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Acta Cryst. (2008). E64, o718    [ doi:10.1107/S1600536808005308 ]

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

M. Bambagiotti-Alberti, G. Bartolucci, B. Bruni, S. Coran and M. Di Vaira

Abstract top

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.

Comment top

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)°.

Related literature top

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

Experimental top

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.

Refinement top

Crystals did not diffract strongly and it was deemed that collecting data at θ higher than 72° would not yield improvement. Hydrogen atoms were in geometrically generated positions, riding, except for the amino H atoms, which were refined freely. The constraint U(H) = 1.2Ueq(C,N), or 1.5Ueq(C) for methyl group H atoms, was applied. Range of bond distances involving refined hydrogen atoms: N—H 0.89–0.95 Å.

Computing details top

Data collection: CrysAlisPro CCD (Oxford Diffraction, 2006); cell refinement: CrysAlisPro CCD (Oxford Diffraction, 2006); 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 (Sheldrick, 2008) and PARST (Nardelli, 1995).

Figures top
[Figure 1] Fig. 1. A view of the molecule of I with the atom numbering schene. Displacement ellipsoids are drawn at the 50% probability level. H atoms are presented as a small spheres of arbitrary radius.
[Figure 2] Fig. 2. A view of the crystal packing in the structure of I, showing the presence of ribbons formed by H–bonded molecules. H–bonds are denoted by dashed lines.
3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate top
Crystal data top
C18H13NO4Z = 2
Mr = 307.29F000 = 320
Triclinic, P1Dx = 1.431 Mg m−3
Hall symbol: -P 1Cu Kα radiation
λ = 1.54180 Å
a = 7.6217 (6) ÅCell parameters from 3411 reflections
b = 9.6142 (7) Åθ = 9.6–53.4º
c = 10.6456 (7) ŵ = 0.85 mm−1
α = 101.618 (6)ºT = 170 (2) K
β = 110.770 (7)ºFlat prism, red
γ = 89.019 (6)º0.60 × 0.20 × 0.05 mm
V = 713.18 (10) Å3
Data collection top
Oxford Diffraction Xcalibur PX Ultra CCD
diffractometer		2453 independent reflections
Radiation source: Fine–focus sealed tube1845 reflections with I > 2σ(I)
Monochromator: Oxford Diffraction Enhance ULTRA assemblyRint = 0.022
Detector resolution: 8.1241 pixels mm-1θmax = 72.4º
T = 170(2) Kθmin = 4.5º
ω scansh = −9→9
Absorption correction: multi-scan
(ABSPACK; Oxford Diffraction, 2006)		k = −11→11
Tmin = 0.501, Tmax = 1.000l = −12→12
6339 measured reflections
Refinement top
Refinement on F2Secondary atom site location: Difmap
Least-squares matrix: FullHydrogen site location: Difmap
R[F2 > 2σ(F2)] = 0.041H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.142  w = 1/[σ2(Fo2) + (0.0941P)2 + 0.0064P]
where P = (Fo2 + 2Fc2)/3
S = 1.12(Δ/σ)max < 0.001
2453 reflectionsΔρmax = 0.17 e Å−3
215 parametersΔρmin = −0.23 e Å−3
Primary atom site location: DirectExtinction correction: None
Crystal data top
C18H13NO4γ = 89.019 (6)º
Mr = 307.29V = 713.18 (10) Å3
Triclinic, P1Z = 2
a = 7.6217 (6) ÅCu Kα
b = 9.6142 (7) ŵ = 0.85 mm−1
c = 10.6456 (7) ÅT = 170 (2) K
α = 101.618 (6)º0.60 × 0.20 × 0.05 mm
β = 110.770 (7)º
Data collection top
Oxford Diffraction Xcalibur PX Ultra CCD
diffractometer		2453 independent reflections
Absorption correction: multi-scan
(ABSPACK; Oxford Diffraction, 2006)		1845 reflections with I > 2σ(I)
Tmin = 0.501, Tmax = 1.000Rint = 0.022
6339 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.041215 parameters
wR(F2) = 0.142H atoms treated by a mixture of
independent and constrained refinement
S = 1.12Δρmax = 0.17 e Å−3
2453 reflectionsΔρmin = −0.23 e Å−3
Special details top

