Literature DB >> 25309227

Crystal structure of 3-[4-(pyrimidin-2-yl)piperazin-1-ium-1-yl]butano-ate.

Thammarse S Yamuna¹, Jerry P Jasinski², Manpreet Kaur¹, Brian J Anderson², H S Yathirajan¹.

Abstract

The title compound, C12H18N4O2, crystallizes in the zwitterionic form with protonation at the N atom of the piperazine ring bearing the carboxylate group. The piperazine ring adopts a slightly distorted chair conformation. In the crystal, N-H⋯O hydrogen bonds are observed, forming chains along [010]. The packing is consolidated by C-H⋯O inter-actions, which generate a three-dimensional network.

Entities: Chemical Disease Gene

Keywords: 3-(piperazin-1-ium-1-yl)butanoate; aza-Michael reactions; crystal structure; fused heterocyclic derivatives; zwitterionic form

Year: 2014 PMID： 25309227 PMCID： PMC4186175 DOI： 10.1107/S1600536814018972

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For general background and pharmacological properties of fused heterocyclic derivatives, see: Amin et al. (2009 ▶); Ibrahim & El-Metwally (2010 ▶); Kuyper et al. (1996 ▶); Onal & Yıldırım (2007 ▶); Padmaja et al. (2009 ▶); Tollefson et al. (1991 ▶). For pharmacological properties of pyrimidines, see: Burdge (2000 ▶). For background to aza-Michael reactions, see: Arend et al.(1998 ▶); Vicario et al. (2005 ▶); Xu & Xia (2005 ▶). For related structures, see: Jin et al. (2012 ▶); Parvez et al. (2004 ▶); Yamuna et al. (2014a ▶,b ▶).

Experimental

Crystal data

C12H18N4O2 M = 250.30 Monoclinic, a = 13.5157 (6) Å b = 7.8454 (3) Å c = 12.2147 (5) Å β = 106.884 (5)° V = 1239.36 (9) Å3 Z = 4 Cu Kα radiation μ = 0.77 mm−1 T = 173 K 0.32 × 0.22 × 0.06 mm

Data collection

Agilent Eos Gemini diffractometer Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012 ▶) T min = 0.854, T max = 1.000 3995 measured reflections 3995 independent reflections 3668 reflections with I > 2σ(I)

Refinement

R[F 2 > 2σ(F 2)] = 0.053 wR(F 2) = 0.149 S = 1.06 3995 reflections 169 parameters H atoms treated by a mixture of independent and constrained refinement Δρmax = 0.36 e Å−3 Δρmin = −0.27 e Å−3

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis RED; program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007 ▶); program(s) used to refine structure: SHELXL2012 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2. Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536814018972/bt6993sup1.cif Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814018972/bt6993Isup2.hkl Click here for additional data file. Supporting information file. DOI: 10.1107/S1600536814018972/bt6993Isup3.cml Click here for additional data file. 12 18 4 2 . DOI: 10.1107/S1600536814018972/bt6993fig1.tif ORTEP drawing of (C12H18N4O2) showing the labeling scheme of the asymmetric unit of the title compound with 30% probability displacement ellipsoids. Click here for additional data file. b . DOI: 10.1107/S1600536814018972/bt6993fig2.tif Molecular packing for (I), viewed along the b axis. Dashed lines indicate weak C—H⋯O intermolecular interactions in addition to N—H⋯O intermolecular hydrogen bonds which together form an extended three-dimensional supramolecular network structure. H atoms not involved in hydrogen bonding have been removed for clarity. CCDC reference: 1020635 Additional supporting information: crystallographic information; 3D view; checkCIF report

C₁₂H₁₈N₄O₂	F(000) = 536
M_r = 250.30	D_x = 1.341 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 13.5157 (6) Å	Cell parameters from 5404 reflections
b = 7.8454 (3) Å	θ = 3.8–71.4°
c = 12.2147 (5) Å	µ = 0.77 mm⁻¹
β = 106.884 (5)°	T = 173 K
V = 1239.36 (9) Å³	Irregular, colourless
Z = 4	0.32 × 0.22 × 0.06 mm

