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ISSN: 2414-3146

(Z)-4,6-Di­chloro-N-(4-chloro­phen­yl)quinoline-3-carbimidoyl chloride

aInstitute for Chemical Technologies and Analytics, Division of Structural Chemistry, TU Wien, Getreidemarkt 9/164-SC, A-1060 Vienna, Austria, and bInstitute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163, A-1060 Vienna, Austria
*Correspondence e-mail: matthias.weil@tuwien.ac.at

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 16 February 2017; accepted 17 February 2017; online 21 February 2017)

The title imidoyl chloride, C16H8Cl4N2, has formed accidentally as a side product during the synthesis of a quinolin-3-one derivative. The mol­ecule is not flat [the dihedral angle between the 4,6-di­chloro­quinoline and the imidoyl chloride planes is 53.43 (5)°], preventing π-conjugation over the complete entity. In the crystal, C—H⋯N hydrogen bonding between a chloro­phenyl C—H group and the quinoline N atom, as well as ππ stacking between neighbouring quinoline rings, consolidate the packing.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Pyrazolo­quinolino­nes are reported as highly active compounds (agonists, antagonists and partial agonists) for the benzodiazepine binding site at the GABAA receptor (Yokoyama et al., 1982[Yokoyama, N., Ritter, B. & Neubert, A. D. (1982). J. Med. Chem. 25, 337-339.]). Additionally, they act as allosteric modulators via the α+β-inter­face (Ramerstorfer et al., 2011[Ramerstorfer, J., Furtmüller, R., Sarto-Jackson, I., Varagic, Z., Sieghart, W. & Ernst, M. (2011). J. Neurosci. 31, 870-877.]; Varagic et al., 2013[Varagic, Z., Wimmer, L., Schnürch, M., Mihovilovic, M. D., Huang, S., Rallapalli, S., Cook, J. M., Mirheydari, P., Ecker, G. F., Sieghart, W. & Ernst, M. (2013). Br. J. Pharmacol. 169, 371-383.]). In the context of this research, we obtained the title compound, (III), as a by-product during the synthesis of ethyl 4,6-di­chloro­quinoline-3-carboxyl­ate, (II) (Fig. 1[link]).

[Figure 1]
Figure 1
The reaction scheme for the synthesis of the title compound, (III), and the originally intended product (II).

The mol­ecular structure of the title compound is displayed in Fig. 2[link]. The 4,6-di­chloro­quinoline moiety is essentially planar (r.m.s. deviation = 0.0198 Å), with one of the substituted Cl atoms having the largest deviation from the mean plane [Cl2, 0.0468 (6) Å]. The complete mol­ecule is not flat, with the imidoyl chloride moiety twisted out of the 4,6-di­chloro­quinoline plane by 53.43 (5)°. The dihedral angles between the imidoyl chloride moiety and the attached 3-chloro­phenyl ring and between the 4,6-di­chloro­quinoline and the 3-chloro­phenyl ring are 71.30 (14) and 18.20 (4)°, respectively. The torsion angle of the backbone connecting the three moieties, i.e. C8—C10—N2—C11, is −178.03 (13)°.

[Figure 2]
Figure 2
The mol­ecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level and H atoms are given as spheres of arbitrary radius.

Individual mol­ecules are arranged in layers parallel to (10[\overline{1}]). Within a layer, ππ stacking between parallel quinoline rings (centroid-to-centroid distance between phenyl and pyridine rings = 3.595 Å; plane-to-plane distance = 3.446 Å) stabilize this arrangement. Mutual inter­molecular C—H⋯N hydrogen-bonding inter­actions between a C—H group of the chloro­phenyl ring and the quinoline N atom of two mol­ecules in neighbouring layers leads to the formation of inversion dimers (Fig. 3[link] and Table 1[link]), with an R22(16) ring motif. Further inter­molecular halogen–halogen contacts, i.e. Cl3⋯Cl3(−x + 1, −y + 1, −z), with a distance of 3.3453 (7) Å, might also help to consolidate the crystal structure.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
C16—H16⋯N1i 0.95 2.55 3.453 (2) 159
Symmetry code: (i) -x, -y+1, -z+1.
[Figure 3]
Figure 3
The packing of the mol­ecules in the crystal structure of the title compound in a view along the b* axis. C—H⋯N inter­actions are shown as magenta dashed lines.

