Crystal structures of 4-(pyrimidin-2-yl)piperazin-1-ium chloride and 4-(pyrimidin-2-yl)piperazin-1-ium nitrate.

The title salts, C8H13N4 (+)·Cl(-), (I), and C8H13N4 (+)·NO3 (-), (II), contain linked pyridinium-piperazine heterocycles. In both salts, the piperazine ring adopts a chair conformation with protonation at the N atom not linked to the other ring. In the crystal of (I), weak N-H⋯Cl inter-actions are observed, leading to zigzag chains along [100]. In the crystal of (II), both H atoms on the NH2 (+) group form bifurcated N-H⋯(O,O) hydrogen bonds. Weak C-H⋯O inter-actions are also observed. These bonds collectively link the components into infinite chains along [100].

Chemical context

Pyrimidine-containing compounds exhibit various biological activities (Goldmann & Stoltefuss, 1991 ▶) and related fused heterocycles are unique classes of heterocyclic compounds that exhibit a broad spectrum of biological activities such as anti­cancer (Amin et al., 2009 ▶; Pandey et al., 2004 ▶), anti­viral (Ibrahim & El-Metwally, 2010 ▶), anti­bacterial (Kuyper et al., 1996 ▶) and anti-oxidant (Padmaja et al., 2009 ▶), anti­depressant (Kim et al., 2010 ▶) and possess anti-inflammatory effects (Clark et al., 2007 ▶). In addition, several piperazine derivatives have reached the stage of clinical application; among the known drugs that are used to treat anxiety is a pyrimidinylpiperazinyl compound, bu­spirone (trade name BuSpar®) (Tollefson et al., 1991 ▶). Our research group has published a number of papers on incorporated heterocyclic ring structures, viz. imatinibium dipicrate (Jasinski et al., 2010 ▶), 1-(2-hy­droxy­eth­yl)-4-[3-(2-tri­fluoro­methyl-9H-thioxanthen-9-yl­idene)prop­yl]piperazine-1,4-diium dichloride, which is the di­hydro­chloride salt of flupentixol (Siddegowda et al., 2011a ▶) and opipramolium fumarate (Siddegowda et al., 2011b ▶). Other related crystal structures are 4-(pyrimidin-2-yl)piperazin-1-ium (E)-3-carb­oxy­prop-2-enoate (Yamuna et al., 2014a ▶), flupentixol tartarate and enrofloxacinium oxalate (Yamuna et al., 2014b ▶,c ▶). As part of our ongoing studies in this area, we report herein the crystal structures of the title salts, (I) and (II).

Structural commentary

The structure of (I) and its atom numbering are shown in Fig. 1 ▶. It consists of a pyrimidylpiperazine cation joined by the C1/N3 atoms of each unit and a chloride anion. The C1—N3 bond is 1.373 (3) Å long, which compares favorably with similar ionic structures containing this cation [1.369 (3) (Yamuna et al., 2014a ▶), and 1.36 (6) and 1.37 (1) Å (Ding et al., 2014 ▶)]. The N3/C5/C6/N4/C7/C8 piperazine unit adopts a slightly distorted chair conformation with protonation at the N4 nitro­gen atom. The structure of (II) and its atom numbering are shown in Fig. 2 ▶. Similarly, it consists of a pyrimidylpiperazine cation joined by the C1/N3 atoms of each unit and a nitrate anion. The C1—N3 bond is 1.369 (3) Å, also in the range of the related structures described above. The N3/C5/C6/N4/C7/C8 piperazine unit also adopts a slightly distorted chair conformation with protonation at the N4 atom.

Figure 1

ORTEP drawing of C8H13N4 +·Cl−, (I), showing 30% probability displacement ellipsoids.

Figure 2

ORTEP drawing of C8H13N4 +·NO3 −, (II), showing 30% probability displacement ellipsoids.

Supra­molecular features

In the crystal of (I), N4—H4A⋯Cl1 and N4—H4B⋯Cl1 inter­actions are observed between pyrimidylpiperazine cations and chloride anions, forming zigzag chains along [100] (Fig. 3 ▶ and Table 1 ▶). In the crystal of (II), both of the H atoms on the N4 atom of the pyrimidylpiperazine cation are bifurcated, forming N—H⋯(O,O) hydrogen bonds (Fig. 4 ▶ and Table 2 ▶). Additional C—H⋯O inter­actions between the pyrimidyl unit and the nitrate anion are present which, in concert with the N—H⋯O hydrogen bonds between the piperazine group and nitrate anions, form infinite chains along [100].

