5,6,7-Trichloro-2-meth­oxy-8-hy­droxy­quinoline

Chen, Q.-M.; Yi, G.-B.; An, L.-K.; Feng, X.-L.

doi:10.1107/S1600536811010853

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 67| Part 5| May 2011| Page o1108

doi:10.1107/S1600536811010853

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5,6,7-Trichloro-2-methoxy-8-hydroxyquinoline

Qiu-Mao Chen,^a,^b Guo-Bin Yi,^a Lin-Kun An ^b and Xiao-Long Feng ^c ^*

^aFaculty of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou 510006, People's Republic of China, ^bSchool of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China, and ^cInstrumental Analysis & Research Center, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China
^*Correspondence e-mail: pusfxl@mail.sysu.edu.cn

(Received 22 February 2011; accepted 23 March 2011; online 13 April 2011)

In the title compound, C₁₀H₆Cl₃NO₂, a mean plane fitted through all non-H atoms has an r.m.s. deviation of 0.035 Å. In the crystal, adjacent molecules are connected by O—H⋯O hydrogen bonds and π–π stacking interactions [centroid–centroid distance = 3.650 (1) Å], resulting in an infinite chain which propagates in the b-axis direction.

Related literature

The title compound was obtained as an unexpected product from an attempt to synthesize a Top1 (DNA topoisomerase IB) inhibitor For general background to Top1, see: Pommier (2006 ). For the synthesis, see: Shen et al. (2008 ); Cheng et al. (2008 ).

Experimental

Crystal data

C₁₀H₆Cl₃NO₂
M_r = 278.51
Monoclinic, P 2₁ /c
a = 10.0782 (3) Å
b = 4.9979 (1) Å
c = 21.5827 (6) Å
β = 99.287 (2)°
V = 1072.87 (5) Å³
Z = 4
Cu Kα radiation
μ = 7.61 mm⁻¹
T = 150 K
0.40 × 0.21 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Onyx Nova diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, England.]$ ) T_min = 0.151, T_max = 0.312
4752 measured reflections
2035 independent reflections
1812 reflections with I > 2σ(I)
R_int = 0.024

Refinement

R[F² > 2σ(F²)] = 0.039
wR(F²) = 0.110
S = 1.04
2035 reflections
147 parameters
H-atom parameters constrained
Δρ_max = 0.98 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2A⋯O2ⁱ	0.84	2.25	2.9844 (16)	146
Symmetry code: (i) $[-x, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: CrysAlis PRO (Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, England.]$ ); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and publCIF (Westrip, 2010 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811010853/nk2089sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811010853/nk2089Isup2.hkl

checkCIF report

Comment top

DNA topoisomerase I (Top1) is an essential nuclear enzyme, and can be used as a target to discovery anticancer agents (Pommier, 2006). In our previous effort to find novel Top1 inhibitor, the title compound was obtained as a unexpected product from an attempt to synthesize 6,7-dichloroquinoline-5,8-dione (Cheng et al., 2008 and Shen et al., 2008).

The asymmetric unit of the title compound is shown in Fig. 1. All non-H atoms of the molecule adopt an approximately planar conformation (r.m.s. deviation = 0.035 Å). In the crystal, adjacent molecules are connected by O—H···O hydrogen bonds and π-π stacking interactions [centroid-centroid distance = 3.650 (1) Å], resulting in supramolecular chains along the b-axis (Fig. 2).

Related literature top

The title compound was obtained as a unexpected product from an attempt to synthesize a Top1 (DNA topoisomerase IB) inhibitor For general background to Top1, see: Pommier (2006). For the synthesis, see: Shen et al. (2008); Cheng et al. (2008).

Experimental top

According to our previously published procedure (Shen et al., 2008), the oxidation of 8-Hydroxyquinoline in concentrated hydrochloric acid with sodium chlorate can give a light yellow solid. The recrystallization of the solid from methanol would give the light yellow crystal.

Computing details top

Data collection: CrysAlis PRO (Oxford Diffraction, 2006); cell refinement: CrysAlis PRO (Oxford Diffraction, 2006); data reduction: CrysAlis PRO (Oxford Diffraction, 2006); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2010).