Synthesis and crystallization

Ethyl 6-chloro-4-oxo-1,4-di­hydro­quinoline-3-carboxyl­ate, (I), was prepared via the Gould–Jacobs reaction (Gould & Jacobs, 1939[Gould, R. G. Jr & Jacobs, W. A. (1939). J. Am. Chem. Soc. 61, 2890-2895.]). 2 g of the crude product were dispersed in 10 ml phosphoryl chloride and refluxed for 2 h. The reaction mixture was then poured on ice, neutralized with saturated NaHCO3 solution and extracted with CH2Cl2 (3 × 40 ml). The organic layer was washed with water (1 × 40 ml) and brine (1 × 40 ml), dried over Na2SO4, filtered and evaporated. The residue was purified via flash column chromatography (5–20% EtOAc in petroleum ether) to give a colourless solid (yield: 1.74 g, 6.45 mmol, 81%) of (II). The side product (III), representing the title compound, consisted of a light-yellow solid (32 mg). We assume that for formation of (III), the 3-chloro­aniline employed in the synthesis of (I) was still present in the crude product and reacted in the following step with (II) to give (III) as a minor by-product.

1H NMR (400 MHz, CDCl3) for (III): δ 7.11 (d, J = 8.6 Hz, 2H, H2′ and H6′), 7.44 (d, J = 8.5 Hz, 2H, H3′ and H5′), 7.80 (dd, J = 8.9, 2.3 Hz, 1H, H7), 8.13 (d, J = 9.0 Hz, 1H, H8), 8.37 (d, J = 2.3 Hz, 1H, H5), 9.06 (s, 1H, H2).

Refinement

Crystal data, data collection, and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C16H8Cl4N2
Mr 370.04
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 100
a, b, c (Å) 9.2595 (14), 9.9204 (15), 10.1731 (15)
α, β, γ (°) 64.259 (4), 72.322 (5), 64.093 (4)
V3) 749.6 (2)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.78
Crystal size (mm) 0.30 × 0.20 × 0.05
 
Data collection
Diffractometer Bruker APEXII CCD
Absorption correction Multi-scan (SADABS; Bruker, 2015[Bruker (2015). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.689, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections 26858, 4335, 3750
Rint 0.033
(sin θ/λ)max−1) 0.703
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.025, 0.068, 1.04
No. of reflections 4335
No. of parameters 199
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.46, −0.20
Computer programs: APEX3 and SAINT (Bruker, 2015[Bruker (2015). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), XP (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data


Computing details top

Data collection: APEX3 (Bruker, 2015); cell refinement: SAINT (Bruker, 2015); data reduction: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: XP (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

(Z)-4,6-Dichloro-N-(4-chlorophenyl)quinoline-3-carbimidoyl chloride top
Crystal data top
C16H8Cl4N2Z = 2
Mr = 370.04F(000) = 372
Triclinic, P1Dx = 1.639 Mg m3
a = 9.2595 (14) ÅMo Kα radiation, λ = 0.71073 Å
b = 9.9204 (15) ÅCell parameters from 9901 reflections
c = 10.1731 (15) Åθ = 2.3–29.9°
α = 64.259 (4)°µ = 0.78 mm1
β = 72.322 (5)°T = 100 K
γ = 64.093 (4)°Plate, light yellow
V = 749.6 (2) Å30.30 × 0.20 × 0.05 mm
Data collection top
Bruker APEXII CCD
diffractometer
3750 reflections with I > 2σ(I)
ω– and φ–scansRint = 0.033
Absorption correction: multi-scan
(SADABS; Bruker, 2015)
θmax = 30.0°, θmin = 2.3°
Tmin = 0.689, Tmax = 0.746h = 1213
26858 measured reflectionsk = 1313
4335 independent reflectionsl = 1414
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.025H-atom parameters constrained
wR(F2) = 0.068 w = 1/[σ2(Fo2) + (0.0357P)2 + 0.2338P]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
4335 reflectionsΔρmax = 0.46 e Å3
199 parametersΔρmin = 0.20 e Å3
Special details top