Figure 3

Mol­ecular packing for C8H13N4 +·Cl−, (I), viewed along the b axis. Dashed lines indicate N—H⋯Cl inter­actions forming zigzag chains along the a axis (see Table 1 ▶ for details). H atoms not involved in hydrogen bonding have been omitted for clarity.

Table 1

Hydrogen-bond geometry (Å, °) for (I)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4A⋯Cl1	0.91	2.21	3.102 (2)	167
N4—H4B⋯Cl1i	0.91	2.21	3.114 (2)	175

Symmetry code: (i) .

Figure 4

Mol­ecular packing for C8H13N4 +·NO3 −, (II), viewed along the c axis. Dashed lines indicate N—H⋯O hydrogen bonds and additional C—H⋯O inter­actions forming infinite chains along [100] (see Table 2 ▶ for details). H atoms not involved in hydrogen bonding have been omitted for clarity.

Table 2

Hydrogen-bond geometry (Å, °) for (II)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4—H4A⋯O2i	0.91	1.92	2.829 (3)	177
N4—H4A⋯O3i	0.91	2.52	3.138 (3)	126
N4—H4B⋯O1	0.91	2.35	3.197 (3)	155
N4—H4B⋯O2	0.91	2.10	2.900 (3)	146
C3—H3⋯O1ii	0.95	2.46	3.240 (3)	140
C4—H4⋯O2iii	0.95	2.51	3.291 (3)	139

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

Database survey

A search of the Cambridge Structural Database (Version 5.35, last update May 2014: Allen 2002 ▶) revealed only three structures containing the 4-(pyrimidin-2-yl)piperazin-1-ium cation similar to the structures reported here. These include the salts of 4-(pyrimidin-2-yl)piperazin-1-ium 3-carb­oxy­prop-2-enoate (Yamuna et al. 2014a ▶), 4-(pyrimidin-2-yl)piperazin-1-ium hydrogen d-tartrate monohydrate (Ding et al., 2014 ▶) and 4-(pyrimidin-2-yl)piperazin-1-ium hydrogen l-tartrate monohydrate (Ding et al. 2014 ▶). The 3-carb­oxy­prop-2-enoate complex crystallizes in space group P21/c while the two hydrogen (D and L)-tartrate monohydrate salts both crystallize in P212121. In comparison, title salt (I) crystallizes in P212121 while (II) crystallizes in space group P21/c. In addition, as a related observation, 109 structures containing the pyrimidine–piperazine unit were also identified in this search. Some of these include, uniquely, the 4-(pyrimidin-2-yl)piperazin-1-yl unit itself. These include 1-[4-(pyrimidin-2-yl)piperazin-1-yl]ethanone, (1-methyl-1H-pyrrol-2-yl)[4-(pyrimidin-2-yl)piperazin-1-yl]methanone, [4-(pyrimidin-2-yl)piperazin-1-yl](2-thien­yl)methanone, (4-fluoro­phen­yl)[4-(pyrimidin-2-yl)piperazin-1-yl]methanone (Spencer et al., 2011 ▶), (E)-1-phenyl-3-[4-(pyrimidin-2-yl)piperazin-1-yl]propan-1-one oxime (Kolasa et al., 2006 ▶), N-(4-chloro­phen­yl)-4-(pyrimidin-2-yl)piperazine-1-carboxamide (Li, 2011 ▶) and 6-{3-[4-(pyrimidin-2-yl)piperazin-1-yl]prop­yl}-2,3-di­hydro-5H-[1,4]dithiino[2,3-c]pyrrole-5,7(6H)-dione (Bielenica et al., 2011 ▶).

Synthesis and crystallization

For the preparation of title salt (I), a mixture of 1-(pyrimidin-2-yl)piperazine (0.2 g) and concentrated hydro­chloric acid (5 ml) was stirred well over a magnetic stirrer at room temperature for 10 min and then warmed at 313 K for another 10 min. A white precipitate was obtained, which was dried in the open air overnight and then dissolved in hot dimethyl sulfoxide solvent. After few days, colourless blocks were obtained on slow evaporation (m.p. above 563 K).