Figures top

	Fig. 1. The structure of the title compound, with atom labels and 50% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Infinite one-dimensional hydrogen bond in the b-axis direction. C-bound H atoms are omitted.

5,6,7-Trichloro-2-methoxy-8-hydroxyquinoline top

Crystal data top

C₁₀H₆Cl₃NO₂	F(000) = 560
M_r = 278.51	D_x = 1.724 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 3109 reflections
a = 10.0782 (3) Å	θ = 2.1–71.2°
b = 4.9979 (1) Å	µ = 7.61 mm⁻¹
c = 21.5827 (6) Å	T = 150 K
β = 99.287 (2)°	Block, light yellow
V = 1072.87 (5) Å³	0.40 × 0.21 × 0.20 mm
Z = 4

Data collection top

Oxford Diffraction Xcalibur Onyx Nova diffractometer	2035 independent reflections
Radiation source: fine-focus sealed tube	1812 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.024
Detector resolution: 8.2417 pixels mm^-1	θ_max = 71.4°, θ_min = 4.2°
ω scans	h = −11→12
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2006)	k = −6→5
T_min = 0.151, T_max = 0.312	l = −17→25
4752 measured reflections

Refinement top

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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.110	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.0765P)² + 0.4225P] where P = (F_o² + 2F_c²)/3
2035 reflections	(Δ/σ)_max = 0.001
147 parameters	Δρ_max = 0.98 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₀H₆Cl₃NO₂	V = 1072.87 (5) Å³
M_r = 278.51	Z = 4
Monoclinic, P2₁/c	Cu Kα radiation
a = 10.0782 (3) Å	µ = 7.61 mm⁻¹
b = 4.9979 (1) Å	T = 150 K
c = 21.5827 (6) Å	0.40 × 0.21 × 0.20 mm
β = 99.287 (2)°

Data collection top

Oxford Diffraction Xcalibur Onyx Nova diffractometer	2035 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2006)	1812 reflections with I > 2σ(I)
T_min = 0.151, T_max = 0.312	R_int = 0.024
4752 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.039	0 restraints
wR(F²) = 0.110	H-atom parameters constrained
S = 1.04	Δρ_max = 0.98 e Å⁻³
2035 reflections	Δρ_min = −0.26 e Å⁻³
147 parameters