Agilent Eos Gemini diffractometer	3995 independent reflections
Radiation source: Enhance (Cu) X-ray Source	3668 reflections with I > 2σ(I)
Detector resolution: 16.0416 pixels mm^-1	θ_max = 71.2°, θ_min = 3.4°
ω scans	h = −16→16
Absorption correction: multi-scan (CrysAlis PRO and CrysAlis RED; Agilent, 2012)	k = −9→9
T_min = 0.854, T_max = 1.000	l = −13→14
3995 measured reflections

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.053	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.149	w = 1/[σ²(F_o²) + (0.0768P)² + 0.6386P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
3995 reflections	Δρ_max = 0.36 e Å⁻³
169 parameters	Δρ_min = −0.27 e Å⁻³
0 restraints

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. Refined as a 2-component twin.

	x	y	z	U_iso*/U_eq
O1	−0.15848 (13)	0.4680 (3)	0.29107 (16)	0.0449 (5)
O2	−0.05978 (12)	0.4109 (2)	0.17822 (15)	0.0339 (4)
N1	0.16438 (12)	0.1694 (2)	0.44116 (14)	0.0217 (4)
H1	0.1313	0.0618	0.4040	0.026*
N2	0.32869 (12)	0.0043 (3)	0.60849 (16)	0.0287 (4)
N3	0.40034 (14)	0.0836 (3)	0.79721 (17)	0.0324 (5)
N4	0.50457 (13)	0.0549 (3)	0.66957 (17)	0.0336 (5)
C1	−0.08258 (15)	0.4025 (3)	0.2726 (2)	0.0277 (5)
C2	−0.00940 (16)	0.2979 (3)	0.3691 (2)	0.0308 (5)
H2A	−0.0174	0.3357	0.4434	0.037*
H2B	−0.0296	0.1763	0.3588	0.037*
C3	0.10322 (15)	0.3150 (3)	0.3722 (2)	0.0260 (5)
H3	0.098 (2)	0.289 (4)	0.289 (3)	0.041 (8)*
C4	0.16425 (15)	0.1604 (3)	0.56333 (18)	0.0261 (5)
H4A	0.0922	0.1532	0.5671	0.031*
H4B	0.1959	0.2650	0.6040	0.031*
C5	0.22479 (15)	0.0048 (3)	0.6211 (2)	0.0290 (5)
H5A	0.2291	0.0053	0.7034	0.035*
H5B	0.1880	−0.1001	0.5866	0.035*
C6	0.32772 (15)	0.0092 (3)	0.48941 (19)	0.0276 (5)
H6A	0.2918	−0.0928	0.4491	0.033*
H6B	0.3995	0.0084	0.4845	0.033*
C7	0.27285 (14)	0.1685 (3)	0.43312 (18)	0.0243 (4)
H7A	0.3102	0.2707	0.4716	0.029*
H7B	0.2719	0.1716	0.3518	0.029*
C8	0.41389 (15)	0.0508 (3)	0.69526 (18)	0.0248 (4)
C9	0.48642 (19)	0.1182 (3)	0.8810 (2)	0.0359 (5)
H9	0.4802	0.1456	0.9545	0.043*
C10	0.58388 (18)	0.1162 (3)	0.8665 (2)	0.0372 (6)
H10	0.6444	0.1349	0.9284	0.045*
C11	0.58837 (17)	0.0857 (3)	0.7574 (2)	0.0376 (6)
H11	0.6540	0.0864	0.7436	0.045*
C12	0.14735 (18)	0.4895 (3)	0.4145 (2)	0.0329 (5)
H12A	0.1545	0.4997	0.4964	0.049*
H12B	0.1007	0.5784	0.3725	0.049*
H12C	0.2153	0.5026	0.4019	0.049*

