2-[6,8-Dibromo-3-(4-hy­droxy­cyclo­hex­yl)-1,2,3,4-tetra­hydro­quinazolin-2-yl]phenol methanol 0.25-solvate

Wang, Z.-G.; Wang, R.; Zhi, F.; Wang, M.-L.

doi:10.1107/S1600536811007987

Volume 67
Part 4
Pages o808-o809
April 2011

Received 23 February 2011
Accepted 2 March 2011
Online 9 March 2011

Key indicators
Single-crystal X-ray study
T = 298 K
Mean (C-C) = 0.013 Å
Disorder in solvent or counterion
R = 0.087
wR = 0.199
Data-to-parameter ratio = 17.6
Details

2-[6,8-Dibromo-3-(4-hydroxycyclohexyl)-1,2,3,4-tetrahydroquinazolin-2-yl]phenol methanol 0.25-solvate

Zhi-Gang Wang,^a Rong Wang,^b Feng Zhi ^b and Ming-Li Wang ^c ^*

^aDepartment of Respiratory Medicine, Third Affiliated Hospital of Soochow University, Changzhou 213003, People's Republic of China,^bModern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou 213003, People's Republic of China, and ^cDepartment of Pharmacy, Third Affiliated Hospital of Soochow University, Changzhou 213003, People's Republic of China
Correspondence e-mail: wangmingli09@163.com

The title compound, C₂₀H₂₂Br₂N₂O₂·0.25CH₄O, was synthesized by the condensation reaction of salicylaldehyde with 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol in methanol. There are four independent main molecules and two half-occupied methanol solvent molecules in the asymmetric unit. The dihedral angles between the two benzene rings in the four molecules are 87.8 (6), 86.6 (6), 89.3 (6) and 83.1 (6)°. Each molecule features an intramolecular O-HN hydrogen bond and a short N-HBr link. In the crystal components are linked by O-HO hydrogen bonds.

Related literature

For details of the pharmaceutical uses of ambroxol, systematic name 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol, a compound closely related to the title compound, see: Gaida et al. (2005); Lee et al. (2004). For the structures of similar compounds, see: Wang et al. (2009, 2010). For standard bond-length data, see: Allen et al. (1987).

Experimental

Crystal data

C₂₀H₂₂Br₂N₂O₂·0.25CH₄O
M_r = 490.23
Triclinic, $[P \overline 1]$
a = 11.733 (2) Å
b = 16.831 (3) Å
c = 21.721 (4) Å
= 94.69 (3)°
= 96.88 (3)°
= 99.44 (3)°
V = 4178.4 (14) Å³
Z = 8
Mo K radiation
= 3.90 mm^-1
T = 298 K
0.23 × 0.23 × 0.20 mm

Data collection

Bruker SMART CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) T_min = 0.468, T_max = 0.509
46008 measured reflections
17573 independent reflections
6508 reflections with I > 2(I)
R_int = 0.108

Refinement

R[F² > 2(F²)] = 0.087
wR(F²) = 0.199
S = 0.95
17573 reflections
1001 parameters
38 restraints
H atoms treated by a mixture of independent and constrained refinement
_max = 1.06 e Å^-3
_min = -0.78 e Å^-3

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
O1-H1N4	0.82	1.93	2.643 (8)	145
N1-H1ABr2	0.91 (8)	2.69 (7)	3.081 (7)	107 (6)
O2-H2O9ⁱ	0.82	1.85	2.660 (15)	167
O3-H3N2	0.82	1.93	2.661 (9)	148
N3-H3BBr4	0.91 (8)	2.77 (8)	3.097 (7)	103 (5)
O4-H4O6ⁱⁱ	0.82	2.13	2.721 (10)	129
O5-H5N6	0.82	1.95	2.650 (9)	143
N5-H5BBr5	0.90 (6)	2.77 (8)	3.110 (7)	104 (6)
O6-H6O8ⁱⁱⁱ	0.82	1.95	2.735 (9)	160
O7-H7N8	0.85 (6)	1.99 (8)	2.717 (9)	142 (6)
N7-H7BBr7	0.90 (6)	2.61 (8)	3.100 (7)	115 (6)
O8-H8O2^iv	0.84 (9)	1.90 (8)	2.713 (11)	162 (8)
O9-H9O10^v	0.82	2.18	2.94 (2)	156
Symmetry codes: (i) x+1, y, z-1; (ii) x, y, z-1; (iii) -x+1, -y, -z+2; (iv) x-1, y, z+1; (v) x-1, y, z.

Data collection: SMART (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5804 ).

Acknowledgements

Financial support from the Third Affiliated Hospital of Soochow University is acknowledged.

References

Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1-19.
Bruker (2002). SAINT and SMART. Bruker AXS Inc., Madison, Wisconsin, USA.
Gaida, W., Klinder, K., Arndt, K. & Weiser, T. (2005). Neuropharmacology, 49, 1220-1227.
Lee, H. J., Joung, S. K., Kim, Y. G., Yoo, J.-Y. & Han, S. B. (2004). Pharm. Res. 49, 93-98.
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.
Wang, Z.-G., Wang, R., Zhang, Y., Zhi, F. & Yang, Y.-L. (2009). Acta Cryst. E65, o550.
Wang, Z.-G., Xia, Z.-L., Wang, R. & Wang, M.-L. (2010). Acta Cryst. E66, o1205-o1206.

organic compounds