Redetermination of {5-[(7-chloro­quinolinium-4-yl)amino]-2-hy­droxy­benz­yl}diethyl­ammonium dichloride dihydrate

Peter Mangwala Kimpende; Luc Van Meervelt

doi:10.1107/S1600536810031806

. 2010 Aug 18;66(Pt 9):o2353–o2354. doi: 10.1107/S1600536810031806

Redetermination of {5-[(7-chloroquinolinium-4-yl)amino]-2-hydroxybenzyl}diethylammonium dichloride dihydrate

Peter Mangwala Kimpende ^a, Luc Van Meervelt ^a,^*

PMCID: PMC3007921 PMID: 21588696

Abstract

The structure of the title compound (common name: amodiaquinium dichloride dihydrate), C₂₀H₂₄ClN₃O₂ ⁺·2Cl⁻·2H₂O, was previously determined from powder diffraction data [Llinàs et al. (2006 ▶). Acta Cryst. E62, o4196-o4199]. It has now been refined from diffractometer data to a significantly higher precision. The dihedral angle between the quinoline and benzene rings is 54.57 (6)°. The central amino N atom interacts more strongly with the quinoline ring than with the benzene ring, as indicated by the shorter C—N bond length [1.341 (2) Å compared to 1.431 (2) Å]. In the crystal, molecules are packed into a three-dimensional network/supramolecular structure through hydrogen bonds between the amodiaquinium cations, chloride anions and water molecules.

Related literature

Amodiaquine, as a dihydrochloride salt, is often used as a synthetic antimalarial drug against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum, see: Olliaro & Taylor (2003 ▶). For related structures, see: Llinàs et al. (2006 ▶); Yennawar & Viswamitra (1991 ▶); Semeniuk et al. (2008 ▶).

Experimental

Crystal data

C₂₀H₂₄ClN₃O²⁺·2Cl⁻·2H₂O
M _r = 464.80
Monoclinic,
a = 7.7622 (1) Å
b = 26.8709 (4) Å
c = 10.7085 (2) Å
β = 92.784 (1)°
V = 2230.91 (6) Å³
Z = 4
Cu Kα radiation
μ = 3.94 mm⁻¹
T = 100 K
0.56 × 0.14 × 0.12 mm

Data collection

Bruker SMART 6000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ▶) T _min = 0.312, T _max = 0.623
31612 measured reflections
3917 independent reflections
3699 reflections with I > 2σ(I)
R _int = 0.088

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.100
S = 1.10
3917 reflections
287 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶) and DIAMOND (Brandenburg, 2010 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810031806/lx2163sup1.cif

e-66-o2353-sup1.cif^{(22.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810031806/lx2163Isup2.hkl

e-66-o2353-Isup2.hkl^{(192KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯Cl2	0.89 (2)	2.32 (2)	3.1913 (16)	166.8 (19)
N2—H2N⋯O2Wⁱ	0.83 (2)	2.07 (2)	2.880 (2)	167 (2)
N3—H3N⋯Cl3	0.85 (2)	2.26 (2)	3.0771 (14)	161 (2)
O1—H1O⋯Cl2ⁱⁱ	0.84	2.22	3.0640 (12)	177
O1W—H1WA⋯Cl3ⁱⁱⁱ	0.88 (3)	2.30 (3)	3.1778 (16)	175 (3)
O1W—H1WB⋯Cl3ⁱ	0.80 (3)	2.42 (3)	3.2100 (16)	171 (3)
O2W—H2WA⋯O1W	0.83 (3)	1.95 (3)	2.775 (2)	174 (2)
O2W—H2WB⋯Cl2ⁱⁱ	0.83 (3)	2.33 (3)	3.1585 (15)	173 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

supplementary crystallographic information

Comment

Amodiaquine, 4-[7-chloro-4-quinolinyl)amino]-2-[(diethylamino)methyl]phenol, is as dihydrochloride salt, often used as synthetic antimalarial drug against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum (Olliaro & Taylor, 2003). The single-crystal structure of the monohydrate form has been reported by Yennawar & Viswamitra (1991) and by Semeniuk et al. (2008). The room temperature structure of the dihydrate form based on powder diffraction at 1.79 Å resolution has been reported by Llinàs et al. (2006). Here we report the crystal structure of the title compound (I) at 100 K and a resolution of 0.84 Å (Fig. 1).

Two N atoms (N1 and N3) are protonated indicating that the dihydrochloride salt of amodiaquine is present. The shape of the molecule is mainly dominated by three torsion angles: C8–C9–N2–C19 (τ₁ = -7.7 (3)°), C9–N2–C10–C11 (τ₂ = -52.8 (2)°) and C11–C12–C16–N3 (τ₃ = -85.85 (18)°). It was suggested by Yennawar & Viswamitra (1991) that the C–N bonds linking both aromatic rings have double-bond character. However, we observe a large difference between both bonds C9–N2 (1.341 (2) Å) and N2–C10 (1.431 (2) Å), indicating that N2 interacts more with the quinoline than with the benzene unit. It is also clear from inspection of τ₁ and τ₂ that the overlap of the lone pair of the sp²-hybridized N2 with the quinoline unit is favoured, and this despite the short H2N···H2 contact distance (2.08 Å). The dihedral angle between the quinoline and benzene units is 54.57 (6)°. An intramolecular close contact between H16A and O1 (2.396 Å) is observed by Llinàs et al. (2006). The r.m.s. deviation when fitting the amodiaquinium units obtained by single-crystal and powder diffraction (Llinàs et al., 2006) is 0.0739 Å. The hydrogen bonds in the crystal packing (Table 1, Fig. 2) are similar to those described by Llinàs et al. (2006).

Experimental

Amodiaquinium dichloride dihydrate was purchased from Sigma-Aldrich (Belgium). Colourless crystals were obtained at room temperature by slow evaporation from a DMSO solution of (I).