3-Methyl-1,4-dioxo-1,4-dihydro­naphthalen-2-yl 4-amino­benzoate

Massimo Bambagiotti-Alberti; Gianluca Bartolucci; Bruno Bruni; Silvia Coran; Massimo Di Vaira

doi:10.1107/S1600536808005308

. 2008 Mar 14;64(Pt 4):o718. doi: 10.1107/S1600536808005308

3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate

Massimo Bambagiotti-Alberti ^a, Gianluca Bartolucci ^a, Bruno Bruni ^a, Silvia Coran ^a, Massimo Di Vaira ^b,^*

PMCID: PMC2961024 PMID: 21202108

Abstract

The crystal structure of the title compound, C₁₈H₁₃NO₄, the oxidized form of the drug aminaftone used in venous disease therapy, is characterized by the presence of ribbons of hydrogen-bonded molecules parallel to the [111] crystallographic direction and by stacking interactions between rings [centroid–centroid distance between quinone rings = 3.684 (3) Å and between aminobenzoate rings = 4.157 (3) Å] along the ribbons.

Related literature

For related literature, see: De Anna et al. (1989 ▶); Martinez et al. (2005 ▶).

Experimental

Crystal data

C₁₈H₁₃NO₄
M _r = 307.29
Triclinic,
a = 7.6217 (6) Å
b = 9.6142 (7) Å
c = 10.6456 (7) Å
α = 101.618 (6)°
β = 110.770 (7)°
γ = 89.019 (6)°
V = 713.18 (10) Å³
Z = 2
Cu Kα radiation
μ = 0.85 mm⁻¹
T = 170 (2) K
0.60 × 0.20 × 0.05 mm

Data collection

Oxford Diffraction Xcalibur PX Ultra CCD diffractometer
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2006 ▶) T _min = 0.501, T _max = 1.000 (expected range = 0.480–0.959)
6339 measured reflections
2453 independent reflections
1845 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.142
S = 1.12
2453 reflections
215 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlisPro CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlisPro CCD; data reduction: CrysAlisPro RED (Oxford Diffraction, 2006 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808005308/rk2078sup1.cif

e-64-0o718-sup1.cif^{(19.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808005308/rk2078Isup2.hkl

e-64-0o718-Isup2.hkl^{(118KB, hkl)}

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
N—H2N⋯O3ⁱ	0.95 (3)	2.13 (3)	2.960 (2)	145.6 (19)
N—H1N⋯O4ⁱⁱ	0.89 (2)	2.25 (2)	3.045 (2)	147.3 (19)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors acknowledge financial support from the Italian Ministero dell’Istruzione, dell’Universitá e della Ricerca.

supplementary crystallographic information

Comment

Previuos studies concerning the quality control of aminaftone, 4–aminobenzoic acid 1,4–dihydroxy–3–methyl–naphtalen–2–yl ester, which is the active pharmaceutical ingredient of some commercial drugs used in the therapy of chronic venous and lymphatic stasis (De Anna et al., 1989; Martinez et al., 2005), have shown that this drug substance rapidly undergoes oxidation in solution at room temperature. The oxidized compound, featuring a quinone ring instead of a hydroquinone moiety, is also a potential impurity of the bulk drug. A structure determination of the oxidized form, I, has been undertaken at 170 K.

There are two molecules of I, related by the inversion centre, in the triclinic unit cell. The molecular geometry and labelling are shown in Fig 1. Bond distances are consistent with the presence of the quinonic form. Each molecule behaves as a hydrogen–bond donor, toward two other molecules, through its aminic H atoms: N—H2N···O3ⁱ (N···O3ⁱ = 2.960 (2) Å, N—H2N···O3ⁱ = 146 (2)°; symmetry code (i): 2 - x, 2 - y, 1 - z) and N—H1N···O4ⁱⁱ (N···O4ⁱⁱ = 3.045 (2) Å, N—H1N···O4ⁱⁱ = 147 (2)°; symmetry code (ii): 1 + x, 1 + y, 1 + z). Conversely, through the above hydrogen bonds each molecule behaves as an acceptor from two separate molecules, by means of its quinone O atoms. As a result, ribbons of hydrogen–bonded molecules, parallel to the crystallographic [1 1 1] direction, are formed (Fig. 2). Moreover, stacking interactions occur along the ribbons, with 3.684 (3)Å distance between the centroids of symmetry–related quinone rings and 4.157 (3)Å distance between the centroids of the aminobenzoic rings, the shortest C···C contact distances between atoms of facing rings being C8···C16ⁱⁱⁱ = 3.532 (3)Å ((iii): 1 - x, 1 - y, -z) and C2···C3ⁱ = 3.286 (2) Å, respectively, for the above two types of interactions. The largest deviation (0.098 (1) Å) from the plane of the aminobenzoic group is presented by the carbonylic O2 atom whereas, among the atoms lying on the naphtoquinone plane, the hinge atom O1 exhibits the largest deviation (0.141 (2) Å) from that plane; the angle between these two planes measures 84.46 (3)°.

Experimental

Samples of aminonaftone were kindly provided by SIMS (SIMS srl, Reggello Firenze, Italy). Crystals of I, suitable for X–ray diffraction analysis, were obtained by slow evaporation from methanol solutions of aminaftone.