1,4-Di­methyl­piperazine-2,3-dione

Khamrang, T.; Ponraj, C.; Hemamalini, M.; Antony, G.J.M.; Saravanan, D.

doi:10.1107/S2414314624009362

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 9| Part 10| October 2024| x240936

https://doi.org/10.1107/S2414314624009362

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1,4-Dimethylpiperazine-2,3-dione

Themmila Khamrang,^a C. Ponraj,^b Madhukar Hemamalini,^c G. Jerald Maria Antony ^b ^* and Dhandayutham Saravanan ^b

^aDepartment of Chemistry, Dhanamanjuri University, Manipur 795 001, India, ^bDepartment of Chemistry, National College, Tiruchirappalli, Tamil Nadu, India, and ^cDepartment of Chemistry, Mother Teresa Women's University, Kodaikanal, Tamil Nadu, India
^*Correspondence e-mail: jerelewin.mine@gmail.com

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 29 August 2024; accepted 23 September 2024; online 4 October 2024)

In the title compound, C₆H₁₀N₂O₂, the piperazine-2,3-dione ring adopts a half-chair conformation. In the crystal, the molecules are linked by weak C—H⋯O hydrogen bonds, forming (010) sheets.

Keywords: crystal Structure; half chair; hydrogen bonding.

CCDC reference: 2386002

Structure description

Piperazine and its derivatives are found within biologically active molecules across a diverse range of therapeutic areas, including antifungal, antibacterial, antimalarial, antipsychotic, antidepressant, and antitumor applications targeting colon, prostate, breast, lung, and leukemia cancers (Brockunier et al., 2004 ; Bogatcheva et al., 2005 ). As part of our studies in this area, we now describe the structure of the title compound, C₆H₁₀N₂O₂.

The asymmetric unit is shown in Fig. 1. The piperazine-2,3-dione ring adopts a half chair conformation, with C1 and C2 displaced from the other ring atoms by 0.279 (3) and −0.342 (3) Å, respectively. The molecule possesses local C₂ symmetry about an axis passing through the midpoints of the C1—C2 and C3—C4 bonds. In the crystal (Fig. 2), the molecules are connected by weak C2—H2A⋯O1 and C5—H5C⋯O2 hydrogen bonds (Table 1) to generate (010) layers.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2A⋯O2ⁱ	0.97	2.49	3.419 (3)	161
C5—H5C⋯O2ⁱⁱ	0.96	2.54	3.481 (3)	168
Symmetry codes: (i) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

Figure 1
The asymmetric unit with displacement ellipsoids drawn at the 50% probability level.

Figure 2
The crystal packing of the title compound.

A search of the Cambridge Structural Database (CSD; Version 5.43, update November 2022; Groom et al., 2016 ) revealed some similar structures to the title compound, including 3,6-dibenzylidene-1,4-dimethylpiperazine-2,5-dione (CSD refcode IQOCEZ; Ge et al., 2019 ), 2,5-bis(1-methyl-2-oxoindol-3-ylidene)-1,4-dimethylpiperazine-3,6-dione acetone solvate (PALVUT; Gompper et al., 1992 ) and 6-(bromobenzyl)-3-benzylidene-6-erythro-hydroxy-1,4-dimethylpiperazine-2,5-dione (SAWSEO; Sterns et al., 1989 ).

Synthesis and crystallization

The title compound was prepared according to the literature method (Haraguchi et al., 2015 ). Recrystallization of the solid from dichloromethane solution gave colorless plates, which were suitable for X-ray diffraction.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₆H₁₀N₂O₂
M_r	142.16
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	293
a, b, c (Å)	7.3781 (6), 8.0050 (6), 12.1306 (8)
β (°)	99.767 (7)
V (Å³)	706.07 (9)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.37 × 0.32 × 0.29

Data collection
Diffractometer	Agilent Xcalibur, Atlas, Gemini
Absorption correction	Analytical (SADABS; Krause et al., 2015 )
T_min, T_max	0.507, 0.578
No. of measured, independent and observed [I > 2σ(I)] reflections	2746, 1624, 1194
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.681

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.063, 0.181, 1.07
No. of reflections	1624
No. of parameters	93
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.45, −0.21
Computer programs: CrysAlis PRO (Agilent, 2012 ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and PLATON (Spek, 2020 ).

