5,12-Dimethyl­pyrazino­[1,2-a:4,5-a′]dibenzimidazole-5,12-diium dichloride dihydrate

Han, J.; Zhao, M.; Zhang, J.; Ma, L.; Fan, G.

doi:10.1107/S1600536812046594

organic compounds

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ISSN: 2056-9890

Volume 68| Part 12| December 2012| Page o3398

doi:10.1107/S1600536812046594

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5,12-Dimethylpyrazino[1,2-a:4,5-a′]dibenzimidazole-5,12-diium dichloride dihydrate

Jie Han,^a ^* Ming-gao Zhao,^b Jun Zhang,^b Lan Ma ^b and Guang Fan ^c

^aResearch Institute of Shaanxi Yanchang Petroleum (Group) Co. Ltd, Ke Ji No. 2 Road 75, Xi'an 710075, Shaanxi, People's Republic of China, ^bDepartment of Pharmacology, School of Pharmacy, Forth Military Medical University, Chang-le West Road 17, Xi'an 710032, Shaanxi, People's Republic of China, and ^cCollege of Chemistry & Chemical Engineering, Xianyang Normal University, Xianyang 712000, Shaanxi, People's Republic of China
^*Correspondence e-mail: eota@163.com

(Received 25 September 2012; accepted 12 November 2012; online 24 November 2012)

The title hydrated salt, C₁₈H₁₈N₄²⁺·2Cl⁻·2H₂O, sits about an inversion centre, such that the asymmetric unit contains one half-molecule. In the crystal, hydrogen bonds occur between the water molecules and chloride anions, and there is π–π stacking of the benzene and imidazole rings of inversion-related pairs of molecules, with a centroid–centroid distance of 3.704 (17) Å.

Related literature

For descriptions of clinical applications of the benzimidazole ring system, see: Harrell et al. (2004 ). For a related structure, see: Sun et al. (2010 ).

Experimental

Crystal data

C₁₈H₁₈N₄²⁺·2Cl⁻·2H₂O
M_r = 397.30
Monoclinic, P 2₁ /c
a = 8.1080 (12) Å
b = 9.0857 (14) Å
c = 12.9188 (19) Å
β = 94.426 (2)°
V = 948.8 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.36 mm⁻¹
T = 296 K
0.38 × 0.28 × 0.17 mm

Data collection

Bruker SMART APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2002 ) T_min = 0.876, T_max = 0.943
4604 measured reflections
1681 independent reflections
1371 reflections with I > 2σ(I)
R_int = 0.021

Refinement

R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.114
S = 1.07
1681 reflections
127 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1C⋯Cl1ⁱ	0.83	2.33	3.1558 (19)	170
O1—H1D⋯Cl1ⁱⁱ	0.83	2.37	3.190 (2)	170
Symmetry codes: (i) x, y, z-1; (ii) -x+1, -y, -z+1.

Data collection: APEX2 (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; 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: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812046594/pk2446sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812046594/pk2446Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812046594/pk2446Isup3.cml

checkCIF report

Comment top

Bis-benzimidazoles are DNA-minor grove binding agents that possess anti-tumor activity. The benzimidazole ring system is present in clinically approved antihistamines, antivirals, anthelmintics, and antiulcer medications (Harrell et al., 2004). In addition to their biological activity, there are numerous other studies, including coordination and corrosion inhibitor abilities of benzimidazoles. Bis-benzimidazoles are also strong chelating agents (Sun et al., 2010). Some of these derivatives are used as photographic materials and dyes. As part of our ongoing investigation of benzimidazole derivatives, the title compound was synthesized and its crystal structure is reported herein.

Related literature top

For descriptions of clinical applications of the benzimidazole ring system, see: Harrell et al. (2004). For a related structure, see: Sun et al. (2010).

Experimental top

N-methylbenzene-1,2-diamine (2.5 mol), 2-chloroacetic acid (3 mmol), polyphosphoric acid (10 ml) and silica gel (1 g) were mixed and introduced in an open Erlenmeyer flask. The reaction mixture was irradiated in a domestic microwave oven for 3 min. After cooling to room temperature, methanol was added (20 ml) and the reaction mixture filtered. The filtrate was evaporated to dryness and subjected to column chromatography (10% hexane/ethyl acetate) to give green needle-like crystals of the title compound.

