organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

(R)-(−)-Quinuclidin-3-ol

aInstitut de Chimie Moleculaire de l'Universite de Bourgogne - ICMUB, UMR CNRS 6302, Universite de Bourgogne, 9, Av. Alain Savary, 21078 Dijon Cedex, France, and bCordenPharma – Synkem, 47 rue de Longvic, 21301 Chenove, France
*Correspondence e-mail: yoann.rousselin@u-bourgogne.fr

(Received 6 September 2013; accepted 1 October 2013; online 19 October 2013)

The structure of the title compound [alternatively called (R)-(−)-1-aza­bicyclo­[2.2.2]octan-3-ol], C7H13NO, at 100 K has hexa­gonal (P61) symmetry. The structure shows a twist along the C—N pseudo-threefold axis. In the crystal, mol­ecules are linked via O—H⋯N hydrogen bonds, forming infinite chains along the c-axis direction. The crystal studied was twinned by merohedry (twin law: 010, 100, 00-1; population: 0.925:0.075)

Related literature

The title compound is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (Naito et al., 2005[Naito, R., Yonetoku, Y., Okamoto, Y., Toyoshima, A., Ikeda, K. & Takeuchi, M. (2005). J. Med. Chem. 48, 6597-6606.]), revatropate (Alabaster, 1997[Alabaster, V. A. (1997). Life Sci. 60, 1053-1060.]) and talsaclidine (Leusch et al., 2000[Leusch, A., Tröger, W., Greischel, A. & Roth, W. (2000). Xenobiotica, 30, 797-813.]). For properties of the title compound, see: Bosak et al. (2005[Bosak, A., Primozic, I., Orsulic, M., Tomic, S. & Simeon-Rudolf, V. (2005). Croat. Chem. Acta, 78, 121-128.]); Carroll et al. (1991[Carroll, F. I., Abraham, P., Gaetano, K., Mascarella, S. W., Wohl, R. A., Lind, J. & Petzoldt, K. (1991). J. Chem. Soc. Perkin Trans. 1, pp. 3017-3026.]); Frackenpohl & Hoffmann (2000[Frackenpohl, J. & Hoffmann, H. M. R. (2000). J. Org. Chem. 65, 3982-3996.]); Day & Motherwell (2006[Day, M. G. & Motherwell, W. D. S. (2006). Cryst. Growth Des. 6, 1985-1990.]); Malone & Armstrong (2006[Malone, K. Y. & Armstrong, E. P. (2006). Pharmacotherapy, 26, 1694-1702.]); Siczek & Lis (2008[Siczek, M. & Lis, T. (2008). Acta Cryst. E64, o842.]); Sterling et al. (1988[Sterling, G. H., Doukas, P. H., Sheldon, R. J. & O?Neill, J. J. (1988). Biochem. Pharmacol. 37, 379-384.]). For puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]); For absolute configuration, see: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]); The twin law was determined using TwinRotMat implemented in PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

[Scheme 1]

Experimental

Crystal data
  • C7H13NO

  • Mr = 127.18

  • Hexagonal, P 61

  • a = 6.2076 (3) Å

  • c = 29.8731 (13) Å

  • V = 996.91 (11) Å3

  • Z = 6

  • Cu Kα1 radiation

  • μ = 0.67 mm−1

  • T = 100 K

  • 0.58 × 0.44 × 0.32 mm

Data collection
  • Bruker D8 VENTURE diffractometer

  • Absorption correction: numerical (SADABS; Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.58, Tmax = 0.74

  • 15447 measured reflections

  • 1240 independent reflections

  • 1240 reflections with I > 2σ(I)

  • Rint = 0.026

Refinement
  • R[F2 > 2σ(F2)] = 0.023

  • wR(F2) = 0.064

  • S = 1.15

  • 1240 reflections

  • 85 parameters

  • 1 restraint

  • H-atom parameters constrained

  • Δρmax = 0.23 e Å−3

  • Δρmin = −0.12 e Å−3

  • Absolute structure: Parsons & Flack (2004[Parsons, S. & Flack, H. (2004). Acta Cryst. A60, s61.]).

  • Absolute structure parameter: 0.01 (4)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1⋯N1i 0.84 2.00 2.8366 (19) 176
Symmetry code: (i) [y-1, -x+y, z-{\script{1\over 6}}].

Data collection: APEX2 (Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2012[Bruker (2012). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: OLEX2.