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R–factor wR and goodness of fit S are based on F2, conventional R–factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R–factors(gt) etc. and is not relevant to the choice of reflections for refinement. R–factors based on F2 are statistically about twice as large as those based on F, and R–factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.6680 (2)1.03157 (16)0.34314 (16)0.0361 (4)
C20.8411 (2)1.01124 (16)0.32984 (16)0.0373 (4)
H20.86130.92340.27870.045*
C30.9857 (3)1.11583 (17)0.38923 (16)0.0392 (4)
H31.10381.09960.37910.047*
C40.9568 (3)1.24645 (17)0.46471 (16)0.0398 (4)
N1.0987 (3)1.35138 (17)0.52199 (17)0.0508 (4)
H1N1.083 (3)1.425 (3)0.582 (2)0.061*
H2N1.225 (4)1.326 (2)0.542 (2)0.061*
C50.7833 (3)1.26644 (17)0.47801 (17)0.0449 (5)
H50.76241.35420.52890.054*
C60.6405 (3)1.16127 (18)0.41876 (17)0.0431 (4)
H60.52261.17700.42940.052*
C70.5122 (3)0.92331 (17)0.27898 (16)0.0384 (4)
O10.57285 (17)0.79775 (12)0.22176 (13)0.0464 (4)
O20.35157 (19)0.93363 (13)0.27039 (14)0.0498 (4)
C80.4401 (2)0.68767 (16)0.14533 (17)0.0377 (4)
C90.4125 (2)0.58405 (18)0.22396 (17)0.0386 (4)
O30.48719 (18)0.60587 (14)0.34797 (12)0.0497 (4)
C100.2922 (2)0.45428 (17)0.14241 (18)0.0388 (4)
C110.2663 (3)0.3494 (2)0.2090 (2)0.0498 (5)
H110.32270.36230.30600.060*
C120.1572 (3)0.2263 (2)0.1317 (2)0.0602 (6)
H120.14140.15360.17610.072*
C130.0713 (3)0.2085 (2)−0.0091 (2)0.0552 (5)
H13−0.00360.1239−0.06070.066*
C140.0936 (3)0.31287 (18)−0.0752 (2)0.0466 (5)
H140.03300.3008−0.17190.056*
C150.2056 (2)0.43605 (16)0.00057 (17)0.0376 (4)
O40.1557 (2)0.53290 (14)−0.19534 (13)0.0593 (4)
C160.2311 (2)0.54714 (17)−0.07165 (17)0.0405 (4)
C170.3535 (2)0.67684 (17)0.01047 (18)0.0393 (4)
C180.3757 (3)0.7879 (2)−0.0642 (2)0.0516 (5)
H1810.49800.8401−0.01440.077*
H1820.27530.8541−0.06990.077*
H1830.36830.7421−0.15700.077*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0393 (10)0.0345 (8)0.0337 (8)0.0027 (8)0.0114 (7)0.0083 (6)
C20.0443 (10)0.0325 (7)0.0329 (8)0.0035 (8)0.0118 (7)0.0059 (6)
C30.0385 (10)0.0398 (8)0.0357 (8)0.0033 (8)0.0088 (7)0.0085 (7)
C40.0435 (11)0.0382 (8)0.0318 (8)−0.0001 (8)0.0065 (7)0.0066 (6)
N0.0484 (10)0.0413 (8)0.0487 (9)−0.0045 (8)0.0063 (7)−0.0016 (7)
C50.0529 (12)0.0360 (8)0.0417 (10)0.0019 (9)0.0175 (8)−0.0017 (7)
C60.0449 (11)0.0407 (9)0.0436 (9)0.0035 (8)0.0176 (8)0.0053 (7)
C70.0443 (11)0.0347 (8)0.0362 (8)0.0032 (8)0.0136 (7)0.0091 (6)
O10.0370 (7)0.0339 (6)0.0615 (8)−0.0006 (5)0.0156 (6)−0.0013 (5)
O20.0410 (8)0.0444 (7)0.0622 (8)0.0016 (6)0.0202 (6)0.0040 (6)
C80.0326 (9)0.0313 (7)0.0480 (10)0.0026 (7)0.0164 (7)0.0021 (7)
C90.0322 (9)0.0423 (8)0.0402 (9)0.0065 (8)0.0137 (7)0.0050 (7)
O30.0438 (8)0.0612 (8)0.0397 (7)0.0022 (6)0.0124 (5)0.0057 (6)
C100.0331 (9)0.0366 (8)0.0476 (10)0.0031 (8)0.0153 (7)0.0092 (7)
C110.0484 (12)0.0500 (10)0.0583 (11)0.0063 (9)0.0248 (9)0.0173 (9)
C120.0629 (14)0.0438 (10)0.0877 (16)−0.0002 (10)0.0405 (12)0.0192 (10)
C130.0464 (12)0.0389 (9)0.0817 (15)−0.0021 (9)0.0316 (10)−0.0003 (9)
C140.0366 (10)0.0391 (9)0.0578 (11)0.0037 (8)0.0157 (8)−0.0017 (8)
C150.0320 (9)0.0330 (8)0.0472 (10)0.0068 (7)0.0168 (7)0.0032 (7)
O40.0774 (11)0.0530 (7)0.0385 (7)0.0067 (7)0.0124 (6)0.0053 (6)
C160.0386 (10)0.0385 (8)0.0414 (10)0.0089 (8)0.0121 (7)0.0064 (7)
C170.0368 (10)0.0355 (8)0.0477 (10)0.0073 (8)0.0173 (8)0.0095 (7)
C180.0535 (12)0.0465 (10)0.0626 (12)0.0078 (9)0.0245 (9)0.0222 (9)
Geometric parameters (Å, °) top
C1—C21.383 (3)C9—O31.213 (2)
C1—C61.398 (2)C9—C101.480 (2)
C1—C71.463 (2)C10—C151.392 (2)
C2—C31.383 (2)C10—C111.397 (2)
C2—H20.9500C11—C121.387 (3)
C3—C41.407 (2)C11—H110.9500
C3—H30.9500C12—C131.382 (3)
C4—N1.371 (2)C12—H120.9500
C4—C51.385 (3)C13—C141.381 (3)
N—H1N0.89 (2)C13—H130.9500
N—H2N0.95 (3)C14—C151.394 (2)
C5—C61.378 (2)C14—H140.9500
C5—H50.9500C15—C161.488 (2)
C6—H60.9500O4—C161.215 (2)
C7—O21.199 (2)C16—C171.487 (2)
C7—O11.388 (2)C17—C181.498 (2)
O1—C81.3827 (19)C18—H1810.9800
C8—C171.333 (2)C18—H1820.9800
C8—C91.485 (2)C18—H1830.9800
C2—C1—C6118.63 (15)C15—C10—C11120.01 (16)
C2—C1—C7122.37 (15)C15—C10—C9120.57 (14)
C6—C1—C7118.99 (16)C11—C10—C9119.42 (16)
C1—C2—C3121.52 (15)C12—C11—C10119.25 (19)
C1—C2—H2119.2C12—C11—H11120.4
C3—C2—H2119.2C10—C11—H11120.4
C2—C3—C4119.58 (17)C13—C12—C11120.62 (17)
C2—C3—H3120.2C13—C12—H12119.7
C4—C3—H3120.2C11—C12—H12119.7
N—C4—C5121.40 (16)C14—C13—C12120.40 (17)
N—C4—C3119.83 (18)C14—C13—H13119.8
C5—C4—C3118.76 (15)C12—C13—H13119.8
C4—N—H1N116.7 (15)C13—C14—C15119.68 (18)
C4—N—H2N119.0 (13)C13—C14—H14120.2
H1N—N—H2N114 (2)C15—C14—H14120.2
C6—C5—C4121.14 (16)C10—C15—C14120.02 (16)