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.47126 (6)	0.33323 (15)	0.06402 (3)	0.0429 (2)
Cl2	0.49339 (5)	0.73083 (11)	0.17798 (3)	0.03287 (19)
Cl3	0.27565 (6)	0.71889 (11)	0.26624 (3)	0.03218 (19)
C1	0.0208 (2)	−0.1743 (5)	0.08460 (10)	0.0290 (5)
C2	0.1158 (2)	−0.1986 (5)	0.04240 (11)	0.0313 (5)
H2	0.1030	−0.3266	0.0094	0.038*
C3	0.2240 (2)	−0.0355 (5)	0.05045 (10)	0.0307 (5)
H3	0.2880	−0.0468	0.0227	0.037*
C4	0.2422 (2)	0.1530 (4)	0.10032 (10)	0.0263 (5)
C5	0.3521 (2)	0.3325 (5)	0.11348 (10)	0.0286 (5)
C6	0.3623 (2)	0.5061 (4)	0.16321 (10)	0.0273 (5)
C7	0.2632 (2)	0.5050 (4)	0.20283 (10)	0.0262 (4)
C8	0.1556 (2)	0.3337 (4)	0.19120 (10)	0.0253 (4)
C9	0.1429 (2)	0.1572 (4)	0.13944 (9)	0.0239 (4)
C10	−0.1871 (3)	−0.3090 (7)	0.11264 (13)	0.0458 (7)
H10A	−0.1477	−0.3474	0.1563	0.069*
H10B	−0.2610	−0.4339	0.0990	0.069*
H10C	−0.2214	−0.1252	0.1095	0.069*
N1	0.03253 (18)	−0.0055 (4)	0.13107 (8)	0.0268 (4)
O1	−0.08538 (18)	−0.3391 (4)	0.07291 (8)	0.0368 (4)
O2	0.06144 (16)	0.3332 (3)	0.22959 (7)	0.0311 (4)
H2A	0.0161	0.1917	0.2241	0.047*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0362 (3)	0.0575 (4)	0.0393 (4)	−0.0108 (3)	0.0186 (3)	−0.0010 (3)
Cl2	0.0250 (3)	0.0306 (3)	0.0418 (3)	−0.0062 (2)	0.0017 (2)	0.0043 (2)
Cl3	0.0324 (3)	0.0297 (3)	0.0335 (3)	−0.0017 (2)	0.0023 (2)	−0.0073 (2)
C1	0.0298 (11)	0.0299 (12)	0.0261 (11)	−0.0015 (9)	0.0009 (9)	0.0037 (9)
C2	0.0351 (13)	0.0340 (12)	0.0242 (10)	0.0016 (10)	0.0029 (9)	−0.0032 (9)
C3	0.0308 (11)	0.0359 (13)	0.0264 (10)	0.0044 (10)	0.0075 (8)	0.0013 (9)
C4	0.0257 (11)	0.0272 (11)	0.0256 (10)	0.0014 (9)	0.0030 (8)	0.0027 (9)
C5	0.0248 (11)	0.0335 (12)	0.0284 (11)	−0.0005 (9)	0.0068 (9)	0.0081 (9)
C6	0.0247 (10)	0.0241 (11)	0.0319 (11)	−0.0018 (9)	0.0013 (8)	0.0057 (9)
C7	0.0277 (10)	0.0220 (10)	0.0284 (10)	0.0023 (8)	0.0027 (8)	0.0007 (8)
C8	0.0245 (10)	0.0262 (11)	0.0257 (10)	0.0024 (9)	0.0057 (8)	0.0030 (8)
C9	0.0229 (10)	0.0244 (11)	0.0242 (10)	0.0007 (8)	0.0035 (8)	0.0036 (8)
C10	0.0373 (14)	0.0620 (18)	0.0399 (14)	−0.0201 (13)	0.0110 (11)	−0.0090 (13)
N1	0.0261 (9)	0.0280 (10)	0.0264 (9)	−0.0019 (8)	0.0047 (7)	0.0016 (7)
O1	0.0368 (9)	0.0393 (10)	0.0346 (9)	−0.0125 (8)	0.0067 (7)	−0.0060 (7)
O2	0.0283 (8)	0.0348 (9)	0.0331 (8)	−0.0051 (7)	0.0132 (7)	−0.0062 (7)

Geometric parameters (Å, º) top

Cl1—C5	1.730 (2)	C5—C6	1.371 (3)
Cl2—C6	1.724 (2)	C6—C7	1.416 (3)
Cl3—C7	1.725 (2)	C7—C8	1.372 (3)
C1—N1	1.302 (3)	C8—O2	1.357 (3)
C1—O1	1.342 (3)	C8—C9	1.413 (3)
C1—C2	1.429 (3)	C9—N1	1.366 (3)
C2—C3	1.350 (3)	C10—O1	1.446 (3)
C2—H2	0.9500	C10—H10A	0.9800
C3—C4	1.420 (3)	C10—H10B	0.9800
C3—H3	0.9500	C10—H10C	0.9800
C4—C9	1.410 (3)	O2—H2A	0.8400
C4—C5	1.418 (3)

N1—C1—O1	120.9 (2)	C8—C7—C6	120.35 (19)
N1—C1—C2	124.0 (2)	C8—C7—Cl3	119.08 (17)
O1—C1—C2	115.1 (2)	C6—C7—Cl3	120.57 (16)
C3—C2—C1	118.5 (2)	O2—C8—C7	119.9 (2)
C3—C2—H2	120.8	O2—C8—C9	119.90 (19)
C1—C2—H2	120.8	C7—C8—C9	120.15 (19)
C2—C3—C4	120.1 (2)	N1—C9—C4	123.60 (19)
C2—C3—H3	120.0	N1—C9—C8	116.37 (18)
C4—C3—H3	120.0	C4—C9—C8	120.0 (2)
C9—C4—C5	118.5 (2)	O1—C10—H10A	109.5
C9—C4—C3	116.5 (2)	O1—C10—H10B	109.5
C5—C4—C3	125.0 (2)	H10A—C10—H10B	109.5
C6—C5—C4	120.9 (2)	O1—C10—H10C	109.5
C6—C5—Cl1	120.67 (18)	H10A—C10—H10C	109.5
C4—C5—Cl1	118.37 (18)	H10B—C10—H10C	109.5
C5—C6—C7	120.0 (2)	C1—N1—C9	117.30 (18)
C5—C6—Cl2	121.00 (17)	C1—O1—C10	116.41 (19)
C7—C6—Cl2	119.02 (16)	C8—O2—H2A	109.5

