2,2′-(Propane-1,3-di­yl)bis­(2H-indazole)

Saúl Ovalle; Sylvain Bernès; Nancy Pérez Rodríguez; Perla Elizondo Martínez

doi:10.1107/S1600536811029011

. 2011 Jul 30;67(Pt 8):o2144. doi: 10.1107/S1600536811029011

2,2′-(Propane-1,3-diyl)bis(2H-indazole)

Saúl Ovalle ^a, Sylvain Bernès ^b, Nancy Pérez Rodríguez ^a, Perla Elizondo Martínez ^a,^*

PMCID: PMC3213583 PMID: 22091160

Abstract

The title molecule, C₁₇H₁₆N₄, is a bis-indazole crystallized in the rare 2H-tautomeric form. Indazole heterocycles are connected by a propane C₃ chain, and the molecule is placed on a general position, in contrast to the analogous compound with a central C₂ ethane bridge, which was previously found to be placed on an inversion center in the same space group. In the title molecule, indazole rings make a dihedral angle of 60.11 (7)°, and the bridging alkyl chain displays a trans conformation, resulting in a W-shaped molecule. In the crystal, molecules interact weakly through π–π contacts between inversion-related pyrazole rings, with a centroid–centroid separation of 3.746 (2) Å.

Related literature

For the synthesis of 2H-indazoles, see: Wu et al. (2010 ▶). For studies of 1H←→2H tautomerism in indazoles, see: Alkorta & Elguero (2005 ▶); Yu et al. (2006 ▶). For 2H-indazole X-ray structures, see: Saczewski et al. (2001 ▶); Rodríguez de Barbarín et al. (2006 ▶); Ramos Silva et al. (2008 ▶); Hurtado et al. (2009 ▶); Zhou et al. (2010 ▶); Long et al. (2011 ▶).

Experimental

Crystal data

C₁₇H₁₆N₄
M _r = 276.34
Orthorhombic,
a = 8.182 (2) Å
b = 10.549 (4) Å
c = 34.179 (9) Å
V = 2950.1 (16) Å³
Z = 8
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 298 K
0.60 × 0.40 × 0.18 mm

Data collection

Siemens P4 diffractometer
8195 measured reflections
2621 independent reflections
1607 reflections with I > 2σ(I)
R _int = 0.042
3 standard reflections every 97 reflections intensity decay: 1.5%

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.162
S = 1.10
2621 reflections
191 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Data collection: XSCANS (Siemens, 1996 ▶); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811029011/aa2015sup1.cif

e-67-o2144-sup1.cif^{(23.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811029011/aa2015Isup2.hkl

e-67-o2144-Isup2.hkl^{(128.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811029011/aa2015Isup3.mol

Supplementary material file. DOI: 10.1107/S1600536811029011/aa2015Isup4.cml

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

Acknowledgments

The authors thank the PAICyT program (Programa de Apoyo a la Investigación Científica y Tecnológica) of the Universidad Autónoma de Nuevo León for supporting this work (project No. T004–09).

supplementary crystallographic information

Comment

Although efficient synthetic routes for 2H-indazoles are available (e.g. Wu et al., 2010) few molecules belonging to this family of heterocyclic compounds have been X-ray characterized up to now. This is due, in part, to the fact that 1H tautomer for indazoles is frequently more stable than the 2H tautomer, although the opposite situation may occur for some derivatives (Alkorta & Elguero, 2005; Yu et al., 2006). On the other hand, in the case of N2-substituted indazoles, only the 2H tautomer is allowed. Tautomerism equilibrium study is important, since bioavailability and other pharmacological properties of indazoles may be dependent on such equilibria (e.g. Ramos Silva et al., 2008). Indazole derivatives have been used, for instance, for their anti-inflammatory activity.

The title compound was prepared through a three steps procedure, the key step being the cyclization of a nitroamine derivative (compound P, see Fig. 1 and Experimental). The resulting bis-indazole consists of two 2H-indazole heterocycles connected by an alkyl C₃ bridge (Fig. 2). The molecule lies in a general position, in space group Pbca. It is worth noting that the analogue compound with a central C₂ bridge, for which we reported the X-ray structure (Rodríguez de Barbarín et al., 2006), was found to crystallize in the same space group, although the molecule was placed on an inversion center. From this pair of structures now determined, we can propose the following general rule for n-alkyl bridged bis(2H-indazoles): even-alkyl compounds should be centrosymmetric, while odd-alkyl derivatives are expected to be non-centrosymmetric, as the title compound.

Molecular dimensions observed in the title compound compare well with those reported for other 2H-indazoles (Saczewski et al., 2001; Rodríguez de Barbarín et al., 2006; Hurtado et al., 2009; Zhou et al., 2010; Long et al., 2011). Indazole rings make a dihedral angle of 60.11 (7)°. Torsion angles N2—C8—C9—C10 and C8—C9—C10—N12, -176.7 (2) and 173.5 (2)° respectively, characterize the trans conformation for the alkyl bridge, resulting in a W-shaped molecule. The crystal structure features π–π interactions of modest strength, between molecules related by inversion (Fig. 3). The separation between the centroid of the pyrazole ring N11/N12/C11/C17/C16 and the symmetry-related centroid at position -x, 1 - y, 1 - z, is 3.746 (2) Å.

Experimental

The title ligand, PI, was obtained by a three steps reaction procedure (Fig. 1). The condensation between 1,3-diaminopropane and 2-nitrobenzaldehyde produced the corresponding imine. Selective reduction of imine bonds with sodium borohydride in methanol gave amine P, which was isolated. Then, 0.044 g of Pd/C was added to a solution of P (0.005 mol) in ethanol. This mixture was refluxed for 5.5 h, with addition of hydrazine monohydrate (0.110 mol) during the first 3 h. The mixture was filtered, distilled, and the organic phase was extracted. The product was purified by column chromatography with silica gel and ethyl acetate:hexane (2:1) as eluent. Suitable crystals were obtained by slow evaporation of an ethanol solution at 298 K. Mp 389.4–390 K; analysis found (calc. for C₁₇H₁₆N₄): C 73.6 (73.9), H 5.8 (5.8), N 20.5% (20.3%); IR RTA: 3108 (CH Ar. ν_s), 2950 (–CH₂– ν_s), 1625 (C=N Ar. δ_s), 1514, 1467 (C=C Ar. ν_s and ν_as). ¹H NMR (300 MHz, CDCl₃): δ, p.p.m.: 2.73 (2H, m, –CH₂–), 4.41 (4H, t, N—CH₂), 7.10 (2H, dd, Ar), 7.31 (2H, dd, Ar), 7.66 (2H, dd, Ar), 7.73 (2H, td, Ar), 7.95 (2H, s, NH).