Bis[2-(4-amino­phen­yl)-4,5-dihydro-1H-imidazol-3-ium] dichloride monohydrate

Krešimir Molčanov; Ivana Stolić; Biserka Kojić-Prodić; Miroslav Bajić

doi:10.1107/S1600536811050070

. 2011 Nov 25;67(Pt 12):o3450–o3451. doi: 10.1107/S1600536811050070

Bis[2-(4-aminophenyl)-4,5-dihydro-1H-imidazol-3-ium] dichloride monohydrate

Krešimir Molčanov ^a,^*, Ivana Stolić ^b, Biserka Kojić-Prodić ^a, Miroslav Bajić ^b

PMCID: PMC3239081 PMID: 22199929

Abstract

The asymmetric unit of the title compound, 2C₉H₁₂N₃ ⁺·2Cl⁻·H₂O, comprises two molecules, two chloride anions and one molecule of crystal water. In the imidazolinium ring, the protonation contributes to delocalization of the positive charge over the two C—N bonds. Both chloride anions are acceptors of four hydrogen bonds in a flattened tetrahedron environment. The donors are NH₂ groups, the NH groups of the imidazolinium rings and the water molecule. These hydrogen bonds and N—H⋯O(H₂O) hydrogen bonds form a three-dimensional network.

Related literature

For background and the biological activity of aromatic amidines, see: Chen et al. (2010 ▶); Hu et al. (2009 ▶); Del Poeta et al. (1998 ▶); Baraldi et al. (2004 ▶); Jarak et al. (2011 ▶); Neidle (2001 ▶); Stolić et al. (2011 ▶). For the synthesis, see Widra et al. (1990 ▶). For related compounds see: Jarak et al. (2005 ▶); Legrand et al. (2008 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶);

Experimental

Crystal data

2C₉H₁₂N₃ ⁺·2Cl⁻·H₂O
M _r = 413.35
Orthorhombic,
a = 10.5307 (2) Å
b = 17.9659 (4) Å
c = 22.4290 (5) Å
V = 4243.42 (16) Å³
Z = 8
Cu Kα radiation
μ = 2.91 mm⁻¹
T = 293 K
0.4 × 0.05 × 0.04 mm

Data collection

Oxford Xcalibur Nova R Ruby diffractometer
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2010 ▶) T _min = 0.389, T _max = 0.892
13695 measured reflections
4375 independent reflections
3054 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.116
S = 1.00
4375 reflections
348 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811050070/bq2316sup1.cif

e-67-o3450-sup1.cif^{(20.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811050070/bq2316Isup2.hkl

e-67-o3450-Isup2.hkl^{(210.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811050070/bq2316Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1A—H11⋯Cl2ⁱ	0.86	2.45	3.296 (2)	170
N1A—H12⋯Cl1	0.86	2.45	3.304 (2)	170
N1B—H21⋯Cl2ⁱⁱ	0.86	2.59	3.448 (2)	174
N1B—H22⋯O1ⁱⁱⁱ	0.86	2.02	2.882 (3)	177
N2A—H2C⋯Cl2	0.86	2.29	3.1113 (18)	160
N2B—H2D⋯Cl1ⁱⁱ	0.86	2.35	3.1615 (19)	157
N3A—H3C⋯Cl1ⁱ	0.86	2.36	3.1900 (17)	162
O1—H1A⋯Cl2^iv	0.93 (2)	2.21 (2)	3.1329 (19)	178 (3)
O1—H1B⋯Cl1^v	0.95 (2)	2.21 (2)	3.147 (2)	170 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

This research was funded by the Croatian Ministry of Science, Education and Sports, grant Nos. 098–1191344-2943 and 053–0982914-2965.

supplementary crystallographic information

Comment

Nucleic acids are important targets for many biomolecules and small molecules. Many anticancer drugs are known to exert their biological activity through bonding into minor groove of DNA. Aromatic amidines which bind strongly into the DNA minor groove exhibit outstandindg antiparasitic (Chen et al., 2010), antibacterial (Hu et al., 2009), antifungal (Del Poeta et al., 1998), and antitumor activity (Baraldi et al., 2004). The amidinium moiety is known to contribute to DNA binding of small molecules by electrostatic, van der Waals and hydrogen bonding interactions (Neidle, 2001). Aminobenzamidine derivatives are very useful building blocks for construction of target complex molecules (Jarak et al., 2011). We found out that 4,5-dihydroimidazoles with cyclic amidine moiety at the terminal positions show sometimes better antitumor activity than corresponding unsubstituted or alkyl substituted amidines (Stolić et al., 2011). Detail analysis of interactions of these compounds with nucleic acids can help to design more potent agents against different types of diseases.

The asymmetric unit of I comprises two molecules (labeled as A and B) and a single molecule of crystal water (Fig. 1). The five-membered rings of the cations are almost planar, the Cremer-Pople (Cremer & Pople, 1975) puckering parameters Θ being 3.2° and 0.6° for A and B molecules, respectively. The cations, however, are not planar, since mean planes of six- and five-membered rings are tilted by 9.3° and 14.8°, respectively. Both imino nitrogen atoms of the imidazolinium ring are protonated, since the imidazole is stronger proton acceptor than the amine nitrogen. The positive charge is delocalized over the two C—N bonds in the five-membered ring (Scheme 1, Fig. 1), further stabilizing the cation. The chloride anions are acceptors of four hydrogen bonds in the shapes of flattened tetrahedra with different donor groups: Cl1 accepts hydrogen bonds from two NH group of the imidazolinium ring, one NH₂ group and a water molecule; Cl2 is surrounded by two NH₂ groups, one imidazolinium NH and a water molecule. The molecule of crystal water is a proton donor to chloride ions and acceptor of N—H···O bonds. Thus, crystal packing comprises three-dimensional hydrogen bonding network (Fig. 2, Table 1).

Experimental

The crude imidate ester hydrochloride (2.39 g, 12.8 mmol) prepared from 4-aminobenzonitrile (1.66 g, 14.1 mmol) in anhydrous methanol by Pinner reaction was suspended in anhydrous methanol (50 ml), 1,2-diaminoethane (12 ml) was added and mixture was refluxed for 12 h under the nitrogen atmosphere. The solvent was removed under reduced pressure and residue was recrystallized from ethanol-diethyl ether to yield 1.27 g (50.5%) of pale brown powder, m.p. 473 K; IR (ν_max/cm^-1): 3353, 3099, 1582, 1502, 1364, 1191, 949, 835; ¹H NMR (DMSO-d6) δ/p.p.m.: 10.12 (s, 2H, NH), 7.76 (s, 2H, NH2), 6.65 (s, 2H, ArH), 6.46 (s, 2H, ArH), 2.50 (s, 4H, CH2).