1,4-Dihydroxy­quinoxaline-2,3(1H,4H)-dione

Abstract

The asymmetric unit of the title compound, C₈H₆N₂O₄, contains one half-mol­ecule; a twofold rotation axis bisects the molecule. The quinoxaline ring is planar, which can be attributed to electron delocalization. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into R ₂ ²(10) motifs, leading to layers, which inter­act via phen­yl–phenyl inter­actions (C⋯C distances in the range 3.238–3.521 Å).

Related literature

For general background, see: Zarranz et al. (2004 ▶); Chowdhury et al. (2004 ▶); Monge et al. (1995 ▶); Fuchs et al. (2001 ▶); Dance (1996 ▶); Bernstein et al. (1995 ▶). For related literature, see: Elina & Tsyrul’nikova (1963 ▶); Akkurt et al. (2004 ▶); Mustaphi et al. (2001 ▶); Oxtoby et al. (2005 ▶); Ley & Seng (1975 ▶); For bond-length data, see: Allen et al. (1987 ▶);

Experimental

Crystal data

• C₈H₆N₂O₄

• M _r = 194.15

• Orthorhombic,

• a = 4.2562 (6) Å

• b = 17.630 (3) Å

• c = 10.4775 (17) Å

• V = 786.2 (2) ų

• Z = 4

• Mo Kα radiation

• μ = 0.14 mm⁻¹

• T = 294 (2) K

• 0.50 × 0.20 × 0.10 mm

Data collection

• Nicolet P3 diffractometer

• Absorption correction: none

• 1004 measured reflections

• 529 independent reflections

• 437 reflections with I > 2σ(I)

• R _int = 0.022

• 3 standard reflections every 50 reflections intensity decay: 2%

Refinement

• R[F ² > 2σ(F ²)] = 0.034

• wR(F ²) = 0.071

• S = 1.07

• 529 reflections

• 69 parameters

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.12 e Å⁻³

• Δρ_min = −0.15 e Å⁻³

Data collection: P3/PC Data Collection Software (Siemens, 1991 ▶); cell refinement: P3/PC Data Collection Software; data reduction: SHELXTL-Plus (Sheldrick, 2008 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL-Plus; software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003 ▶).

Supplementary Material

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
O1—H1⋯O2i	0.96 (3)	1.63 (3)	2.584 (2)	174 (3)

Symmetry code: (i) .

supplementary crystallographic information

Comment

Quinoxalines are of interest owing to their biological activities. They seem to have very interesting anticancer activity (Zarranz et al., 2004). For example, 3-aminoquinoxaline-2-carbonitrile 1,4-dioxide have been studied extensively as bioreductive cytotoxic agent. It was found to be an efficient agent and causes redox-activated DNA damage (Chowdhury et al., 2004), even more active than the first drug clinically used as bioreductive cytotoxic agent (Monge et al., 1995; Fuchs et al., 2001). A nonconvenient synthesis of the title compound, (I), was reported previously (Elina & Tsyruľ nikova, 1963), via the hydrolysis of 2-amino-3-hydroxyquinoxaline 1,4-dioxide, which results as a side product (4%) from oxidation of 2-acetamidoquinoxaline with acetic peroxide acid using boiling HCl solution. We report herein a novel simple synthetic method for (I), along with its crystal structure.

The new synthetic strategy for (I), (Fig. 1), is based on the reaction of (1) with NaOH solution, yielding (2) in an S_NAr reaction, which upon hydrolysis with boiling HCl solution, via protonation of amine followed by the attack of water molecule, yielded (I) in a good amount (90%).