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0322 (9)	0.0605 (12)	0.0415 (11)	0.0190 (8)	0.0099 (8)	0.0110 (9)
O2	0.0282 (8)	0.0318 (8)	0.0409 (10)	0.0066 (6)	0.0087 (7)	0.0019 (7)
N1	0.0143 (7)	0.0280 (9)	0.0214 (9)	0.0003 (6)	0.0028 (6)	0.0038 (7)
N2	0.0138 (8)	0.0488 (11)	0.0234 (9)	0.0065 (7)	0.0053 (7)	0.0076 (8)
N3	0.0284 (9)	0.0427 (11)	0.0266 (10)	0.0100 (8)	0.0088 (8)	0.0026 (8)
N4	0.0184 (8)	0.0522 (12)	0.0303 (10)	0.0007 (8)	0.0070 (8)	−0.0065 (9)
C1	0.0200 (9)	0.0303 (11)	0.0295 (11)	−0.0011 (8)	0.0018 (8)	0.0025 (9)
C2	0.0222 (10)	0.0364 (12)	0.0335 (12)	0.0054 (9)	0.0078 (9)	0.0073 (10)
C3	0.0200 (9)	0.0287 (10)	0.0259 (10)	0.0018 (8)	0.0014 (8)	0.0052 (9)
C4	0.0166 (9)	0.0379 (12)	0.0245 (10)	0.0041 (8)	0.0072 (8)	0.0033 (9)
C5	0.0158 (9)	0.0441 (13)	0.0282 (11)	0.0042 (8)	0.0084 (8)	0.0112 (10)
C6	0.0169 (9)	0.0424 (13)	0.0233 (10)	0.0046 (8)	0.0059 (8)	0.0012 (9)
C7	0.0154 (9)	0.0373 (11)	0.0204 (10)	−0.0038 (8)	0.0055 (7)	0.0012 (9)
C8	0.0184 (9)	0.0304 (10)	0.0254 (11)	0.0077 (8)	0.0062 (8)	0.0044 (9)
C9	0.0359 (12)	0.0428 (13)	0.0264 (12)	0.0102 (10)	0.0051 (10)	−0.0020 (10)
C10	0.0297 (11)	0.0408 (13)	0.0336 (13)	0.0035 (10)	−0.0027 (10)	−0.0052 (10)
C11	0.0199 (10)	0.0495 (14)	0.0407 (14)	0.0000 (10)	0.0046 (9)	−0.0103 (11)
C12	0.0322 (11)	0.0287 (11)	0.0337 (13)	−0.0001 (9)	0.0032 (10)	0.0024 (10)

O1—C1	1.226 (3)	C4—H4A	0.9900
O2—C1	1.278 (3)	C4—H4B	0.9900
N1—H1	1.0000	C4—C5	1.524 (3)
N1—C3	1.514 (2)	C5—H5A	0.9900
N1—C4	1.494 (3)	C5—H5B	0.9900
N1—C7	1.498 (2)	C6—H6A	0.9900
N2—C5	1.457 (2)	C6—H6B	0.9900
N2—C6	1.451 (3)	C6—C7	1.513 (3)
N2—C8	1.369 (3)	C7—H7A	0.9900
N3—C8	1.335 (3)	C7—H7B	0.9900
N3—C9	1.335 (3)	C9—H9	0.9500
N4—C8	1.351 (3)	C9—C10	1.379 (3)
N4—C11	1.336 (3)	C10—H10	0.9500
C1—C2	1.538 (3)	C10—C11	1.373 (4)
C2—H2A	0.9900	C11—H11	0.9500
C2—H2B	0.9900	C12—H12A	0.9800
C2—C3	1.518 (3)	C12—H12B	0.9800
C3—H3	1.01 (3)	C12—H12C	0.9800
C3—C12	1.523 (3)