N1—C1—C2—C3	−0.7 (4)	Cl3—C7—C8—O2	−0.4 (3)
O1—C1—C2—C3	178.7 (2)	C6—C7—C8—C9	−0.1 (3)
C1—C2—C3—C4	0.6 (3)	Cl3—C7—C8—C9	179.78 (16)
C2—C3—C4—C9	0.1 (3)	C5—C4—C9—N1	179.7 (2)
C2—C3—C4—C5	179.5 (2)	C3—C4—C9—N1	−0.8 (3)
C9—C4—C5—C6	0.2 (3)	C5—C4—C9—C8	−1.3 (3)
C3—C4—C5—C6	−179.3 (2)	C3—C4—C9—C8	178.2 (2)
C9—C4—C5—Cl1	−178.18 (16)	O2—C8—C9—N1	0.5 (3)
C3—C4—C5—Cl1	2.4 (3)	C7—C8—C9—N1	−179.7 (2)
C4—C5—C6—C7	1.0 (3)	O2—C8—C9—C4	−178.55 (19)
Cl1—C5—C6—C7	179.29 (16)	C7—C8—C9—C4	1.3 (3)
C4—C5—C6—Cl2	−178.17 (17)	O1—C1—N1—C9	−179.3 (2)
Cl1—C5—C6—Cl2	0.2 (3)	C2—C1—N1—C9	0.0 (3)
C5—C6—C7—C8	−1.0 (3)	C4—C9—N1—C1	0.8 (3)
Cl2—C6—C7—C8	178.16 (17)	C8—C9—N1—C1	−178.2 (2)
C5—C6—C7—Cl3	179.09 (17)	N1—C1—O1—C10	2.7 (3)
Cl2—C6—C7—Cl3	−1.8 (2)	C2—C1—O1—C10	−176.6 (2)
C6—C7—C8—O2	179.70 (19)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···O2ⁱ	0.84	2.25	2.9844 (16)	146

Symmetry code: (i) −x, y−1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₀H₆Cl₃NO₂
M_r	278.51
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	150
a, b, c (Å)	10.0782 (3), 4.9979 (1), 21.5827 (6)
β (°)	99.287 (2)
V (Å³)	1072.87 (5)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	7.61
Crystal size (mm)	0.40 × 0.21 × 0.20

Data collection
Diffractometer	Oxford Diffraction Xcalibur Onyx Nova diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Oxford Diffraction, 2006)
T_min, T_max	0.151, 0.312
No. of measured, independent and observed [I > 2σ(I)] reflections	4752, 2035, 1812
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.615

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.110, 1.04
No. of reflections	2035
No. of parameters	147
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.98, −0.26

Computer programs: CrysAlis PRO (Oxford Diffraction, 2006), SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2010).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2A···O2ⁱ	0.84	2.25	2.9844 (16)	146

Symmetry code: (i) −x, y−1/2, −z+1/2.

Acknowledgements

The authors acknowledge financial support from the National Natural Science Foundation of China (No. 30801425) and Guangdong Natural Science Fund (No. 10151008901000022).

References

Cheng, Y., An, L. K., Wu, N., Wang, X. D., Bu, X. Z., Huang, Z. S. & Gu, L. Q. (2008). Bioorg. Med. Chem. 16, 4617–4625. Web of Science CrossRef PubMed CAS Google Scholar
Oxford Diffraction (2006). CrysAlis PRO. Oxford Diffraction Ltd, Abingdon, England. Google Scholar
Pommier, Y. (2006). Nature Rev. 6, 789–802. CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Shen, D. Q., Cheng, Y., An, L. K., Bu, X. Z., Huang, Z. S. & Gu, L. Q. (2008). Chin. Chem. Lett. 19, 533–536. Web of Science CrossRef CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar