Diethyl 2-[phen­yl(pyrazol-1-yl)meth­yl]propane­dioate

Ihssan Meskini; Maria Daoudi; Jean-Claude Daran; Hafid Zouihri; Taibi Ben Hadda

doi:10.1107/S1600536810011748

. 2010 Apr 2;66(Pt 5):o1014. doi: 10.1107/S1600536810011748

Diethyl 2-[phenyl(pyrazol-1-yl)methyl]propanedioate

Ihssan Meskini ^a, Maria Daoudi ^a, Jean-Claude Daran ^b, Hafid Zouihri ^c,^*, Taibi Ben Hadda ^d

PMCID: PMC2979074 PMID: 21579078

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₁₇H₂₀N₂O₄, which differ slightly in the orientation of the phenyl ring and carbonyl groups with respect to the pyrazole unit. In the first molecule, the dihedral angle between the phenyl and pyrazole rings is 68.99 (13)° while the two carbonyl groups make a dihedral angle of 72.1 (4)°. The corresponding values in the second molecule are 68.54 (14) and 71.5 (4)°, respectively.

Related literature

For related compounds displaying biological activity, see: Dayam et al. (2007 ▶); Patil et al. (2007 ▶); Ramkumar et al. (2008 ▶); Sechi et al. (2009a ▶,b ▶); Zeng et al. (2008a ▶,b ▶). For a related structures, see: Akkurt et al. (2007 ▶). For the synthetic procedure, see: Pommier & Neamati (2006 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₇H₂₀N₂O₄
M _r = 316.36
Monoclinic,
a = 19.6279 (8) Å
b = 8.1538 (3) Å
c = 21.6002 (9) Å
β = 104.675 (2)°
V = 3344.2 (2) Å³
Z = 8
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.35 × 0.22 × 0.17 mm

Data collection

Bruker X8 APEXII CCD area-detector diffractometer
34259 measured reflections
6348 independent reflections
4175 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.122
S = 1.06
6346 reflections
419 parameters
H-atom parameters constrained
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); 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 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810011748/kj2142sup1.cif

e-66-o1014-sup1.cif^{(26.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810011748/kj2142Isup2.hkl

e-66-o1014-Isup2.hkl^{(310.6KB, hkl)}

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

Acknowledgments

This work was supported by grants from Project PGR-UMP-BH-2005, the Centre National de Recherche Scientifique, CNRS (France) and the Centre National pour la Recherche Scientifique et Technique, CNRST (Morocco).

supplementary crystallographic information

Comment

The rational design of new HIV-1 Integrase (H-I) inhibitors, one validated target for chemotherapeutic intervention (Dayam et al., 2007), is fundamentally based on intermolecular coordination between H-I / chemical inhibitor / metals (Mg⁺² and Mn⁺², co-factors of the enzyme), leading to the formation of bimetallic complexes (Zeng et al., 2008a; Sechi et al., 2009a). Therefore several bimetallic metal complexes, in many cases exploring the well-known polydentate ligands, appear in this scenario as the most promising concept to employ in either enzyme / drug interaction or electron transfer process, in the last case involving biological oxygen transfer (Sechi et al., 2009b; Ramkumar et al., 2008). Another exciting example of the application of such polydentate ligands involves the synergic water activation, that occurs via the so-called remote metallic atoms. Such organometallic compounds are expected to promote or block the H-I activity [Zeng et al. (2008b)]. The examples given above clearly demonstrate that polydentate ligands are of special interest in the field of bioorganometallic chemistry [Patil et al. (2007)].

The structure of the title compound was established by ¹H and ¹³C NMR and confirmed by its elemental analyses and single-crystal X-ray structure. Crystals of the title compound contain two molecules in the asymmetric unit. The difference between the molecules lies in the orientation of the phenyl and pyrazol rings and carbonyl planes in each molecule as shown in the fitting drawing (Fig. 2). Thus in the first molecule (C11 to C143) the dihedral angles between the phenyl and pyrazol rings is 68.99 (13)° and between the two carbonyl groups is 72.1 (4)°. Whereas in the second molecule (C21 to C243), equivalent angles have as values 68.54 (14)° and 71.5 (4)°, respectively. The conformational difference between the independent molecules, as shown in Fig. 2, can also be described by torsion angles: N11—C11···C131—C132 = 79.71 (15), C11—C12···O11O12 = 46.54 (9) and C11—C12···O13—O14 = 47.02 (9) in the first molecule. In the second molecule, the corresponding values are 54.31 (14), 41.77 (9) and 47.44 (9), respectively. The bond lengths and angles in the title compound (Fig. 1) are found to have normal values [Allen et al., 1987].

Experimental

To a solution of diethyl benzylpropanedioate (5 mmol) in water (25 ml) was added 1H-pyrazol (6 mmol) in the presence of acetic acid (0.1% mol). The mixture was stirred continuously at room temperature until the starting material was completely consumed. After removing the solvent, the crude products were dissolved in diethyl ether (2 x 40 ml) and washed with water until the pH became neutral. The organic solvent was dried with sodium sulphate and then evaporated. The residue was purified by recrystallization from a mixture ether/hexane (1:1) to give a white solid in 74% yield. R_f = 0.45 (ether/hexane: 1/1). Elemental analysis for C₁₇H₂₀N₂O₄: Calcd (Found): C 67.82 (67.79), H 5.89 (5.87), N (2.73 (2.72). The purity of the compound was checked by determining its melting point (87-89°C). Suitable single crystal of the title compound were obtained by recrystallization from ethanol.