The hydrochloride salt of l-ecgonine, a congener of cocaine

The title compound, (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2.1]octane-2-carboxylic acid chloride, C9H16NO3 +·Cl−, is both a metabolite and a precursor of the tropane alkaloid l-cocaine. The carboxyl group is not involved in dimerization, but instead donates a hydrogen bond to the chloride counter-ion, which participates in two additional hydrogen bonds. The chloride ion is thus trigonally hydrogen bonded to three l-ecgonine cations. The quarternary N proton is intramolecularly hydrogen bonded to the carboxyl C=O group, an arrangement identical to that reported for both (−)-norcocaine and the tetrachloroaurate(III) salt of l-cocaine. One close intermolecular C—H⋯O contact exists.

The title compound, (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8azoniabicyclo[3.2.1]octane-2-carboxylic acid chloride, C 9 H 16 NO 3 + ÁCl À , is both a metabolite and a precursor of the tropane alkaloid l-cocaine. The carboxyl group is not involved in dimerization, but instead donates a hydrogen bond to the chloride counter-ion, which participates in two additional hydrogen bonds. The chloride ion is thus trigonally hydrogen bonded to three l-ecgonine cations. The quarternary N proton is intramolecularly hydrogen bonded to the carboxyl C O group, an arrangement identical to that reported for both (À)norcocaine and the tetrachloroaurate(III) salt of l-cocaine.
Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL software used to prepare material for publication: SHELXTL. Comment l-Ecgonine is a naturally occurring alkaloid found in the leaves of the coca plant, Erythroxylum coca. This tropane alkaloid is both a metabolite and a precursor of its congener, l-cocaine; it is the hydroxy acid obtained by complete acidic, alkaline, or enzymatic hydrolysis of both ester functions in l-cocaine. The presence of l-ecgonine in postmortem blood specimens demonstrates cocaine use when the provenance of the specimen is unknown, when preservation has been inadequate, or when other cocaine metabolites have been shown to be undetectable (Logan, 2001).
The authors have begun a study of the three-dimensional structures of several cocaine derivatives and report here the structure of the hydrochloride salt (I) of l-ecgonine. We have previously reported the absolute configuration of the gold(III) tetrachloride salt of l-cocaine (Wood et al., 2007).  (Wood et al., 2007). In the structure of (-)-norcocaine, Zhu et al. (1994) found an arrangement identical to that in (I), with N···O = 2.306 (2) Å and N-H···O = 129°. However, in the structure of l-cocaine·HCl, Zhu et al. (1999) (Table 1).
Experimental l-Ecgonine hydrochloride (I) was dissolved in water to yield a 500 µg ml −1 solution, 200 µl of which was combined with 200 µl of 0.5% gold(III) chloride (HAuCl 4 ·3H 2 O) solution acidified with HCl and allowed to crystallize by slow evaporation.
supplementary materials sup-2 Refinement All H atoms for (I) were found in electron-density difference maps. The amine, acid and the hydroxyl Hs were all allowed to refine fully. The methyl H atoms were put in ideally staggered positions with C-H distances of 0.98 Å and U iso (H) = 1.5U eq (C). The methylene and methine Hs were placed in geometrically idealized positions and constrained to ride on their parent C atoms with C-H distances of 0.99 and 1.00 Å, respectively, and U iso (H) = 1.2U eq (C).   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 > 2sigma(F 2 ) is used only for calculating R-factors(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.