Computing details top

Data collection: APEX2 (Bruker, 2002); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT (Bruker, 2002); 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: SHELXTL (Sheldrick, 2008).

Figures top

	Fig. 1. A view of the molecular structure of title compound. Displacement ellipsoids are drawn at the 35% probability level. Unlabelled atoms are related by inversion (1-x, -y, 1-z) to their labelled counterparts.
	Fig. 2. A three dimensional stacking diagram of (1) viewed down the b axis.

10,20-Dimethyl-3,10,13,20- tetraazapentacyclo[11.7.0.0^3,11.0^4,9.0^14,19]icosa- 1(20),4(9),5,7,10,14,16,18-octaene-10,20-diium top

Crystal data top

C₁₈H₁₈N₄²⁺·2Cl⁻·2H₂O	F(000) = 416
M_r = 397.30	D_x = 1.391 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 1814 reflections
a = 8.1080 (12) Å	θ = 2.5–26.8°
b = 9.0857 (14) Å	µ = 0.36 mm⁻¹
c = 12.9188 (19) Å	T = 296 K
β = 94.426 (2)°	Block, white
V = 948.8 (2) Å³	0.38 × 0.28 × 0.17 mm
Z = 2

Data collection top

Bruker SMART APEXII CCD diffractometer	1681 independent reflections
Radiation source: fine-focus sealed tube	1371 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.021
ϕ and ω scans	θ_max = 25.1°, θ_min = 2.5°
Absorption correction: multi-scan (SADABS; Bruker, 2002)	h = −9→9
T_min = 0.876, T_max = 0.943	k = −10→10
4604 measured reflections	l = −10→15

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)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.114	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ²(F_o²) + (0.0587P)² + 0.1961P] where P = (F_o² + 2F_c²)/3
1681 reflections	(Δ/σ)_max < 0.001
127 parameters	Δρ_max = 0.16 e Å⁻³
2 restraints	Δρ_min = −0.20 e Å⁻³

Crystal data top

C₁₈H₁₈N₄²⁺·2Cl⁻·2H₂O	V = 948.8 (2) Å³
M_r = 397.30	Z = 2
Monoclinic, P2₁/c	Mo Kα radiation
a = 8.1080 (12) Å	µ = 0.36 mm⁻¹
b = 9.0857 (14) Å	T = 296 K
c = 12.9188 (19) Å	0.38 × 0.28 × 0.17 mm
β = 94.426 (2)°

Data collection top

Bruker SMART APEXII CCD diffractometer	1681 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2002)	1371 reflections with I > 2σ(I)
T_min = 0.876, T_max = 0.943	R_int = 0.021
4604 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.038	2 restraints
wR(F²) = 0.114	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	Δρ_max = 0.16 e Å⁻³
1681 reflections	Δρ_min = −0.20 e Å⁻³
127 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
Cl1	0.49232 (8)	0.17546 (7)	0.85285 (4)	0.0755 (3)
N1	0.35268 (18)	0.00311 (15)	0.44209 (10)	0.0454 (4)
N2	0.2397 (2)	0.17478 (16)	0.53127 (12)	0.0521 (4)
O1	0.7107 (3)	0.0906 (2)	0.05725 (17)	0.0961 (6)
C1	0.4743 (2)	−0.0970 (2)	0.40528 (14)	0.0532 (5)
H1A	0.5002	−0.0687	0.3360	0.064*
H1B	0.4301	−0.1962	0.4021	0.064*
C2	0.3745 (2)	0.09265 (19)	0.52381 (13)	0.0462 (4)
C3	0.2198 (3)	0.2890 (2)	0.60909 (19)	0.0701 (6)
H3A	0.2912	0.2682	0.6701	0.105*
H3B	0.1069	0.2908	0.6268	0.105*
H3C	0.2482	0.3830	0.5815	0.105*
C4	0.1255 (2)	0.1382 (2)	0.44954 (16)	0.0557 (5)
C5	−0.0348 (3)	0.1869 (3)	0.4213 (2)	0.0725 (7)
H5	−0.0854	0.2590	0.4590	0.087*
C6	−0.1142 (3)	0.1222 (3)	0.3345 (2)	0.0825 (8)
H6	−0.2216	0.1515	0.3136	0.099*
C7	−0.0399 (3)	0.0149 (3)	0.2772 (2)	0.0805 (7)
H7	−0.0981	−0.0247	0.2188	0.097*
C8	0.1178 (3)	−0.0338 (2)	0.30476 (16)	0.0642 (6)
H8	0.1682	−0.1056	0.2667	0.077*
C9	0.1975 (2)	0.0297 (2)	0.39233 (14)	0.0509 (5)
H1C	0.653 (3)	0.101 (3)	0.0016 (12)	0.081 (8)*
H1D	0.667 (4)	0.021 (2)	0.087 (2)	0.105 (11)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0922 (5)	0.0875 (5)	0.0477 (3)	0.0113 (3)	0.0113 (3)	−0.0030 (2)
N1	0.0513 (9)	0.0469 (8)	0.0380 (8)	0.0018 (6)	0.0036 (6)	0.0004 (6)
N2	0.0584 (10)	0.0490 (9)	0.0508 (9)	0.0069 (7)	0.0152 (7)	0.0038 (6)
O1	0.0995 (15)	0.1007 (15)	0.0839 (14)	−0.0151 (12)	−0.0199 (11)	0.0121 (12)
C1	0.0599 (12)	0.0587 (11)	0.0414 (9)	0.0051 (9)	0.0068 (8)	−0.0074 (8)
C2	0.0525 (11)	0.0475 (10)	0.0396 (9)	0.0030 (8)	0.0103 (8)	0.0028 (7)
C3	0.0826 (15)	0.0569 (12)	0.0742 (14)	0.0093 (10)	0.0278 (12)	−0.0077 (10)
C4	0.0539 (11)	0.0548 (10)	0.0593 (12)	0.0024 (9)	0.0102 (9)	0.0165 (9)
C5	0.0604 (13)	0.0688 (14)	0.0901 (17)	0.0111 (10)	0.0171 (12)	0.0306 (12)
C6	0.0567 (14)	0.0892 (17)	0.0993 (19)	−0.0038 (12)	−0.0093 (13)	0.0444 (16)
C7	0.0726 (16)	0.0880 (17)	0.0773 (16)	−0.0122 (13)	−0.0181 (13)	0.0283 (14)
C8	0.0688 (13)	0.0683 (13)	0.0538 (12)	−0.0082 (10)	−0.0063 (10)	0.0120 (10)
C9	0.0504 (11)	0.0549 (10)	0.0472 (10)	−0.0026 (8)	0.0023 (8)	0.0117 (8)

Geometric parameters (Å, º) top

N1—C2	1.334 (2)	C3—H3B	0.9600
N1—C9	1.389 (2)	C3—H3C	0.9600
N1—C1	1.448 (2)	C4—C9	1.388 (3)
N2—C2	1.333 (2)	C4—C5	1.394 (3)
N2—C4	1.390 (3)	C5—C6	1.382 (4)
N2—C3	1.462 (3)	C5—H5	0.9300
O1—H1C	0.830 (10)	C6—C7	1.389 (4)
O1—H1D	0.827 (10)	C6—H6	0.9300
C1—C2ⁱ	1.473 (3)	C7—C8	1.374 (3)
C1—H1A	0.9700	C7—H7	0.9300
C1—H1B	0.9700	C8—C9	1.385 (3)
C2—C1ⁱ	1.473 (3)	C8—H8	0.9300
C3—H3A	0.9600