C6—C5—H5119.4C10—C15—C16120.62 (14)
C4—C5—H5119.4C14—C15—C16119.37 (16)
C5—C6—C1120.36 (17)O4—C16—C17120.01 (15)
C5—C6—H6119.8O4—C16—C15121.32 (15)
C1—C6—H6119.8C17—C16—C15118.67 (14)
O2—C7—O1121.27 (15)C8—C17—C16118.88 (14)
O2—C7—C1128.52 (16)C8—C17—C18123.35 (16)
O1—C7—C1110.20 (15)C16—C17—C18117.75 (15)
C8—O1—C7118.14 (13)C17—C18—H181109.5
C17—C8—O1120.33 (14)C17—C18—H182109.5
C17—C8—C9124.77 (14)H181—C18—H182109.5
O1—C8—C9114.83 (14)C17—C18—H183109.5
O3—C9—C10122.82 (15)H181—C18—H183109.5
O3—C9—C8120.89 (15)H182—C18—H183109.5
C10—C9—C8116.28 (14)
C6—C1—C2—C3−0.1 (2)C8—C9—C10—C11177.37 (17)
C7—C1—C2—C3178.82 (14)C15—C10—C11—C121.4 (3)
C1—C2—C3—C4−0.2 (2)C9—C10—C11—C12−178.40 (17)
C2—C3—C4—N−178.97 (15)C10—C11—C12—C13−1.5 (3)
C2—C3—C4—C50.3 (2)C11—C12—C13—C140.3 (3)
N—C4—C5—C6179.17 (15)C12—C13—C14—C150.8 (3)
C3—C4—C5—C6−0.1 (3)C11—C10—C15—C14−0.3 (3)
C4—C5—C6—C1−0.2 (3)C9—C10—C15—C14179.56 (16)
C2—C1—C6—C50.3 (2)C11—C10—C15—C16179.70 (16)
C7—C1—C6—C5−178.65 (15)C9—C10—C15—C16−0.5 (3)
C2—C1—C7—O2−171.14 (16)C13—C14—C15—C10−0.9 (3)
C6—C1—C7—O27.8 (3)C13—C14—C15—C16179.15 (17)
C2—C1—C7—O17.5 (2)C10—C15—C16—O4−179.69 (17)
C6—C1—C7—O1−173.56 (14)C14—C15—C16—O40.3 (3)
O2—C7—O1—C84.8 (2)C10—C15—C16—C171.0 (3)
C1—C7—O1—C8−174.01 (13)C14—C15—C16—C17−179.01 (16)
C7—O1—C8—C1789.9 (2)O1—C8—C17—C16171.84 (14)
C7—O1—C8—C9−92.86 (17)C9—C8—C17—C16−5.1 (3)
C17—C8—C9—O3−175.24 (17)O1—C8—C17—C18−7.0 (3)
O1—C8—C9—O37.7 (2)C9—C8—C17—C18176.11 (16)
C17—C8—C9—C105.5 (3)O4—C16—C17—C8−177.60 (17)
O1—C8—C9—C10−171.56 (14)C15—C16—C17—C81.7 (2)
O3—C9—C10—C15178.30 (17)O4—C16—C17—C181.3 (3)
C8—C9—C10—C15−2.5 (2)C15—C16—C17—C18−179.42 (16)
O3—C9—C10—C11−1.9 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N—H2N···O3i0.95 (3)2.13 (3)2.960 (2)145.6 (19)
N—H1N···O4ii0.89 (2)2.25 (2)3.045 (2)147.3 (19)
Symmetry codes: (i) −x+2, −y+2, −z+1; (ii) x+1, y+1, z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N—H2N···O3i0.95 (3)2.13 (3)2.960 (2)145.6 (19)
N—H1N···O4ii0.89 (2)2.25 (2)3.045 (2)147.3 (19)
Symmetry codes: (i) −x+2, −y+2, −z+1; (ii) x+1, y+1, z+1.
Acknowledgements top

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

references
References top

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Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.