2-[3,5-Dioxo-4-(pyridin-3-yl)piperazin-1-yl]acetic acid

Mosslemin, M.H.

doi:10.1107/S1600536812003455

organic compounds

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Volume 68| Part 3| March 2012| Page o583

doi:10.1107/S1600536812003455

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2-[3,5-Dioxo-4-(pyridin-3-yl)piperazin-1-yl]acetic acid

Mohammad Hossein Mosslemin ^a ^*

^aDepartment of Chemistry, Yazd Branch, Islamic Azad University, PO Box 89195-155, Yazd, Iran
^*Correspondence e-mail: mhmosslemin@yahoo.com

(Received 21 January 2012; accepted 26 January 2012; online 4 February 2012)

In the title compound, C₁₁H₁₁N₃O₄, the 3,5-dioxopiperazine ring adopts an envelope conformation, with the N atom connecting to the –CH₂COOH group on the flap. In the crystal, molecules are linked by O—H⋯N hydrogen bonds to produce a linear chain running along the c axis. π–π stacking is observed between parallel pyridine rings of adjacent molecules, the centroid–centroid distance being 3.834 (2) Å.

Related literature

For the pharmaceutical activity, see: Parcel (1961 ); Creighton et al. (1969 ); Hasinoff et al. (1998 ). For related structures, see: Hasinoff et al. (2004 ); Mancilla et al. (2002 ); Skrzypczak-Jankun et al. (1999 ); Hempel et al. (1981 ); Jolley et al. (1999 ); Liu et al. (1998 ); Davies et al. (1998 ); Smith et al. (1992 ).

Experimental

Crystal data

C₁₁H₁₁N₃O₄
M_r = 249.23
Orthorhombic, P b c a
a = 12.762 (2) Å
b = 7.9495 (10) Å
c = 22.218 (3) Å
V = 2254.0 (6) Å³
Z = 8
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 298 K
0.3 × 0.07 × 0.06 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.986, T_max = 0.996
5235 measured reflections
2181 independent reflections
1355 reflections with I > 2σ(I)
R_int = 0.082

Refinement

R[F² > 2σ(F²)] = 0.083
wR(F²) = 0.139
S = 1.13
2181 reflections
167 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N1ⁱ	0.83 (3)	1.83 (3)	2.655 (4)	173 (5)
Symmetry code: (i) $[x, -y+{\script{5\over 2}}, z+{\script{1\over 2}}]$ .

Data collection: SMART (Bruker, 2007 ); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536812003455/xu5454sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812003455/xu5454Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812003455/xu5454Isup3.cml

checkCIF report

Comment top

The interest in derivatives of piperazine-2,6-dione has significantly increased because of their practical usage. Some piperazine-2,6-diones were found to have pharmaceutical activity (Parcel, 1961). In this regard, piperazine-2,6-diones have been studied for the anticancerous activity, an interaction with other anticancerous drugs and sensitivity to radiation (Creighton et al., 1969; Hasinoff, et al., 1998). In spite of the importance of these compounds, at present, only 12 crystal structures of piperazines are available in the literature, (Hasinoff et al., 2004; Mancilla et al., 2002; Skrzypczak-Jankun et al., 1999; Hempel et al., 1981; Jolley et al., 1999; Liu et al., 1998; Davies et al., 1998 and Smith et al., 1992). Here, we report the synthesis and characterization of the title compound, I.

In this molecule, the six membered piperazine-2,6-dionering has an envelope conformation with the N3 atom out of plane. The dihedral angle between the pyridine ring and the five-atom planar portion of the piperazine-2,6-dione ring is 77.9 (9)°. Also, the angle between mean plane containing acetic acid moiety and pyridine ring is 15.7 (8)°. As it is clear from figure 2, in the crystal packing of title molecule, the intermolecular O—H···N hydrogen bonds (Table 1) seem to be effective in the stabilization of the crystal structure.

Related literature top

For the pharmaceutical activity, see: Parcel (1961); Creighton et al. (1969); Hasinoff et al. (1998). For related structures, see: Hasinoff et al. (2004); Mancilla et al. (2002); Skrzypczak-Jankun et al. (1999); Hempel et al. (1981); Jolley et al. (1999); Liu et al. (1998); Davies et al. (1998); Smith et al. (1992).

Experimental top

A solution of 3-aminopyridine (0.94 gr, 0.01 mole) in 20 ml pyridine was added to a solution of 1.91 gr (0.01 mole) nitrilotriacetic acid in 20 ml pyridine. The resulting solution was stirred at 313 K for 1 h, then 2.6 ml triphenyl phosphite was added dropwise, and the reaction mixture was stirred at 373 K for 10 h and at ambient temperature for 48 h. the product was obtained by addition of cold water to oyridine solution. X-ray quality crystals were obtained by slow diffusion of diethyl ether into a CH₂Cl₂ solution at room temperature.

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
	Fig. 2. Unit-cell packing diagram for (I).

2-[3,5-Dioxo-4-(pyridin-3-yl)piperazin-1-yl]acetic acid top

Crystal data top

C₁₁H₁₁N₃O₄	F(000) = 1040
M_r = 249.23	D_x = 1.469 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 5235 reflections
a = 12.762 (2) Å	θ = 2.4–26°
b = 7.9495 (10) Å	µ = 0.11 mm⁻¹
c = 22.218 (3) Å	T = 298 K
V = 2254.0 (6) Å³	Block, colorless
Z = 8	0.3 × 0.07 × 0.06 mm

Data collection top

Bruker SMART 1000 CCD diffractometer	1355 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.082
ϕ and ω scans	θ_max = 26.0°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −15→13
T_min = 0.986, T_max = 0.996	k = −9→8
5235 measured reflections	l = −27→18
2181 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.083	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.139	H atoms treated by a mixture of independent and constrained refinement
S = 1.13	w = 1/[σ²(F_o²) + (0.0234P)² + 2.3505P] where P = (F_o² + 2F_c²)/3
2181 reflections	(Δ/σ)_max = 0.003
167 parameters	Δρ_max = 0.19 e Å⁻³
1 restraint	Δρ_min = −0.18 e Å⁻³

Crystal data top

C₁₁H₁₁N₃O₄	V = 2254.0 (6) Å³
M_r = 249.23	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 12.762 (2) Å	µ = 0.11 mm⁻¹
b = 7.9495 (10) Å	T = 298 K
c = 22.218 (3) Å	0.3 × 0.07 × 0.06 mm

Data collection top

Bruker SMART 1000 CCD diffractometer	2181 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	1355 reflections with I > 2σ(I)
T_min = 0.986, T_max = 0.996	R_int = 0.082
5235 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.083	1 restraint
wR(F²) = 0.139	H atoms treated by a mixture of independent and constrained refinement
S = 1.13	Δρ_max = 0.19 e Å⁻³
2181 reflections	Δρ_min = −0.18 e Å⁻³
167 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.6306 (3)	0.9688 (5)	0.48064 (15)	0.0465 (10)
H1	0.6305	0.9635	0.4388	0.056*
C2	0.6268 (3)	0.8204 (5)	0.51293 (17)	0.0468 (10)
H2	0.624	0.7174	0.4932	0.056*
C3	0.6274 (3)	0.8274 (5)	0.57515 (16)	0.0409 (9)
H3	0.6243	0.7296	0.598	0.049*
C4	0.6326 (3)	0.9824 (4)	0.60224 (14)	0.0352 (8)
C5	0.6357 (3)	1.1239 (5)	0.56714 (15)	0.0420 (9)
H5	0.6388	1.2282	0.5861	0.05*
C6	0.5383 (3)	1.0558 (4)	0.69368 (15)	0.0353 (8)
C7	0.5406 (3)	1.0795 (5)	0.76080 (15)	0.0429 (9)
H7A	0.5573	1.1957	0.7701	0.051*
H7B	0.4721	1.0547	0.7774	0.051*
C8	0.7256 (3)	0.9787 (5)	0.69787 (16)	0.0396 (9)
C9	0.7218 (3)	1.0056 (5)	0.76503 (15)	0.0422 (9)
H9A	0.7722	0.9324	0.7845	0.051*
H9B	0.7404	1.1211	0.7742	0.051*
C10	0.6095 (4)	0.9576 (4)	0.85320 (15)	0.0459 (10)
H10A	0.6585	0.8723	0.8668	0.055*
H10B	0.5396	0.9184	0.8629	0.055*
C11	0.6299 (3)	1.1167 (5)	0.88859 (15)	0.0403 (9)
N1	0.6345 (3)	1.1197 (4)	0.50719 (13)	0.0436 (8)
N2	0.6320 (2)	1.0005 (4)	0.66694 (11)	0.0347 (7)
N3	0.6179 (2)	0.9703 (3)	0.78789 (11)	0.0368 (7)
O1	0.4629 (2)	1.0852 (4)	0.66345 (12)	0.0542 (8)
O2	0.8058 (2)	0.9448 (4)	0.67151 (13)	0.0665 (9)
O3	0.6582 (3)	1.2471 (3)	0.86656 (12)	0.0666 (9)
O4	0.6119 (3)	1.0957 (4)	0.94599 (11)	0.0555 (8)
H4	0.624 (4)	1.184 (3)	0.9643 (18)	0.075 (16)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.046 (2)	0.073 (3)	0.0202 (16)	0.001 (2)	−0.0019 (16)	−0.0060 (17)
C2	0.047 (2)	0.054 (2)	0.039 (2)	0.005 (2)	−0.0012 (18)	−0.0145 (18)
C3	0.048 (2)	0.040 (2)	0.0349 (19)	0.003 (2)	−0.0048 (18)	0.0003 (15)
C4	0.0376 (19)	0.042 (2)	0.0254 (17)	−0.0002 (17)	−0.0022 (15)	−0.0012 (15)
C5	0.050 (2)	0.045 (2)	0.032 (2)	−0.0020 (19)	−0.0027 (17)	−0.0003 (16)
C6	0.043 (2)	0.0343 (18)	0.0291 (17)	0.0007 (17)	−0.0040 (15)	0.0005 (15)
C7	0.042 (2)	0.057 (2)	0.0298 (19)	0.002 (2)	0.0034 (16)	−0.0072 (17)
C8	0.039 (2)	0.049 (2)	0.0312 (19)	0.0054 (18)	−0.0010 (16)	0.0000 (16)
C9	0.048 (2)	0.055 (2)	0.0230 (17)	0.011 (2)	−0.0047 (15)	0.0000 (16)
C10	0.069 (3)	0.041 (2)	0.0267 (19)	−0.002 (2)	0.0033 (18)	−0.0004 (15)
C11	0.047 (2)	0.047 (2)	0.0272 (18)	0.0006 (19)	0.0003 (16)	−0.0007 (16)
N1	0.0453 (19)	0.059 (2)	0.0262 (16)	−0.0008 (17)	−0.0003 (14)	0.0072 (14)
N2	0.0394 (16)	0.0410 (17)	0.0237 (14)	0.0048 (14)	0.0025 (12)	0.0010 (12)
N3	0.053 (2)	0.0360 (15)	0.0218 (14)	−0.0003 (15)	0.0027 (13)	0.0013 (11)
O1	0.0466 (16)	0.077 (2)	0.0385 (15)	0.0163 (16)	−0.0113 (12)	−0.0093 (14)
O2	0.0398 (16)	0.121 (3)	0.0391 (17)	0.0152 (18)	−0.0009 (13)	−0.0150 (17)
O3	0.112 (3)	0.0494 (16)	0.0379 (15)	−0.0274 (19)	0.0120 (17)	−0.0063 (14)
O4	0.091 (2)	0.0530 (18)	0.0222 (13)	−0.0052 (18)	0.0078 (14)	−0.0028 (12)

Geometric parameters (Å, º) top

C1—N1	1.338 (5)	C7—H7A	0.97
C1—C2	1.381 (5)	C7—H7B	0.97
C1—H1	0.93	C8—O2	1.210 (4)
C2—C3	1.383 (5)	C8—N2	1.389 (4)
C2—H2	0.93	C8—C9	1.508 (5)
C3—C4	1.373 (5)	C9—N3	1.446 (4)
C3—H3	0.93	C9—H9A	0.97
C4—C5	1.369 (5)	C9—H9B	0.97
C4—N2	1.445 (4)	C10—N3	1.459 (4)
C5—N1	1.332 (4)	C10—C11	1.511 (5)
C5—H5	0.93	C10—H10A	0.97
C6—O1	1.197 (4)	C10—H10B	0.97
C6—N2	1.406 (4)	C11—O3	1.202 (4)
C6—C7	1.504 (4)	C11—O4	1.307 (4)
C7—N3	1.446 (4)	O4—H4	0.829 (10)

N1—C1—C2	122.5 (3)	O2—C8—C9	122.5 (3)
N1—C1—H1	118.7	N2—C8—C9	116.4 (3)
C2—C1—H1	118.7	N3—C9—C8	110.4 (3)
C1—C2—C3	119.0 (4)	N3—C9—H9A	109.6
C1—C2—H2	120.5	C8—C9—H9A	109.6
C3—C2—H2	120.5	N3—C9—H9B	109.6
C4—C3—C2	118.3 (4)	C8—C9—H9B	109.6
C4—C3—H3	120.8	H9A—C9—H9B	108.1
C2—C3—H3	120.8	N3—C10—C11	116.6 (3)
C5—C4—C3	119.3 (3)	N3—C10—H10A	108.1
C5—C4—N2	119.0 (3)	C11—C10—H10A	108.1
C3—C4—N2	121.7 (3)	N3—C10—H10B	108.1
N1—C5—C4	123.2 (4)	C11—C10—H10B	108.1
N1—C5—H5	118.4	H10A—C10—H10B	107.3
C4—C5—H5	118.4	O3—C11—O4	124.1 (4)
O1—C6—N2	120.5 (3)	O3—C11—C10	124.2 (3)
O1—C6—C7	123.3 (3)	O4—C11—C10	111.8 (3)
N2—C6—C7	116.2 (3)	C5—N1—C1	117.7 (3)
N3—C7—C6	110.6 (3)	C8—N2—C6	124.2 (3)
N3—C7—H7A	109.5	C8—N2—C4	118.4 (3)
C6—C7—H7A	109.5	C6—N2—C4	117.1 (3)
N3—C7—H7B	109.5	C7—N3—C9	111.2 (3)
C6—C7—H7B	109.5	C7—N3—C10	113.9 (3)
H7A—C7—H7B	108.1	C9—N3—C10	115.5 (3)
O2—C8—N2	121.1 (3)	C11—O4—H4	110 (3)

N1—C1—C2—C3	−0.2 (6)	O2—C8—N2—C4	−0.3 (6)
C1—C2—C3—C4	−0.5 (6)	C9—C8—N2—C4	177.6 (3)
C2—C3—C4—C5	0.8 (6)	O1—C6—N2—C8	173.7 (3)
C2—C3—C4—N2	179.1 (3)	C7—C6—N2—C8	−4.6 (5)
C3—C4—C5—N1	−0.4 (6)	O1—C6—N2—C4	0.4 (5)
N2—C4—C5—N1	−178.7 (3)	C7—C6—N2—C4	−177.9 (3)
O1—C6—C7—N3	154.6 (3)	C5—C4—N2—C8	−99.6 (4)
N2—C6—C7—N3	−27.2 (5)	C3—C4—N2—C8	82.1 (5)
O2—C8—C9—N3	−154.6 (4)	C5—C4—N2—C6	74.1 (4)
N2—C8—C9—N3	27.5 (5)	C3—C4—N2—C6	−104.2 (4)
N3—C10—C11—O3	−4.7 (6)	C6—C7—N3—C9	60.3 (4)
N3—C10—C11—O4	174.7 (4)	C6—C7—N3—C10	−167.1 (3)
C4—C5—N1—C1	−0.4 (6)	C8—C9—N3—C7	−60.4 (4)
C2—C1—N1—C5	0.7 (6)	C8—C9—N3—C10	167.8 (3)
O2—C8—N2—C6	−173.6 (4)	C11—C10—N3—C7	−64.7 (5)
C9—C8—N2—C6	4.4 (5)	C11—C10—N3—C9	65.9 (5)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1ⁱ	0.83 (3)	1.83 (3)	2.655 (4)	173 (5)

Symmetry code: (i) x, −y+5/2, z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₁H₁₁N₃O₄
M_r	249.23
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	298
a, b, c (Å)	12.762 (2), 7.9495 (10), 22.218 (3)
V (Å³)	2254.0 (6)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.3 × 0.07 × 0.06

Data collection
Diffractometer	Bruker SMART 1000 CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.986, 0.996
No. of measured, independent and observed [I > 2σ(I)] reflections	5235, 2181, 1355
R_int	0.082
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.083, 0.139, 1.13
No. of reflections	2181
No. of parameters	167
No. of restraints	1
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.18

Computer programs: SMART (Bruker, 2007), SAINT (Bruker, 2007), SHELXTL (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1ⁱ	0.83 (3)	1.83 (3)	2.655 (4)	173 (5)

Symmetry code: (i) x, −y+5/2, z+1/2.

Acknowledgements

The author is grateful to the Islamic Azad University, Yazd Branch, for financial support.

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