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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3120–o3121.
Published online 2009 November 21. doi:  10.1107/S160053680904834X
PMCID: PMC2971810

4-[(2-Chloro­ethyl)amino]quinolinium chloride monohydrate

Abstract

In the title salt hydrate, C11H12ClN2 +·Cl·H2O, the quinolin­ium core is essentially planar (r.m.s. deviation = 0.027 Å) with the chloro­ethyl side chain being almost orthogonal to the core [C—N—C—C torsion angle = −80.0 (3)°]. In the crystal packing, the water mol­ecule bridges three species, forming donor inter­actions to two chloride anions and accepting a hydrogen bond from the quinolinium H atom. The chloride anion accepts a hydrogen bond from the amine N atom with the result that a two-dimensional supra­molecular array is formed in the ac plane. A C—H(...)Cl interaction also occurs.

Related literature

For background to malaria, see: Snow et al. (1999 [triangle]); Breman (2001 [triangle]); World Health Organization (1999 [triangle]). For background information on the pharmacological activity of quinoline derivatives, see: Elslager et al. (1969 [triangle]); Font et al. (1997 [triangle]); Kaminsky & Meltzer (1968 [triangle]); Musiol et al. (2006 [triangle]); Nakamura et al. (1999 [triangle]); Palmer et al. (1993 [triangle]); Ridley (2002 [triangle]); Sloboda et al. (1991 [triangle]); Tanenbaum & Tuffanelli (1980 [triangle]); Warshakoon et al. (2006 [triangle]). For recent studies on quinoline-based anti-malarials, see: Andrade et al. (2007 [triangle]); Cunico et al. (2006 [triangle]); da Silva et al. (2003 [triangle]); de Souza et al. (2005 [triangle]). For a related crystallographic study on a neutral species related to the title compound, see: Kaiser et al. (2009 [triangle]). For the synthesis, see: Elderfield et al. (1946 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3120-scheme1.jpg

Experimental

Crystal data

  • C11H12ClN2 +·Cl·H2O
  • M r = 261.14
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3120-efi1.jpg
  • a = 18.7513 (7) Å
  • b = 14.1030 (5) Å
  • c = 4.606 (1) Å
  • V = 1218.1 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.51 mm−1
  • T = 120 K
  • 0.46 × 0.03 × 0.03 mm

Data collection

  • Bruker–Nonius 95mm CCD camera on κ-goniostat diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003 [triangle]) T min = 0.816, T max = 1
  • 11264 measured reflections
  • 2681 independent reflections
  • 2390 reflections with I > 2σ(I)
  • R int = 0.049

Refinement

  • R[F 2 > 2σ(F 2)] = 0.032
  • wR(F 2) = 0.065
  • S = 1.06
  • 2681 reflections
  • 151 parameters
  • 4 restraints
  • H-atom parameters constrained
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.21 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1123 Friedel pairs
  • Flack parameter: 0.03 (6)

Data collection: COLLECT (Hooft, 1998 [triangle]); cell refinement: DENZO (Otwinowski & Minor, 1997 [triangle]) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: DIAMOND (Brandenburg, 2006 [triangle]); software used to prepare material for publication: publCIF (Westrip, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680904834X/hg2592sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053680904834X/hg2592Isup2.hkl

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

Acknowledgments

The use of the EPSRC X-ray crystallographic service at the University of Southampton, England and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES (Brazil).

supplementary crystallographic information

Comment

The majority of drugs used against malaria, such as chloroquine (Tanenbaum & Tuffanelli, 1980), mefloquine (Palmer et al., 1993), primaquine (Elslager et al., 1969) and amodiaquine (Ridley, 2002) possess a quinoline ring which has been the mainstay of malaria chemotherapy for much of the past 40 years (Font et al., 1997; Kaminsky & Meltzer, 1968; Musiol et al., 2006; Nakamura et al., 1999; Sloboda et al., 1991; Warshakoon et al., 2006). However, their effectiveness has been seriously eroded in recent years, mainly as a result of the development of parasite resistance (Ridley, 2002). Malaria remains one of the most important diseases of humans with over half of the world population at risk of infection. It affects mainly those living in tropical and subtropical areas with an incidence of 500 million cases per year globally (Snow et al., 1999; Breman, 2001; World Health Organization, 1999). As part of our studies (de Souza et al., 2005; Andrade et al., 2007; da Silva et al., 2003; Cunico et al., 2006) of drugs for neglected diseases, various quinoline derivatives with potential antimalarial activities have been investigated. It was during this study that the the title salt hydrate, (I), was characterized.