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

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl20.47318 (3)0.78291 (3)0.06212 (3)0.02002 (7)
Cl30.44918 (4)0.43177 (3)0.18302 (3)0.01907 (7)
Cl40.82948 (4)0.21042 (3)0.69589 (3)0.02329 (8)
Cl10.10737 (4)1.41289 (3)0.17857 (4)0.02702 (8)
N20.36407 (12)0.44659 (11)0.45370 (11)0.01588 (19)
N10.03955 (12)0.86631 (12)0.30708 (11)0.0181 (2)
C80.23627 (14)0.68779 (13)0.26551 (12)0.0139 (2)
C50.15842 (13)0.96888 (12)0.11060 (12)0.0136 (2)
C100.34979 (13)0.52050 (13)0.31946 (12)0.0140 (2)
C40.00070 (14)0.98888 (13)0.19243 (13)0.0154 (2)
C110.47579 (14)0.28773 (13)0.50743 (12)0.0144 (2)
C90.07433 (14)0.72394 (14)0.34052 (13)0.0172 (2)
H90.04690.63890.42040.021*
C120.64151 (15)0.25868 (14)0.47403 (13)0.0178 (2)
H120.68000.34370.41120.021*
C70.27708 (13)0.81186 (13)0.15223 (12)0.0132 (2)
C130.75057 (15)0.10521 (14)0.53263 (14)0.0186 (2)
H130.86390.08460.51090.022*
C10.06808 (15)1.24874 (13)0.03627 (13)0.0186 (2)
C20.08890 (15)1.27159 (14)0.04404 (14)0.0195 (2)
H20.17111.37490.02090.023*
C140.69239 (14)0.01764 (13)0.62317 (13)0.0166 (2)
C30.12176 (14)1.14356 (14)0.15572 (14)0.0186 (2)
H30.22781.15820.20940.022*
C60.19062 (14)1.10229 (13)0.00598 (13)0.0159 (2)
H60.29541.09020.06210.019*
C150.52756 (15)0.00998 (14)0.65689 (13)0.0191 (2)
H150.48970.07570.71840.023*
C160.41786 (15)0.16421 (13)0.59996 (13)0.0179 (2)
H160.30450.18510.62400.021*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl20.01386 (13)0.01335 (12)0.02513 (15)0.00307 (10)0.00064 (10)0.00410 (10)
Cl30.02500 (15)0.01218 (12)0.01400 (13)0.00016 (10)0.00392 (10)0.00510 (10)
Cl40.02391 (15)0.01314 (13)0.02437 (15)0.00239 (10)0.01131 (12)0.00309 (11)
Cl10.03162 (17)0.01036 (12)0.03095 (17)0.00513 (11)0.01023 (13)0.00125 (11)
N20.0173 (5)0.0109 (4)0.0146 (5)0.0015 (3)0.0033 (4)0.0031 (3)
N10.0156 (5)0.0163 (5)0.0182 (5)0.0027 (4)0.0028 (4)0.0051 (4)
C80.0153 (5)0.0107 (4)0.0132 (5)0.0019 (4)0.0037 (4)0.0038 (4)
C50.0160 (5)0.0104 (4)0.0139 (5)0.0016 (4)0.0061 (4)0.0042 (4)
C100.0137 (5)0.0113 (4)0.0143 (5)0.0025 (4)0.0013 (4)0.0047 (4)
C40.0151 (5)0.0138 (5)0.0161 (5)0.0013 (4)0.0059 (4)0.0056 (4)
C110.0181 (5)0.0107 (5)0.0109 (5)0.0010 (4)0.0043 (4)0.0033 (4)
C90.0164 (5)0.0152 (5)0.0153 (5)0.0042 (4)0.0016 (4)0.0031 (4)
C120.0198 (6)0.0131 (5)0.0183 (5)0.0052 (4)0.0042 (4)0.0034 (4)
C70.0123 (5)0.0117 (5)0.0139 (5)0.0016 (4)0.0033 (4)0.0048 (4)
C130.0159 (5)0.0167 (5)0.0212 (6)0.0026 (4)0.0059 (4)0.0061 (4)
C10.0254 (6)0.0106 (5)0.0193 (6)0.0038 (4)0.0105 (5)0.0025 (4)
C20.0206 (6)0.0123 (5)0.0239 (6)0.0021 (4)0.0117 (5)0.0072 (4)
C140.0207 (6)0.0113 (5)0.0143 (5)0.0002 (4)0.0081 (4)0.0036 (4)
C30.0154 (5)0.0163 (5)0.0218 (6)0.0009 (4)0.0065 (4)0.0087 (4)
C60.0179 (5)0.0117 (5)0.0168 (5)0.0035 (4)0.0050 (4)0.0040 (4)
C150.0228 (6)0.0128 (5)0.0160 (5)0.0050 (4)0.0033 (4)0.0012 (4)
C160.0172 (5)0.0142 (5)0.0160 (5)0.0028 (4)0.0024 (4)0.0027 (4)
Geometric parameters (Å, º) top
Cl2—C71.7268 (12)C11—C161.3933 (16)
Cl3—C101.7680 (11)C9—H90.9500
Cl4—C141.7424 (11)C12—C131.3881 (15)
Cl1—C11.7407 (12)C12—H120.9500
N2—C101.2551 (15)C13—C141.3861 (17)
N2—C111.4224 (13)C13—H130.9500
N1—C91.3121 (14)C1—C61.3698 (15)
N1—C41.3704 (15)C1—C21.4083 (18)
C8—C71.3768 (15)C2—C31.3678 (17)
C8—C91.4255 (16)C2—H20.9500
C8—C101.4817 (14)C14—C151.3858 (17)
C5—C61.4190 (15)C3—H30.9500
C5—C41.4202 (16)C6—H60.9500
C5—C71.4237 (14)C15—C161.3920 (15)
C4—C31.4209 (15)C15—H150.9500
C11—C121.3911 (17)C16—H160.9500
C10—N2—C11122.47 (10)C5—C7—Cl2118.57 (8)
C9—N1—C4117.52 (10)C14—C13—C12119.30 (11)
C7—C8—C9117.66 (10)C14—C13—H13120.4
C7—C8—C10124.91 (10)C12—C13—H13120.4
C9—C8—C10117.38 (10)C6—C1—C2122.32 (11)
C6—C5—C4119.79 (10)C6—C1—Cl1119.01 (10)
C6—C5—C7123.51 (10)C2—C1—Cl1118.67 (9)
C4—C5—C7116.71 (10)C3—C2—C1119.32 (10)
N2—C10—C8121.50 (10)C3—C2—H2120.3
N2—C10—Cl3123.61 (9)C1—C2—H2120.3
C8—C10—Cl3114.73 (8)C15—C14—C13121.29 (10)
N1—C4—C5123.25 (10)C15—C14—Cl4119.47 (9)
N1—C4—C3117.90 (11)C13—C14—Cl4119.25 (9)
C5—C4—C3118.85 (10)C2—C3—C4120.85 (11)
C12—C11—C16120.60 (10)C2—C3—H3119.6
C12—C11—N2119.73 (10)C4—C3—H3119.6
C16—C11—N2119.57 (10)C1—C6—C5118.87 (11)
N1—C9—C8124.64 (11)C1—C6—H6120.6
N1—C9—H9117.7C5—C6—H6120.6
C8—C9—H9117.7C14—C15—C16119.52 (11)
C13—C12—C11119.87 (11)C14—C15—H15120.2
C13—C12—H12120.1C16—C15—H15120.2
C11—C12—H12120.1C15—C16—C11119.41 (11)
C8—C7—C5120.21 (10)C15—C16—H16120.3
C8—C7—Cl2121.19 (8)C11—C16—H16120.3
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C16—H16···N1i0.952.553.453 (2)159
Symmetry code: (i) x, y+1, z+1.
 