For the preparation of title salt (II), a mixture of 1-(pyrim­idin-2-yl)piperazine, from Sigma–Aldrich (0.2 g), and concentrated nitric acid (5 ml) was stirred well over a magnetic stirrer at room temperature for 10 min. A white precipitate was obtained immediately, which was dried in the open air overnight and then dissolved in water. After a few days, colourless blocks were obtained on slow evaporation (m.p. 463–470 K).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3 ▶. In both (I) and (II), all of the H atoms were placed in their calculated positions and then refined using a riding model with C—H bond lengths of 0.93 (CH) or 0.97 Å (CH2) and N—H bond lengths of 0.97 Å. Isotropic displacement parameters for these atoms were set at 1.2U eq(CH,CH2,NH).

Table 3

Experimental details

	(I)	(II)
Crystal data
Chemical formula	C8H13N4 +·Cl−	C8H13N4 +·NO3 −
M r	200.67	227.23
Crystal system, space group	Orthorhombic, P212121	Monoclinic, P21/c
Temperature (K)	173	173
a, b, c (Å)	6.84764 (17), 7.27667 (18), 19.1751 (5)	10.5272 (6), 7.2230 (3), 14.1575 (7)
α, β, γ (°)	90, 90, 90	90, 107.341 (6), 90
V (Å3)	955.46 (4)	1027.58 (9)
Z	4	4
Radiation type	Cu Kα	Cu Kα
μ (mm−1)	3.21	0.98
Crystal size (mm)	0.26 × 0.14 × 0.08	0.22 × 0.16 × 0.06
Data collection
Diffractometer	Agilent Agilent Eos Gemini	Agilent Agilent Eos Gemini
Absorption correction	Multi-scan (CrysAlis RED; Agilent, 2012 ▶)	Multi-scan (CrysAlis RED; Agilent, 2012 ▶)
T min, T max	0.417, 1.000	0.727, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	5514, 1841, 1761	6218, 1960, 1752
R int	0.045	0.040
(sin θ/λ)max (Å−1)	0.615	0.613
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.035, 0.091, 1.08	0.058, 0.163, 1.10
No. of reflections	1841	1960
No. of parameters	119	146
H-atom treatment	H-atom parameters constrained	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.23, −0.20	0.42, −0.25
Absolute structure	Flack x determined using 687 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al. (2013 ▶)	–
Absolute structure parameter	0.056 (15)	–

Computer programs: CrysAlis PRO and CrysAlis RED (Agilent, 2012 ▶), SUPERFLIP (Palatinus & Chapuis, 2007 ▶), SHELXL2012 (Sheldrick, 2008 ▶) and OLEX2 (Dolomanov et al., 2009 ▶).

Crystal structure: contains datablock(s) global, I, II. DOI: 10.1107/S1600536814020169/hb7279sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814020169/hb7279Isup2.hkl

Structure factors: contains datablock(s) II. DOI: 10.1107/S1600536814020169/hb7279IIsup3.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S1600536814020169/hb7279Isup4.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S1600536814020169/hb7279IIsup5.cml

CCDC references: 1023201, 1023202

Additional supporting information: crystallographic information; 3D view; checkCIF report

C8H13N4+·NO3−	F(000) = 480
Mr = 227.23	Dx = 1.469 Mg m−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54184 Å
a = 10.5272 (6) Å	Cell parameters from 2763 reflections
b = 7.2230 (3) Å	θ = 6.2–71.4°
c = 14.1575 (7) Å	µ = 0.98 mm−1
β = 107.341 (6)°	T = 173 K
V = 1027.58 (9) Å3	Irregular, colourless
Z = 4	0.22 × 0.16 × 0.06 mm

Agilent Agilent Eos Gemini diffractometer	1960 independent reflections
Radiation source: Cu Kα	1752 reflections with I > 2σ(I)
Detector resolution: 16.0416 pixels mm-1	Rint = 0.040
ω scans	θmax = 71.0°, θmin = 4.4°
Absorption correction: multi-scan (CrysAlis RED; Agilent, 2012)	h = −9→12
Tmin = 0.727, Tmax = 1.000	k = −8→8
6218 measured reflections	l = −17→16

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.058	w = 1/[σ2(Fo2) + (0.0789P)2 + 0.9595P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.163	(Δ/σ)max < 0.001
S = 1.10	Δρmax = 0.42 e Å−3
1960 reflections	Δρmin = −0.25 e Å−3
146 parameters	Extinction correction: SHELXL2012 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraints	Extinction coefficient: 0.0099 (14)
Primary atom site location: structure-invariant direct methods

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.