The quinolinium core in (I), Fig. 1, is essentially planar with a RMS deviation of the 10 atoms comprising the framework being 0.027 Å, with a maximum deviation exhibited by the C3 atom [0.031 (2) Å]. The amine side-chain deviates significantly from this plane starting with the N2 atom which lies 0.082 (2) Å above the plane. Further along the side-chain, the C11 and Cl1 atoms are almost orthogonal to the quinolinium core as seen in the magnitude of the C3/N2/C10/C11 torsion angle of -80.0 (3) °. The N—H group is orientated towards the aromatic ring. These conformational features are as found in the neutral parent compound (Kaiser et al. (2009). The most significant difference between the geometric parameters in the neutral and protonated forms is found in the angles subtended at the N1 atom, i.e. this has widened considerably in (I), 121.00 (19) Å, compared with 115.3 (2) ° in the neutral form, consistent with protonation in the former.

As expected from the composition of (I), there are significant hydrogen bonding interactions operating in the crystal structure, Table 1. The quinolinium nitrogen atom forms a donor interaction to the water molecule which in turn forms two donor interactions to the Cl2 anion. The Cl2 anion accepts a hydrogen bond from the amine-H with the result that a 2-D supramolecular array is formed in the ac plane, Fig. 2. Additional stability to the array is provided by C–H···Cl interactions involving the Cl1 atom, Table 1. Layers stack along the b axis to consolidate the crystal structure.

Experimental

A mixture of 7-chloro-N-(2-hydroxyethyl)quinolin-4-amine) (Kaiser et al., 2009) (0.5 g, 2.2 mmol), thionyl chloride (33 ml, 45 mmol) and DMF (0.3 ml, 0.22 mol) was stirred under nitrogen at room temperature for 24 h. The resulting mixture was treated with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield solid (I); yield: 94%.The compound was recrystallized from ethanol, m. pt.: 402–403 K. The melting point of the free base was reported to be 427 K (Elderfield et al., 1946).

Refinement

The C-bound H atoms were geometrically placed (C–H = 0.95–0.99 Å) and refined as riding with Uiso(H) = 1.2Ueq(C). The N-bound H atoms were located from a difference map and included in their idealized positions with N–H = 0.88 Å, and with Uiso(H) = 1.2Ueq(N). The water-H atoms were located from a difference map and refined with O–H = 0.840±0.001 Å and H···H = 1.39±0.01 Å, and with Uiso(H) = 1.5Ueq(O).

Figures

Fig. 1.
The asymmetric unit in (I) showing the atom-labelling scheme and displacement ellipsoids at the 50% probability level. Hydrogen bonding between the water molecule and Cl2 anion (orange dashed line), and between the amine-N1—H and Cl2 anion (blue ...
Fig. 2.
Supramolecular 2-D array in (I) in the ac plane. The N–H···O (blue), N–H···Cl and O–H···Cl (orange), and C–H···O (green) interactions ...

Crystal data

C11H12ClN2+·Cl·H2OF(000) = 544
Mr = 261.14Dx = 1.424 Mg m3
Orthorhombic, Pna21Mo Kα radiation, λ = 0.71070 Å
Hall symbol: P 2c -2nCell parameters from 1650 reflections
a = 18.7513 (7) Åθ = 2.9–27.5°
b = 14.1030 (5) ŵ = 0.51 mm1
c = 4.606 (1) ÅT = 120 K
V = 1218.1 (3) Å3Needle, colourless
Z = 40.46 × 0.03 × 0.03 mm

Data collection

Bruker–Nonius 95mm CCD camera on κ-goniostat diffractometer2681 independent reflections
Radiation source: Bruker-Nonius FR591 rotating anode2390 reflections with I > 2σ(I)
graphiteRint = 0.049
Detector resolution: 9.091 pixels mm-1θmax = 27.5°, θmin = 3.1°
[var phi] & ω scansh = −19→24
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)k = −18→18
Tmin = 0.816, Tmax = 1l = −5→5
11264 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H-atom parameters constrained
wR(F2) = 0.065w = 1/[σ2(Fo2) + (0.0173P)2 + 0.5206P] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
2681 reflectionsΔρmax = 0.22 e Å3
151 parametersΔρmin = −0.21 e Å3
4 restraintsAbsolute structure: Flack (1983), 1123 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.03 (6)

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.

