1-(3,5-Dinitrobenzoyl)-4-(2-methoxyphenyl)piperazine

The molecules of the title compound are linked into sheets by two π–π stacking interactions.


Structure description
Piperazines are found in a wide range of compounds that are active across a number of different therapeutic areas as they exhibit antibacterial, antidepressant antifungal, antimalarial, antipsychotic, and antitumour activity (Brockunier et al., 2004;Bogatcheva et al., 2006), and a number of these areas have recently been reviewed (Elliott, 2011;Kharb et al., 2012;Asif, 2015;Brito et al., 2019). N-(2-Methoxyphenyl)piperazine has been used as a building block in the synthesis of both 5-HT 1 A receptor ligands (Orjales et al., 1995) and dopamine D 2 and D 3 ligands (Hackling et al., 2003), and also as a building block for the synthesis of derivatives exhibiting antidepressant-like activity (Waszkielewicz et al., 2015). The isomeric N-(4-methoxyphenyl)piperazine has been found to inhibit the reuptake and accelerate the release of monoamine neurotransmitters such as dopamine and serotonin, with a mechanism of action similar to that of recreational drugs such as amphetamines, but with significantly lower abuse potential (Nagai et al., 2007). We have recently reported the structures of a range of 1-aroyl-4-(4-methoxyphenyl)piperazines (Harish Chinthal et al., 2020), and in a continuation of that work, we report here the structure of the title compound ( Fig. 1), which was prepared using a carbodiimide-data reports mediated condensation reaction between N-(2-methoxyphenyl)piperazine and 3,5-dinitrobenzoic acid.
The piperazine ring in the title compound ( Fig. 1) adopts a conformation that is close to an ideal chair form. The ringpuckering angle (Cremer & Pople, 1975), calculated for the atom sequence (N1,C2,C3,N4,C5,C6) is 12.69 (18) , whereas this value would be zero for an ideal chair form (Boeyens, 1978). The geometry at the amidic atom N1 is planar within experimental uncertainty, but that at N4 is markedly pyramidal: the exocyclic substituents at both of these atoms occupy equatorial sites. In the dinitrobenezene ring, the two nitro groups are both rotated out of the ring plane; the nitro groups bonded to atoms C13 and C15 make dihedral angles with the ring (C11-C16) of 20.52 (9) and 2.34 (12) , respectively, with a dihedral angle of 22.09 (10) between the planes of the two nitro groups, so that the rotations occur in a conrotatory sense. In the 2-methoxybenzene substituent, the methoxy atom C47 is nearly coplanar with the adjacent ring, with a displacement from the ring plane of only 0.308 (5) Å . Associated with this near planarity, the two exocyclic angles at C42 are markedly different. Thus, C41-C42-O42 is 115.51 (16) and C43-C42-O42 is 124.36 (18) , as typically found in planar or nearplanar alkoxyarenes (Seip & Seip, 1973;Ferguson et al., 1996).
Despite the presence within the molecule of six O atoms and two N atoms, all of which are potential hydrogen-bond acceptors, the structure contains no intermolecular C-HÁ Á ÁO or C-HÁ Á ÁN hydrogen bonds, nor are there any C-HÁ Á Á(arene) interactions. However, twostacking interactions are present. The nitrobenzene ring at (x, y, z) makes a dihedral angle of 8.44 (9) with the methoxybenzene rings at both (x, 1 À y, 1 2 + z) and (x, 2 À y, 1 2 + z), i.e. in the molecules related to the reference molecule by the c-glide planes at y = 0.5 and 1, respectively. The ring-centroid separations are 3.9197 (12) and 3.8444 (12) Å , respectively, and the shortest distances between the centroid of one ring and the plane of the other are 3.3822 (8) and 3.2468 (8) Å , respectively, leading to the formation of a -stacked sheet lying parallel to (100) in the domain 0.25 < x < 0.5 (Fig. 2). Three other sheets of this type pass through the unit cell, in the domains 0 < x < 0.25, 0.5 < x < 0.75, and 0.75 < x < 1.0, but there are no direction-specific interactions between adjacent sheets.

Synthesis and crystallization
For the synthesis of the title compound, 1-(3-dimethylaminopropyl)-3-ethylcarbodimide (134 mg, 0.7 mmol), 1-hydroxybenzotriazole (68 mg, 0.5 mmol) and triethylamine (0.5 ml, 1.5 mmol) were added to a solution of 3,5-dinitrobenzoic acid (114 mg, 0.5 mmol) in methanol (10 ml). This mixture was heated to 323 K, with stirring, for a few minutes before being set aside at ambient temperature. After two days, a solution of N-(2-methoxyphenyl)piperazine (100 mg, 0.52 mmol) in N,N-dimethylformamide (5 ml) was added and the resulting mixture was stirred overnight at ambient temperature. When the reaction was complete, as judged using thin layer chromatography, the mixture was quenched with water (10 ml) and extracted with ethyl acetate (20 ml). The organic fraction was separated and washed successively with an aqueous hydrochloric acid solution (1 mol dm À3 ), a saturated solution of sodium hydrogen carbonate and finally with brine. The organic phase was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the resulting product was recrystallized from methanol-ethyl acetate (1:1, v/v), m.p. 390-392 K. Crystals suitable for singlecrystal X-ray diffraction were grown by slow evaporation, at ambient temperature and in the presence of air, of its ethyl acetate solution.

Figure 2
A view of the molecular packing of the title compound showing the formation of a -stacked sheet lying parallel to (100). For the sake of clarity, the H atoms have been omitted.

Figure 1
The molecular structure of the title compound showing the atomlabelling scheme. Displacement ellipsoids are drawn at the 30% probability level. where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.22 e Å −3 Δρ min = −0.19 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.