	x	y	z	Uiso*/Ueq
O1	0.4119 (2)	0.6964 (4)	0.41222 (17)	0.0615 (7)
O2	0.50951 (18)	0.6257 (2)	0.30424 (14)	0.0381 (5)
O3	0.55020 (17)	0.8884 (2)	0.37996 (13)	0.0323 (5)
N5	0.49103 (17)	0.7390 (3)	0.36677 (13)	0.0238 (4)
N1	0.00592 (19)	0.2396 (3)	0.48106 (14)	0.0291 (5)
N2	−0.11846 (18)	0.3821 (3)	0.32856 (15)	0.0273 (5)
N3	0.10930 (18)	0.3372 (3)	0.36702 (14)	0.0268 (5)
N4	0.33344 (18)	0.3134 (3)	0.29632 (15)	0.0278 (5)
H4A	0.3814	0.2536	0.2617	0.033*
H4B	0.3777	0.4191	0.3216	0.033*
C1	−0.0049 (2)	0.3204 (3)	0.39365 (16)	0.0220 (5)
C2	−0.1085 (3)	0.2126 (3)	0.50188 (19)	0.0346 (6)
H2	−0.1054	0.1544	0.5627	0.042*
C3	−0.2307 (2)	0.2647 (4)	0.4398 (2)	0.0362 (6)
H3	−0.3111	0.2420	0.4553	0.043*
C4	−0.2290 (2)	0.3519 (3)	0.3537 (2)	0.0329 (6)
H4	−0.3113	0.3927	0.3097	0.039*
C5	0.2387 (2)	0.2876 (4)	0.43489 (16)	0.0282 (5)
H5A	0.2266	0.2035	0.4867	0.034*
H5B	0.2848	0.4005	0.4676	0.034*
C6	0.3222 (2)	0.1932 (3)	0.37877 (17)	0.0270 (5)
H6A	0.4121	0.1674	0.4242	0.032*
H6B	0.2808	0.0738	0.3519	0.032*
C7	0.1993 (2)	0.3620 (3)	0.22801 (17)	0.0277 (5)
H7A	0.1537	0.2483	0.1960	0.033*
H7B	0.2095	0.4461	0.1755	0.033*
C8	0.1166 (2)	0.4552 (3)	0.28517 (17)	0.0276 (5)
H8A	0.1571	0.5756	0.3112	0.033*
H8B	0.0258	0.4789	0.2407	0.033*

	U11	U22	U33	U12	U13	U23
O1	0.0614 (14)	0.0836 (17)	0.0562 (13)	−0.0362 (13)	0.0431 (11)	−0.0184 (12)
O2	0.0436 (10)	0.0314 (10)	0.0460 (11)	−0.0072 (8)	0.0238 (8)	−0.0153 (8)
O3	0.0379 (9)	0.0249 (9)	0.0353 (9)	−0.0045 (7)	0.0129 (7)	−0.0021 (7)
N5	0.0175 (9)	0.0301 (10)	0.0240 (9)	−0.0015 (7)	0.0064 (7)	0.0012 (8)
N1	0.0292 (10)	0.0327 (11)	0.0282 (10)	0.0020 (8)	0.0126 (8)	0.0038 (8)
N2	0.0210 (9)	0.0270 (10)	0.0331 (11)	0.0037 (7)	0.0071 (8)	0.0001 (8)
N3	0.0189 (9)	0.0380 (11)	0.0243 (9)	0.0068 (8)	0.0075 (7)	0.0087 (8)
N4	0.0231 (9)	0.0278 (10)	0.0368 (11)	−0.0042 (8)	0.0153 (8)	−0.0045 (8)
C1	0.0207 (10)	0.0220 (10)	0.0246 (11)	0.0023 (8)	0.0087 (8)	−0.0035 (8)
C2	0.0416 (14)	0.0328 (13)	0.0372 (13)	−0.0021 (11)	0.0235 (11)	−0.0014 (10)
C3	0.0300 (13)	0.0340 (13)	0.0525 (15)	−0.0049 (10)	0.0247 (11)	−0.0130 (12)
C4	0.0224 (11)	0.0304 (12)	0.0456 (15)	0.0020 (9)	0.0098 (10)	−0.0063 (11)
C5	0.0208 (11)	0.0395 (13)	0.0234 (11)	0.0087 (9)	0.0054 (9)	0.0023 (9)
C6	0.0219 (10)	0.0296 (12)	0.0293 (11)	0.0038 (9)	0.0074 (9)	0.0014 (9)
C7	0.0291 (11)	0.0305 (12)	0.0255 (11)	−0.0013 (9)	0.0111 (9)	0.0039 (9)
C8	0.0267 (11)	0.0290 (12)	0.0283 (11)	0.0033 (9)	0.0098 (9)	0.0080 (9)