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

xyzUiso*/Ueq
Cl10.13741 (3)0.81412 (4)0.18205 (16)0.02165 (12)
Cl20.21007 (3)0.53250 (3)0.01935 (15)0.02136 (12)
O10.10851 (8)0.59720 (11)0.5181 (4)0.0271 (4)
H1W0.12830.58580.67800.041*
H2W0.13650.58520.38050.041*
N10.48246 (10)0.82732 (12)0.3467 (4)0.0188 (4)
H10.52410.84700.41040.023*
N20.29024 (9)0.73519 (11)0.0155 (4)0.0163 (3)
H20.27420.67960.07280.020*
C10.44596 (12)0.88075 (15)0.1575 (5)0.0203 (5)
H1A0.46570.93970.09820.024*
C20.38179 (12)0.85382 (14)0.0472 (5)0.0184 (4)
H2A0.35720.8943−0.08390.022*
C30.35148 (11)0.76568 (14)0.1268 (4)0.0158 (5)
C40.39002 (11)0.70904 (15)0.3390 (5)0.0152 (4)
C50.36387 (12)0.62250 (15)0.4527 (4)0.0179 (5)
H50.31940.59850.38730.021*
C60.40215 (12)0.57290 (15)0.6566 (5)0.0208 (5)
H60.38370.51530.73280.025*
C70.46856 (13)0.60686 (16)0.7533 (5)0.0230 (5)
H70.49510.57150.89170.028*
C80.49518 (11)0.69039 (15)0.6493 (5)0.0192 (5)
H80.53990.71330.71590.023*
C90.45584 (11)0.74244 (15)0.4426 (4)0.0158 (5)
C100.24785 (13)0.78772 (16)−0.1954 (5)0.0181 (5)
H10A0.21620.7429−0.29930.022*
H10B0.28020.8167−0.34020.022*
C110.20268 (11)0.86510 (15)−0.0584 (4)0.0177 (5)
H11A0.17830.9017−0.21250.021*
H11B0.23370.90910.05150.021*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0166 (3)0.0257 (3)0.0227 (3)−0.0021 (2)0.0006 (2)0.0039 (3)
Cl20.0218 (3)0.0193 (2)0.0230 (3)−0.0009 (2)−0.0043 (2)0.0008 (3)
O10.0220 (9)0.0335 (9)0.0258 (8)0.0085 (7)0.0002 (8)0.0060 (9)
N10.0138 (10)0.0193 (10)0.0234 (10)−0.0035 (8)−0.0001 (8)−0.0019 (8)
N20.0164 (9)0.0140 (8)0.0186 (8)0.0010 (7)−0.0025 (8)0.0033 (9)
C10.0211 (11)0.0162 (10)0.0235 (11)−0.0012 (9)0.0026 (10)0.0002 (10)
C20.0187 (11)0.0169 (10)0.0196 (11)0.0036 (9)0.0018 (10)0.0010 (10)
C30.0136 (11)0.0169 (10)0.0168 (12)0.0041 (8)0.0021 (8)−0.0028 (8)
C40.0135 (11)0.0158 (10)0.0163 (11)0.0040 (8)0.0009 (8)−0.0036 (8)
C50.0172 (12)0.0158 (10)0.0206 (12)−0.0003 (9)−0.0029 (8)−0.0015 (9)
C60.0235 (12)0.0156 (10)0.0235 (11)0.0031 (9)−0.0009 (11)0.0002 (10)
C70.0237 (13)0.0235 (12)0.0217 (13)0.0108 (10)−0.0031 (9)−0.0017 (9)
C80.0139 (11)0.0241 (11)0.0196 (12)0.0031 (9)−0.0012 (10)−0.0062 (9)
C90.0160 (11)0.0162 (10)0.0151 (11)0.0020 (9)0.0022 (8)−0.0032 (8)
C100.0175 (12)0.0193 (11)0.0175 (11)0.0016 (9)−0.0032 (9)0.0011 (8)
C110.0155 (12)0.0186 (11)0.0192 (12)−0.0011 (9)0.0009 (8)0.0029 (8)

