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

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.

In the title salt hydrate, C 11 H 12 ClN 2 + ÁCl À ÁH 2 O, 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 = À80.0 (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-HÁ Á ÁCl interaction also occurs.
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).

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).

supplementary materials sup-2 Refinement
The C-bound H atoms were geometrically placed (C-H = 0.95-0.99 Å) and refined as riding with U iso (H) = 1.2U eq (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 U iso (H) = 1.2U eq (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 U iso (H) = 1.5U eq (O). 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 dashed line) are highlighted.   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Figures
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )