7-Chloro-4-[(E)-N′-(4-fluoro­benzyl­idene)hydrazin­yl]quinoline monohydrate

Marcus V N de Souza; R Alan Howie; Edward R T Tiekink; James L Wardell; Solange M S V Wardell

doi:10.1107/S1600536809053367

. 2009 Dec 16;66(Pt 1):o152–o153. doi: 10.1107/S1600536809053367

7-Chloro-4-[(E)-N′-(4-fluorobenzylidene)hydrazinyl]quinoline monohydrate

Marcus V N de Souza ^a, R Alan Howie ^b, Edward R T Tiekink ^c,^*, James L Wardell ^d,^‡, Solange M S V Wardell ^e

PMCID: PMC2980273 PMID: 21580042

Abstract

The molecule of the title hydrate, C₁₆H₁₁ClFN₃·H₂O, is slightly twisted, as indicated by the dihedral angle of 9.55 (10)° formed between the quinoline ring system and the benzene ring. The conformation about the C=N double bond is E, and the amine-H atom is oriented towards the quinoline residue. In the crystal structure, the water molecule accepts an N—H⋯O and makes two O—H⋯N_quinoline hydrogen bonds, generating a two-dimensional array in the ab plane, which is further stabilized by C—H⋯O interactions. The most significant contacts between layers are of the type C—H⋯F.

Related literature

For background information on the pharmacological activity of quinoline derivatives, see: Elslager et al. (1969 ▶); Font et al. (1997 ▶); Kaminsky & Meltzer (1968 ▶); Musiol et al. (2006 ▶); Nakamura et al. (1999 ▶); Palmer et al. (1993 ▶); Ridley (2002 ▶); Sloboda et al. (1991 ▶); Tanenbaum & Tuffanelli (1980 ▶); Warshakoon et al. (2006 ▶). For recent studies into quinoline-based anti-malarials, see: Andrade et al. (2007 ▶); Cunico et al. (2006 ▶); da Silva et al. (2003 ▶); de Souza et al. (2005 ▶). For crystallographic studies on molecules related to the title compound, see: Kaiser et al. (2009 ▶); de Souza et al. (2009 ▶); de Ferreira et al. (2009 ▶). For the synthesis, see: Pellerano et al. (1976 ▶).

Experimental

Crystal data

C₁₆H₁₁ClFN₃·H₂O
M _r = 317.74
Monoclinic,
a = 3.7795 (2) Å
b = 15.4188 (11) Å
c = 24.8576 (16) Å
β = 90.286 (4)°
V = 1448.57 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 120 K
0.90 × 0.04 × 0.04 mm

Data collection

Nonius KappaCCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.614, T _max = 0.746
19494 measured reflections
3291 independent reflections
2009 reflections with I > 2σ(I)
R _int = 0.098

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.131
S = 1.04
3291 reflections
205 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.37 e Å⁻³

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

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809053367/lh2970sup1.cif

e-66-0o152-sup1.cif^{(19.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809053367/lh2970Isup2.hkl

e-66-0o152-Isup2.hkl^{(158.2KB, 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
O1w—H1w⋯N1ⁱ	0.84 (2)	2.28 (2)	2.999 (3)	144 (2)
O1w—H2w⋯N1ⁱⁱ	0.85 (2)	1.93 (2)	2.761 (3)	166 (3)
N2—H2n⋯O1wⁱⁱⁱ	0.88	2.01	2.865 (3)	165
C5—H5⋯O1wⁱⁱⁱ	0.95	2.45	3.379 (3)	164
C10—H10⋯O1wⁱⁱⁱ	0.95	2.50	3.302 (3)	142
C1—H1⋯F1^iv	0.95	2.56	3.399 (3)	147
C6—H6⋯F1^v	0.95	2.56	3.477 (3)	161

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

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 title compound, crystallized as a hydrate, (I), was prepared as part of continuing studies designed to develop antimalarial compounds based on the quinoline nucleus (Andrade et al., 2007; Cunico et al., 2006; da Silva et al., 2003; de Souza et al., 2005). The systematic examination of quinoline derivatives comes about owing to the fact that the majority of antimalarial agents, including chloroquine (Tanenbaum & Tuffanelli, 1980), mefloquine (Palmer et al., 1993), primaquine (Elslager et al., 1969) and amodiaquine (Ridley, 2002), have a quinoline ring substructure, 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). Allied with these investigations are structural studies aimed at elucidating systematic structural trends in these molecules (Kaiser et al. 2009; de Souza et al. 2009; de Ferreira et al. 2009).

The molecule in (I), Fig. 1, features an effectively planar quinoline residue (maximum deviations of 0.018 (2) Å for atom C4 and -0.025 (2) Å for atom C2) which forms a dihedral angle of 9.55 (10) ° with the C11–C16 benzene ring. Twists in the molecule are evident about the N2–C3 and C10–C11 bonds as seen in the values of the N3–N2–C3–C2 and N3–C10–C11—C12 torsion angles of 6.9 (4) and -6.6 (4) °, respectively. As observed in related systems, the amine-H is orientated over the quinoline residue (Kaiser et al. 2009; de Souza et al. 2009; de Ferreira et al., 2009). The conformation about the N3═C10 double bond is E. The molecule crystallizes as a hydrate and the latter species is pivotal in stabilizing the crystal structure. Thus, the water-H atoms form donor O–H···N hydrogen bonds to quinoline-N atoms derived from two molecules. At the same time, the water-O atom accepts a N–H···O hydrogen bond from the amine-N2 of another molecule. Thus, the water molecule provides links between three molecules, leading to the formation of a 2-D array, Fig. 2 and Table 1. The resultant layer in the ab plane is further stabilized by C–H···O interactions, Table 1, and weak π···π contacts [ring centroid(N1,C1—C4,C9)···ring centroid(C4–C9)ⁱ = 3.7070 (14) Å, dihedral angle = 1.45 (11) ° for i: -1 + x, y, z]. Layers stack along the c direction with the most significant contacts between layers being of the type C–H···F whereby the fluoride is bifurcated, Table 1 and Fig. 3.

Experimental

A solution of 7-chloro-4-hydrazinoquinoline (0.20 g, 1.0 mmol) and 4-fluorobenzaldehyde (0.15 g, 1.2 mmol) in EtOH (5 ml) was maintained at room temperature overnight and rotary evaporated. The solid residue, was washed with cold Et₂O (3 x 10 ml) and recrystallized from EtOH m.pt. 518–519 K, lit. value 518 K (Pellerano et al., 1976), yield 74%. The sample for the X-ray study was slowly grown from moist EtOH and was found to be the monohydrate. ¹H NMR (400 MHz, DMSO-d₆) δ: 7.28–7.32 (3H, m), 7.54 (1H, d, J = 8.4 Hz), 7.84–7.88 (3H, m), 8.34–8.40 (3H, m), 11.3 (1H, br.s, NH). MS/ESI: [M^+. - H]: 298. IR ν_max (cm^-1; KBr disc): 3232 (N–H), 1585 (C═N), 817 (C–F).