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

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.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.042
• wR factor = 0.106
• Data-to-parameter ratio = 7.4

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.41
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          5
PLAT369_ALERT_2_C Long   C(sp2)-C(sp2) Bond  C3     -   C4     ...       1.54 Ang.
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.14
           From the CIF: _reflns_number_total               1519
           Count of symmetry unique reflns         1519
           Completeness (_total/calc)            100.00%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          2
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C8     ...          S
PLAT791_ALERT_4_G Confirm the Absolute Configuration of C10    ...          R

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   6 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. 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.

Related literature

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

S2. 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).

S3. Refinement

Hydroxyl H atoms were located in a difference map and refined freely. Water H atoms were found in a difference map and refined with a restrained geometry, O—H = 0.84 (2) Å. Other H atoms were positioned geometrically and refined using a riding model, with C—H = 0.96-0.98 Å, N—H = 0.86 Å and U_iso(H) = 1.2 or 1.5 U_eq of the carrier atom. Friedel pairs were merged and the absolute configuration was assigned from starting materials.

Computing details

Data collection: CAD–4 Software (Enraf–Nonius, 1989); cell refinement: CAD–4 Software (Enraf–Nonius, 1989); 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).

Figures

	Fig. 1. A view of the molecular structure of (I), showing displacement ellipsoids at the 30% probability level. Dashed lines indicate O—H···O and N—H···O hydrogen bonds.
	Fig. 2. A packing diagram for (I). Hydrogen bonds are shown as dashed lines.

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

Crystal data

C11H17N3O6·H2O	F(000) = 648
Mr = 305.29	Dx = 1.382 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 25 reflections
a = 9.4640 (19) Å	θ = 10–13°
b = 11.389 (2) Å	µ = 0.12 mm^−1
c = 13.611 (3) Å	T = 293 K
V = 1467.1 (5) Å^3	Block, colourless
Z = 4	0.40 × 0.30 × 0.20 mm

