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Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1732.
Published online 2008 August 9. doi:  10.1107/S1600536808025002
PMCID: PMC2960499

(2S,3S)-3-(4-Chloro­phen­yl)-8-methyl­tropane-2-carboxylic acid

Abstract

In the title compound, C15H18ClNO2, the inter­nal torsion angles of the tropane ring are comparable to those of tropane rings in the crystal structures reported for cocaine and its derivatives. There is an intra­molecular hydrogen bond between the N atom in the tropane ring and the O atom of the carboxyl group. The crystal structure is further stabilized by many weak C—H(...)O inter­actions between the mol­ecules in the ab plane, forming a two-dimensional supra­molecular network.

Related literature

For general background, see: Clarke et al. (1973 [triangle]); Carroll et al. (1991 [triangle], 2005 [triangle]). For related structures, see: Meltzer et al. (1997 [triangle], 2001 [triangle]); Zhu et al. (1999 [triangle]). For related literature, see: Meegalla et al. (1997 [triangle]). For a description of the Cambridge Structural Database, see: Allen (2002 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1732-scheme1.jpg

Experimental

Crystal data

  • C15H18ClNO2
  • M r = 279.75
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1732-efi1.jpg
  • a = 8.219 (6) Å
  • b = 6.501 (4) Å
  • c = 12.731 (8) Å
  • β = 100.692 (10)°
  • V = 668.4 (8) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.28 mm−1
  • T = 293 (2) K
  • 0.20 × 0.10 × 0.10 mm

Data collection

  • Bruker SMART APEX CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.956, T max = 0.976
  • 3374 measured reflections
  • 2760 independent reflections
  • 2264 reflections with I > 2σ(I)
  • R int = 0.042

Refinement

  • R[F 2 > 2σ(F 2)] = 0.052
  • wR(F 2) = 0.125
  • S = 0.99
  • 2760 reflections
  • 177 parameters
  • 2 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.21 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1135 Friedel pairs
  • Flack parameter: −0.15 (9)

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808025002/fj2136sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808025002/fj2136Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

This work was supported by the National Natural Science Foundation of China (30570518), the High Technology Research and Development Program of Jiangsu Province of China (BG2007603) and the Science Foundation of the Health Department of Jiangsu Province (H200401).

supplementary crystallographic information

Comment

(2S,3S)-3-(4-halogen-phenyl)tropane-2-carboxylic acid methyl ester and analogues, the so-called "WIN compounds" reported by Clarke et al. (1973), been used extensively in medicine as monoamine uptake inhibitors and dopamine transporter (Carroll et al., 1991, 2005). Among these, only several crystal structures have been reported (Meltzer et al., 1997, 2001; Zhu et al.,1999) (Cambridge Structural Database, Version 5.29, update of November 2007; Allen, 2002). As a vital intermediate compound for the stepwise reactions of dopamine transporter-imaging agent, the crystal structure of the title compound, (I) (Fig. 1), has not been studied yet. The internal torsion angles of the tropane ring in (I) are comparable to those tropane rings in the crystal structures reported for cocaine and its derivatives. There is an intramolecular hydrogen bond between the N10 atom in the tropane ring and O1 atom of the carboxylate group (Table 1). The crystal structure is further stabilized by many weak C—H···O interactions between the intramolecules along ab plane to form two-dimensional supramolecular network.(Fig. 2 and Table 1).

Experimental

Compound (I) was synthesized according to the method reported in the literature (Meegalla et al.,1997). A white powder was obtained (yield 41%) and was recrystallized from a mixed solvent composed of acetone, methanol and ether (1:1:1 v/v/v); white block-shaped crystals were obtained after several days (yield 36%). Analysis calculated for C15H18ClNO2: C 64.40, H 6.95, N 5.01%; found: C 64.17, H 6.98, N 4.90%.

Refinement

H atoms bonded to N atom was located in a difference map and refined with distance restraints of N—H = 0.881 (17) Å, and with Uiso(H) = 1.2Ueq(N). Other H atoms were positioned geometrically and refined using a riding model (including free rotation about the ethanol C—C bond), with C—H = 0.93–0.98 Å and with Uiso(H) = 1.2 (1.5 for methyl groups) times Ueq(C).

Figures

Fig. 1.
The molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms.
Fig. 2.
Perspective view of the supramolecular network along ab plane built from intermolecular weak C—H···O hydrogen bonding interactions (dashed lines). H atoms not involved in hydrogen bonding have been omitted.

