R(30) rectangular rings in 2,5-dioxopiperazine-1,4-di­acetic acid

Molecules of the title 2,5-dioxopiperazinedione derivative, C₈H₁₀N₂O₆, occupy centres of symmetry in the crystal structure. The six-membered ring has an almost planar conformation, with the substituent on nitrogen nearly perpendicular to the ring. The ideal geometry of the isolated mol­ecule, as determined by ab initio HF-LCAO quantum-mechanical calculations, is slightly more puckered than that observed in the solid state. In the crystal structure, a strong hydrogen bond joins neighbouring mol­ecules, thus forming a network of rectangular R₄⁴(30) rings.

S1. Comment

The condensation of amino acids or their esters leads to 2,5-piperazinediones, an important class of nitrogen-containing organic compounds. These cyclic compounds are found in nature as the result of protein degradation (Bray et al., 1991; Steinberg & Lada, 1983) and are also described as antibiotics (Nakatsuka et al., 1983), antitumorals (Arison & Beck, 1973) and models for protein studies (Benedetti et al., 1976; Radding et al., 1980). The dimerization of iminodiacetic acid or its esters leads naturally to N-substituted 2,5-piperazinediones, although the synthesis is generally a low-yield process (Jongkees, 1908; Dubsky & Granacher, 1917; Tapia-Benavides et al., 1997). We have synthesized the title compound, (I), by the cyclization of iminodiacetic acid dimethyl ester in the presence of NiCl₂.

The N-substituted 2,5-piperazinedione molecule occupies a crystallographic centre of symmetry. The six-membered ring has an almost planar conformation (extremely flattened chair), with a weighted average torsion angle of 7.63 (12)° and puckering parameters (Cremer & Pople, 1975) Q, θ and ϕ of 0.067 (2) Å and 7.5 (2) and 0° (Fig. 1). The ideal geometry of the isolated molecule as determined by an ab initio HF-LCAO quantum-mechanical calculation using the GAMESS program (Schmidt et al., 1993) and a 631(d,p) basis set, shows a slightly more puckered conformation, with an average torsion angle within the ring of 13.09°. N,N'-Dimethyldiketopiperazine (Groth, 1969) exhibits a ring conformation close to that of (I), with a weighted average torsion angle of 6.9 (4)°; however, even more puckering has been found, e.g. in 1,6-bis(methoxycarbonylmethyl)-2,5-piperazinedione, for which a weighted average torsion angle of 18.1 (2)° was reported (Tapia-Benavides et al., 1997). Atoms O3 and C2 share the plane of the ring atoms, their deviations from the least-squares plane being 0.087 (4) and 0.086 (4) Å, respectively. The N-substituent is also planar and is almost perpendicular to the ring, the angle between the two least-squares planes being 89.55 (8)°. The C4—N1—C2—C1 torsion angle is −84.4 (2) and the C3—N1—C2—C1 torsion angle is 85.7 (3)°; the corresponding ideal values for the isolated molecule are −84.76 and 81.04°, respectively. The corresponding torsion angles in 1,6-bis(methoxycarbonylmethyl)-2,5-piperazinedione (Tapia-Benavides et al., 1997) are −78.04 and 84.94°.

The large asymmetry in the two carboxy C—O distances [O1—C1 = 1.192 (3) Å and O2—C1 = 1.317 (3) Å] reflects the fact that the H atom is retained by the carboxy group. This H atom is involved in a strong O2—H2···O3(x − 1, −y − 1/2, z − 1/2) hydrogen bond linking the molecules together, with a donor–acceptor distance of 2.726 (3) Å and a D—H···A angle of 166 (3)°. Using graph set analysis (Bernstein et al., 1995) to describe patterns in the hydrogen-bond network, we find rectangular-shaped R₄⁴(30) rings (Fig.2).

S2. Experimental

Iminodiacetic acid was mixed with NiCl₂ in a solution of ethanol and water and heated to 333 K overnight. The solution was left to cool and evaporate slowly at room temperature; after a few months, small single crystals had grown (with a slight green superficial tint caused by impurities). Prior to data collection, Laue photographs were taken from the crystal to appraize its quality.

S3. Refinement

The position of the carboxy H atom was determined from a difference Fourier map and refined freely, with the U_iso value constrained to 1.5U_eq(O). The remaining H atoms were constrained to an ideal geometry and were refined riding on their parent atoms. Examination of the crystal structure with PLATON (Spek, 2003) showed that there are no solvent-accessible voids in the crystal lattice.

Computing details

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. ORTEPII plot (Johnson, 1976) of (I). Displacement ellipsoids are drawn at the 50% level.
	Fig. 2. A view of the extended structure of (I), with hydrogen bonds shown as dashed lines. H atoms not partipating in hydrogen bonding have been omitted for clarity.

2,5-dioxopiperazine-1,4-diacetic acid

Crystal data

C8H10N2O6	F(000) = 240
Mr = 230.18	Dx = 1.618 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 5.5322 (6) Å	Cell parameters from 14 reflections
b = 9.1505 (13) Å	θ = 7.7–13.6°
c = 9.8235 (8) Å	µ = 0.14 mm^−1
β = 108.189 (7)°	T = 293 K
V = 472.44 (9) Å^3	Plate, colourless
Z = 2	0.27 × 0.23 × 0.09 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.045
Radiation source: fine-focus sealed tube	θmax = 25.5°, θmin = 3.1°
Graphite monochromator	h = −6→6
profile data from ω–2θ scans	k = −11→11
2943 measured reflections	l = −11→11
872 independent reflections	3 standard reflections every 180 min
604 reflections with I > 2σ(I)	intensity decay: 3%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0482P)^2 + 0.2592P] where P = (Fo^2 + 2Fc^2)/3
872 reflections	(Δ/σ)max < 0.001
76 parameters	Δρmax = 0.31 e Å^−3
0 restraints	Δρmin = −0.26 e Å^−3

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
O1	−0.3192 (4)	−0.2214 (2)	−0.28891 (19)	0.0692 (7)
O2	−0.3017 (4)	−0.1464 (2)	−0.50026 (18)	0.0611 (6)
H2	−0.411 (7)	−0.221 (4)	−0.528 (3)	0.092*
O3	0.3075 (3)	−0.16118 (19)	−0.10313 (17)	0.0487 (5)
N1	−0.0172 (3)	−0.00327 (19)	−0.14474 (18)	0.0347 (5)
C1	−0.2441 (5)	−0.1380 (3)	−0.3599 (2)	0.0430 (6)
C2	−0.0649 (5)	−0.0134 (3)	−0.2987 (2)	0.0400 (6)
H2A	0.0944	−0.0289	−0.3184	0.048*
H2B	−0.1385	0.0774	−0.3439	0.048*
C3	0.1656 (4)	−0.0844 (2)	−0.0576 (2)	0.0352 (5)
C4	−0.2048 (4)	0.0785 (2)	−0.0999 (2)	0.0387 (6)
H4A	−0.3709	0.0361	−0.1464	0.046*
H4B	−0.2082	0.1779	−0.1347	0.046*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0841 (15)	0.0716 (13)	0.0492 (11)	−0.0344 (12)	0.0168 (10)	−0.0023 (9)
O2	0.0741 (14)	0.0711 (13)	0.0358 (10)	−0.0218 (11)	0.0138 (9)	−0.0109 (9)
O3	0.0485 (10)	0.0551 (11)	0.0444 (10)	0.0151 (8)	0.0174 (8)	−0.0037 (8)
N1	0.0354 (10)	0.0372 (10)	0.0316 (10)	0.0023 (8)	0.0106 (7)	−0.0007 (7)
C1	0.0447 (14)	0.0467 (14)	0.0369 (13)	0.0005 (11)	0.0120 (11)	−0.0042 (11)
C2	0.0454 (14)	0.0420 (13)	0.0335 (12)	−0.0010 (10)	0.0136 (10)	0.0015 (9)
C3	0.0350 (12)	0.0328 (12)	0.0375 (12)	−0.0032 (10)	0.0108 (10)	−0.0022 (9)
C4	0.0373 (13)	0.0399 (13)	0.0378 (12)	0.0052 (10)	0.0102 (10)	0.0005 (9)

Geometric parameters (Å, º)

O1—C1	1.192 (3)	C1—C2	1.507 (3)
O2—C1	1.317 (3)	C2—H2A	0.9700
O2—H2	0.89 (4)	C2—H2B	0.9700
O3—C3	1.236 (3)	C3—C4^i	1.495 (3)
N1—C3	1.329 (3)	C4—H4A	0.9700
N1—C2	1.455 (3)	C4—H4B	0.9700
C1—O2—H2	106 (2)	C1—C2—H2B	109.6
C3—N1—C2	119.23 (19)	H2A—C2—H2B	108.1
C3—N1—C4	124.31 (18)	O3—C3—N1	121.7 (2)
C2—N1—C4	115.65 (17)	O3—C3—C4^i	119.4 (2)
O1—C1—O2	124.1 (2)	N1—C3—C4^i	118.8 (2)
O1—C1—C2	123.8 (2)	N1—C4—C3^i	116.46 (18)
O2—C1—C2	112.1 (2)	N1—C4—H4A	108.2
N1—C2—C1	110.26 (18)	C3^i—C4—H4A	108.2
N1—C2—H2A	109.6	N1—C4—H4B	108.2
C1—C2—H2A	109.6	C3^i—C4—H4B	108.2
N1—C2—H2B	109.6	H4A—C4—H4B	107.3
C3—N1—C2—C1	85.7 (3)	C4—N1—C3—O3	174.0 (2)
C4—N1—C2—C1	−84.4 (2)	C2—N1—C3—C4^i	−177.1 (2)
O1—C1—C2—N1	−5.0 (4)	C4—N1—C3—C4^i	−7.9 (4)
O2—C1—C2—N1	176.95 (19)	C3—N1—C4—C3^i	7.7 (4)
C2—N1—C3—O3	4.8 (3)	C2—N1—C4—C3^i	177.29 (19)

Symmetry code: (i) −x, −y, −z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O3^ii	0.89 (4)	1.85 (4)	2.726 (3)	166 (3)

Symmetry code: (ii) x−1, −y−1/2, z−1/2.