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

Zhi-Gang Wang; Rong Wang; Feng Zhi; Ming-Li Wang

doi:10.1107/S1600536811007987

. 2011 Mar 9;67(Pt 4):o808–o809. doi: 10.1107/S1600536811007987

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, Ming-Li Wang ^c,^*

PMCID: PMC3099869 PMID: 21754095

Abstract

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—H⋯N hydrogen bond and a short N—H⋯Br link. In the crystal components are linked by O—H⋯O 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,
a = 11.733 (2) Å
b = 16.831 (3) Å
c = 21.721 (4) Å
α = 94.69 (3)°
β = 96.88 (3)°
γ = 99.44 (3)°
V = 4178.4 (14) Å³
Z = 8
Mo Kα radiation
μ = 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 > 2σ(I)
R _int = 0.108

Refinement

R[F ² > 2σ(F ²)] = 0.087
wR(F ²) = 0.199
S = 0.95
17573 reflections
1001 parameters
38 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 1.06 e Å⁻³
Δρ_min = −0.78 e Å⁻³

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 Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811007987/hb5804sup1.cif

e-67-0o808-sup1.cif^{(45.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811007987/hb5804Isup2.hkl

e-67-0o808-Isup2.hkl^{(858.8KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N4	0.82	1.93	2.643 (8)	145
N1—H1A⋯Br2	0.91 (8)	2.69 (7)	3.081 (7)	107 (6)
O2—H2⋯O9ⁱ	0.82	1.85	2.660 (15)	167
O3—H3⋯N2	0.82	1.93	2.661 (9)	148
N3—H3B⋯Br4	0.91 (8)	2.77 (8)	3.097 (7)	103 (5)
O4—H4⋯O6ⁱⁱ	0.82	2.13	2.721 (10)	129
O5—H5⋯N6	0.82	1.95	2.650 (9)	143
N5—H5B⋯Br5	0.90 (6)	2.77 (8)	3.110 (7)	104 (6)
O6—H6⋯O8ⁱⁱⁱ	0.82	1.95	2.735 (9)	160
O7—H7⋯N8	0.85 (6)	1.99 (8)	2.717 (9)	142 (6)
N7—H7B⋯Br7	0.90 (6)	2.61 (8)	3.100 (7)	115 (6)
O8—H8⋯O2^iv	0.84 (9)	1.90 (8)	2.713 (11)	162 (8)
O9—H9⋯O10^v	0.82	2.18	2.94 (2)	156

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

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

supplementary crystallographic information

Comment

Ambroxol [or 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol] is an expectorant agent which leads to bronchial secretion due to its mucolytic properties (Gaida et al., 2005; Lee et al., 2004). Recently, we reported the crystal structures of two derivatives of Ambroxol (Wang et al., 2009; Wang et al., 2010). In this paper, the crystal structure of the title compound, derived from the condensation reaction of salicylaldehyde with 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol in methanol, is reported.

There are four independent molecules and two methanol molecules in the asymmetric unit of the title compound, Fig. 1. The dihedral angles between the two benzene rings in the four molecules are 87.8 (6), 86.6 (6), 90.7 (6), and 96.9 (6)°, respectively. The cyclohexyl rings adopt chair configurations. All bond lengths are within normal ranges (Allen et al., 1987).

Experimental

Salicylaldehyde (1.0 mol, 122.1 mg) and 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol (1.0 mmol, 378.1 mg) were dissolved in methanol (30 ml). The mixture was stirred at room temperature to give a clear colorless solution. Colourless blocks of the title compound were formed by gradual evaporation of the solvent for a few days at room temperature.