C3—N1—H1	106.5	N2—C5—H5B	109.4
C4—N1—H1	106.5	C4—C5—H5A	109.4
C4—N1—C3	115.63 (17)	C4—C5—H5B	109.4
C4—N1—C7	110.51 (15)	H5A—C5—H5B	108.0
C7—N1—H1	106.5	N2—C6—H6A	109.7
C7—N1—C3	110.70 (15)	N2—C6—H6B	109.7
C6—N2—C5	112.18 (17)	N2—C6—C7	109.75 (18)
C8—N2—C5	122.52 (19)	H6A—C6—H6B	108.2
C8—N2—C6	121.99 (18)	C7—C6—H6A	109.7
C8—N3—C9	115.4 (2)	C7—C6—H6B	109.7
C11—N4—C8	115.6 (2)	N1—C7—C6	109.51 (16)
O1—C1—O2	125.4 (2)	N1—C7—H7A	109.8
O1—C1—C2	118.0 (2)	N1—C7—H7B	109.8
O2—C1—C2	116.65 (19)	C6—C7—H7A	109.8
C1—C2—H2A	109.0	C6—C7—H7B	109.8
C1—C2—H2B	109.0	H7A—C7—H7B	108.2
H2A—C2—H2B	107.8	N3—C8—N2	117.45 (18)
C3—C2—C1	112.91 (18)	N3—C8—N4	126.3 (2)
C3—C2—H2A	109.0	N4—C8—N2	116.26 (19)
C3—C2—H2B	109.0	N3—C9—H9	118.3
N1—C3—C2	109.19 (17)	N3—C9—C10	123.5 (2)
N1—C3—H3	105.9 (16)	C10—C9—H9	118.3
N1—C3—C12	113.11 (17)	C9—C10—H10	122.0
C2—C3—H3	100.5 (16)	C11—C10—C9	116.1 (2)
C2—C3—C12	112.28 (19)	C11—C10—H10	122.0
C12—C3—H3	115.0 (17)	N4—C11—C10	123.0 (2)
N1—C4—H4A	109.6	N4—C11—H11	118.5
N1—C4—H4B	109.6	C10—C11—H11	118.5
N1—C4—C5	110.12 (17)	C3—C12—H12A	109.5
H4A—C4—H4B	108.1	C3—C12—H12B	109.5
C5—C4—H4A	109.6	C3—C12—H12C	109.5
C5—C4—H4B	109.6	H12A—C12—H12B	109.5
N2—C5—C4	110.96 (17)	H12A—C12—H12C	109.5
N2—C5—H5A	109.4	H12B—C12—H12C	109.5

O1—C1—C2—C3	−144.6 (2)	C6—N2—C5—C4	−57.3 (3)
O2—C1—C2—C3	36.8 (3)	C6—N2—C8—N3	163.5 (2)
N1—C4—C5—N2	54.5 (2)	C6—N2—C8—N4	−18.1 (3)
N2—C6—C7—N1	−59.2 (2)	C7—N1—C3—C2	172.41 (18)
N3—C9—C10—C11	3.7 (4)	C7—N1—C3—C12	−61.8 (2)
C1—C2—C3—N1	−161.91 (18)	C7—N1—C4—C5	−55.5 (2)
C1—C2—C3—C12	71.8 (3)	C8—N2—C5—C4	102.5 (2)
C3—N1—C4—C5	177.77 (16)	C8—N2—C6—C7	−100.4 (2)
C3—N1—C7—C6	−172.54 (17)	C8—N3—C9—C10	−1.8 (4)
C4—N1—C3—C2	−61.0 (2)	C8—N4—C11—C10	−1.8 (4)
C4—N1—C3—C12	64.8 (2)	C9—N3—C8—N2	176.1 (2)
C4—N1—C7—C6	58.0 (2)	C9—N3—C8—N4	−2.2 (3)
C5—N2—C6—C7	59.5 (2)	C9—C10—C11—N4	−1.7 (4)
C5—N2—C8—N3	5.7 (3)	C11—N4—C8—N2	−174.3 (2)
C5—N2—C8—N4	−175.9 (2)	C11—N4—C8—N3	4.0 (4)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	1.00	1.67	2.653 (2)	168
C2—H2B···O2ⁱ	0.99	2.51	3.277 (3)	134
C4—H4B···O1ⁱⁱ	0.99	2.58	3.428 (3)	144
C7—H7B···O1ⁱ	0.99	2.53	3.147 (3)	120
C11—H11···O1ⁱⁱⁱ	0.95	2.47	3.352 (3)	155

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	1.00	1.67	2.653 (2)	168
C2—H2B⋯O2ⁱ	0.99	2.51	3.277 (3)	134
C4—H4B⋯O1ⁱⁱ	0.99	2.58	3.428 (3)	144
C7—H7B⋯O1ⁱ	0.99	2.53	3.147 (3)	120
C11—H11⋯O1ⁱⁱⁱ	0.95	2.47	3.352 (3)	155

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

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