2-[6,8-Dibromo-3-(4-hydroxy-cyclo-hexyl)-1,2,3,4-tetra-hydro-quinazolin-2-yl]-6-methoxy-phenol.

The title compound, C(21)H(24)Br(2)N(2)O(3), was synthesized by the condensation reaction of 3-methoxy-salicylaldehyde with 4-(2-amino-3,5-dibromo-benzyl-amino)cyclo-hexa-nol in a methanol solution. The dihedral angle between the two benzene rings is 76.4 (3)°. The cyclo-hexyl ring adopts a chair configuration. There is an intra-molecular O-H⋯N hydrogen bond which affects the solid state conformation of the mol-ecule. The crystal structure is stabilized by inter-molecular O-H⋯O hydrogen bonds, forming chains running along the b axis.

Related literature

For details of the pharmaceutical uses of the closely related compound ambroxol, systematic name 4-(2-amino-3,5-di­bromo­benzyl­amino)cyclo­hexa­nol, see: Felix et al. (2008 ▶); Gaida et al. (2005 ▶); Lee et al. (2004 ▶). For bond length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C21H24Br2N2O3

M = 512.24

Triclinic,

a = 8.695 (2) Å

b = 11.124 (3) Å

c = 12.090 (2) Å

α = 73.870 (3)°

β = 78.226 (3)°

γ = 67.031 (2)°

V = 1028.2 (4) Å3

Z = 2

Mo Kα radiation

μ = 3.97 mm−1

T = 298 K

0.30 × 0.30 × 0.30 mm

Data collection

Bruker SMART CCD area detector diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.382, T max = 0.382 (expected range = 0.304–0.304)

8514 measured reflections

4305 independent reflections

3035 reflections with I > 2σ(I)

R int = 0.032

Refinement

R[F 2 > 2σ(F 2)] = 0.042

wR(F 2) = 0.096

S = 1.02

4305 reflections

256 parameters

H-atom parameters constrained

Δρmax = 0.51 e Å−3

Δρmin = −0.41 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.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809005182/sj2575sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809005182/sj2575Isup2.hkl

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

C21H24Br2N2O3	Z = 2
Mr = 512.24	F(000) = 516
Triclinic, P1	Dx = 1.655 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.695 (2) Å	Cell parameters from 2079 reflections
b = 11.124 (3) Å	θ = 2.3–24.6°
c = 12.090 (2) Å	µ = 3.97 mm−1
α = 73.870 (3)°	T = 298 K
β = 78.226 (3)°	Block, colorless
γ = 67.031 (2)°	0.30 × 0.30 × 0.30 mm
V = 1028.2 (4) Å3

Bruker SMART CCD area detector diffractometer	4305 independent reflections
Radiation source: fine-focus sealed tube	3035 reflections with I > 2σ(I)
graphite	Rint = 0.032
ω scans	θmax = 27.0°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −11→10
Tmin = 0.382, Tmax = 0.382	k = −14→14
8514 measured reflections	l = −15→15

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.096	H-atom parameters constrained
S = 1.02	w = 1/[σ2(Fo2) + (0.0423P)2 + 0.0168P] where P = (Fo2 + 2Fc2)/3
4305 reflections	(Δ/σ)max = 0.001
256 parameters	Δρmax = 0.51 e Å−3
0 restraints	Δρmin = −0.41 e Å−3

