2-(4-Amino­phen­yl)-3,4,5,6-tetra­hydro­pyrimidin-1-ium chloride

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

doi:10.1107/S1600536812014493

. 2012 Apr 13;68(Pt 5):o1360. doi: 10.1107/S1600536812014493

2-(4-Aminophenyl)-3,4,5,6-tetrahydropyrimidin-1-ium chloride

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

PMCID: PMC3344492 PMID: 22590254

Abstract

In the title compound, C₁₀H₁₄N₃ ⁺·Cl⁻, the tetrahydropyridinium ring of the cation, which adopts a slightly distorted envelope conformation, is disordered over two orientations with an occupancy ratio of 0.653 (5):0.347 (5). The amidinium fragment of the major conformer is twisted relative to the benzene ring by 22.5 (6)° and the two C—N bond lengths of this fragment are similar [1.3228 (16) and 1.319 (2) Å]. In the crystal, the chloride anions are involved in three N—H⋯Cl hydrogen bonds, which link the components into a two-dimensional hydrogen-bonded network parallel to (010).

Related literature

For the synthesis, see: Wydra et al. (1990 ▶); Stolić et al. (2009 ▶, 2011 ▶). For related compounds, see: Molčanov et al. (2011 ▶); Jarak et al. (2005 ▶); Legrand et al. (2008 ▶). For the biological activity of compounds comprising a cyclic amidine system, see: Boykin (2002 ▶); Chaires et al. (2004 ▶); Farahat et al. (2011 ▶); Hall et al. (1998 ▶). For the GAMESS program package, see: Schmidt et al. (1993 ▶).

Experimental

Crystal data

C₁₀H₁₄N₃ ⁺·Cl⁻
M _r = 211.69
Orthorhombic,
a = 15.0055 (2) Å
b = 8.0884 (1) Å
c = 17.8088 (3) Å
V = 2161.46 (5) Å³
Z = 8
Cu Kα radiation
μ = 2.84 mm⁻¹
T = 293 K
0.15 × 0.10 × 0.09 mm

Data collection

Oxford Diffraction Xcalibur Nova R diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011 ▶) T _min = 0.676, T _max = 0.784
6131 measured reflections
2242 independent reflections
1760 reflections with I > 2σ(I)
R _int = 0.017

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.098
S = 1.05
2242 reflections
146 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.16 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2011 ▶); 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/S1600536812014493/gk2441sup1.cif

e-68-o1360-sup1.cif^{(24.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812014493/gk2441Isup2.hkl

e-68-o1360-Isup2.hkl^{(108.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812014493/gk2441Isup3.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
N1—H1NA⋯Cl1ⁱ	0.90	2.47	3.3271 (16)	160
N2B—H2N⋯Cl1	0.90	2.27	3.1126 (12)	156
N3B—H3N⋯Cl1ⁱⁱ	0.90	2.42	3.250 (17)	153

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Symmetry codes: (i) Inline graphic ; (ii) .

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

Natural and synthetic aromatic amidines that bind in the DNA minor groove have proved to be clinically useful agents primarly as antiparasitic agents.(Boykin, 2002; Farahat et al., 2011). In addition to their antiparasitic properties, certain diamidines display a useful spectrum of antitumor, antiviral and antifungal activities. (Chaires et al., 2004; Hall et al., 1998; Stolić et al. 2009; Stolić et al. 2011). Cyclic amidine moiety is known in a number of potential antitumor agents; some of them have 4-(1,4,5,6-tetrahydropirimidin-2-yl)phenylamine as the building unit (Stolić et al., 2011; Molčanov et al., 2011).

The asymmetric unit contains a single formula unit of 2-(4-aminophenyl)-3,4,5,6-tetrahydropyrimidin-1-ium chloride. The tetrahydropyrimidinium ring is disordered over two positions designated as A and B (Fig. 1). Their respective occupancies are 0.347 (5)/ 0.653 (5). While there is a formal double C=N bond in the neutral tetrahydropyrimidine, both C—N bonds in the cation are approximately equal. However, the positive charge is localized on the C7 atom, as confirmed by DFT calculations (Fig. 3). Such a delocalization poses a significant restraint to conformation of the tetrahydropyrimidine ring. Cremer-Pople puckering parameters are Q = 0.454 (5)°, Θ = 132.8 (6)°, Φ = 55.2 (9)° for the conformer A (atom sequence N2B–C7B–N3B–C10B–C9B–C8B) and Q = 0.527 (12)°, Θ = 51.4 (11)°, Φ = 197.7 (13)° for the conformer B (atom sequence N2B–C7B–N3B–C10B–C9B–C8B) indicating the envelope form for the A ring and the conformation intermediate between half-chair and boat for the ring B. The chloride anions are coordinated by three N—H···Cl hydrogen bonds in the pyramidal arrangement. The crystal packing is dominated by hydrogen bonded layers parallel to (0 1 0) (Fig. 2, Table 1)

Experimental

The crude imidate ester hydrochloride (1.61 g, 8.6 mmol) prepared from 4-aminobenzonitrile (1.12 g, 9.5 mmol) in anhydrous methanol by Pinner reaction was suspended in anhydrous methanol (100 ml), 1,3-diaminopropane (4 ml) was added and mixture was stirred at room temperature for 4 days under the nitrogen atmosphere. The solvent was removed under reduced pressure and residue was recrystallized from ethanol-diethyl ether to yield 1.06 g (57.6%) of white powder, IR (ν_max/cm^-1): 2883, 2023, 1595, 1472, 1101, 727, 635; ¹H NMR (DMSO-d6) δ/p.p.m.: 8.28 (s, 2H, NH), 7.54 (d, 2H, J = 8.5 Hz, ArH), 6.65 (d, 2H, J = 8.1 Hz, ArH), 6.10 (s, 2H, NH₂), 2.88 (t, 4H, J = 7.4 Hz, CH₂), 1.90 (m, 2H, J = 7.4 Hz, CH₂).

DFT calculations. The structure, obtained from the X-ray structural analysis was optimized without symmetry constrains by using MP2/6–31+G(d,p) level of theory implemented in the GAMESS program package (Schmidt et al., 1993) . Tight convergence criteria were used in the optimization. The calculation was checked for convergence and frequencies were calculated in order to prove that the optimized structure was the minimum. The optimized geometry shows agreement with experimental one (conformer B); only four bonds (N1—C1, N3—C7, C2—C3 and C5–C6) differ more than 3 e.s.d.'s.