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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2012 Apr 21;68(Pt 5):o1498. doi: 10.1107/S1600536812014924

4,7-Dichloro­quinoline

Amol A Kulkarni a,*, Christopher King b, Ray J Butcher b, Joseph M D Fortunak b
PMCID: PMC3344607  PMID: 22590369

Abstract

The two mol­ecules in the asymmetric unit of the title compound, C9H5Cl2N, are both essentially planar (r.m.s. deviations for all non-H atoms = 0.014 and 0.026 Å). There are no close C—H⋯Cl contacts.

Related literature  

4,7-dichloro­quinoline is a commonly used starting material for the synthesis of a variety of anti-malarial drugs, such as amodiquine {systematic name: 4-[(7-chloro­quinolin-4-yl)amino]-2-[(diethyl­amino)­meth­yl]phenol}, see: Dongre et al. (2007 ▶); O’Neill et al. (2003 ▶); Lawrence et al. (2008 ▶); Saha et al. (2009 ▶).graphic file with name e-68-o1498-scheme1.jpg

Experimental  

Crystal data  

  • C9H5Cl2N

  • M r = 198.04

  • Monoclinic, Inline graphic

  • a = 18.2243 (17) Å

  • b = 3.8253 (5) Å

  • c = 23.622 (3) Å

  • β = 96.61 (1)°

  • V = 1635.8 (4) Å3

  • Z = 8

  • Cu Kα radiation

  • μ = 6.59 mm−1

  • T = 123 K

  • 0.35 × 0.23 × 0.16 mm

Data collection  

  • Oxford Diffraction Xcalibur Ruby Gemini diffractometer

  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007 ▶) T min = 0.233, T max = 1.000

  • 5147 measured reflections

  • 3188 independent reflections

  • 2148 reflections with I > 2σ(I)

  • R int = 0.090

Refinement  

  • R[F 2 > 2σ(F 2)] = 0.096

  • wR(F 2) = 0.327

  • S = 1.08

  • 3188 reflections

  • 217 parameters

  • H-atom parameters constrained

  • Δρmax = 0.68 e Å−3

  • Δρmin = −0.49 e Å−3

Data collection: CrysAlis PRO (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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 datablock(s) I, global. DOI: 10.1107/S1600536812014924/bt5833sup1.cif

e-68-o1498-sup1.cif (18.1KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812014924/bt5833Isup2.hkl

e-68-o1498-Isup2.hkl (156.4KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536812014924/bt5833Isup3.cml

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

Acknowledgments

AAK wishes to acknowledge RCMI, Howard University and the CDRD, College of Pharmacy, Howard University. RJB wishes to acknowledge the NSF–MRI program (grant CHE-0619278) for funds to purchase the diffractometer. This project was supported by grant No. D34HP16042-03-03 from the Health Resources and Services Administration (HRSA).

supplementary crystallographic information

Comment

The crystal structure of 4,7-dichloroquinoline has not previously been reported. Recrystallization of 4,7-dichloroquinoline from hexane or similar hydrocarbon solvents removes low levels (1–4%) of 4,5-dichloroquinoline that are present from the manufacturing process. Impurities that arise from the presence of 4,5-dichloroquinoline in 4,7-DCQ are otherwise difficult to remove from the manufacturing process of commercial malaria drugs, including amodiaquine and piperaquine (Dongre et al., 2007).

In view of the importance of this pharmaceutically active compound its crystal structure was determined. There are two molecules in the asymmetric unit (Z' = 2) and there are no close C—H···Cl contacts.

Experimental

Hexanes (100 ml) were transferred to an Erlenmeyer flask and heated to a gentle reflux. 4,7-Dichloroquinoline (20 g, commercially available from Sigma-Aldrich) was slowly added to hexanes and the solution was maintained at 65 °C, resulting in a colorless solution. The solution was slowly cooled to room temperature and maintained at room temperature for 12 h. Long, colorless needles were observed to slowly crystallize from solution. The colorless needles obtained were isolated by filtration and dried to a constant weight, mp 83–84 °C; 1H-NMR (CDCl3) d 8.78 (d, J = 4.8 Hz, 1H), 8.15 (d, J = 9.2 Hz, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.59 (dd, J = 9.2, 2.4 Hz, 1H), 7.48 (d, J = 4.8 Hz, 1H).

