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

Rousselin, Y.; Bruel, A.; Clavel, A.

doi:10.1107/S1600536812045813

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 (C-C) = 0.006 Å
Disorder in solvent or counterion
R = 0.072
wR = 0.137
Data-to-parameter ratio = 16.5
Details

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

Yoann Rousselin,^a ^* Amelie Bruel ^b and Alexandre Clavel ^b

^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-HO hydrogen bonds and weak N-HCl, O-HCl, and O-HCl interactions, producing layers along (010).

Related literature

For the synthesis of the enantiopure title product, see: Jas et al. (2011). For a study of related isomers, see: Cini et al. (1990); Peeters et al. (1993); Tuchalski et al. (2006, 2008). For pharmacological properties of nebivolol, see: Van Lommen et al., (1990). For distance computations in water molecules, see: Stewart (2009). For puckering parameters, see: Cremer & Pople, (1975).

Experimental

Crystal data

C₂₂H₂₆F₂NO₄⁺·Cl^-·0.5H₂O
M_r = 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 radiation
= 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(I)
R_int = 0.000

Refinement

R[F² > 2(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
_max = 0.43 e Å^-3
_min = -0.31 e Å^-3
Absolute structure: Flack (2003), 1998 Friedel pairs
Flack parameter: 0.02 (12)

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
N1-H1NCl1ⁱ	0.80 (5)	2.75 (5)	3.333 (4)	131 (4)
N1-H2NCl1ⁱⁱ	1.00 (5)	2.20 (5)	3.175 (4)	165 (4)
O2-H2ACl1ⁱⁱⁱ	0.84	2.25	3.084 (3)	172
O3-H3O2ⁱⁱⁱ	0.84	2.25	2.963 (4)	143
O3-H3O1ⁱⁱⁱ	0.84	2.27	2.893 (4)	131
O5-H1OO3^iv	0.94 (2)	2.12 (3)	3.026 (6)	161 (6)
O5-H2OCl1	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); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012).

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.
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.
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.
Flack, H. D. (2003). Helv. Chim. Acta, 86, 905-921.
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.
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Stewart, J. P. (2009). MOPAC2009. Stewart Computational Chemistry. Available from: http://OpenMOPAC.net.
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Tuchalski, G., Hänsicke, A., Reck, G. & Emmerling, F. (2008). Acta Cryst. E64, o54.
Van Lommen, G. R. E., de Bruyn, M. F. L. & Schroven, M. F. J. (1990). J. Pharm. Belg. 45, 355-360.

organic compounds