Geometric parameters (Å, °)

Cl1—C111.800 (2)C4—C51.416 (3)
O1—H1W0.8400C5—C61.374 (3)
O1—H2W0.8401C5—H50.9500
N1—C11.340 (3)C6—C71.407 (3)
N1—C91.370 (3)C6—H60.9500
N1—H10.8800C7—C81.366 (3)
N2—C31.329 (3)C7—H70.9500
N2—C101.457 (3)C8—C91.411 (3)
N2—H20.8800C8—H80.9500
C1—C21.360 (3)C10—C111.519 (3)
C1—H1A0.9500C10—H10A0.9900
C2—C31.415 (3)C10—H10B0.9900
C2—H2A0.9500C11—H11A0.9900
C3—C41.454 (3)C11—H11B0.9900
C4—C91.405 (3)
H1W—O1—H2W110.3C5—C6—H6119.8
C1—N1—C9121.00 (19)C7—C6—H6119.8
C1—N1—H1119.5C8—C7—C6120.4 (2)
C9—N1—H1119.5C8—C7—H7119.8
C3—N2—C10124.33 (17)C6—C7—H7119.8
C3—N2—H2117.8C7—C8—C9119.6 (2)
C10—N2—H2117.8C7—C8—H8120.2
N1—C1—C2122.5 (2)C9—C8—H8120.2
N1—C1—H1A118.7N1—C9—C4120.24 (19)
C2—C1—H1A118.7N1—C9—C8118.81 (19)
C1—C2—C3120.2 (2)C4—C9—C8120.95 (19)
C1—C2—H2A119.9N2—C10—C11113.12 (18)
C3—C2—H2A119.9N2—C10—H10A109.0
N2—C3—C2122.08 (19)C11—C10—H10A109.0
N2—C3—C4120.73 (18)N2—C10—H10B109.0
C2—C3—C4117.2 (2)C11—C10—H10B109.0
C9—C4—C5117.89 (19)H10A—C10—H10B107.8
C9—C4—C3118.74 (19)C10—C11—Cl1110.35 (15)
C5—C4—C3123.36 (19)C10—C11—H11A109.6
C6—C5—C4120.7 (2)Cl1—C11—H11A109.6
C6—C5—H5119.6C10—C11—H11B109.6
C4—C5—H5119.6Cl1—C11—H11B109.6
C5—C6—C7120.4 (2)H11A—C11—H11B108.1
C9—N1—C1—C2−1.0 (3)C5—C6—C7—C81.2 (3)
N1—C1—C2—C3−1.1 (4)C6—C7—C8—C9−0.4 (3)
C10—N2—C3—C2−0.3 (3)C1—N1—C9—C41.2 (3)
C10—N2—C3—C4179.32 (19)C1—N1—C9—C8−177.8 (2)
C1—C2—C3—N2−177.4 (2)C5—C4—C9—N1−177.87 (18)
C1—C2—C3—C42.9 (3)C3—C4—C9—N10.7 (3)
N2—C3—C4—C9177.64 (19)C5—C4—C9—C81.2 (3)
C2—C3—C4—C9−2.7 (3)C3—C4—C9—C8179.73 (18)
N2—C3—C4—C5−3.9 (3)C7—C8—C9—N1178.23 (19)
C2—C3—C4—C5175.8 (2)C7—C8—C9—C4−0.8 (3)
C9—C4—C5—C6−0.4 (3)C3—N2—C10—C11−80.0 (3)
C3—C4—C5—C6−178.9 (2)N2—C10—C11—Cl1−63.9 (2)
C4—C5—C6—C7−0.8 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.881.842.710 (2)172
N2—H2···Cl20.882.413.2298 (18)155
O1—H1w···Cl2ii0.842.323.1288 (19)161
O1—H2w···Cl20.842.293.1204 (19)173
C5—H5···Cl20.952.823.730 (2)161

Symmetry codes: (i) x+1/2, −y+3/2, z; (ii) x, y, z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HG2592).

References

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