Acknowledgements

The X-ray centre of TU Wien is acknowledged for financial support and providing access to the single-crystal diffrac­tometer.

References

First citationBruker (2015). APEX3, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.  Google Scholar
First citationGould, R. G. Jr & Jacobs, W. A. (1939). J. Am. Chem. Soc. 61, 2890–2895.  CrossRef CAS Google Scholar
First citationMacrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.  Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
First citationRamerstorfer, J., Furtmüller, R., Sarto-Jackson, I., Varagic, Z., Sieghart, W. & Ernst, M. (2011). J. Neurosci. 31, 870–877.  CrossRef CAS PubMed Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationSheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.  Web of Science CrossRef IUCr Journals Google Scholar
First citationVaragic, Z., Wimmer, L., Schnürch, M., Mihovilovic, M. D., Huang, S., Rallapalli, S., Cook, J. M., Mirheydari, P., Ecker, G. F., Sieghart, W. & Ernst, M. (2013). Br. J. Pharmacol. 169, 371–383.  CrossRef CAS PubMed Google Scholar
First citationWestrip, S. P. (2010). J. Appl. Cryst. 43, 920–925.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationYokoyama, N., Ritter, B. & Neubert, A. D. (1982). J. Med. Chem. 25, 337–339.  CrossRef CAS PubMed Google Scholar

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