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Acta Cryst. (2008). E64, o1732    [ doi:10.1107/S1600536808025002 ]

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

Z.-P. Chen, S.-P. Wang, X.-M. Li, J. Tang and J.-G. Lin

Abstract top

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.

Comment top

(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).

Related literature top

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

Experimental top

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 top

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).

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms.
[Figure 2] 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.
(2S,3S)3-(4-Chlorophenyl)-8-methyltropane-2-carboxylic acid top
Crystal data top
C15H18ClNO2F000 = 296
Mr = 279.75Dx = 1.390 Mg m−3
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 mm−1
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 top
Bruker SMART APEX CCD
diffractometer		2760 independent reflections
Radiation source: fine-focus sealed tube2264 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.042
T = 293(2) Kθmax = 27.2º
φ 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 top
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 Å−3
2760 reflectionsΔρmin = −0.21 e Å−3
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
Crystal data top
C15H18ClNO2V = 668.4 (8) Å3
Mr = 279.75Z = 2
Monoclinic, P21Mo Kα
a = 8.219 (6) ŵ = 0.28 mm−1
b = 6.501 (4) ÅT = 293 (2) K
c = 12.731 (8) Å0.20 × 0.10 × 0.10 mm
β = 100.692 (10)º
Data collection top
Bruker SMART APEX CCD
diffractometer		2760 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		2264 reflections with I > 2σ(I)
Tmin = 0.956, Tmax = 0.976Rint = 0.042
3374 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.052H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.125Δρmax = 0.25 e Å−3
S = 0.99Δρmin = −0.21 e Å−3
2760 reflectionsAbsolute structure: Flack (1983), 1135 Friedel pairs
177 parametersFlack parameter: −0.15 (9)
2 restraints
Special details top

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) top
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) top
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, °) top
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, °) top
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.
Table 1
Hydrogen-bond geometry (Å, °) top
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.
Acknowledgements top

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).

references
References top

Allen, F. H. (2002). Acta Cryst. B58, 380–388.

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.

Carroll, F. I., Tyagi, S., Blough, B. E., Kuhar, M. J. & Navarro, H. A. (2005). J. Med. Chem. 48, 3852–3857.

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.

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.

Meltzer, P. C., Liang, A. Y., Blundell, P., Gonzalez, M. D., Chen, Z. M. & Madras, B. K. (1997). J. Med. Chem. 40, 2661–2673.

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.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Zhu, N., Harrison, A., Trudell, M. L. & Klein-Stevens, C. L. (1999). Struct. Chem. 10, 91–103.