Refinement

H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms with a C—H distance of 0.95Å and U(H) = 1.2Ueq(C).

Figures

Fig. 1.

Fig. 1.

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A view of the title compound, C9H5Cl2N, showing atom numbering scheme and the two molecules in the asymmetric unit.

Crystal data

C9H5Cl2N F(000) = 800
Mr = 198.04 Dx = 1.608 Mg m−3
Monoclinic, P21/n Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2yn Cell parameters from 1283 reflections
a = 18.2243 (17) Å θ = 2.9–75.6°
b = 3.8253 (5) Å µ = 6.59 mm−1
c = 23.622 (3) Å T = 123 K
β = 96.61 (1)° Prism, colorless
V = 1635.8 (4) Å3 0.35 × 0.23 × 0.16 mm
Z = 8
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Data collection

Oxford Diffraction Xcalibur Ruby Gemini diffractometer 3188 independent reflections
Radiation source: Enhance (Cu) X-ray Source 2148 reflections with I > 2σ(I)
Graphite monochromator Rint = 0.090
Detector resolution: 10.5081 pixels mm-1 θmax = 75.8°, θmin = 2.9°
ω scans h = −22→16
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007) k = −4→4
Tmin = 0.233, Tmax = 1.000 l = −23→29
5147 measured reflections
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Refinement

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)] = 0.096 Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.327 H-atom parameters constrained
S = 1.08 w = 1/[σ2(Fo2) + (0.1577P)2 + 4.2615P] where P = (Fo2 + 2Fc2)/3
3188 reflections (Δ/σ)max < 0.001
217 parameters Δρmax = 0.68 e Å−3
0 restraints Δρmin = −0.49 e Å−3
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Special details