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq
Br1	1.17738 (5)	0.24247 (4)	0.32321 (4)	0.04726 (14)
Br2	1.28346 (5)	0.54977 (4)	0.58131 (3)	0.04402 (14)
O1	0.2331 (3)	0.9422 (3)	0.3052 (2)	0.0418 (7)
H1	0.1581	0.9883	0.2635	0.063*
O2	0.9413 (3)	0.8807 (3)	−0.1082 (2)	0.0430 (7)
H2	0.8961	0.8692	−0.0416	0.065*
O3	1.1435 (4)	0.9116 (3)	−0.2940 (2)	0.0510 (7)
N1	1.0518 (4)	0.5182 (3)	0.1542 (2)	0.0305 (7)
H1A	1.0527	0.4432	0.1469	0.037*
N2	0.9133 (3)	0.7617 (3)	0.1103 (2)	0.0249 (6)
C1	1.1053 (4)	0.6460 (3)	0.2638 (3)	0.0265 (8)
C2	1.1080 (4)	0.5243 (3)	0.2507 (3)	0.0263 (7)
C3	1.1674 (4)	0.4110 (3)	0.3381 (3)	0.0287 (8)
C4	1.2199 (4)	0.4172 (3)	0.4357 (3)	0.0317 (8)
H4	1.2586	0.3405	0.4931	0.038*
C5	1.2143 (4)	0.5386 (4)	0.4468 (3)	0.0302 (8)
C6	1.1591 (4)	0.6523 (3)	0.3620 (3)	0.0306 (8)
H6	1.1576	0.7334	0.3702	0.037*
C7	1.0414 (4)	0.7698 (3)	0.1692 (3)	0.0259 (7)
H7A	0.9929	0.8481	0.2027	0.031*
H7B	1.1349	0.7799	0.1128	0.031*
C8	0.7481 (4)	0.7705 (3)	0.1797 (3)	0.0269 (8)
H8	0.7560	0.6812	0.2263	0.032*
C9	0.6954 (4)	0.8659 (4)	0.2601 (3)	0.0377 (9)
H9A	0.6977	0.9525	0.2156	0.045*
H9B	0.7751	0.8324	0.3168	0.045*
C10	0.5210 (5)	0.8823 (4)	0.3222 (3)	0.0410 (10)
H10A	0.5213	0.7973	0.3722	0.049*
H10B	0.4908	0.9464	0.3705	0.049*
C11	0.3920 (4)	0.9293 (3)	0.2392 (3)	0.0322 (8)
H11	0.3880	1.0175	0.1918	0.039*
C12	0.4406 (4)	0.8330 (4)	0.1607 (3)	0.0414 (10)
H12A	0.3600	0.8662	0.1045	0.050*
H12B	0.4380	0.7468	0.2062	0.050*
C13	0.6155 (4)	0.8160 (4)	0.0976 (3)	0.0378 (9)
H13A	0.6452	0.7509	0.0504	0.045*
H13B	0.6143	0.9006	0.0463	0.045*
C14	0.9912 (4)	0.6381 (3)	0.0655 (3)	0.0255 (7)
H14	0.9030	0.6289	0.0329	0.031*
C15	1.1251 (4)	0.6565 (4)	−0.0355 (3)	0.0296 (8)
C16	1.0875 (4)	0.7752 (4)	−0.1185 (3)	0.0298 (8)
C17	1.1986 (5)	0.7917 (4)	−0.2178 (3)	0.0367 (9)
C18	1.3514 (5)	0.6900 (5)	−0.2301 (3)	0.0454 (11)
H18	1.4274	0.7007	−0.2951	0.055*
C19	1.3921 (5)	0.5718 (4)	−0.1457 (4)	0.0476 (11)
H19	1.4954	0.5038	−0.1541	0.057*
C20	1.2793 (4)	0.5554 (4)	−0.0496 (3)	0.0368 (9)
H20	1.3068	0.4759	0.0063	0.044*
C21	1.2282 (7)	0.9219 (5)	−0.4076 (3)	0.0797 (17)
H21A	1.3418	0.9132	−0.4048	0.120*
H21B	1.1715	1.0074	−0.4549	0.120*
H21C	1.2288	0.8521	−0.4400	0.120*

