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

Cláudia M B Neves; José A Fernandes; Mário M Q Simões; M Graça P M S Neves; José A S Cavaleiro; Filipe A Almeida Paz

doi:10.1107/S1600536811042619

. 2011 Oct 22;67(Pt 11):o3022–o3023. doi: 10.1107/S1600536811042619

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

Cláudia M B Neves ^a, José A Fernandes ^b, Mário M Q Simões ^a, M Graça P M S Neves ^a, José A S Cavaleiro ^a, Filipe A Almeida Paz ^b,^*

PMCID: PMC3247420 PMID: 22220038

Abstract

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].

Related literature

For background to diclofenac oxidation reactions using metalloporphyrins as catalysts, see: Othman et al. (2000 ▶). For oxidation of other drugs and other organic compounds by hydrogen peroxide catalysed by metalloporphyrins, see: Othman et al. (2000 ▶); Bernadou & Meunier (2004 ▶); Mansuy (2007 ▶); Neves et al. (2011 ▶); Simões et al. (2009 ▶); Rebelo et al. (2004a ▶,b ▶, 2005 ▶). For crystallographic studies from our research group of compounds with biological activity, see: Fernandes et al. (2010 ▶, 2011 ▶); Loughzail et al. (2011 ▶). For a description of the graph-set notation, see: Grell et al. (1999 ▶).

Experimental

Crystal data

C₁₃H₈Cl₂N₂O₂
M _r = 295.11
Monoclinic,
a = 17.1738 (14) Å
b = 10.5718 (8) Å
c = 14.1457 (11) Å
β = 101.192 (5)°
V = 2519.4 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.51 mm⁻¹
T = 150 K
0.07 × 0.04 × 0.01 mm

Data collection

Bruker X8 KappaCCD APEXII diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ▶) T _min = 0.965, T _max = 0.995
24324 measured reflections
4600 independent reflections
3466 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.085
S = 1.02
4600 reflections
355 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT-Plus (Bruker, 2005 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: DIAMOND (Brandenburg, 2009 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811042619/tk2799sup1.cif

e-67-o3022-sup1.cif^{(23.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811042619/tk2799Isup2.hkl

e-67-o3022-Isup2.hkl^{(225.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811042619/tk2799Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2X⋯Cl1ⁱ	0.92 (1)	2.60 (1)	3.4590 (18)	156 (2)
N2—H2Y⋯O1	0.92 (1)	2.08 (2)	2.722 (2)	126 (2)
N2—H2Y⋯O4ⁱ	0.92 (1)	2.26 (2)	2.933 (2)	130 (2)
N4—H4X⋯O1ⁱ	0.93 (1)	2.04 (1)	2.916 (2)	155 (2)
N4—H4Y⋯O3	0.92 (1)	2.01 (2)	2.666 (3)	127 (2)

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

We are grateful to the Fundação para a Ciência 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.

supplementary crystallographic information

Comment

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., 2004a, 2004b, 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, C₁₃H₈Cl₂N₂O₂, 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., 2010, 2011; Loughzail 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 C₁₃H₈Cl₂N₂O₂ (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 NH₂ 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 R¹₁(6) and R²₂(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.

Experimental

All chemicals were purchased from commercial sources and were used as received without further purification.

The oxidation reactions were carried out using 0.1 mmol of diclofenac (sodium salt, Sigma-Aldrich), 1.33 µmol of chloro[5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III) ([Mn(TDCPP)Cl, as catalyst) and 15 mg of co-catalyst (ammonium acetate, Fluka) in CH₃CN: H₂O (10:1), in a total volume of 2.0 ml under normal atmosphere at 30 °C. The oxidant employed was aqueous hydrogen peroxide 30% (w/w) (Riedel-de Haën) diluted 1:5 in CH₃CN. 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.