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

x y z Uiso*/Ueq
Cl1A 0.46391 (11) 0.7593 (6) 0.94032 (9) 0.0625 (6)
Cl2A 0.31181 (11) 0.9079 (6) 0.65527 (9) 0.0630 (6)
N1A 0.5405 (3) 0.4243 (18) 0.7726 (3) 0.0560 (15)
C2A 0.5808 (4) 0.369 (2) 0.8223 (4) 0.0544 (18)
H2AA 0.6274 0.2581 0.8219 0.065*
C3A 0.5587 (4) 0.467 (2) 0.8763 (4) 0.0560 (18)
H3AA 0.5892 0.4193 0.9108 0.067*
C4A 0.4924 (4) 0.6317 (19) 0.8765 (3) 0.0501 (16)
C5A 0.3766 (4) 0.8694 (19) 0.8220 (4) 0.0544 (18)
H5AA 0.3579 0.9425 0.8560 0.065*
C6A 0.3371 (4) 0.9282 (19) 0.7711 (4) 0.0517 (17)
H6AA 0.2906 1.0420 0.7694 0.062*
C7A 0.3646 (4) 0.822 (2) 0.7200 (4) 0.0541 (18)
C8A 0.4305 (4) 0.652 (2) 0.7206 (4) 0.0531 (17)
H8AA 0.4475 0.5771 0.6860 0.064*
C9A 0.4735 (4) 0.5904 (19) 0.7737 (4) 0.0506 (16)
C10A 0.4461 (4) 0.6984 (18) 0.8250 (3) 0.0498 (16)
Cl1B 0.50197 (10) 0.9725 (5) 0.58983 (9) 0.0589 (6)
Cl2B 0.80689 (11) 0.2033 (5) 0.48184 (10) 0.0625 (6)
N1B 0.7313 (3) 0.6479 (18) 0.6687 (3) 0.0559 (16)
C2B 0.6835 (4) 0.802 (2) 0.6981 (4) 0.0569 (18)
H2BA 0.6984 0.8463 0.7373 0.068*
C3B 0.6115 (4) 0.908 (2) 0.6755 (4) 0.0527 (17)
H3BA 0.5797 1.0195 0.6991 0.063*
C4B 0.5891 (4) 0.848 (2) 0.6205 (4) 0.0528 (17)
C5B 0.6209 (4) 0.615 (2) 0.5258 (4) 0.0559 (19)
H5BA 0.5730 0.6680 0.5077 0.067*
C6B 0.6720 (4) 0.472 (2) 0.4941 (4) 0.0539 (17)
H6BA 0.6609 0.4309 0.4544 0.065*
C7B 0.7417 (4) 0.388 (2) 0.5232 (4) 0.0565 (19)
C8B 0.7602 (4) 0.439 (2) 0.5800 (4) 0.0527 (17)
H8BA 0.8074 0.3700 0.5978 0.063*
C9B 0.7092 (4) 0.5951 (19) 0.6121 (3) 0.0483 (16)
C10B 0.6378 (4) 0.6840 (19) 0.5843 (4) 0.0526 (17)
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
Cl1A 0.0557 (11) 0.0571 (11) 0.0757 (13) 0.0000 (8) 0.0113 (9) −0.0010 (9)
Cl2A 0.0476 (10) 0.0611 (11) 0.0788 (13) 0.0022 (8) 0.0012 (8) 0.0029 (9)
N1A 0.036 (3) 0.050 (3) 0.082 (4) −0.002 (3) 0.010 (3) 0.001 (3)
C2A 0.041 (4) 0.049 (4) 0.076 (5) 0.001 (3) 0.018 (3) 0.002 (3)
C3A 0.043 (4) 0.044 (4) 0.080 (5) −0.004 (3) 0.001 (3) 0.008 (3)
C4A 0.045 (4) 0.044 (3) 0.063 (4) −0.005 (3) 0.013 (3) −0.005 (3)
C5A 0.041 (4) 0.038 (3) 0.086 (5) −0.002 (3) 0.014 (3) −0.004 (3)
C6A 0.035 (3) 0.044 (3) 0.077 (5) −0.001 (3) 0.012 (3) −0.001 (3)
C7A 0.039 (4) 0.045 (4) 0.078 (5) −0.005 (3) 0.003 (3) 0.004 (3)
C8A 0.045 (4) 0.043 (4) 0.072 (5) −0.002 (3) 0.013 (3) −0.007 (3)
C9A 0.036 (3) 0.039 (3) 0.077 (5) −0.004 (3) 0.011 (3) −0.001 (3)
C10A 0.043 (4) 0.038 (3) 0.069 (4) −0.005 (3) 0.007 (3) −0.002 (3)
Cl1B 0.0374 (9) 0.0560 (10) 0.0837 (13) 0.0058 (7) 0.0087 (8) 0.0054 (9)
Cl2B 0.0474 (10) 0.0558 (10) 0.0875 (14) 0.0036 (8) 0.0205 (8) −0.0008 (9)
N1B 0.038 (3) 0.049 (3) 0.080 (4) −0.002 (3) 0.005 (3) 0.006 (3)
C2B 0.040 (4) 0.047 (4) 0.083 (5) −0.002 (3) 0.005 (3) 0.006 (4)
C3B 0.035 (3) 0.052 (4) 0.072 (5) −0.004 (3) 0.011 (3) 0.004 (3)
C4B 0.041 (4) 0.044 (4) 0.074 (5) −0.005 (3) 0.012 (3) 0.011 (3)
C5B 0.041 (4) 0.050 (4) 0.075 (5) −0.008 (3) −0.003 (3) 0.011 (3)
C6B 0.038 (4) 0.058 (4) 0.068 (5) −0.004 (3) 0.016 (3) 0.001 (3)
C7B 0.031 (3) 0.048 (4) 0.093 (6) −0.003 (3) 0.018 (3) 0.005 (4)
C8B 0.034 (3) 0.044 (4) 0.081 (5) −0.001 (3) 0.008 (3) 0.002 (3)
C9B 0.034 (3) 0.042 (3) 0.069 (4) −0.002 (3) 0.008 (3) 0.006 (3)
C10B 0.034 (3) 0.040 (3) 0.084 (5) −0.002 (3) 0.008 (3) 0.006 (3)
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Geometric parameters (Å, º)

