Crystal structure of (Z)-ethyl 3-[2-(5-methyl-7-nitro-1H-indole-2-carbonyl)hydrazinylidene]butanoate

The reaction of 5-methyl-7-nitro-1H-indole-2-carbohydrazide with ethyl acetoacetate yielded the title molecule, C16H18N4O5, in which the indole ring is almost planar, with the greatest deviation from the mean plane being 0.006 (2) Å. The nine atoms of the indole ring are almost perpendicular to the mean plane through the ethyl acetate group, as indicated by the dihedral angle of 87.02 (4)° between them. In the crystal, centrosymmetric supramolecular dimers are formed via N—H⋯O hydrogen bonds and eight-membered amide {⋯HNCO}2 synthons. These are consolidated into a three-dimensional architecture by C—H⋯O contacts, and by π–π interactions between six-membered rings [inter-centroid distance = 3.499 (2) Å].


S1. Comment
The indole nucleus is probably the most widely distributed heterocyclic ring system found in nature (Kuethe et al., 2005).
Due to the existence of a vast array of structurally diverse and biologically active indoles, it is not surprising that the indole nucleus is an important feature in many medicinal agents and the most important of all structural classes in drug discovery (Smith et al., 1998). For example, the identification of new and selective cox-2 inhibitors (Penning et al., 1997), for the relief of pain, and the treatment of the symptoms of arthritis and related diseases has been an important advance in modern anti-inflammatory therapy. In a related area, heterocycle-appended pyrazoles have been reported (Dumas et al., 2000) to be potent and selective as inhibitors of the mitogen-activated protein kinase p38 and consequently provide a novel approach for the treatment of rheumatoid arthritis and related inflammatory diseases. The synthesis and reactivity of indole derivatives have been a topic of research interest for well over a century. Due to the potent biological activity exhibited by various indoles derivatives, there is a continuous demand for novel synthetic procedures in this area.
The fused five-and six-membered rings, part of the title compound, are essentially planar with the largest deviation from the mean plane being 0.006 (2) Å at C1 atom as shown in Fig. 1. The mean plane through the ethyl acetate group is virtually perpendicular to the indasol ring as indicated by the dihedral angle of 87.02 (4) ° between them. The cohesion of the crystal is ensured by C-H···O and N-H···O hydrogen bonds, and by π-π interactions between phenyl rings [intercentroid distance = 3.499 (2) Å], as shown in Fig. 2 and Table 2.

S2. Experimental
The ethyl 3-(2-(5-methyl-7-nitro-1H-indole-2-cabonyl)hydrazono)butanoate was synthesized from a mixture of 5methyl-7-nitroindole-2-carbohydrazide (4.6 mmol) and ethyl acetoacetate (35 mmol) in ethanol which was heated on a steam bath at 353 K until dissolution. The mixture was kept at this temperature for 4 h. The crude product was filtered and crystallized from ethanol. Yellow crystals appeared after two weeks. The crystals were washed with cold ethanol and dried in air at room temperature.

Figure 1
Plot of the molecule with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against all reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on all data will be even larger.