PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 January 1; 65(Pt 1): o79.
Published online 2008 December 10. doi:  10.1107/S1600536808041068
PMCID: PMC2967988

1,2,3,4-Tetra­hydro-1,4-methano­naphthalene-2,3-diol

Abstract

The title compound, C11H12O2, is an inter­mediate in the synthesis of Varenicline, a nicotinic receptor partial agonist used to treat smoking addiction. In the crystal structure, there is an intra­molecular O—H(...)O hydrogen bond that generates an S(5) ring motif. Inter­molecular O—H(...)O hydrogen bonds form centrosymmetric dimers and also link these dimers into chains along the a axis.

Related literature

For background to the use of Varenicline to treat smoking addiction, see: Vetelino, (2004 [triangle]); Coe (2005 [triangle]). For details of graph-set analysis of hydrogen-bonding patterns, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-00o79-scheme1.jpg

Experimental

Crystal data

  • C11H12O2
  • M r = 176.21
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-00o79-efi1.jpg
  • a = 10.240 (2) Å
  • b = 6.2370 (12) Å
  • c = 27.503 (6) Å
  • V = 1756.5 (6) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 (2) K
  • 0.30 × 0.20 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.973, T max = 0.991
  • 1581 measured reflections
  • 1581 independent reflections
  • 1045 reflections with I > 2σ(I)
  • 3 standard reflections every 200 reflections intensity decay: none

Refinement

  • R[F 2 > 2σ(F 2)] = 0.063
  • wR(F 2) = 0.168
  • S = 1.03
  • 1581 reflections
  • 118 parameters
  • H-atom parameters constrained
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.27 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808041068/sj2556sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808041068/sj2556Isup2.hkl

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

Acknowledgments

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

supplementary crystallographic information

Comment

The title compound, I, is an important intermediate in the synthesis of Varenicline, a nicotinic receptor partial agonist used to treat smoking addiction (Vetelino, 2004). Varenicline came onto the market in 2006 and displays high affinity for neuronal nicotinic acetylcholine receptors (nAChRs), which mediate the dependence-producing effects of nicotine (Coe, 2005).

We report here the crystal structure of the title compound, (I), Fig. 1. The saturated six-membered C4,C5,C7···C10 ring of the anthracene group carries hydroxy substituents on C8 and C9 and is bridged by the C11 methylene group. In the crystal structure an intramolecular O1—H1A···O2 hydrogen bond generates an S5 ring motif (Bernstein et al., 1995). Intermolecular O1—H1A···O2 hydrogen bonds form centrosymmetric dimers and link these dimers into chains along the a axis, Table 2, Figure 2.

Experimental

1,4-Dihydro-1,4-methanonaphthalene (79.5 g, 560 mmol) in acetone (800 ml) and H2O (100 ml) was stirred with N-methyl morpholine N-oxide (67.5 g, 576 mmol). OsO4 (15 ml of a 15 mol% t-BuOH solution, 1.48 mmol,0.26mol%) was added and the mixture was stirred vigorously. After 60 h, the solution was filtered, and the white solid product rinsed with acetone and air-dried (60.9 g). The mother liquor was partially concentrated to an oily solid which was triturated with acetone, filtered and rinsed with acetone to provide additional amounts of the title compound (27.4 g, total 88.3 g, 89%). An X-ray grade crystal of I was grown from acetone (10 ml) at room temperature.

Refinement

H atoms bound to O were located in a difference Fourier map and fixed in these positions with Uiso = 1.5Ueq (O). Other H-atoms were positioned geometrically and refined using a riding model with d(C-H) = 0.93Å, Uiso = 1.2Ueq (C) for aromatic 0.98Å, Uiso = 1.2Ueq (C) for CH, 0.97Å, Uiso = 1.2Ueq (C) for CH2 groups.

Figures

Fig. 1.
The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids at the 30% probability level.
Fig. 2.
Crystal packing of (I) viewed down the c axis with hydrogen bonds drawn as dashed lines.