Structural data

CCDC reference: 2386002

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314624009362/hb4484sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314624009362/hb4484Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314624009362/hb4484Isup3.cml

checkCIF report

Computing details top

1,4-Dimethylpiperazine-2,3-dione top

Crystal data top

C₆H₁₀N₂O₂	F(000) = 304
M_r = 142.16	D_x = 1.337 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 7.3781 (6) Å	Cell parameters from 9307 reflections
b = 8.0050 (6) Å	θ = 3.5–26.4°
c = 12.1306 (8) Å	µ = 0.10 mm⁻¹
β = 99.767 (7)°	T = 293 K
V = 706.07 (9) Å³	Plate, colourless
Z = 4	0.37 × 0.32 × 0.29 mm

Data collection top

Agilent Xcalibur, Atlas, Gemini diffractometer	1194 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.016
ω scans	θ_max = 29.0°, θ_min = 3.1°
Absorption correction: analytical (SADABS; Krause et al., 2015)	h = −10→8
T_min = 0.507, T_max = 0.578	k = −10→5
2746 measured reflections	l = −6→16
1624 independent reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.063	H-atom parameters constrained
wR(F²) = 0.181	w = 1/[σ²(F_o²) + (0.0839P)² + 0.2479P] where P = (F_o² + 2F_c²)/3
S = 1.07	(Δ/σ)_max < 0.001
1624 reflections	Δρ_max = 0.45 e Å⁻³
93 parameters	Δρ_min = −0.21 e Å⁻³
0 restraints

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. All the H atoms were positioned geometrically (C—H = 0.96–0.97 Å) and were refined using a riding model, with U_iso(H) = 1.2U_eq(C) or 1.5U_eq(methyl C).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O2	0.4932 (2)	0.2262 (2)	0.62587 (12)	0.0591 (5)
O1	0.8009 (2)	0.3382 (3)	0.55770 (14)	0.0642 (6)
N1	0.6498 (2)	0.3592 (2)	0.38031 (14)	0.0427 (5)
N2	0.3516 (2)	0.1982 (2)	0.44717 (14)	0.0421 (5)
C4	0.6624 (3)	0.3190 (3)	0.48783 (16)	0.0380 (5)
C3	0.4923 (3)	0.2422 (2)	0.52590 (15)	0.0364 (5)
C5	0.7995 (4)	0.4489 (4)	0.3415 (2)	0.0616 (7)
H5A	0.899882	0.462273	0.402473	0.092*
H5B	0.756751	0.556833	0.313902	0.092*
H5C	0.840112	0.386644	0.282610	0.092*
C1	0.4771 (4)	0.3452 (3)	0.30300 (18)	0.0547 (7)
H1A	0.502520	0.333921	0.227477	0.066*
H1B	0.406408	0.446718	0.306177	0.066*
C2	0.3670 (4)	0.2011 (3)	0.32859 (19)	0.0555 (6)
H2A	0.245130	0.207406	0.283752	0.067*
H2B	0.424361	0.098582	0.309359	0.067*
C6	0.1915 (3)	0.1170 (4)	0.4791 (3)	0.0649 (8)
H6A	0.223240	0.073267	0.553547	0.097*
H6B	0.151882	0.027484	0.428037	0.097*
H6C	0.093814	0.196898	0.476737	0.097*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O2	0.0637 (11)	0.0816 (12)	0.0319 (8)	−0.0121 (9)	0.0082 (7)	0.0062 (8)
O1	0.0445 (9)	0.0987 (14)	0.0438 (9)	−0.0153 (9)	−0.0083 (7)	0.0067 (9)
N1	0.0455 (10)	0.0500 (10)	0.0318 (9)	−0.0055 (8)	0.0045 (7)	0.0017 (7)
N2	0.0376 (9)	0.0480 (10)	0.0393 (10)	−0.0067 (8)	0.0023 (7)	−0.0029 (8)
C4	0.0358 (10)	0.0455 (11)	0.0307 (10)	0.0003 (9)	−0.0004 (8)	−0.0013 (8)
C3	0.0388 (10)	0.0384 (10)	0.0308 (10)	0.0031 (8)	0.0023 (8)	0.0000 (8)
C5	0.0650 (15)	0.0706 (17)	0.0544 (15)	−0.0116 (13)	0.0250 (12)	0.0023 (12)
C1	0.0653 (15)	0.0642 (15)	0.0299 (10)	−0.0058 (12)	−0.0055 (10)	0.0061 (10)
C2	0.0572 (14)	0.0649 (15)	0.0377 (12)	−0.0054 (12)	−0.0113 (10)	−0.0033 (10)
C6	0.0440 (13)	0.0738 (17)	0.0774 (19)	−0.0156 (12)	0.0118 (12)	−0.0092 (14)

