4-[6,8-Dibromo-2-(2-chloro-5-nitro­phen­yl)-1,2,3,4-tetra­hydro­quinazolin-3-yl]cyclo­hexa­nol

Zhi-Gang Wang; Zong-Lin Xia; Rong Wang; Ming-Li Wang

doi:10.1107/S1600536810015023

. 2010 Apr 28;66(Pt 5):o1205–o1206. doi: 10.1107/S1600536810015023

4-[6,8-Dibromo-2-(2-chloro-5-nitrophenyl)-1,2,3,4-tetrahydroquinazolin-3-yl]cyclohexanol

Zhi-Gang Wang ^a, Zong-Lin Xia ^b, Rong Wang ^c, Ming-Li Wang ^b,^*

PMCID: PMC2979269 PMID: 21579236

Abstract

The title compound, C₂₀H₂₀Br₂ClN₃O₃, was synthesized by the condensation reaction of 2-chloro-5-nitrobenzaldehyde with 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol in a methanol solution. There are two independent molecules in the asymmetric unit and in one molecule the atoms of the cyclohexane ring are disordered over two sets of sites with refined occupancies of 0.657 (12) and 0.343 (12). The dihedral angle between the two benzene rings is 89.5 (2)° in one molecule and 82.9 (2)° in the other. In the crystal structure, intermolecular N—H⋯O and O—H⋯O hydrogen bonds link the molecules into chains propagating along [01 Inline graphic ].

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: Felix et al. (2008 ▶); Gaida et al. (2005 ▶); Lee et al. (2004 ▶). For a related structure, see: Wang et al. (2009 ▶). For standard bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₂₀H₂₀Br₂ClN₃O₃
M _r = 545.66
Triclinic,
a = 10.2614 (13) Å
b = 13.1418 (17) Å
c = 16.931 (2) Å
α = 83.764 (2)°
β = 73.309 (2)°
γ = 84.750 (2)°
V = 2169.8 (5) Å³
Z = 4
Mo Kα radiation
μ = 3.89 mm⁻¹
T = 298 K
0.30 × 0.28 × 0.28 mm

Data collection

Bruker SMART CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.389, T _max = 0.409
11972 measured reflections
8470 independent reflections
4874 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.055
wR(F ²) = 0.154
S = 1.02
8470 reflections
578 parameters
122 restraints
H-atom parameters constrained
Δρ_max = 1.56 e Å⁻³
Δρ_min = −1.07 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/S1600536810015023/lh5014sup1.cif

e-66-o1205-sup1.cif^{(31.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810015023/lh5014Isup2.hkl

e-66-o1205-Isup2.hkl^{(414.3KB, 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
N3—H3N⋯O4ⁱ	0.86	2.33	2.942 (7)	129
O3—H3⋯O6′ⁱⁱ	0.84	1.89	2.713 (12)	166
O6—H6⋯O3ⁱⁱⁱ	0.84	2.04	2.877 (17)	179
O6′—H6′⋯O3ⁱⁱⁱ	0.84	1.85	2.694 (10)	179

Open in a new tab

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

Acknowledgments

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

supplementary crystallographic information

Comment

Ambroxol, 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol, is an expectorant agent which leads to bronchial secretion due to its mucolytic properties (Felix et al., 2008; Gaida et al., 2005; Lee et al., 2004). Recently, we reported the crystal structure of a derivative of Ambroxol (Wang et al., 2009). In this paper, the crystal structure of the title compound, derived from the condensation reaction of 2-chloro-5-nitrobenzaldehyde with 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol in methanol solution, is reported.

There are two independent molecules in the asymmetric unit of the title compound, Fig. 1. The dihedral angle between the two benzene rings is 89.5 (2)° in one molecule and 82.9 (2)° in the other. The cyclohexyl rings adopt chair configurations. All bond lengths are within normal ranges (Allen et al., 1987).

Experimental

2-Chloro-5-nitrobenzaldehyde (1.0 mol, 185.6 mg) and 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol (1.0 mmol, 378.1 mg) were dissolved in a methanol solution (30 ml). The mixture was stirred at room temperature to give a clear colorless solution. Crystals of the title compound were formed by gradual evaporation of the solvent for a week at room temperature.