Cl1A—C4A 1.720 (8) Cl1B—C4B 1.734 (8)
Cl2A—C7A 1.742 (8) Cl2B—C7B 1.769 (8)
N1A—C2A 1.328 (11) N1B—C2B 1.313 (11)
N1A—C9A 1.379 (10) N1B—C9B 1.368 (10)
C2A—C3A 1.432 (12) C2B—C3B 1.418 (11)
C2A—H2AA 0.9500 C2B—H2BA 0.9500
C3A—C4A 1.362 (11) C3B—C4B 1.338 (12)
C3A—H3AA 0.9500 C3B—H3BA 0.9500
C4A—C10A 1.422 (11) C4B—C10B 1.443 (11)
C5A—C6A 1.348 (12) C5B—C6B 1.373 (12)
C5A—C10A 1.420 (11) C5B—C10B 1.407 (12)
C5A—H5AA 0.9500 C5B—H5BA 0.9500
C6A—C7A 1.417 (12) C6B—C7B 1.410 (11)
C6A—H6AA 0.9500 C6B—H6BA 0.9500
C7A—C8A 1.364 (11) C7B—C8B 1.359 (12)
C8A—C9A 1.421 (11) C8B—C9B 1.400 (11)
C8A—H8AA 0.9500 C8B—H8BA 0.9500
C9A—C10A 1.422 (11) C9B—C10B 1.429 (10)
C2A—N1A—C9A 117.2 (8) C2B—N1B—C9B 116.3 (7)
N1A—C2A—C3A 124.2 (7) N1B—C2B—C3B 124.9 (8)
N1A—C2A—H2AA 117.9 N1B—C2B—H2BA 117.6
C3A—C2A—H2AA 117.9 C3B—C2B—H2BA 117.6
C4A—C3A—C2A 117.7 (7) C4B—C3B—C2B 118.8 (8)
C4A—C3A—H3AA 121.1 C4B—C3B—H3BA 120.6
C2A—C3A—H3AA 121.1 C2B—C3B—H3BA 120.6
C3A—C4A—C10A 121.2 (8) C3B—C4B—C10B 120.7 (7)
C3A—C4A—Cl1A 119.5 (7) C3B—C4B—Cl1B 121.4 (6)
C10A—C4A—Cl1A 119.4 (6) C10B—C4B—Cl1B 117.9 (6)
C6A—C5A—C10A 120.2 (8) C6B—C5B—C10B 121.7 (7)
C6A—C5A—H5AA 119.9 C6B—C5B—H5BA 119.1
C10A—C5A—H5AA 119.9 C10B—C5B—H5BA 119.1
C5A—C6A—C7A 120.5 (7) C5B—C6B—C7B 117.0 (8)
C5A—C6A—H6AA 119.8 C5B—C6B—H6BA 121.5
C7A—C6A—H6AA 119.8 C7B—C6B—H6BA 121.5
C8A—C7A—C6A 121.7 (8) C8B—C7B—C6B 123.7 (7)
C8A—C7A—Cl2A 119.7 (7) C8B—C7B—Cl2B 119.8 (6)
C6A—C7A—Cl2A 118.6 (6) C6B—C7B—Cl2B 116.5 (7)
C7A—C8A—C9A 118.9 (8) C7B—C8B—C9B 119.4 (7)
C7A—C8A—H8AA 120.6 C7B—C8B—H8BA 120.3
C9A—C8A—H8AA 120.6 C9B—C8B—H8BA 120.3
N1A—C9A—C8A 117.3 (8) N1B—C9B—C8B 117.0 (7)
N1A—C9A—C10A 123.3 (7) N1B—C9B—C10B 124.4 (7)
C8A—C9A—C10A 119.5 (7) C8B—C9B—C10B 118.7 (7)
C4A—C10A—C5A 124.2 (8) C5B—C10B—C9B 119.3 (7)
C4A—C10A—C9A 116.4 (7) C5B—C10B—C4B 125.8 (7)
C5A—C10A—C9A 119.3 (7) C9B—C10B—C4B 114.9 (7)
C9A—N1A—C2A—C3A 0.9 (12) C9B—N1B—C2B—C3B 1.5 (12)
N1A—C2A—C3A—C4A −1.0 (12) N1B—C2B—C3B—C4B 0.3 (12)
C2A—C3A—C4A—C10A 1.1 (11) C2B—C3B—C4B—C10B −1.2 (11)
C2A—C3A—C4A—Cl1A −179.2 (6) C2B—C3B—C4B—Cl1B −179.5 (6)
C10A—C5A—C6A—C7A −0.2 (11) C10B—C5B—C6B—C7B 1.7 (12)
C5A—C6A—C7A—C8A 1.1 (12) C5B—C6B—C7B—C8B 0.4 (12)
C5A—C6A—C7A—Cl2A −179.4 (6) C5B—C6B—C7B—Cl2B 179.9 (6)
C6A—C7A—C8A—C9A −1.7 (11) C6B—C7B—C8B—C9B −2.4 (12)
Cl2A—C7A—C8A—C9A 178.8 (6) Cl2B—C7B—C8B—C9B 178.1 (6)
C2A—N1A—C9A—C8A 179.4 (7) C2B—N1B—C9B—C8B 178.4 (7)
C2A—N1A—C9A—C10A −0.9 (11) C2B—N1B—C9B—C10B −2.5 (11)
C7A—C8A—C9A—N1A −178.8 (7) C7B—C8B—C9B—N1B −178.5 (7)
C7A—C8A—C9A—C10A 1.4 (11) C7B—C8B—C9B—C10B 2.3 (11)
C3A—C4A—C10A—C5A −179.7 (7) C6B—C5B—C10B—C9B −1.7 (11)
Cl1A—C4A—C10A—C5A 0.5 (10) C6B—C5B—C10B—C4B 177.0 (7)
C3A—C4A—C10A—C9A −1.1 (11) N1B—C9B—C10B—C5B −179.5 (7)
Cl1A—C4A—C10A—C9A 179.2 (5) C8B—C9B—C10B—C5B −0.3 (11)
C6A—C5A—C10A—C4A 178.6 (7) N1B—C9B—C10B—C4B 1.7 (11)
C6A—C5A—C10A—C9A 0.0 (11) C8B—C9B—C10B—C4B −179.2 (7)
N1A—C9A—C10A—C4A 1.0 (10) C3B—C4B—C10B—C5B −178.5 (7)
C8A—C9A—C10A—C4A −179.3 (7) Cl1B—C4B—C10B—C5B −0.1 (10)
N1A—C9A—C10A—C5A 179.7 (7) C3B—C4B—C10B—C9B 0.3 (10)
C8A—C9A—C10A—C5A −0.6 (10) Cl1B—C4B—C10B—C9B 178.6 (5)
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Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT5833).