	U11	U22	U33	U12	U13	U23
Br1	0.0577 (3)	0.0246 (2)	0.0575 (3)	−0.00942 (19)	−0.0134 (2)	−0.00831 (19)
Br2	0.0490 (3)	0.0547 (3)	0.0320 (2)	−0.0205 (2)	−0.01256 (18)	−0.00628 (18)
O1	0.0277 (14)	0.0408 (16)	0.0439 (16)	−0.0053 (13)	0.0025 (12)	−0.0038 (13)
O2	0.0370 (16)	0.0440 (16)	0.0302 (14)	−0.0040 (13)	0.0040 (12)	−0.0011 (12)
O3	0.0602 (19)	0.0570 (18)	0.0303 (15)	−0.0259 (16)	0.0092 (13)	−0.0038 (14)
N1	0.0405 (18)	0.0227 (15)	0.0294 (16)	−0.0106 (14)	−0.0055 (14)	−0.0073 (13)
N2	0.0216 (15)	0.0262 (15)	0.0263 (15)	−0.0077 (12)	−0.0019 (12)	−0.0068 (12)
C1	0.0208 (18)	0.0288 (19)	0.0291 (18)	−0.0088 (15)	−0.0031 (15)	−0.0048 (15)
C2	0.0186 (18)	0.0276 (18)	0.0313 (19)	−0.0066 (15)	0.0006 (14)	−0.0094 (15)
C3	0.028 (2)	0.0219 (18)	0.036 (2)	−0.0074 (16)	−0.0032 (16)	−0.0082 (16)
C4	0.027 (2)	0.029 (2)	0.031 (2)	−0.0038 (17)	−0.0074 (16)	−0.0005 (16)
C5	0.0239 (19)	0.039 (2)	0.0297 (19)	−0.0106 (17)	−0.0051 (15)	−0.0097 (17)
C6	0.0249 (19)	0.032 (2)	0.037 (2)	−0.0127 (16)	0.0005 (16)	−0.0098 (17)
C7	0.0232 (18)	0.0268 (18)	0.0297 (18)	−0.0096 (15)	−0.0042 (15)	−0.0073 (15)
C8	0.0257 (19)	0.0221 (17)	0.0311 (19)	−0.0081 (15)	−0.0016 (15)	−0.0047 (15)
C9	0.030 (2)	0.048 (2)	0.035 (2)	−0.0078 (18)	−0.0039 (17)	−0.0168 (18)
C10	0.036 (2)	0.048 (2)	0.032 (2)	−0.0031 (19)	−0.0032 (18)	−0.0155 (18)
C11	0.028 (2)	0.0266 (19)	0.036 (2)	−0.0076 (16)	0.0033 (16)	−0.0049 (16)
C12	0.027 (2)	0.050 (2)	0.050 (2)	−0.0111 (19)	−0.0040 (18)	−0.018 (2)
C13	0.027 (2)	0.054 (3)	0.039 (2)	−0.0119 (19)	−0.0026 (17)	−0.0247 (19)
C14	0.0221 (18)	0.0295 (19)	0.0270 (18)	−0.0080 (15)	−0.0046 (14)	−0.0098 (15)
C15	0.027 (2)	0.039 (2)	0.0253 (18)	−0.0134 (17)	−0.0032 (15)	−0.0096 (16)
C16	0.025 (2)	0.037 (2)	0.0259 (18)	−0.0096 (17)	−0.0037 (15)	−0.0072 (16)
C17	0.038 (2)	0.049 (2)	0.028 (2)	−0.020 (2)	0.0007 (17)	−0.0109 (18)
C18	0.035 (2)	0.073 (3)	0.037 (2)	−0.026 (2)	0.0066 (19)	−0.024 (2)
C19	0.026 (2)	0.062 (3)	0.054 (3)	−0.003 (2)	−0.001 (2)	−0.032 (2)
C20	0.026 (2)	0.042 (2)	0.041 (2)	−0.0053 (18)	−0.0057 (17)	−0.0149 (18)
C21	0.131 (5)	0.086 (4)	0.029 (2)	−0.063 (4)	0.027 (3)	−0.013 (2)