The asymmetric unit of the title compound, (I), (Fig. 2) contains one half-molecule. The quinoxaline ring is planar, which can be attributed to a wide range of electron delocalization. Bond lengths and angles are in accordance with the corresponding reported values in 1,4-dihydroquinoxaline -2,3-dione core (Oxtoby et al., 2005) and other similar N-alkyl quinoxalines (Akkurt et al., 2004; Mustaphi et al., 2001). The existence of (I) in the dione form is evident from C1—O2 [1.226 (3) Å] bond, being smaller than a pure single bond, which confirms the double bond character (Allen et al., 1987). The C1—C1ⁱ [1.503 (4) Å] bond has single bond character compared to multiple bond characters in C2—C2ⁱ [1.381 (4) Å], C2—C3 [1.391 (3) Å], C3—C4 [1.382 (3) Å] and C4—C4ⁱ [1.372 (6) Å] [symmetry code: (i) -x, y, 1/2 - z]. The N1—C1 [1.345 (3) Å] bond is significantly shorter than N1—C2 [1.404 (3) Å] and it is an intermediate between those typical for the corresponding single and double bonds, suggesting some degree of delocalization. The N1—C1 bond length is closer to the average C_ar—N_sp² (planar) value of 1.353 (7) Å rather than the C_ar—N_sp³ (pyramidal) value of 1.419 (17) Å (Allen et al., 1987), with the sum of the bond angles around atom N1 [359.81 (18)°], indicating sp² hybridization.

In the crystal structure, intermolecular O—H···O hydrogen bonds (Table 1) link the molecules into R₂²(10) motifs (Fig. 3) (Bernstein et al., 1995) leading to layers running along the c axis (Fig. 4). Molecules within layers are further interacting via phenyl···phenyl interactions (Dance, 1996), where the layers parallel to a axis interact in an offset stacking motif (C···C distances in the range of 3.238–3.521 Å).

Experimental

For the preparation of (I), to a suspension solution of (1) (2.02 g, 10 mmol) (Ley & Seng, 1975) in ethanol (20 ml), NaOH (20 ml, 10%) was added to give a deep blue solution. After refluxing for 5 h, the brown solution was allowed to cool to room temperature. The resulting mixture was then treated with HCl (30 ml, 10%), refluxed for another 5 h and then allowed to stand undisturbed. The resulting residual brown solid was filtered off, washed with cold water (5 ml) and then by cold ethanol (5 ml). The title compound, (I), was recrystallized from ethanol solution (yield; 1.76 g, 90%, m.p. 535–536 K decomposition). Analysis found: C 49.45, H 3.27, N 14.41%; C₈H₆N₂O₄ requires: C 49.49, H 3.12, N 14.43%. ¹H NMR (300 MHz, DMSO-d₆): δ = 7.36 (m, 2H; H4/H7), 7.56 (m, 2H; H5/H6); ¹³C NMR (75 MHz, DMSO-d₆): δ = 111.6 (C4/C7), 123.3 (C5/C6), 124.0 (C4a/C7a), 150.4 (C2/C3) p.p.m.. ESI: m/z = 217.02 (C₈H₆N₂O₄Na).

Refinement

H atom (for OH) was located in a difference synthesis and refined isotropically [O—H = 0.96 (3) Å; U_iso(H) = 0.072 (10) Ų]. The remaining H atoms were positioned geometrically, with C—H = 0.93 Å for aromatic H and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C).

Figures

Fig. 1.

Schematic representation for the steps through which reaction proceeds.

Fig. 2.

The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.

Fig. 3.

Part of the crystal structure of (I), showing the formation of R22(10) motifs.

Fig. 4.

A packing diagram of (I), showing the layers of molecules parallel to c axis. All hydrogen atoms were omitted for clarity. Hydrogen bonds are shown as dashed lines [symmetry codes: (i) -x, y, -z + 1/2, (ii) x, -y + 1, -z].

Crystal data

C8H6N2O4	F000 = 400
Mr = 194.15	Dx = 1.640 Mg m−3
Orthorhombic, C2221	Mo Kα radiation λ = 0.71073 Å
Hall symbol: C 2c 2	Cell parameters from 20 reflections
a = 4.2562 (6) Å	θ = 14–16º
b = 17.630 (3) Å	µ = 0.14 mm−1
c = 10.4775 (17) Å	T = 294 (2) K
V = 786.2 (2) Å3	Plates, colourless
Z = 4	0.50 × 0.20 × 0.10 mm

Data collection

Nicolet P3 diffractometer	Rint = 0.022
Radiation source: fine-focus sealed tube	θmax = 27.0º
Monochromator: graphite	θmin = 2.3º
T = 294(2) K	h = 0→5
Wyckoff scan	k = 0→22
Absorption correction: none	l = −13→13
1004 measured reflections	3 standard reflections
529 independent reflections	every 50 reflections
437 reflections with I > 2σ(I)	intensity decay: 2%

Refinement

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.034	w = 1/[σ2(Fo2) + (0.0208P)2 + 0.4073P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.071	(Δ/σ)max < 0.001
S = 1.07	Δρmax = 0.12 e Å−3
529 reflections	Δρmin = −0.15 e Å−3
69 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.013 (2)
Secondary atom site location: difference Fourier map

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 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 > σ(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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.2116 (4)	0.41727 (11)	0.15388 (16)	0.0350 (5)
C1	0.1130 (6)	0.48556 (11)	0.1948 (2)	0.0364 (6)
O1	0.4527 (4)	0.41624 (10)	0.06569 (15)	0.0456 (5)
H1	0.357 (7)	0.4338 (15)	−0.012 (3)	0.072 (10)*
C2	0.1068 (5)	0.34702 (11)	0.2004 (2)	0.0332 (5)
O2	0.1965 (5)	0.54622 (9)	0.14878 (15)	0.0531 (6)
C3	0.2131 (7)	0.27901 (13)	0.1487 (2)	0.0456 (7)
H3	0.3541	0.2788	0.0808	0.055*
C4	0.1046 (7)	0.21177 (13)	0.2002 (2)	0.0557 (8)
H4	0.1745	0.1659	0.1669	0.067*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
N1	0.0369 (10)	0.0401 (9)	0.0279 (8)	0.0022 (10)	0.0011 (9)	−0.0011 (8)
C1	0.0452 (15)	0.0371 (12)	0.0269 (10)	−0.0036 (11)	−0.0014 (13)	−0.0019 (9)
O1	0.0416 (9)	0.0631 (10)	0.0320 (8)	0.0113 (10)	0.0045 (9)	0.0052 (9)
C2	0.0354 (14)	0.0334 (10)	0.0309 (10)	0.0004 (10)	−0.0096 (12)	−0.0007 (8)
O2	0.0823 (16)	0.0374 (8)	0.0397 (9)	−0.0123 (10)	0.0136 (13)	0.0017 (7)
C3	0.0519 (16)	0.0435 (13)	0.0415 (13)	0.0099 (13)	−0.0118 (16)	−0.0077 (10)
C4	0.072 (2)	0.0336 (11)	0.0615 (16)	0.0086 (13)	−0.0242 (18)	−0.0079 (11)

Geometric parameters (Å, °)

N1—C1	1.345 (3)	C2—C2i	1.381 (4)
N1—O1	1.381 (2)	C2—C3	1.391 (3)
N1—C2	1.404 (3)	C3—C4	1.382 (3)
C1—O2	1.226 (3)	C3—H3	0.9300
C1—C1i	1.503 (4)	C4—C4i	1.372 (6)
O1—H1	0.96 (3)	C4—H4	0.9300
C1—N1—O1	117.21 (19)	C2i—C2—N1	118.08 (11)
C1—N1—C2	125.42 (18)	C3—C2—N1	121.5 (2)
O1—N1—C2	117.18 (18)	C4—C3—C2	118.6 (2)
O2—C1—N1	124.4 (2)	C4—C3—H3	120.7
O2—C1—C1i	119.22 (14)	C2—C3—H3	120.7
N1—C1—C1i	116.41 (12)	C4i—C4—C3	120.93 (16)
N1—O1—H1	104.2 (17)	C4i—C4—H4	119.5
C2i—C2—C3	120.47 (15)	C3—C4—H4	119.5
O1—N1—C1—O2	8.8 (3)	C1—N1—C2—C3	177.4 (2)
C2—N1—C1—O2	−176.4 (2)	O1—N1—C2—C3	−7.8 (3)
O1—N1—C1—C1i	−170.8 (2)	C2i—C2—C3—C4	−1.1 (4)
C2—N1—C1—C1i	4.1 (4)	N1—C2—C3—C4	178.9 (2)
C1—N1—C2—C2i	−2.5 (4)	C2—C3—C4—C4i	0.3 (5)
O1—N1—C2—C2i	172.3 (2)

Symmetry codes: (i) −x, y, −z+1/2.

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ii	0.96 (3)	1.63 (3)	2.584 (2)	174 (3)

Symmetry codes: (ii) x, −y+1, −z.