Supporting information


Comment top

(R)-(-)-quinuclidin-3-ol (Figure 1) is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (M3 receptor antagonist),(Naito et al., 2005) revatropate (M3 receptor antagonist),(Alabaster, 1997) and talsaclidine (M1 receptor agonist),(Leusch et al., 2000).

The asymetric unit of the crystal (Figure 1) consists of one single (R)-(-)-quinuclidin-3-ol molecule.

The quinuclidinol moiety has pseudo-threefold symmetry about the N1-C3 axis with C6-N1-C1, C1-N1-C5 and C5-N1-N6 angles of 108.86 (15)°, 108.73 (14)° and 108.72 (14)° respectively, and N1-C1-C2-C3, N1-C6-C7-C3 and N1-C5-C4-C3 torsion angles of -0.9 (3)°, 0.4 (2)° and 0.2 (2)° respectively.

The three piperidine rings formed by (N1, C1, C2, C3, C4, C5), (N1, C5, C4, C3, C7, C6) and (N1, C6, C7, C3, C2, C1) adopt a boat conformation with total puckering amplitutdes QT of 0.8218 (0) (with Θ = 91.84 (0)° and ϕ = -0.2 (0)°), QT of 0.8141 (1) (with Θ = 91.55 (0)° and ϕ = 0.19 (0)°) and QT of 0.8123 (0) (with Θ = 90.95 (0)° and ϕ = -0.17 (0)°), respectively (Cremer & Pople, (1975)).

There is a hydrogen bond (Table 1) which links molecules into infinite chains along the c axis (Figure 2).

Related literature top

The title compound is a key building block for the syntheses of muscarinic receptor ligands, including solifenacin (Naito et al., 2005), revatropate (Alabaster, 1997) and talsaclidine (Leusch et al., 2000). For properties of the title compound, see: Bosak et al. (2005); Carroll et al. (1991); Frackenpohl & Hoffmann (2000); Day & Motherwell (2006); Malone & Armstrong (2006); Siczek & Lis (2008); Sterling et al. (1988). For puckering parameters, see: Cremer & Pople (1975); For absolute configuration, see: Flack (1983); The twin law was determined using TwinRotMat implemented in PLATON (Spek, 2009).

Refinement top

All H atoms, on carbon atom or oxygen atom, were placed at calculated positions using a riding model with C-H = 1 Å (methine), 0.99 Å (methylene) or O-H = 0.84 Å with Uiso(H) = 1.2Ueq(CH), Uiso(H) = 1.2Ueq(CH2) or Uiso(H) = 1.5Ueq(OH).

TWIN/BASF refinement type was used to determine absolute configuration from anomalous scattering using the Flack method. (Flack, 1983). The structure display a merohedral twinning and the twin law was found by using TwinRotMat implemented in Platon (Spek, 2009). The use of twin law (0 1 0 1 0 0 0 0 -1) with a population of 0.925/0.075 reduced the R1(for I> 2σ(I)) and Flack parameter from 4.96%, 0.2 (9) to 2.34%, 0.01 (4).