Data collection

Enraf–Nonius CAD-4 diffractometer	1287 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Graphite monochromator	θmax = 25.1°, θmin = 2.3°
ω/2θ scans	h = 0→11
Absorption correction: ψ scan (North et al., 1968)	k = 0→13
Tmin = 0.955, Tmax = 0.977	l = 0→16
1519 measured reflections	3 standard reflections every 200 reflections
1519 independent reflections	intensity decay: <1%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.105	w = 1/[σ^2(Fo^2) + (0.0652P)^2 + 0.1558P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max < 0.001
1519 reflections	Δρmax = 0.16 e Å^−3
205 parameters	Δρmin = −0.16 e Å^−3
2 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.037 (4)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.2982 (5)	0.8688 (4)	0.3149 (3)	0.0802 (14)
H1A	0.2231	0.9061	0.2793	0.120*
H1B	0.3779	0.9207	0.3183	0.120*
H1C	0.2666	0.8505	0.3802	0.120*
C2	0.3399 (4)	0.7585 (3)	0.2637 (3)	0.0517 (9)
H2A	0.2588	0.7066	0.2601	0.062*
H2B	0.3683	0.7771	0.1970	0.062*
C3	0.5900 (3)	0.7122 (3)	0.2851 (2)	0.0401 (7)
C4	0.7064 (3)	0.6501 (3)	0.3450 (2)	0.0385 (7)
C5	0.5156 (3)	0.5303 (3)	0.4161 (3)	0.0549 (10)
H5A	0.4893	0.4738	0.3659	0.066*
H5B	0.4997	0.4945	0.4798	0.066*
C6	0.4272 (3)	0.6364 (3)	0.4065 (3)	0.0544 (9)
H6B	0.3282	0.6145	0.4091	0.065*
H6C	0.4461	0.6891	0.4609	0.065*
C7	0.7632 (3)	0.4841 (3)	0.4570 (2)	0.0403 (7)
C8	1.0033 (3)	0.4380 (3)	0.5054 (2)	0.0373 (7)
H8A	0.9525	0.4006	0.5598	0.045*
C9	1.1128 (3)	0.5210 (3)	0.5489 (2)	0.0390 (7)
C10	1.0768 (3)	0.3423 (3)	0.4465 (2)	0.0425 (7)
H10A	1.1384	0.2984	0.4913	0.051*
C11	0.9774 (4)	0.2570 (3)	0.3990 (3)	0.0570 (9)
H11A	1.0306	0.1992	0.3633	0.085*
H11B	0.9161	0.2982	0.3547	0.085*
H11C	0.9219	0.2188	0.4487	0.085*
N1	0.4564 (2)	0.6970 (2)	0.31326 (19)	0.0416 (7)
N2	0.6683 (3)	0.5610 (2)	0.4054 (2)	0.0397 (6)
N3	0.9022 (2)	0.5055 (2)	0.44847 (19)	0.0383 (6)
H3A	0.9314	0.5594	0.4091	0.046*
O1	0.6257 (2)	0.7700 (3)	0.21398 (19)	0.0635 (8)
O2	0.8292 (2)	0.6821 (2)	0.33274 (19)	0.0534 (7)
O3	0.7145 (3)	0.4047 (2)	0.5047 (2)	0.0648 (8)
O4	1.1991 (3)	0.4638 (2)	0.6080 (2)	0.0654 (8)
H4	1.254 (6)	0.501 (4)	0.632 (3)	0.072 (15)*
O5	1.1208 (2)	0.6236 (2)	0.53094 (18)	0.0506 (6)
O6	1.1642 (3)	0.4009 (2)	0.3763 (2)	0.0600 (7)
H6	1.217 (5)	0.354 (4)	0.347 (3)	0.064 (12)*
O7	0.9118 (3)	0.9195 (3)	0.3221 (2)	0.0663 (8)
H7A	0.894 (5)	0.847 (2)	0.332 (3)	0.080*
H7B	0.909 (5)	0.937 (4)	0.2641 (17)	0.080*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.071 (3)	0.088 (3)	0.081 (3)	0.038 (3)	−0.034 (3)	−0.023 (3)
C2	0.0347 (16)	0.063 (2)	0.057 (2)	0.0056 (17)	−0.0130 (16)	−0.0023 (18)
C3	0.0329 (15)	0.0434 (17)	0.0441 (17)	0.0010 (14)	0.0026 (14)	0.0032 (15)
C4	0.0277 (15)	0.0402 (16)	0.0476 (17)	−0.0004 (13)	0.0058 (14)	0.0067 (15)
C5	0.0280 (15)	0.056 (2)	0.081 (3)	−0.0076 (15)	0.0075 (17)	0.017 (2)
C6	0.0271 (15)	0.067 (2)	0.069 (2)	−0.0013 (16)	0.0102 (17)	0.016 (2)
C7	0.0325 (15)	0.0342 (15)	0.0541 (18)	−0.0024 (13)	0.0063 (15)	0.0054 (16)
C8	0.0310 (14)	0.0399 (15)	0.0410 (15)	−0.0004 (14)	−0.0004 (13)	0.0091 (15)
C9	0.0337 (15)	0.0446 (17)	0.0389 (16)	0.0053 (14)	0.0036 (14)	−0.0016 (14)
C10	0.0366 (15)	0.0394 (16)	0.0515 (17)	0.0076 (15)	−0.0094 (16)	−0.0010 (15)
C11	0.051 (2)	0.0486 (18)	0.071 (2)	0.0071 (17)	−0.016 (2)	−0.0059 (19)
N1	0.0261 (12)	0.0516 (16)	0.0471 (15)	0.0005 (11)	0.0009 (12)	0.0043 (13)
N2	0.0228 (11)	0.0387 (13)	0.0577 (15)	−0.0007 (11)	0.0055 (12)	0.0078 (13)
N3	0.0283 (12)	0.0399 (14)	0.0468 (14)	0.0006 (11)	0.0037 (12)	0.0092 (12)
O1	0.0382 (13)	0.0902 (19)	0.0622 (14)	0.0059 (13)	0.0057 (12)	0.0350 (15)
O2	0.0280 (11)	0.0555 (14)	0.0765 (16)	0.0003 (11)	0.0077 (12)	0.0252 (13)
O3	0.0400 (13)	0.0541 (15)	0.100 (2)	−0.0055 (12)	0.0030 (14)	0.0349 (15)
O4	0.0657 (18)	0.0583 (16)	0.0722 (18)	−0.0039 (15)	−0.0344 (16)	0.0042 (14)
O5	0.0444 (13)	0.0402 (12)	0.0672 (15)	−0.0013 (11)	0.0009 (12)	−0.0009 (12)
O6	0.0441 (13)	0.0687 (17)	0.0672 (16)	0.0033 (14)	0.0184 (13)	−0.0123 (14)
O7	0.0633 (16)	0.0645 (16)	0.0710 (16)	−0.0032 (15)	0.0206 (16)	−0.0012 (16)

Geometric parameters (Å, º)