Geometric parameters (Å, º) top

O2—C3	1.218 (2)	C5—H5B	0.9600
O1—C4	1.222 (2)	C5—H5C	0.9600
N1—C4	1.331 (3)	C1—C2	1.474 (3)
N1—C1	1.452 (3)	C1—H1A	0.9700
N1—C5	1.461 (3)	C1—H1B	0.9700
N2—C3	1.333 (3)	C2—H2A	0.9700
N2—C6	1.457 (3)	C2—H2B	0.9700
N2—C2	1.462 (3)	C6—H6A	0.9600
C4—C3	1.537 (3)	C6—H6B	0.9600
C5—H5A	0.9600	C6—H6C	0.9600

C4—N1—C1	121.47 (18)	N1—C1—C2	112.27 (18)
C4—N1—C5	120.23 (19)	N1—C1—H1A	109.2
C1—N1—C5	117.27 (18)	C2—C1—H1A	109.2
C3—N2—C6	119.7 (2)	N1—C1—H1B	109.2
C3—N2—C2	121.30 (18)	C2—C1—H1B	109.2
C6—N2—C2	118.05 (19)	H1A—C1—H1B	107.9
O1—C4—N1	124.1 (2)	N2—C2—C1	110.93 (19)
O1—C4—C3	118.12 (18)	N2—C2—H2A	109.5
N1—C4—C3	117.77 (17)	C1—C2—H2A	109.5
O2—C3—N2	123.9 (2)	N2—C2—H2B	109.5
O2—C3—C4	118.32 (18)	C1—C2—H2B	109.5
N2—C3—C4	117.82 (17)	H2A—C2—H2B	108.0
N1—C5—H5A	109.5	N2—C6—H6A	109.5
N1—C5—H5B	109.5	N2—C6—H6B	109.5
H5A—C5—H5B	109.5	H6A—C6—H6B	109.5
N1—C5—H5C	109.5	N2—C6—H6C	109.5
H5A—C5—H5C	109.5	H6A—C6—H6C	109.5
H5B—C5—H5C	109.5	H6B—C6—H6C	109.5

C1—N1—C4—O1	−175.3 (2)	N1—C4—C3—O2	−170.0 (2)
C5—N1—C4—O1	−7.2 (3)	O1—C4—C3—N2	−170.1 (2)
C1—N1—C4—C3	5.3 (3)	N1—C4—C3—N2	9.4 (3)
C5—N1—C4—C3	173.39 (19)	C4—N1—C1—C2	−35.3 (3)
C6—N2—C3—O2	−3.8 (3)	C5—N1—C1—C2	156.3 (2)
C2—N2—C3—O2	−172.4 (2)	C3—N2—C2—C1	−37.7 (3)
C6—N2—C3—C4	176.84 (19)	C6—N2—C2—C1	153.5 (2)
C2—N2—C3—C4	8.3 (3)	N1—C1—C2—N2	49.3 (3)
O1—C4—C3—O2	10.5 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C2—H2A···O2ⁱ	0.97	2.49	3.419 (3)	161
C5—H5C···O2ⁱⁱ	0.96	2.54	3.481 (3)	168

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

References

Agilent (2012). CrysAlis PRO and CrysAlis RED. Agilent Technologies Ltd, Yarnton, England. Google Scholar
Bogatcheva, E., Hanrahan, C., Nikonenko, B., Samala, R., Chen, P., Gearhart, J., Barbosa, F., Einck, L., Nacy, C. A. & Protopopova, M. (2005). J. Med. Chem. 49, 3045–3048. Web of Science CrossRef Google Scholar
Brockunier, L. L., He, J., Colwell, L. F. Jr, Habulihaz, B., He, H., Leiting, B., Lyons, K. A., Marsilio, F., Patel, R. A., Teffera, Y., Wu, J. K., Thornberry, N. A., Weber, A. E. & Parmee, E. R. (2004). Bioorg. Med. Chem. Lett. 14, 4763–4766. Web of Science CrossRef PubMed CAS Google Scholar
Ge, Y., Han, Z., Wang, Z. & Ding, K. (2019). J. Am. Chem. Soc. 141, 8981–8988. Web of Science CSD CrossRef CAS PubMed Google Scholar
Gompper, R., Kellner, R. & Polborn, K. (1992). Angew. Chem. Int. Ed. Engl. 31, 1202–1205. CSD CrossRef Web of Science Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Haraguchi, R., Takada, Y. & Matsubara, S. (2015). Org. Biomol. Chem. 13, 241–247. Web of Science CrossRef CAS PubMed Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Sterns, M., Patrick, J. M., Patrick, V. A. & White, A. H. (1989). Aust. J. Chem. 42, 349. CSD CrossRef Web of Science Google Scholar

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