Crystal data

C15H18ClNO2F000 = 296
Mr = 279.75Dx = 1.390 Mg m3
Monoclinic, P21Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 742 reflections
a = 8.219 (6) Åθ = 3.3–26.8º
b = 6.501 (4) ŵ = 0.28 mm1
c = 12.731 (8) ÅT = 293 (2) K
β = 100.692 (10)ºBlock, white
V = 668.4 (8) Å30.20 × 0.10 × 0.10 mm
Z = 2

Data collection

Bruker SMART APEX CCD diffractometer2760 independent reflections
Radiation source: fine-focus sealed tube2264 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.042
T = 293(2) Kθmax = 27.2º
[var phi] and ω scansθmin = 1.6º
Absorption correction: multi-scan(SADABS; Bruker, 2001)h = −8→10
Tmin = 0.956, Tmax = 0.976k = −8→8
3374 measured reflectionsl = −16→13

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.052  w = 1/[σ2(Fo2) + (0.0695P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.125(Δ/σ)max < 0.001
S = 0.99Δρmax = 0.25 e Å3
2760 reflectionsΔρmin = −0.21 e Å3
177 parametersExtinction correction: none
2 restraintsAbsolute structure: Flack (1983), 1135 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: −0.15 (9)
Secondary atom site location: difference Fourier map

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
Cl10.58072 (10)0.59422 (16)0.46455 (6)0.0650 (3)
O10.9356 (2)1.0348 (4)0.03436 (15)0.0508 (6)
O20.7924 (2)1.2275 (4)0.12844 (18)0.0614 (6)
C10.9057 (3)0.6847 (5)0.2742 (2)0.0414 (7)
H20.93760.61700.21690.050*
C20.7841 (3)0.6008 (5)0.3216 (2)0.0439 (7)
H30.73540.47630.29720.053*
C30.7350 (3)0.7004 (5)0.4043 (2)0.0433 (7)
C40.8053 (4)0.8847 (5)0.4423 (2)0.0464 (7)
H40.77030.95230.49850.056*
C50.9290 (3)0.9666 (5)0.3950 (2)0.0432 (7)
H50.97791.09020.42060.052*
C60.9824 (3)0.8694 (4)0.3104 (2)0.0335 (6)
C71.1233 (3)0.9616 (4)0.2641 (2)0.0350 (6)
H71.20840.99960.32560.042*
C81.0761 (3)1.1622 (4)0.2018 (2)0.0333 (6)
H81.05361.26650.25280.040*
C91.2231 (3)1.2388 (5)0.1525 (2)0.0361 (6)
H91.19761.37070.11590.043*
N101.2558 (3)1.0745 (4)0.07558 (17)0.0362 (5)
H10X1.157 (2)1.032 (5)0.045 (2)0.039 (8)*
C111.3402 (4)0.9115 (5)0.1503 (2)0.0463 (8)
H111.39690.81170.11210.056*
C121.2061 (4)0.8080 (4)0.1992 (2)0.0413 (7)
H12A1.25450.69670.24540.050*
H12B1.12330.74970.14280.050*
C131.3871 (3)1.2488 (5)0.2315 (3)0.0478 (8)
H13A1.36881.28140.30270.057*
H13B1.45921.35240.20990.057*
C141.4630 (3)1.0344 (6)0.2289 (2)0.0532 (8)
H14A1.56881.04200.20570.064*
H14B1.47970.97170.29920.064*
C150.9197 (3)1.1414 (4)0.1143 (2)0.0377 (6)
C161.3556 (4)1.1475 (5)−0.0028 (2)0.0484 (8)
H16A1.35831.0429−0.05570.073*
H16B1.46641.17660.03340.073*
H16C1.30681.2702−0.03690.073*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0584 (5)0.0864 (7)0.0526 (4)−0.0214 (5)0.0165 (4)0.0042 (5)
O10.0448 (12)0.0607 (15)0.0420 (11)−0.0054 (10)−0.0048 (9)−0.0107 (10)
O20.0358 (11)0.0697 (15)0.0758 (16)0.0112 (11)0.0029 (11)−0.0032 (13)
C10.0427 (15)0.0443 (18)0.0368 (14)−0.0029 (13)0.0060 (12)−0.0063 (12)
C20.0450 (15)0.0397 (16)0.0451 (15)−0.0061 (14)0.0033 (12)−0.0024 (14)
C30.0341 (14)0.059 (2)0.0348 (14)−0.0067 (13)0.0003 (12)0.0086 (14)
C40.0455 (17)0.060 (2)0.0342 (15)−0.0006 (15)0.0076 (12)−0.0077 (14)
C50.0429 (16)0.0426 (17)0.0424 (15)−0.0034 (13)0.0036 (12)−0.0102 (14)
C60.0327 (14)0.0343 (15)0.0311 (13)0.0039 (11)−0.0008 (11)0.0017 (11)
C70.0349 (14)0.0312 (14)0.0366 (13)0.0003 (11)0.0008 (11)−0.0014 (11)
C80.0336 (13)0.0300 (14)0.0352 (13)−0.0006 (10)0.0035 (11)−0.0050 (11)
C90.0365 (14)0.0340 (15)0.0352 (14)−0.0047 (12)0.0001 (11)−0.0025 (12)
N100.0327 (11)0.0390 (13)0.0359 (11)−0.0026 (10)0.0041 (9)−0.0007 (10)
C110.0444 (17)0.0428 (18)0.0535 (18)0.0140 (13)0.0141 (14)0.0073 (14)
C120.0468 (17)0.0317 (15)0.0478 (17)0.0072 (12)0.0152 (14)0.0047 (12)
C130.0370 (16)0.059 (2)0.0447 (17)−0.0138 (15)0.0005 (13)−0.0033 (15)
C140.0316 (14)0.074 (2)0.0516 (18)0.0067 (15)0.0024 (13)0.0168 (16)
C150.0334 (14)0.0333 (14)0.0441 (15)−0.0019 (11)0.0012 (12)0.0058 (12)
C160.0463 (16)0.055 (2)0.0462 (15)−0.0037 (14)0.0140 (13)0.0037 (14)