O1—N5	1.233 (3)	C2—C3	1.376 (4)
O2—N5	1.263 (2)	C3—H3	0.9500
O3—N5	1.232 (2)	C3—C4	1.377 (4)
N1—C1	1.342 (3)	C4—H4	0.9500
N1—C2	1.337 (3)	C5—H5A	0.9900
N2—C1	1.349 (3)	C5—H5B	0.9900
N2—C4	1.333 (3)	C5—C6	1.512 (3)
N3—C1	1.369 (3)	C6—H6A	0.9900
N3—C5	1.459 (3)	C6—H6B	0.9900
N3—C8	1.459 (3)	C7—H7A	0.9900
N4—H4A	0.9100	C7—H7B	0.9900
N4—H4B	0.9100	C7—C8	1.512 (3)
N4—C6	1.487 (3)	C8—H8A	0.9900
N4—C7	1.496 (3)	C8—H8B	0.9900
C2—H2	0.9500
O1—N5—O2	118.2 (2)	C3—C4—H4	118.2
O3—N5—O1	121.9 (2)	N3—C5—H5A	109.7
O3—N5—O2	119.82 (18)	N3—C5—H5B	109.7
C2—N1—C1	115.6 (2)	N3—C5—C6	109.86 (18)
C4—N2—C1	115.5 (2)	H5A—C5—H5B	108.2
C1—N3—C5	121.45 (19)	C6—C5—H5A	109.7
C1—N3—C8	121.92 (18)	C6—C5—H5B	109.7
C5—N3—C8	114.01 (18)	N4—C6—C5	110.12 (18)
H4A—N4—H4B	108.0	N4—C6—H6A	109.6
C6—N4—H4A	109.4	N4—C6—H6B	109.6
C6—N4—H4B	109.4	C5—C6—H6A	109.6
C6—N4—C7	111.33 (17)	C5—C6—H6B	109.6
C7—N4—H4A	109.4	H6A—C6—H6B	108.2
C7—N4—H4B	109.4	N4—C7—H7A	109.7
N1—C1—N2	126.0 (2)	N4—C7—H7B	109.7
N1—C1—N3	116.88 (19)	N4—C7—C8	109.99 (18)
N2—C1—N3	117.06 (19)	H7A—C7—H7B	108.2
N1—C2—H2	118.3	C8—C7—H7A	109.7
N1—C2—C3	123.4 (2)	C8—C7—H7B	109.7
C3—C2—H2	118.3	N3—C8—C7	109.85 (18)
C2—C3—H3	122.1	N3—C8—H8A	109.7
C2—C3—C4	115.8 (2)	N3—C8—H8B	109.7
C4—C3—H3	122.1	C7—C8—H8A	109.7
N2—C4—C3	123.6 (2)	C7—C8—H8B	109.7
N2—C4—H4	118.2	H8A—C8—H8B	108.2
N1—C2—C3—C4	−1.3 (4)	C4—N2—C1—N1	−2.7 (3)
N3—C5—C6—N4	55.5 (3)	C4—N2—C1—N3	175.4 (2)
N4—C7—C8—N3	−55.3 (2)	C5—N3—C1—N1	−6.3 (3)
C1—N1—C2—C3	−0.7 (4)	C5—N3—C1—N2	175.4 (2)
C1—N2—C4—C3	0.2 (3)	C5—N3—C8—C7	56.9 (3)
C1—N3—C5—C6	141.1 (2)	C6—N4—C7—C8	56.9 (2)
C1—N3—C8—C7	−141.2 (2)	C7—N4—C6—C5	−57.0 (2)
C2—N1—C1—N2	2.9 (3)	C8—N3—C1—N1	−166.9 (2)
C2—N1—C1—N3	−175.2 (2)	C8—N3—C1—N2	14.8 (3)
C2—C3—C4—N2	1.6 (4)	C8—N3—C5—C6	−57.0 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N4—H4A···O2i	0.91	1.92	2.829 (3)	177
N4—H4A···O3i	0.91	2.52	3.138 (3)	126
N4—H4B···O1	0.91	2.35	3.197 (3)	155
N4—H4B···O2	0.91	2.10	2.900 (3)	146
C3—H3···O1ii	0.95	2.46	3.240 (3)	140
C4—H4···O2iii	0.95	2.51	3.291 (3)	139