2-Amino-6-[(2,6-dichlorophenyl)imino]-3-oxocyclohexa-1,4-dienecarbaldehyde

The title compound, C13H8Cl2N2O2, was obtained by the oxidation of diclofenac {systematic name: 2-[2-(2,6-dichlorophenylamino)phenyl]acetic acid}, an anti-inflammatory drug, with hydrogen peroxide catalysed by chlorido[5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III), using ammonium acetate as co-catalyst. The asymmetric unit contains two crystallographically independent molecules of the title compound (Z′ = 2). The close packing of individual molecules is mediated by a series of strong and rather directional N—H⋯Cl and N—H⋯O hydrogen bonds, plus weak π–π [distance between the individual double bonds of symmetry-related iminoquinone rings = 3.7604 (13) Å] and Cl⋯O interactions [3.0287 (18) Å].

We are grateful to the Fundaçã o para a Ciê ncia e a Tecnologia (FCT/FEDER, Portugal) for their general financial support to QOPNA and CICECO, and for the post-doctoral research grant No. SFRH/BPD/63736/2009 (to JAF). Thanks are also due to the FCT for specific funding toward the purchase of the single-crystal diffractometer. The possibility of using synthetic metalloporphyrins as biomimetic catalysts, which are able to mimic cytochrome P450 enzymes, has attracted the interest of many research groups (Othman et al., 2000;Bernadou et al., 2004;Mansuy, 2007), including ours (Neves et al., 2011;Simões et al., 2009;Rebelo et al., 2004aRebelo et al., , 2004bRebelo et al., , 2005. In particular, our current research is focused on the preparation of putative metabolites by the in vitro oxidation of drugs. These studies will allow the production of metabolites in the amounts of milligrams, the isolation and identification of unstable intermediates and the understanding of the mechanism of action of drugs (Bernadou et al., 2004). The title compound, C 13 H 8 Cl 2 N 2 O 2 , was obtained by the oxidation of 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid (diclofenac), an anti-inflammatory drug, with hydrogen peroxide catalysed by chloro [5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III) using ammonium acetate as co-catalyst. Following our on-going interest on the structural features of compounds with biological activity (Fernandes et al., 2010Loughzail et al. 2011) here we wish to report the crystal structure of the oxidation product of diclofenac.
The asymmetric unit of the title compound comprises two whole molecules of C 13 H 8 Cl 2 N 2 O 2 (Fig. 1). A comparison between the geometrical features of the two molecules reveals that bond distances and angles involving equivalent atoms are very similar (deviations smaller than 0.012 Å and 1.6°, respectively). There are, however, some considerable differences concerning torsion angles, namely those subtended by the two six-membered rings in each molecule: 71.97 (10)° for molecule A and 75.89 (10)° for molecule B.
The crystal is rich in supramolecular interactions, namely π-π (involving the individual double bonds of the iminoquinone rings), Cl···O and hydrogen bonding interactions. The π-π interactions occur between pairs of molecules A involving the aromatic and the iminoquinone rings, or two iminoquinone rings [distance between centroids of 3.7604 (13) and 3.9595 (13) Å, respectively -purple dashed bonds in Figure 2]. A pair of B molecules also exhibits a short Cl···O interaction (Cl···O distance 3.0287 (18) Å, not shown].
The two crystallographically independent molecules have a different behaviour concerning the hydrogen bonding network in which they are involved ( Figure 2 and Table 1 for geometric details). Molecule A is engaged in a bifurcated N-H···(O,O) hydrogen bond, which is shared by the aldehyde group (intramolecular) and the ketone group of a neighbouring B molecule. The remaining N-H moiety of molecule A donates the hydrogen atom to a Cl atom of a neighbouring A molecule. The NH 2 group of molecule B participates in two N-H···O aldehyde interactions, of which one is intramolecular and the other occurs with molecule A. The hydrogen bonds form discrete clusters (violet dashed lines in Fig. 2) which can be described as the merging of two rings with a graph set notations R 1 1 (6) and R 2 2 (11), respectively (Grell et al., 1999).
Unequivocally, the strongest connection among adjacent molecules corresponds to that of the latter graph set, which leads to the formation of dimers as depicted in Fig. 2. The crystal packing is, thus, promoted by the close packing of such dimers: firstly, and mediated by the aforementioned weak π-π contacts, dimers form columnar arrangements along the c-axis of the unit cell. Secondly, columns pack in the ab plane in a typical brick-wall-type fashion as depicted in Fig. 3.
supplementary materials sup-2 Experimental All chemicals were purchased from commercial sources and were used as received without further purification.
The oxidant employed was aqueous hydrogen peroxide 30% (w/w) (Riedel-de Haën) diluted 1:5 in CH 3 CN. The oxidant (0.05 mmol) was added to the reaction mixture every 15 min. After 8 h of reaction, the mixture was extracted with dichloromethane and purified by preparative TLC using the same solvent as eluent. The product was dissolved in a minimum amount of dichloromethane and crystallized in hexane at around -16 °C to isolate crystals of the title compound.

Refinement
Hydrogen atoms bound to carbon were placed at their idealized positions and were included in the final structural model in riding-motion approximation with C-H = 0.95 Å. The isotropic thermal displacement parameters for these hydrogen atoms were fixed at 1.2×U eq of the respective parent carbon atom.
Hydrogen atoms bound to nitrogen were directly located from difference Fourier maps and included in the final structural model with the N-H and H···H distances restrained to 0.95 (1) and 1.55 (1) Å, respectively. The U iso of these hydrogen atoms was fixed at 1.5×U eq of the nitrogen atom to which they are attached. two graph set motifs: R 1 1 (6) and R 2 2 (11). On the right, weak π-π contacts involving double bonds of the iminoquinone and aromatic rings further ensure supramolecular connections among A molecules. For geometric details on the represented hydrogen bonds see Table 1. Symmetry transformations used to generate equivalent atoms have been omitted for simplicity.