References

  1. Dongre, V. G., Karmuse, P. P., Ghugare, P. D., Gupta, M., Nerurkar, B., Shaha, C. & Kumar, A. (2007). J. Pharm. Biomed. Anal. 43, 185–195. [DOI] [PubMed]
  2. Lawrence, R. M., Dennis, K. C., O’Neill, P. M., Hahn, D. U., Roeder, M. & Struppe, C. (2008). Org. Process Res. Dev. 12, 294–297.
  3. O’Neill, P. M., Mukhtar, A., Stocks, P. A., Randle, L. E., Hindley, S., Ward, S. A., Storr, R. C., Bickley, J. E., O’Neil, I. A., Maggs, J. L., Hughes, R. H., Winstanley, P. A., Bray, P. G. & Prak, B. K. (2003). J. Med. Chem. 46, 4993–4945. [DOI] [PubMed]
  4. Oxford Diffraction (2007). CrysAlis PRO and CrysAlis RED Oxford Diffraction Ltd, Abingdon, England.
  5. Saha, C. N., Bhattacharya, S. & Chetia, D. (2009). Int. J. ChemTech Res. 1, 322–328.
  6. Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [DOI] [PubMed]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812014924/bt5833sup1.cif

e-68-o1498-sup1.cif (18.1KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812014924/bt5833Isup2.hkl

e-68-o1498-Isup2.hkl (156.4KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536812014924/bt5833Isup3.cml

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

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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