Crystal data

C11H12O2F(000) = 752
Mr = 176.21Dx = 1.333 Mg m3
Orthorhombic, PbcaMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2abCell parameters from 25 reflections
a = 10.240 (2) Åθ = 10–13°
b = 6.2370 (12) ŵ = 0.09 mm1
c = 27.503 (6) ÅT = 293 K
V = 1756.5 (6) Å3White, colourless
Z = 80.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1045 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.0000
graphiteθmax = 25.2°, θmin = 1.5°
ω/2θ scansh = 0→12
Absorption correction: ψ scan (North et al., 1968)k = 0→7
Tmin = 0.973, Tmax = 0.991l = 0→32
1581 measured reflections3 standard reflections every 200 reflections
1581 independent reflections intensity decay: none

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.063Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.168H-atom parameters constrained
S = 1.02w = 1/[σ2(Fo2) + (0.06P)2 + 3P] where P = (Fo2 + 2Fc2)/3
1581 reflections(Δ/σ)max < 0.001
118 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = −0.27 e Å3

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
O10.65327 (18)0.2295 (4)0.51706 (7)0.0289 (5)
H1A0.60830.17980.49360.035*
C10.5544 (4)0.5675 (6)0.71478 (12)0.0417 (9)
H1B0.59500.64680.73910.050*
O20.40283 (18)0.1947 (3)0.51141 (7)0.0287 (6)
H2A0.32700.22140.50400.043*
C20.4181 (4)0.5663 (6)0.71136 (12)0.0392 (9)
H2B0.36860.64630.73320.047*
C30.3563 (3)0.4465 (5)0.67558 (11)0.0333 (8)
H3A0.26570.44560.67330.040*
C40.4303 (3)0.3299 (5)0.64387 (10)0.0235 (7)
C50.5676 (3)0.3324 (5)0.64679 (10)0.0258 (7)
C60.6296 (3)0.4508 (6)0.68204 (11)0.0359 (8)
H6A0.72030.45290.68400.043*
C70.3981 (3)0.1886 (5)0.60039 (10)0.0260 (7)
H7A0.30960.12860.60030.031*
C80.4366 (2)0.3095 (5)0.55428 (10)0.0202 (6)
H8A0.39910.45400.55400.024*
C90.5897 (2)0.3180 (5)0.55809 (10)0.0214 (7)
H9A0.61740.46730.56210.026*
C100.6168 (3)0.1942 (5)0.60542 (10)0.0281 (8)
H10A0.70590.13950.60910.034*
C110.5087 (3)0.0226 (5)0.60427 (11)0.0313 (8)
H11A0.5142−0.07060.57610.038*
H11B0.5046−0.06170.63390.038*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0170 (9)0.0410 (13)0.0288 (11)−0.0049 (10)0.0050 (9)−0.0077 (10)
C10.062 (2)0.034 (2)0.0297 (18)−0.0094 (19)−0.0103 (17)−0.0012 (16)
O20.0185 (10)0.0364 (13)0.0311 (12)0.0070 (10)−0.0050 (9)−0.0120 (10)
C20.056 (2)0.034 (2)0.0277 (18)0.0070 (18)0.0077 (16)−0.0010 (15)
C30.0305 (17)0.0378 (19)0.0315 (17)0.0057 (16)0.0044 (14)0.0014 (15)
C40.0233 (15)0.0265 (17)0.0206 (15)0.0022 (13)0.0038 (12)0.0031 (13)
C50.0254 (15)0.0266 (17)0.0255 (16)0.0016 (13)−0.0039 (12)0.0037 (13)
C60.0338 (18)0.041 (2)0.0324 (18)−0.0073 (17)−0.0066 (15)0.0035 (16)
C70.0203 (14)0.0264 (17)0.0315 (17)−0.0076 (13)0.0012 (12)−0.0020 (14)
C80.0156 (14)0.0181 (15)0.0270 (15)0.0034 (12)−0.0020 (12)−0.0022 (13)
C90.0146 (13)0.0233 (15)0.0263 (15)−0.0023 (12)0.0022 (12)−0.0024 (13)
C100.0200 (15)0.0345 (19)0.0297 (16)0.0114 (14)−0.0018 (12)0.0050 (15)
C110.0453 (19)0.0222 (16)0.0265 (16)0.0034 (15)0.0021 (14)0.0030 (14)

Geometric parameters (Å, °)