Computing details top

Data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. A view of (R)-(-)-quinuclidin-3-ol with atom labelling scheme. The thermal displacement ellipsoids are drawn at 50% probability level.
[Figure 2] Fig. 2. A view of molecular packing showing chains running along the c direction. The hydrogen bonds are shown as dashed lines. The thermal displacement ellipsoids are drawn at 50% probability level.
(R)-(-)-Quinuclidin-3-ol top
Crystal data top
C7H13NODx = 1.271 Mg m3
Mr = 127.18Melting point: 492(2) K
Hexagonal, P61Cu Kα1 radiation, λ = 1.54178 Å
a = 6.2076 (3) ŵ = 0.67 mm1
c = 29.8731 (13) ÅT = 100 K
V = 996.91 (11) Å3Prism, clear light colourless
Z = 60.58 × 0.44 × 0.32 mm
F(000) = 420
Data collection top
Bruker D8 VENTURE
diffractometer
1240 independent reflections
Radiation source: sealed X-ray tube, high brilliance microfocus sealed tube, Cu1240 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
Detector resolution: 1024 x 1024 pixels mm-1θmax = 69.2°, θmin = 4.4°
ϕ and ω scansh = 77
Absorption correction: numerical
(SADABS; Bruker, 2012)
k = 77
Tmin = 0.58, Tmax = 0.74l = 3435
15447 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.023 w = 1/[σ2(Fo2) + (0.0394P)2 + 0.1183P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.064(Δ/σ)max < 0.001
S = 1.15Δρmax = 0.23 e Å3
1240 reflectionsΔρmin = 0.12 e Å3
85 parametersExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.0156 (15)
0 constraintsAbsolute structure: Parsons & Flack (2004).
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.01 (4)
Crystal data top
C7H13NOZ = 6
Mr = 127.18Cu Kα1 radiation
Hexagonal, P61µ = 0.67 mm1
a = 6.2076 (3) ÅT = 100 K
c = 29.8731 (13) Å0.58 × 0.44 × 0.32 mm
V = 996.91 (11) Å3
Data collection top
Bruker D8 VENTURE
diffractometer
1240 independent reflections
Absorption correction: numerical
(SADABS; Bruker, 2012)
1240 reflections with I > 2σ(I)
Tmin = 0.58, Tmax = 0.74Rint = 0.026
15447 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.023H-atom parameters constrained
wR(F2) = 0.064Δρmax = 0.23 e Å3
S = 1.15Δρmin = 0.12 e Å3
1240 reflectionsAbsolute structure: Parsons & Flack (2004).
85 parametersAbsolute structure parameter: 0.01 (4)
1 restraint
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. Refined as a 2-component twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.1928 (2)0.4528 (2)0.48963 (4)0.0175 (3)
H10.22530.42640.46220.026*
N10.3057 (3)0.6832 (3)0.56404 (5)0.0157 (4)
C20.5095 (3)0.8018 (3)0.48879 (6)0.0166 (4)
H2A0.53250.95000.47220.020*
H2B0.63780.76250.47860.020*
C40.0565 (3)0.6495 (3)0.49520 (5)0.0149 (4)
H40.08120.79990.47850.018*
C10.5354 (4)0.8550 (4)0.53973 (6)0.0208 (4)
H1A0.67520.83800.55150.025*
H1B0.57441.02830.54500.025*
C70.2139 (3)0.3542 (3)0.50634 (5)0.0159 (4)
H7A0.33690.30670.49660.019*
H7B0.04500.21110.50130.019*
C50.0986 (4)0.7091 (4)0.54597 (5)0.0188 (4)
H5A0.13400.88140.55100.023*
H5B0.05570.59560.56240.023*
C30.2487 (3)0.5801 (3)0.47977 (6)0.0141 (4)
H30.22790.54060.44710.017*
C60.2509 (4)0.4253 (4)0.55649 (6)0.0204 (4)
H6A0.09840.30950.57320.024*
H6B0.38970.40680.56840.024*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0134 (6)0.0222 (6)0.0150 (6)0.0076 (5)0.0012 (4)0.0004 (5)
N10.0176 (7)0.0155 (8)0.0128 (7)0.0074 (6)0.0005 (6)0.0014 (5)
C20.0149 (8)0.0186 (9)0.0145 (8)0.0069 (7)0.0009 (7)0.0010 (6)
C40.0150 (8)0.0161 (8)0.0138 (8)0.0079 (7)0.0002 (6)0.0006 (7)
C10.0176 (9)0.0215 (9)0.0164 (9)0.0045 (8)0.0020 (6)0.0034 (7)
C70.0150 (8)0.0151 (8)0.0177 (8)0.0077 (7)0.0012 (6)0.0028 (7)
C50.0207 (9)0.0237 (9)0.0153 (8)0.0135 (8)0.0006 (7)0.0042 (7)
C30.0135 (8)0.0158 (8)0.0124 (8)0.0068 (7)0.0011 (6)0.0024 (7)
C60.0292 (9)0.0186 (9)0.0159 (9)0.0139 (8)0.0003 (8)0.0013 (7)
Geometric parameters (Å, º) top
O1—H10.8400C1—H1A0.9900
O1—C41.423 (2)C1—H1B0.9900
N1—C11.475 (2)C7—H7A0.9900
N1—C51.475 (2)C7—H7B0.9900
N1—C61.479 (2)C7—C31.530 (2)
C2—H2A0.9900C7—C61.546 (2)
C2—H2B0.9900C5—H5A0.9900
C2—C11.548 (2)C5—H5B0.9900
C2—C31.536 (2)C3—H31.0000
C4—H41.0000C6—H6A0.9900
C4—C51.552 (2)C6—H6B0.9900
C4—C31.528 (2)
C4—O1—H1109.5C3—C7—H7A110.1
C1—N1—C6108.86 (15)C3—C7—H7B110.1
C5—N1—C1108.73 (14)C3—C7—C6107.96 (13)
C5—N1—C6108.72 (14)C6—C7—H7A110.1
H2A—C2—H2B108.4C6—C7—H7B110.1
C1—C2—H2A110.0N1—C5—C4112.56 (14)
C1—C2—H2B110.0N1—C5—H5A109.1
C3—C2—H2A110.0N1—C5—H5B109.1
C3—C2—H2B110.0C4—C5—H5A109.1
C3—C2—C1108.29 (15)C4—C5—H5B109.1
O1—C4—H4109.6H5A—C5—H5B107.8
O1—C4—C5107.46 (13)C2—C3—H3109.9
O1—C4—C3112.96 (14)C4—C3—C2108.41 (14)
C5—C4—H4109.6C4—C3—C7109.25 (14)
C3—C4—H4109.6C4—C3—H3109.9
C3—C4—C5107.45 (13)C7—C3—C2109.45 (14)
N1—C1—C2111.72 (14)C7—C3—H3109.9
N1—C1—H1A109.3N1—C6—C7112.19 (14)
N1—C1—H1B109.3N1—C6—H6A109.2
C2—C1—H1A109.3N1—C6—H6B109.2
C2—C1—H1B109.3C7—C6—H6A109.2
H1A—C1—H1B107.9C7—C6—H6B109.2
H7A—C7—H7B108.4H6A—C6—H6B107.9
O1—C4—C5—N1122.04 (17)C5—C4—C3—C259.75 (17)
O1—C4—C3—C2178.09 (13)C5—C4—C3—C759.46 (17)
O1—C4—C3—C758.88 (17)C3—C2—C1—N10.9 (2)
C1—N1—C5—C459.38 (18)C3—C4—C5—N10.20 (19)
C1—N1—C6—C759.78 (19)C3—C7—C6—N10.4 (2)
C1—C2—C3—C460.54 (19)C6—N1—C1—C259.72 (19)
C1—C2—C3—C758.55 (18)C6—N1—C5—C459.01 (19)
C5—N1—C1—C258.6 (2)C6—C7—C3—C258.56 (18)
C5—N1—C6—C758.53 (19)C6—C7—C3—C460.01 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···N1i0.842.002.8366 (19)176
Symmetry code: (i) y1, x+y, z1/6.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···N1i0.842.002.8366 (19)175.7
Symmetry code: (i) y1, x+y, z1/6.
 

Acknowledgements

We thank Ms Marie-Jose Penouilh for the NMR and ESI mass spectra.

References

First citationAlabaster, V. A. (1997). Life Sci. 60, 1053–1060.  CrossRef CAS PubMed Web of Science
First citationBosak, A., Primozic, I., Orsulic, M., Tomic, S. & Simeon-Rudolf, V. (2005). Croat. Chem. Acta, 78, 121–128.  CAS
First citationBruker (2012). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
First citationCarroll, F. I., Abraham, P., Gaetano, K., Mascarella, S. W., Wohl, R. A., Lind, J. & Petzoldt, K. (1991). J. Chem. Soc. Perkin Trans. 1, pp. 3017–3026.  CSD CrossRef Web of Science
First citationCremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.  CrossRef CAS Web of Science
First citationDay, M. G. & Motherwell, W. D. S. (2006). Cryst. Growth Des. 6, 1985–1990.  Web of Science CSD CrossRef CAS
First citationDolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.  Web of Science CrossRef CAS IUCr Journals
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals
First citationFrackenpohl, J. & Hoffmann, H. M. R. (2000). J. Org. Chem. 65, 3982–3996.  Web of Science CSD CrossRef PubMed CAS
First citationLeusch, A., Tröger, W., Greischel, A. & Roth, W. (2000). Xenobiotica, 30, 797–813.  CrossRef PubMed CAS
First citationMalone, K. Y. & Armstrong, E. P. (2006). Pharmacotherapy, 26, 1694–1702.  Web of Science PubMed
First citationNaito, R., Yonetoku, Y., Okamoto, Y., Toyoshima, A., Ikeda, K. & Takeuchi, M. (2005). J. Med. Chem. 48, 6597–6606.  Web of Science CrossRef PubMed CAS
First citationParsons, S. & Flack, H. (2004). Acta Cryst. A60, s61.  CrossRef IUCr Journals
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationSiczek, M. & Lis, T. (2008). Acta Cryst. E64, o842.  Web of Science CSD CrossRef IUCr Journals
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals
First citationSterling, G. H., Doukas, P. H., Sheldon, R. J. & O?Neill, J. J. (1988). Biochem. Pharmacol. 37, 379–384.

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds