(2S,3R)-2-[(4-Ethyl-2,3-dioxopiperazin-1-yl)carbonyl­amino]-3-hydroxy­butyric acid monohydrate

Chun-xiang Ji; Yong-tao Cui; Dong-ling Yang; Cheng Guo

doi:10.1107/S1600536808017832

. 2008 Jun 19;64(Pt 7):o1292. doi: 10.1107/S1600536808017832

(2S,3R)-2-[(4-Ethyl-2,3-dioxopiperazin-1-yl)carbonylamino]-3-hydroxybutyric acid monohydrate

Chun-xiang Ji ^a, Yong-tao Cui ^a, Dong-ling Yang ^b, Cheng Guo ^a,^*

PMCID: PMC2961655 PMID: 21202922

Abstract

In the title compound, C₁₁H₁₇N₃O₆·H₂O, an important building block of the medicine cefbuperazone sodium, the piperazine ring adopts a screw-boat conformation. Intermolecular O—H⋯O and intramolecular N—H⋯O hydrogen bonds are observed. The water molecule participates as both donor and acceptor in this framework.

Related literature

For related literature, see: Anger et al. (2001 ▶); Özcan et al. (2003 ▶); Rondu et al. (1997 ▶); Saikawa et al. (1981 ▶).

Experimental

Crystal data

C₁₁H₁₇N₃O₆·H₂O
M _r = 305.29
Orthorhombic,
a = 9.4640 (19) Å
b = 11.389 (2) Å
c = 13.611 (3) Å
V = 1467.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.12 mm⁻¹
T = 293 (2) K
0.40 × 0.30 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.955, T _max = 0.977
1519 measured reflections
1519 independent reflections
1287 reflections with I > 2σ(I)
3 standard reflections every 200 reflections intensity decay: <1%

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.105
S = 1.04
1519 reflections
205 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ▶); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808017832/bh2173sup1.cif

e-64-o1292-sup1.cif^{(18KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808017832/bh2173Isup2.hkl

e-64-o1292-Isup2.hkl^{(74.9KB, 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
N3—H3A⋯O2	0.86	1.99	2.647 (3)	132
O7—H7A⋯O2	0.85 (2)	1.98 (2)	2.817 (4)	169 (5)
O4—H4⋯O7ⁱ	0.75 (5)	1.85 (5)	2.593 (4)	170 (5)
O6—H6⋯O1ⁱⁱ	0.83 (4)	1.95 (4)	2.772 (3)	167 (4)
O7—H7B⋯O6ⁱⁱⁱ	0.815 (19)	2.07 (3)	2.803 (4)	149 (4)

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

supplementary crystallographic information

Comment

Some derivatives of piperazine are important chemical materials (Saikawa et al., 1981) with pharmaceutical properties (Rondu et al., 1997) for example against migraine, and are calcium channel antagonist (Anger et al., 2001). As part of our studies in this area, we report here the crystal structure of the title compound, (I).

The refined molecular structure of (I) is shown in Fig. 1. The title compound includes a piperzaine and a threonine moieties, and the asymmetric unit is completed by one lattice water molecule. The piperazine ring adopts a screw-boat conformation with atoms C4 and C6 displaced by 0.104 (8) and 0.596 (2) Å, respectively, from the mean plane through atoms N1, C3, N2 and C5. The dihedral angle between N1/C3/N2/C5 and N2/C7/N3/C8 planes is 4.1°.

The threonine molecular group has two chiral atoms, C8 and C10, and adopts a configuration in agreement with previous reports (e.g. Özcan et al., 2003). The separation O6···O1 suggests an interaction between the ketone and the carboxyl group (Table 1). The water molecule is linked to the main molecule via O—H···O hydrogen bonds. These hydrogen bonds are effective in the stabilization of the crystal structure.

Experimental

To a suspension of 2.0 g of L-threonine [(2S,3R)-2-amino-3-hydroxybutanoic acid] in methylene chloride (50 ml), 6.6 ml of trimethylchlorosilane were added, after which 7.1 ml of triethylamine were added dropwise at 273 K. The mixture was heated to 293 K for 2 h, and then a mixture of 4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride and triethylamine was added to the reaction mixture. After stirring for 1 h, the solvent was removed under reduced pressure. To the residue, 30 ml of water was added, and the pH was adjusted to 8 with NaHCO₃, after which the solution was washed with 50 ml of ethyl acetate. Acetonitrile (50 ml) was added to the solution. The pH of the mixture was adjusted to 1 with HCl. The mixture was then saturated with NaCl, and the acetonitrile layer was thereafter separated. The aqueous layer was extracted with acetonitrile (3 × 50 ml), the combined acetonitrile layers were washed with saturated NaCl, and then distilled in vacuo to remove the solvent. The residue was recrystallized from ethanol to obtain 3.2 g of (I). Crystals of (I) suitable for X-ray diffraction were obtained by slow evaporation of an ethanol solution. ¹H NMR (DMSO): δ 3.78–4.30 (m, 4H), 3.28–3.75 (m, 4H), 1.13 (d, 3H), 1.11 (t, 3H).