O1—C91.415 (3)C5—C101.513 (4)
O1—H1A0.8501C6—H6A0.9300
C1—C61.390 (5)C7—C81.527 (4)
C1—C21.399 (5)C7—C111.538 (4)
C1—H1B0.9300C7—H7A0.9800
O2—C81.422 (3)C8—C91.572 (4)
O2—H2A0.8200C8—H8A0.9800
C2—C31.388 (5)C9—C101.539 (4)
C2—H2B0.9300C9—H9A0.9800
C3—C41.365 (4)C10—C111.540 (4)
C3—H3A0.9300C10—H10A0.9800
C4—C51.408 (4)C11—H11A0.9700
C4—C71.522 (4)C11—H11B0.9700
C5—C61.374 (4)
C9—O1—H1A119.8C11—C7—H7A115.1
C6—C1—C2120.4 (3)O2—C8—C7112.1 (2)
C6—C1—H1B119.8O2—C8—C9108.3 (2)
C2—C1—H1B119.8C7—C8—C9102.6 (2)
C8—O2—H2A109.5O2—C8—H8A111.1
C3—C2—C1120.3 (3)C7—C8—H8A111.1
C3—C2—H2B119.8C9—C8—H8A111.1
C1—C2—H2B119.8O1—C9—C10113.4 (2)
C4—C3—C2119.1 (3)O1—C9—C8113.1 (2)
C4—C3—H3A120.4C10—C9—C8102.6 (2)
C2—C3—H3A120.4O1—C9—H9A109.2
C3—C4—C5120.8 (3)C10—C9—H9A109.2
C3—C4—C7133.6 (3)C8—C9—H9A109.2
C5—C4—C7105.5 (2)C5—C10—C9106.9 (2)
C6—C5—C4120.5 (3)C5—C10—C1199.9 (2)
C6—C5—C10133.1 (3)C9—C10—C11101.7 (2)
C4—C5—C10106.4 (3)C5—C10—H10A115.5
C5—C6—C1118.9 (3)C9—C10—H10A115.5
C5—C6—H6A120.6C11—C10—H10A115.5
C1—C6—H6A120.6C7—C11—C1093.6 (2)
C4—C7—C8108.1 (2)C7—C11—H11A113.0
C4—C7—C11100.1 (2)C10—C11—H11A113.0
C8—C7—C11101.5 (2)C7—C11—H11B113.0
C4—C7—H7A115.1C10—C11—H11B113.0
C8—C7—H7A115.1H11A—C11—H11B110.4
C6—C1—C2—C30.8 (5)C11—C7—C8—C9−37.4 (3)
C1—C2—C3—C40.0 (5)O2—C8—C9—O15.3 (3)
C2—C3—C4—C5−0.7 (5)C7—C8—C9—O1124.1 (2)
C2—C3—C4—C7−178.0 (3)O2—C8—C9—C10−117.2 (2)
C3—C4—C5—C60.7 (5)C7—C8—C9—C101.5 (3)
C7—C4—C5—C6178.6 (3)C6—C5—C10—C9−107.6 (4)
C3—C4—C5—C10−177.9 (3)C4—C5—C10—C970.6 (3)
C7—C4—C5—C100.1 (3)C6—C5—C10—C11146.8 (3)
C4—C5—C6—C10.2 (5)C4—C5—C10—C11−34.9 (3)
C10—C5—C6—C1178.2 (3)O1—C9—C10—C5168.1 (2)
C2—C1—C6—C5−0.9 (5)C8—C9—C10—C5−69.6 (3)
C3—C4—C7—C8106.6 (4)O1—C9—C10—C11−87.6 (3)
C5—C4—C7—C8−71.0 (3)C8—C9—C10—C1134.7 (3)
C3—C4—C7—C11−147.6 (3)C4—C7—C11—C10−53.4 (2)
C5—C4—C7—C1134.8 (3)C8—C7—C11—C1057.6 (2)
C4—C7—C8—O2−176.5 (2)C5—C10—C11—C753.4 (2)
C11—C7—C8—O278.7 (3)C9—C10—C11—C7−56.4 (2)
C4—C7—C8—C967.4 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O1—H1A···O20.852.162.578 (3)110
O1—H1A···O2i0.852.342.818 (3)116
O2—H2A···O1ii0.821.902.714 (3)176

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2556).

References

  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Coe, J. W. (2005). J. Med. Chem.48, 3474–3477. [PubMed]
  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Vetelino, M. G. (2004). Synthesis, 11, 1755–1758.

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