C2—N1—C9	108.69 (15)	H3A—C3—H3C	109.5
C2—N1—C1	126.20 (15)	H3B—C3—H3C	109.5
C9—N1—C1	124.93 (15)	C9—C4—N2	106.96 (16)
C2—N2—C4	108.25 (15)	C9—C4—C5	120.5 (2)
C2—N2—C3	125.56 (18)	N2—C4—C5	132.5 (2)
C4—N2—C3	126.12 (17)	C6—C5—C4	116.4 (2)
H1C—O1—H1D	104 (3)	C6—C5—H5	121.8
N1—C1—C2ⁱ	109.51 (14)	C4—C5—H5	121.8
N1—C1—H1A	109.8	C5—C6—C7	122.5 (2)
C2ⁱ—C1—H1A	109.8	C5—C6—H6	118.7
N1—C1—H1B	109.8	C7—C6—H6	118.7
C2ⁱ—C1—H1B	109.8	C8—C7—C6	121.4 (2)
H1A—C1—H1B	108.2	C8—C7—H7	119.3
N2—C2—N1	109.82 (16)	C6—C7—H7	119.3
N2—C2—C1ⁱ	125.99 (16)	C7—C8—C9	116.3 (2)
N1—C2—C1ⁱ	124.19 (15)	C7—C8—H8	121.8
N2—C3—H3A	109.5	C9—C8—H8	121.8
N2—C3—H3B	109.5	C8—C9—C4	122.85 (19)
H3A—C3—H3B	109.5	C8—C9—N1	130.88 (19)
N2—C3—H3C	109.5	C4—C9—N1	106.27 (16)

C2—N1—C1—C2ⁱ	3.6 (3)	N2—C4—C5—C6	−178.57 (19)
C9—N1—C1—C2ⁱ	178.11 (15)	C4—C5—C6—C7	−0.4 (3)
C4—N2—C2—N1	−0.86 (19)	C5—C6—C7—C8	0.6 (4)
C3—N2—C2—N1	−177.88 (17)	C6—C7—C8—C9	0.0 (3)
C4—N2—C2—C1ⁱ	179.73 (17)	C7—C8—C9—C4	−0.8 (3)
C3—N2—C2—C1ⁱ	2.7 (3)	C7—C8—C9—N1	178.01 (18)
C9—N1—C2—N2	1.22 (19)	N2—C4—C9—C8	179.65 (17)
C1—N1—C2—N2	176.48 (16)	C5—C4—C9—C8	1.1 (3)
C9—N1—C2—C1ⁱ	−179.35 (16)	N2—C4—C9—N1	0.56 (19)
C1—N1—C2—C1ⁱ	−4.1 (3)	C5—C4—C9—N1	−177.98 (17)
C2—N2—C4—C9	0.16 (19)	C2—N1—C9—C8	179.92 (19)
C3—N2—C4—C9	177.16 (17)	C1—N1—C9—C8	4.6 (3)
C2—N2—C4—C5	178.5 (2)	C2—N1—C9—C4	−1.08 (19)
C3—N2—C4—C5	−4.5 (3)	C1—N1—C9—C4	−176.42 (16)
C9—C4—C5—C6	−0.5 (3)

Symmetry code: (i) −x+1, −y, −z+1.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1C···Cl1ⁱⁱ	0.83	2.33	3.1558 (19)	170
O1—H1D···Cl1ⁱ	0.83	2.37	3.190 (2)	170

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

Experimental details

Crystal data
Chemical formula	C₁₈H₁₈N₄²⁺·2Cl⁻·2H₂O
M_r	397.30
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	8.1080 (12), 9.0857 (14), 12.9188 (19)
β (°)	94.426 (2)
V (Å³)	948.8 (2)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.36
Crystal size (mm)	0.38 × 0.28 × 0.17

Data collection
Diffractometer	Bruker SMART APEXII CCD diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.876, 0.943
No. of measured, independent and observed [I > 2σ(I)] reflections	4604, 1681, 1371
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.597

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.038, 0.114, 1.07
No. of reflections	1681
No. of parameters	127
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.16, −0.20

Computer programs: APEX2 (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1C···Cl1ⁱ	0.83	2.33	3.1558 (19)	169.6
O1—H1D···Cl1ⁱⁱ	0.83	2.37	3.190 (2)	170.2

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

Acknowledgements

The work was supported by 2009ZX09103–111, the China Postdoctoral Science Foundation (No. 2009041446), the Special Research Fund of the Education Department of Shaanxi Province (12 J K0631) and the Special Research Fund of Xianyang Normal University (11XSYK204). We thank the Instrumental Analysis Center of Northwest University for the data collection.

References

Bruker (2002). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Harrell, C. C., Kohli, P., Siwy, Z. & Martin, C. R. (2004). J. Am. Chem. Soc. 126, 15646–15647. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sun, T., Li, K., Lai, Y., Chen, R. & Wu, H. (2010). Acta Cryst. E66, m1058. Web of Science CSD CrossRef IUCr Journals Google Scholar

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