Geometric parameters (Å, °)

Cl1—C31.742 (3)C9—N101.506 (4)
O1—C151.258 (3)C9—C131.526 (4)
O2—C151.229 (3)C9—H90.9800
C1—C21.373 (4)N10—C161.482 (3)
C1—C61.394 (4)N10—C111.505 (4)
C1—H20.9300N10—H10X0.881 (17)
C2—C31.360 (4)C11—C141.511 (5)
C2—H30.9300C11—C121.520 (4)
C3—C41.378 (5)C11—H110.9800
C4—C51.380 (4)C12—H12A0.9700
C4—H40.9300C12—H12B0.9700
C5—C61.388 (4)C13—C141.530 (5)
C5—H50.9300C13—H13A0.9700
C6—C71.517 (4)C13—H13B0.9700
C7—C121.533 (4)C14—H14A0.9700
C7—C81.538 (4)C14—H14B0.9700
C7—H70.9800C16—H16A0.9599
C8—C151.542 (4)C16—H16B0.9599
C8—C91.544 (4)C16—H16C0.9599
C8—H80.9800
C2—C1—C6121.2 (3)C11—N10—C9101.8 (2)
C2—C1—H2119.4C16—N10—H10X112.8 (17)
C6—C1—H2119.4C11—N10—H10X110 (2)
C3—C2—C1119.7 (3)C9—N10—H10X104.4 (19)
C3—C2—H3120.1N10—C11—C14102.7 (3)
C1—C2—H3120.1N10—C11—C12106.7 (2)
C2—C3—C4121.4 (3)C14—C11—C12114.1 (3)
C2—C3—Cl1119.8 (2)N10—C11—H11111.0
C4—C3—Cl1118.8 (2)C14—C11—H11111.0
C3—C4—C5118.5 (3)C12—C11—H11111.0
C3—C4—H4120.8C11—C12—C7111.1 (2)
C5—C4—H4120.8C11—C12—H12A109.4
C4—C5—C6121.8 (3)C7—C12—H12A109.4
C4—C5—H5119.1C11—C12—H12B109.4
C6—C5—H5119.1C7—C12—H12B109.4
C5—C6—C1117.4 (3)H12A—C12—H12B108.0
C5—C6—C7119.7 (2)C9—C13—C14105.1 (3)
C1—C6—C7122.8 (2)C9—C13—H13A110.7
C6—C7—C12113.6 (2)C14—C13—H13A110.7
C6—C7—C8113.4 (2)C9—C13—H13B110.7
C12—C7—C8111.7 (2)C14—C13—H13B110.7
C6—C7—H7105.8H13A—C13—H13B108.8
C12—C7—H7105.8C11—C14—C13105.7 (2)
C8—C7—H7105.8C11—C14—H14A110.6
C7—C8—C15113.2 (2)C13—C14—H14A110.6
C7—C8—C9109.9 (2)C11—C14—H14B110.6
C15—C8—C9110.2 (2)C13—C14—H14B110.6
C7—C8—H8107.8H14A—C14—H14B108.7
C15—C8—H8107.8O2—C15—O1126.1 (3)
C9—C8—H8107.8O2—C15—C8118.2 (3)
N10—C9—C13102.5 (2)O1—C15—C8115.7 (2)
N10—C9—C8106.5 (2)N10—C16—H16A109.5
C13—C9—C8114.1 (2)N10—C16—H16B109.5
N10—C9—H9111.1H16A—C16—H16B109.5
C13—C9—H9111.1N10—C16—H16C109.5
C8—C9—H9111.1H16A—C16—H16C109.5
C16—N10—C11113.8 (2)H16B—C16—H16C109.5
C16—N10—C9113.5 (2)
C6—C1—C2—C31.0 (4)C13—C9—N10—C16−77.9 (3)
C1—C2—C3—C4−0.2 (4)C8—C9—N10—C16162.0 (2)
C1—C2—C3—Cl1−180.0 (2)C13—C9—N10—C1144.8 (3)
C2—C3—C4—C5−0.6 (4)C8—C9—N10—C11−75.3 (2)
Cl1—C3—C4—C5179.2 (2)C16—N10—C11—C1477.3 (3)
C3—C4—C5—C60.6 (5)C9—N10—C11—C14−45.3 (2)
C4—C5—C6—C10.2 (4)C16—N10—C11—C12−162.4 (2)
C4—C5—C6—C7−177.7 (3)C9—N10—C11—C1275.1 (3)
C2—C1—C6—C5−1.0 (4)N10—C11—C12—C7−62.0 (3)
C2—C1—C6—C7176.8 (3)C14—C11—C12—C750.7 (3)
C5—C6—C7—C12160.8 (2)C6—C7—C12—C11177.2 (2)
C1—C6—C7—C12−16.9 (4)C8—C7—C12—C1147.4 (3)
C5—C6—C7—C8−70.3 (3)N10—C9—C13—C14−27.1 (3)
C1—C6—C7—C8112.0 (3)C8—C9—C13—C1487.5 (3)
C6—C7—C8—C15−53.2 (3)N10—C11—C14—C1328.0 (3)
C12—C7—C8—C1576.6 (3)C12—C11—C14—C13−87.0 (3)
C6—C7—C8—C9−177.0 (2)C9—C13—C14—C11−0.5 (3)
C12—C7—C8—C9−47.1 (3)C7—C8—C15—O2109.1 (3)
C7—C8—C9—N1062.1 (2)C9—C8—C15—O2−127.3 (3)
C15—C8—C9—N10−63.3 (3)C7—C8—C15—O1−70.6 (3)
C7—C8—C9—C13−50.1 (3)C9—C8—C15—O153.0 (3)
C15—C8—C9—C13−175.6 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N10—H10X···O10.881 (17)1.80 (2)2.599 (3)150 (3)
C9—H9···O1i0.982.283.148 (4)146
C16—H16A···O2ii0.962.483.282 (4)141
C14—H14A···O2iii0.972.543.439 (4)154

