The crystal structure of free base cocaine, C₁₇H₂₁NO₄

Abstract

. Can. J. Chem. 61, 481 (1983).The crystal structure of free base cocaine has been determined in order to compare the conformation with that observed in its salts, and to clarify the powder pattern of the pure compound. Crystals of (-)-cocaine are monoclinic, space group P 2 , , a = 10.130(1), b = 9.866(2), c = 8.445(1) A, P = 106.92(1)", Z = 2, D, = 1.25 g cm-j. Data were collected with MoK, radiation on a modified Picker diffractometer using the NRCC diffractomcter control system. The structure was solved by direct methods and refined by least squares to final R and R,,, of 0.065 and 0.062 ( w = l / u 2 (F)) using the 1818 independent reflections with sin 8/X < 0.7048 and IFJ/u(~F() 5 3.0.The free base exists in a piperidine chair conformation similar to the methiodide salt and the hydrochloride salt. H!wever, the piperidine ring carbon-nitrogen bondso in the free base are shorter than those in the salts; 1.460(7) and 1.467(6) A in the free base compared to 1.55(2) and 1.5 l(2) A in the methiodide salt and 1.50(1) and 1.49(1) A in the hydrochloride salt. Further, the orientations of the benzoxy group and the methoxycarbonyl group, with respect to the piperidine rings, are significantly different from that common to both salts. The calculated powder diffraction pattern of (-)-cocaine showed that several previously reported weak lines in powder diffraction data for this alkaloid should not be present. On a dktermink la structure du cristal de la base libre cocaine dans le but de comparer sa conformation avec celle de ses sels et dans le but de clarifier le diagramme de poudre du composk pur. La base libre existe sous une conformation chaise de la pipkridine semblable au mkthiodure et au chlorhydra~e. Cependant les liaisons C-N du cycle pipkridine de la base libre sont plus courtes que celle des sels; 1,460(7) et 1,467(6) A dans la base libre comparCes 1,55(2) et 1,51(2) A pour le mkthiodure et 1,49(1) A pour le chlorhydrate. De plus, les orientations du groupe benzoxy et du groupe mkthoxycarbonyle par rapport au cycle de la pipkridine sont significativement diffkrentes de celles communes au deux sels. Le diagramme de diffraction de la poudre calculk pour la (-)-cocaine montre que plusieurs des lignes faibles rapportkes antkrieurement dans les donnkes de diffraction de poudre pour cet alcaloide ne devraient pas &tre prCsentes.[Traduit par le journal]

A semiempirical SCF MO study of the interaction of odorant molecules with a biological substrate

“…The calculations predict that the piperidine ring of cocaine adopts a chair conformation with the N-methyl group being equatorial. These features as well as the predicted bond lengths and bond angles were in reasonable agreement with those found for the solid free base by X-ray diffraction [22] and from an NMR and molecular mechanics study [23]. They were also in accord with a recent AM^ study of the conformations of cocaine and its diastereomers [24].…”

Powder crystallography of pharmaceutical materials by combined crystal structure prediction and solid-state 1H NMR spectroscopy

“…The reference crystal structure of cocaine, (CSD entry code: COCAIN10) (Scheme 1-I), was previously determined by single crystal X-ray diffraction (XRD) 39 at room temperature. The structure is comprised of 2 symmetry equivalent molecules in the unit cell, and it belongs to the P2 1 monoclinic space group with unit cell dimensions: a = 10.130(1) Å, b = 9.866(2) Å, c = 8.445(1) Å. Powdered flutamide (2-methyl-N(4-nitro-3-(trifluoromethyl)phenyl)propamide) was purchased from Sigma-Aldrich and used without further purification.…”

Determination of the N-invertomer stereochemistry in N-substituted nortropanones and norgranatanones using computational and NMR methods

“…Crystal structures indicated that the N-methyl in tropinone [27] and N-phenyl in the granatanone derivative [28] display the axial configuration in the solid state. The N-methyl configuration in the crystals depended on the derivative and was determined to be equatorial in cocaine [29] and its salts [30] as well as in phenyltropane [31], tropinone aldols [32,33], tropinone aldol tosylhydrazone [21], and granatanone aldols [34], but axial in scopolamine [35]. In some conformational studies of granatane derivatives by NMR methods [36], the N-methyl stereochemistry remained undetermined.…”