(E)-1-Ethyl-4-oxo-N′-(4-pyridylmethyl­ene)-1,4-dihydroquinoline-3-carbo­hydrazide

Fernanda da C Santos; Pedro Netto Batalha; Anna Claudia Cunha; Rafael A Alão; Vitor Francisco Ferreira; Maria Cecilia B V de Souza; Sauli Santos, Jr

doi:10.1107/S160053680903654X

. 2009 Sep 16;65(Pt 10):o2476–o2477. doi: 10.1107/S160053680903654X

(E)-1-Ethyl-4-oxo-N′-(4-pyridylmethylene)-1,4-dihydroquinoline-3-carbohydrazide

Fernanda da C Santos ^a, Pedro Netto Batalha ^a, Anna Claudia Cunha ^a, Rafael A Alão ^a, Vitor Francisco Ferreira ^a, Maria Cecilia B V de Souza ^a, Sauli Santos Jr ^b,^*

PMCID: PMC2970413 PMID: 21577928

Abstract

In the title compound, C₁₈H₁₆N₄O₂, the plane defined by the ethyl C atoms and the attached N atom is inclined to the adjacent pyridine ring at an angle of 67.87 (16)°. The dihedral angle between the two heterocyclic rings is 3.33 (16)°. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond and the crystal structure by intermolecular C—H⋯O hydrogen bonds, forming a one-dimensional structure.

Related literature

For the biological properties of oxoquinoline derivatives, see: Van Bambeke et al. (2005 ▶); Canuto et al. (2007 ▶); Lucero et al. (2006 ▶). For their potential use in the treatment of fungal and viral infections, see: Brideau et al. (2002 ▶); Souza et al. (2008 ▶) and in cancer chemotherapy, see: Chu et al. (1992 ▶). For acylhydrazones and their antileishmanial activity, see: Bernadino et al. (2006 ▶); Cunha et al. (2003 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₈H₁₆N₄O₂
M _r = 320.35
Monoclinic,
a = 7.6460 (12) Å
b = 19.205 (2) Å
c = 10.7050 (9) Å
β = 99.722 (10)°
V = 1549.4 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.5 × 0.2 × 0.2 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: none
7914 measured reflections
2586 independent reflections
2001 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.102
S = 1.07
2586 reflections
222 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.13 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: HKL SCALEPACK (Otwinowski & Minor 1997 ▶); data reduction: HKL DENZO (Otwinowski & Minor 1997 ▶) and SCALEPACK; program(s) used to solve structure: SIR2002 (Burla et al., 2003 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: WinGX publication routines (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680903654X/wn2340sup1.cif

e-65-o2476-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680903654X/wn2340Isup2.hkl

e-65-o2476-Isup2.hkl^{(124.4KB, 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
N3—H3N⋯O1	0.92 (2)	1.85 (2)	2.639 (2)	143.1 (17)
C10—H10A⋯O2ⁱ	0.97	2.46	3.398 (2)	163

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge the financial support from FAPERJ, CAPES and CNPq; they also thank Dra Maria G.F. Vaz, Marilene M. do Canto-Cavaleiro and Vanessa P. Rodrigues for useful discussions.

supplementary crystallographic information

Comment

Since the discovery of nalidixic acid, the parent compound of the 1,4-dihydro-4-oxoquinoline antibiotics, the molecular structures of oxoquinolines have been extensively modified to improve their pharmacological properties and pharmacokinetic profiles (Van Bambeke et al., 2005). 1,4-Dihydro-4-oxoquinolines have a broad antimicrobial spectrum, are orally and parenterally active and, apart from a few exceptions, are non-toxic compounds. Therefore, they are important agents against microbial pathogens. They have also been considered for the treatment of fungal and viral (Brideau et al., 2002; Souza et al., 2008) infections and for cancer chemotherapy (Chu et al., 1992). Our research group has designed and synthesized new oxoquinoline derivatives, such as ribonucleosides (Canuto et al., 2007) and acyclonucleosides (Lucero et al., 2006). These compounds exhibited interesting activity against HIV-1 and HSV viruses, respectively.

Continuing our interest in the chemistry of oxoquinolinic molecules, we decided to prepare a congener series of new acylhydrazones (Cunha et al., 2003) and test them for antileishmanial activity. These studies showed that the hydrazone group plays an important role in antileishmanial activity (Bernadino et al., 2006). Among these compounds, (E)-1-ethyl-N'-[(pyrid-4'-yl)methylene]-1,4-dihydro-4- oxoquinoline-3-carbohydrazide, was found to exhibit a significant activity against Leishmania amazonensis.

As an extension of our work on the structural characterization of oxoquinolinic derivatives (Canuto et al., 2007; Lucero et al. 2006). the crystal structure of the title compound is reported here. In the title compound (Fig. 1), the dihedral angle between the C1,C6-C9/N1 ring and the C14-C18/N4 pyridine ring is 3.33 (16)°. The plane defined by N1,C10,C11 is inclined to the C1,C6-C9/N1 ring at an angle of 67.87 (16)°. The torsion angles C8—C12—N3—N2, C12—N3—N2—C13 and N3—N2—C13—C14 are 0.79 (14), 1.38 (16) and 1.53 (14)°, respectively. All the bond lengths are within normal ranges (Allen et al., 1987). The molecular structure is stabilized by an intramolecular N—H···O hydrogen bond (Table 1). The crystal structure is stabilized by intermolecular C—H···O hydrogen bonds, forming a one-dimensional structure (Table 1 and Fig. 2).

Experimental

A solution of 1-ethyl-1,4-dihydro-4-oxoquinoline ethyl carboxylate (3.70 mmol) and 3.7 ml of 80% hydrazine monohydrate in 10 ml of dimethylformamide was stirred under reflux for two hours. The reaction mixture was poured into ice, giving rise to a white solid that was collected by filtration, washed with cold ethyl acetate and dried under vacuum, leading to the pure desired 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carbohydrazide, in 90% yield. This carbohydrazide (1.00 mmol) and pyridine-4-carbaldehyde (1.10 mmol) in 5 ml of dimethylformamide and a catalytic amount of 35% HCl were stirred at room temperature. The reaction mixture was poured into ice, leading to a white solid that was collected by filtration, giving (E)-1-ethyl-N'-[(pyrid-4'-yl)methylene]-1,4-dihydro-4-oxoquinoline-3-carbohydrazide in 83% yield after purification.