Symmetry codes: (i) −x+2, y+1/2, −z; (ii) −x+2, y−1/2, −z; (iii) x+1, y, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FJ2136).

References

  • Allen, F. H. (2002). Acta Cryst. B58, 380–388. [PubMed]
  • Bruker (2001). SMART and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • Carroll, F. I., Gao, Y. G., Rahman, M. A., Abraham, P., Parham, K., Lewin, A. H., Boja, J. W. & Kuhart, M. J. (1991). J. Med. Chem.34, 2719–2725. [PubMed]
  • Carroll, F. I., Tyagi, S., Blough, B. E., Kuhar, M. J. & Navarro, H. A. (2005). J. Med. Chem.48, 3852–3857. [PubMed]
  • Clarke, R. L., Daum, S. J., Gambino, A. J., Aceto, M. D., Pearl, J., Levitt, M., Cumiskey, W. R. & Bogado, E. F. (1973). J. Med. Chem.16, 1260–1267. [PubMed]
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Meegalla, S. K., Plossl, K., Kung, M. P., Chumpradit, S., Stevenson, D. A., Kushner, S. A., McElgin, W. T., Mozley, P. D. & Kung, H. F. (1997). J. Med. Chem.40, 9–17. [PubMed]
  • Meltzer, P. C., Liang, A. Y., Blundell, P., Gonzalez, M. D., Chen, Z. M. & Madras, B. K. (1997). J. Med. Chem.40, 2661–2673. [PubMed]
  • Meltzer, P. C., Wang, B., Chen, Z. M., Blundell, P., Jayaraman, M., Gonzalez, M. D., George, C. & Madras, B. K. (2001). J. Med. Chem.44, 2619–2635. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Zhu, N., Harrison, A., Trudell, M. L. & Klein-Stevens, C. L. (1999). Struct. Chem.10, 91–103.

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography