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Volume 68 
Part 12 
Page o3352  
December 2012  

Received 1 October 2012
Accepted 6 November 2012
Online 14 November 2012

Key indicators
Single-crystal X-ray study
T = 115 K
Mean [sigma](C-C) = 0.006 Å
Disorder in solvent or counterion
R = 0.072
wR = 0.137
Data-to-parameter ratio = 16.5
Details
Open access

(S,S,S,S)-Nebivolol hydrochloride hemihydrate

aUniversite de Bourgogne, ICMUB-UMR6302, 9 avenue Alain Savary, 21000 Dijon, France, and bCordenPharma-Synkem, 47 rue de Longvic, 21301, Chenove, France
Correspondence e-mail: yoann.rousselin@u-bourgogne.fr

The asymmetric unit of the title hydrated salt, C22H26F2NO4+·Cl-·0.5H2O, consists of an (S,S,S,S)-nebivolol {nebivol = bis[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]ammonium} cation, a chloride anion and a half-occupancy water molecule. The dihedral angle between the mean planes of the benzene rings is 50.34 (12)°. The pyran rings adopt half-chair conformations. The crystal packing features O-H...O hydrogen bonds and weak N-H...Cl, O-H...Cl, and O-H...Cl interactions, producing layers along (010).

Related literature

For the synthesis of the enantiopure title product, see: Jas et al. (2011[Jas, G., Freifeld, I. & Kesseler, K. (2011). Patent WO 2011091968 (Corden PharmaChem GmbH).]). For a study of related isomers, see: Cini et al. (1990[Cini, M., Crotti, P. & Macchia, F. (1990). Tetrahedron Lett. 31, 4661-4664.]); Peeters et al. (1993[Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2154-2157.]); Tuchalski et al. (2006[Tuchalski, G., Emmerling, F., Groger, K., Hansicke, A., Nagel, T. & Reck, G. (2006). J. Mol. Struct. 800, 28-44.], 2008[Tuchalski, G., Hänsicke, A., Reck, G. & Emmerling, F. (2008). Acta Cryst. E64, o54.]). For pharmacological properties of nebivolol, see: Van Lommen et al., (1990[Van Lommen, G. R. E., de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355-360.]). For distance computations in water molecules, see: Stewart (2009[Stewart, J. P. (2009). MOPAC2009. Stewart Computational Chemistry. Available from: http://OpenMOPAC.net.]). For puckering parameters, see: Cremer & Pople, (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.]).

[Scheme 1]

Experimental

Crystal data
  • C22H26F2NO4+·Cl-·0.5H2O

  • Mr = 450.89

  • Orthorhombic, P 21 21 21

  • a = 7.5173 (3) Å

  • b = 8.1495 (3) Å

  • c = 34.1660 (11) Å

  • V = 2093.09 (13) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.23 mm-1

  • T = 115 K

  • 0.10 × 0.07 × 0.02 mm

Data collection
  • Nonius Kappa APEXII diffractometer

  • 4782 measured reflections

  • 4782 independent reflections

  • 4271 reflections with I > 2[sigma](I)

  • Rint = 0.000

Refinement
  • R[F2 > 2[sigma](F2)] = 0.072

  • wR(F2) = 0.137

  • S = 1.27

  • 4782 reflections

  • 290 parameters

  • 3 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • [Delta][rho]max = 0.43 e Å-3

  • [Delta][rho]min = -0.31 e Å-3

  • Absolute structure: Flack (2003[Flack, H. D. (2003). Helv. Chim. Acta, 86, 905-921.]), 1998 Friedel pairs

  • Flack parameter: 0.02 (12)

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
N1-H1N...Cl1i 0.80 (5) 2.75 (5) 3.333 (4) 131 (4)
N1-H2N...Cl1ii 1.00 (5) 2.20 (5) 3.175 (4) 165 (4)
O2-H2A...Cl1iii 0.84 2.25 3.084 (3) 172
O3-H3...O2iii 0.84 2.25 2.963 (4) 143
O3-H3...O1iii 0.84 2.27 2.893 (4) 131
O5-H1O...O3iv 0.94 (2) 2.12 (3) 3.026 (6) 161 (6)
O5-H2O...Cl1 0.93 (2) 2.28 (3) 3.187 (6) 163 (6)
Symmetry codes: (i) [-x+1, y-{\script{3\over 2}}, -z+{\script{3\over 2}}]; (ii) x-1, y-1, z; (iii) [-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]; (iv) [-x+1, y+{\script{3\over 2}}, -z+{\script{3\over 2}}].

Data collection: COLLECT (Nonius, 1998[Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1993[Altomare, A., Cascarano, G., Giacovazzo, C. & Guagliardi, A. (1993). J. Appl. Cryst. 26, 343-350.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]); software used to prepare material for publication: WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).


Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: JJ2154 ).


Acknowledgements

We thank Ms Marie-José Penouilh for the NMR spectra and for ESI mass spectra. This study was co-financed by OSEO Burgundy and the European Regional Development Fund.

References

Altomare, A., Cascarano, G., Giacovazzo, C. & Guagliardi, A. (1993). J. Appl. Cryst. 26, 343-350.  [CrossRef] [ISI] [details]
Cini, M., Crotti, P. & Macchia, F. (1990). Tetrahedron Lett. 31, 4661-4664.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.  [CrossRef] [ChemPort] [ISI]
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.  [ISI] [CrossRef] [ChemPort] [details]
Flack, H. D. (2003). Helv. Chim. Acta, 86, 905-921.  [CrossRef] [ChemPort]
Jas, G., Freifeld, I. & Kesseler, K. (2011). Patent WO 2011091968 (Corden PharmaChem GmbH).
Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.
Peeters, O. M., Blaton, N. M. & De Ranter, C. J. (1993). Acta Cryst. C49, 2154-2157.  [CrossRef] [details]
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Stewart, J. P. (2009). MOPAC2009. Stewart Computational Chemistry. Available from: http://OpenMOPAC.net.
Tuchalski, G., Emmerling, F., Groger, K., Hansicke, A., Nagel, T. & Reck, G. (2006). J. Mol. Struct. 800, 28-44.  [ISI] [CSD] [CrossRef] [ChemPort]
Tuchalski, G., Hänsicke, A., Reck, G. & Emmerling, F. (2008). Acta Cryst. E64, o54.  [CSD] [CrossRef] [details]
Van Lommen, G. R. E., de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355-360.  [PubMed] [ChemPort]


Acta Cryst (2012). E68, o3352  [ doi:10.1107/S1600536812045813 ]

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