C1—C2	1.491 (5)	C7—N3	1.343 (4)
C1—H1A	0.9600	C7—N2	1.438 (4)
C1—H1B	0.9600	C8—N3	1.451 (4)
C1—H1C	0.9600	C8—C10	1.521 (4)
C2—N1	1.470 (4)	C8—C9	1.522 (4)
C2—H2A	0.9700	C8—H8A	0.9800
C2—H2B	0.9700	C9—O5	1.196 (4)
C3—O1	1.218 (4)	C9—O4	1.319 (4)
C3—N1	1.333 (4)	C10—O6	1.430 (4)
C3—C4	1.542 (4)	C10—C11	1.499 (5)
C4—O2	1.229 (3)	C10—H10A	0.9800
C4—N2	1.354 (4)	C11—H11A	0.9600
C5—C6	1.476 (5)	C11—H11B	0.9600
C5—N2	1.495 (4)	C11—H11C	0.9600
C5—H5A	0.9700	N3—H3A	0.8600
C5—H5B	0.9700	O4—H4	0.75 (5)
C6—N1	1.470 (4)	O6—H6	0.83 (4)
C6—H6B	0.9700	O7—H7A	0.85 (2)
C6—H6C	0.9700	O7—H7B	0.815 (19)
C7—O3	1.205 (4)
C2—C1—H1A	109.5	N3—C8—C10	113.6 (2)
C2—C1—H1B	109.5	N3—C8—C9	109.1 (2)
H1A—C1—H1B	109.5	C10—C8—C9	109.8 (2)
C2—C1—H1C	109.5	N3—C8—H8A	108.1
H1A—C1—H1C	109.5	C10—C8—H8A	108.1
H1B—C1—H1C	109.5	C9—C8—H8A	108.1
N1—C2—C1	112.7 (3)	O5—C9—O4	124.6 (3)
N1—C2—H2A	109.1	O5—C9—C8	124.8 (3)
C1—C2—H2A	109.1	O4—C9—C8	110.6 (3)
N1—C2—H2B	109.1	O6—C10—C11	112.2 (3)
C1—C2—H2B	109.1	O6—C10—C8	106.4 (3)
H2A—C2—H2B	107.8	C11—C10—C8	113.9 (3)
O1—C3—N1	124.2 (3)	O6—C10—H10A	108.1
O1—C3—C4	118.0 (3)	C11—C10—H10A	108.1
N1—C3—C4	117.8 (3)	C8—C10—H10A	108.1
O2—C4—N2	123.8 (3)	C10—C11—H11A	109.5
O2—C4—C3	117.8 (3)	C10—C11—H11B	109.5
N2—C4—C3	118.3 (2)	H11A—C11—H11B	109.5
C6—C5—N2	110.3 (3)	C10—C11—H11C	109.5
C6—C5—H5A	109.6	H11A—C11—H11C	109.5
N2—C5—H5A	109.6	H11B—C11—H11C	109.5
C6—C5—H5B	109.6	C3—N1—C2	121.2 (3)
N2—C5—H5B	109.6	C3—N1—C6	119.2 (3)
H5A—C5—H5B	108.1	C2—N1—C6	118.6 (2)
N1—C6—C5	110.7 (3)	C4—N2—C7	125.9 (2)
N1—C6—H6B	109.5	C4—N2—C5	119.5 (3)
C5—C6—H6B	109.5	C7—N2—C5	114.4 (2)
N1—C6—H6C	109.5	C7—N3—C8	120.2 (3)
C5—C6—H6C	109.5	C7—N3—H3A	119.9
H6B—C6—H6C	108.1	C8—N3—H3A	119.9
O3—C7—N3	123.9 (3)	C9—O4—H4	115 (4)
O3—C7—N2	118.8 (3)	C10—O6—H6	111 (3)
N3—C7—N2	117.3 (3)	H7A—O7—H7B	113 (5)
O1—C3—C4—O2	16.1 (5)	C1—C2—N1—C6	72.6 (4)
N1—C3—C4—O2	−165.3 (3)	C5—C6—N1—C3	−44.8 (4)
O1—C3—C4—N2	−161.7 (3)	C5—C6—N1—C2	146.7 (3)
N1—C3—C4—N2	16.9 (4)	O2—C4—N2—C7	−6.0 (5)
N2—C5—C6—N1	55.3 (4)	C3—C4—N2—C7	171.7 (3)
N3—C8—C9—O5	−6.4 (4)	O2—C4—N2—C5	179.1 (3)
C10—C8—C9—O5	118.6 (3)	C3—C4—N2—C5	−3.2 (4)
N3—C8—C9—O4	174.5 (3)	O3—C7—N2—C4	−176.4 (3)
C10—C8—C9—O4	−60.4 (3)	N3—C7—N2—C4	3.4 (5)
N3—C8—C10—O6	67.5 (3)	O3—C7—N2—C5	−1.3 (5)
C9—C8—C10—O6	−54.9 (3)	N3—C7—N2—C5	178.5 (3)
N3—C8—C10—C11	−56.5 (4)	C6—C5—N2—C4	−32.7 (5)
C9—C8—C10—C11	−179.0 (3)	C6—C5—N2—C7	151.8 (3)
O1—C3—N1—C2	−5.0 (5)	O3—C7—N3—C8	−5.7 (5)
C4—C3—N1—C2	176.5 (3)	N2—C7—N3—C8	174.5 (2)
O1—C3—N1—C6	−173.2 (3)	C10—C8—N3—C7	101.8 (3)
C4—C3—N1—C6	8.3 (4)	C9—C8—N3—C7	−135.4 (3)
C1—C2—N1—C3	−95.7 (4)

Hydrogen-bond geometry (Å, º)

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···O7^i	0.75 (5)	1.85 (5)	2.593 (4)	170 (5)
O6—H6···O1^ii	0.83 (4)	1.95 (4)	2.772 (3)	167 (4)
O7—H7B···O6^iii	0.82 (2)	2.07 (3)	2.803 (4)	149 (4)

Symmetry codes: (i) x+1/2, −y+3/2, −z+1; (ii) −x+2, y−1/2, −z+1/2; (iii) −x+2, y+1/2, −z+1/2.