Br1—C3	1.900 (3)	C9—C10	1.514 (5)
Br2—C5	1.895 (3)	C9—H9A	0.9700
O1—C11	1.423 (4)	C9—H9B	0.9700
O1—H1	0.8200	C10—C11	1.499 (5)
O2—C16	1.364 (4)	C10—H10A	0.9700
O2—H2	0.8200	C10—H10B	0.9700
O3—C17	1.363 (4)	C11—C12	1.509 (5)
O3—C21	1.416 (4)	C11—H11	0.9800
N1—C2	1.381 (4)	C12—C13	1.520 (5)
N1—C14	1.448 (4)	C12—H12A	0.9700
N1—H1A	0.8600	C12—H12B	0.9700
N2—C14	1.476 (4)	C13—H13A	0.9700
N2—C7	1.482 (4)	C13—H13B	0.9700
N2—C8	1.490 (4)	C14—C15	1.535 (4)
C1—C6	1.389 (4)	C14—H14	0.9800
C1—C2	1.396 (4)	C15—C16	1.385 (5)
C1—C7	1.517 (4)	C15—C20	1.388 (5)
C2—C3	1.395 (5)	C16—C17	1.397 (5)
C3—C4	1.376 (4)	C17—C18	1.381 (5)
C4—C5	1.376 (5)	C18—C19	1.391 (6)
C4—H4	0.9300	C18—H18	0.9300
C5—C6	1.374 (5)	C19—C20	1.379 (5)
C6—H6	0.9300	C19—H19	0.9300
C7—H7A	0.9700	C20—H20	0.9300
C7—H7B	0.9700	C21—H21A	0.9600
C8—C9	1.513 (5)	C21—H21B	0.9600
C8—C13	1.518 (4)	C21—H21C	0.9600
C8—H8	0.9800
C11—O1—H1	109.5	H10A—C10—H10B	107.9
C16—O2—H2	109.5	O1—C11—C10	107.9 (3)
C17—O3—C21	117.3 (3)	O1—C11—C12	112.8 (3)
C2—N1—C14	120.0 (3)	C10—C11—C12	109.8 (3)
C2—N1—H1A	120.0	O1—C11—H11	108.8
C14—N1—H1A	120.0	C10—C11—H11	108.8
C14—N2—C7	107.0 (2)	C12—C11—H11	108.8
C14—N2—C8	112.1 (2)	C11—C12—C13	110.9 (3)
C7—N2—C8	116.3 (2)	C11—C12—H12A	109.5
C6—C1—C2	120.2 (3)	C13—C12—H12A	109.5
C6—C1—C7	121.4 (3)	C11—C12—H12B	109.5
C2—C1—C7	118.4 (3)	C13—C12—H12B	109.5
N1—C2—C3	121.7 (3)	H12A—C12—H12B	108.1
N1—C2—C1	120.4 (3)	C8—C13—C12	112.7 (3)
C3—C2—C1	118.0 (3)	C8—C13—H13A	109.1
C4—C3—C2	121.9 (3)	C12—C13—H13A	109.1
C4—C3—Br1	118.5 (3)	C8—C13—H13B	109.1
C2—C3—Br1	119.6 (3)	C12—C13—H13B	109.1
C5—C4—C3	118.9 (3)	H13A—C13—H13B	107.8
C5—C4—H4	120.6	N1—C14—N2	113.6 (3)
C3—C4—H4	120.6	N1—C14—C15	113.8 (3)
C6—C5—C4	121.1 (3)	N2—C14—C15	109.0 (3)
C6—C5—Br2	119.3 (3)	N1—C14—H14	106.7
C4—C5—Br2	119.6 (3)	N2—C14—H14	106.7
C5—C6—C1	119.9 (3)	C15—C14—H14	106.7
C5—C6—H6	120.0	C16—C15—C20	118.9 (3)
C1—C6—H6	120.0	C16—C15—C14	118.9 (3)
N2—C7—C1	111.6 (3)	C20—C15—C14	122.1 (3)
N2—C7—H7A	109.3	O2—C16—C15	122.2 (3)
C1—C7—H7A	109.3	O2—C16—C17	116.8 (3)
N2—C7—H7B	109.3	C15—C16—C17	121.0 (3)
C1—C7—H7B	109.3	O3—C17—C18	126.0 (3)
H7A—C7—H7B	108.0	O3—C17—C16	114.9 (3)
N2—C8—C9	112.9 (3)	C18—C17—C16	119.1 (4)
N2—C8—C13	108.8 (3)	C17—C18—C19	120.2 (4)
C9—C8—C13	109.3 (3)	C17—C18—H18	119.9
N2—C8—H8	108.6	C19—C18—H18	119.9
C9—C8—H8	108.6	C20—C19—C18	120.1 (4)
C13—C8—H8	108.6	C20—C19—H19	120.0
C8—C9—C10	112.0 (3)	C18—C19—H19	120.0
C8—C9—H9A	109.2	C19—C20—C15	120.6 (4)
C10—C9—H9A	109.2	C19—C20—H20	119.7
C8—C9—H9B	109.2	C15—C20—H20	119.7
C10—C9—H9B	109.2	O3—C21—H21A	109.5
H9A—C9—H9B	107.9	O3—C21—H21B	109.5
C11—C10—C9	112.0 (3)	H21A—C21—H21B	109.5
C11—C10—H10A	109.2	O3—C21—H21C	109.5
C9—C10—H10A	109.2	H21A—C21—H21C	109.5
C11—C10—H10B	109.2	H21B—C21—H21C	109.5
C9—C10—H10B	109.2

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···N2	0.82	1.89	2.614 (3)	147
O1—H1···O3i	0.82	2.41	3.048 (4)	135
O1—H1···O2i	0.82	2.13	2.897 (4)	155

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯N2	0.82	1.89	2.614 (3)	147
O1—H1⋯O3i	0.82	2.41	3.048 (4)	135
O1—H1⋯O2i	0.82	2.13	2.897 (4)	155

Symmetry code: (i) .