to a reduction in the unit cell volume of approximately 2.4% from the previously calculated value. Overall the basic structural parameters, such as the space group, P2 1 , are in agreement with earlier work (Simon et al., 1992).

Experimental
The material for this work was purchased from Sigma-Aldrich and was used without any further purification.

Refinement
H atoms were located in a difference map and refined freely.
supplementary materials sup-2 Figures   Fig. 1. The molecular structure of the title compound, with the atom numbering scheme and thermal ellipsoids drawn at 50% probability level.   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.