2-[(E)-(6-Amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-5-yl)imino­meth­yl]pyridinium chloride monohydrate

Irvin Booysen; Muhammed Ismail; Thomas Gerber; Eric Hosten; Richard Betz

doi:10.1107/S1600536811033307

. 2011 Aug 27;67(Pt 9):o2436–o2437. doi: 10.1107/S1600536811033307

2-[(E)-(6-Amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)iminomethyl]pyridinium chloride monohydrate

Irvin Booysen ^a, Muhammed Ismail ^a, Thomas Gerber ^b, Eric Hosten ^b, Richard Betz ^b,^*

PMCID: PMC3200829 PMID: 22065128

Abstract

The title compound, C₁₂H₁₄N₅O₂ ⁺·Cl⁻·H₂O, is the monohydrate of the hydrochloride of an oxopurine-derived Schiff base in which protonation took place at the pyridine N atom. The organic cation is essentially planar (r.m.s. of all fitted non-H atoms = 0.0373 Å). In the crystal, N—H⋯O and N—H⋯Cl hydrogen bonds as well as C—H⋯O and C—H⋯Cl contacts connect the different entities into a three-dimensional network. The shortest centroid–centroid distance between two pyrimidine rings is 3.6364 (9) Å.

Related literature

For the development of radiopharmaceuticals, see: Gerber et al. (2011 ▶). For the crystal structure of the neutral organic parent ligand, see: Booysen et al. (2011a ▶). For the crystal structures of polymorphs of 6-amino-1,3-dimethyl-5-[(E-2-(methylsulfanyl)benzylideneamino]pyrimidine-2,4(1H,3H)-dione, see: Booysen et al. (2011b ▶,c ▶). For graph-set analysis of hydrogen bonds, see: Etter et al. (1990 ▶); Bernstein et al. (1995 ▶). For puckering analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₁₂H₁₄N₅O₂ ⁺·Cl⁻·H₂O
M _r = 313.75
Orthorhombic,
a = 13.3797 (4) Å
b = 15.7975 (5) Å
c = 12.9998 (4) Å
V = 2747.71 (15) Å³
Z = 8
Mo Kα radiation
μ = 0.30 mm⁻¹
T = 200 K
0.49 × 0.09 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.879, T _max = 1.000
24436 measured reflections
3415 independent reflections
2327 reflections with I > 2σ(I)
R _int = 0.053

Refinement

R[F ² > 2σ(F ²)] = 0.042
wR(F ²) = 0.111
S = 1.03
3415 reflections
212 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: APEX2 (Bruker, 2010 ▶); cell refinement: SAINT (Bruker, 2010 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811033307/dn2714sup1.cif

e-67-o2436-sup1.cif^{(23.1KB, cif)}

Supplementary material file. DOI: 10.1107/S1600536811033307/dn2714Isup2.cdx

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811033307/dn2714Isup3.hkl

e-67-o2436-Isup3.hkl^{(167.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811033307/dn2714Isup4.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
N4—H741⋯O90ⁱ	0.82 (2)	2.12 (2)	2.901 (2)	158 (2)
N4—H742⋯Cl1	0.94 (2)	2.29 (2)	3.1565 (16)	153 (2)
N5—H751⋯Cl1	0.90 (2)	2.19 (2)	3.0255 (16)	155 (2)
O90—H901⋯O1ⁱⁱ	0.89 (3)	2.01 (3)	2.874 (2)	164 (3)
O90—H902⋯Cl1	0.82 (3)	2.43 (3)	3.213 (2)	159 (3)
C5—H5A⋯Cl1ⁱⁱⁱ	0.98	2.83	3.642 (2)	141
C9—H9⋯Cl1^iv	0.95	2.71	3.5912 (19)	155
C10—H10⋯O1^v	0.95	2.65	3.564 (2)	163
C12—H12⋯O2^vi	0.95	2.37	3.294 (2)	164

Open in a new tab

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

Acknowledgments

The authors thank Mrs Jaci Neale-Shutte for helpful discussions.

supplementary crystallographic information

Comment

Next to cardiovascular diseases, cancer has become one of the main fatal diseases in industrialized countries. Apart from classical surgery, chemo- and radiotherapeutic treatments have entered the arsenal of possible cures for certain types of cancer. All methods, however, suffer from their own set of problematic side-effects and, as a consequence, the development of radiopharmaceuticals – combining the advantages of chemotherapy as well as radiation methods while at the same time avoiding their unique respective undesired side-effects – has been a topic of research (Gerber et al., 2011). Tailoring and fine-tuning of the envisioned radiopharmaceuticals' properties such as lipophilicity and, in particular, inertness is of paramount importance with respect to possible future in vivo applications in contemporary medicine and requires sound knowledge about structural parameters of the ligands applied if a more heuristic approach in the synthesis is to triumph over pure trial-and-error as it is encountered in this specific field of coordination chemistry up to the present day. To allow for an assessment of changes in structural features upon coordination has taken place, the molecular and crystal structure of the title compound has been determined. Information about metrical parameters of the neutral compound (Booysen et al., 2011a) as well as other 6-amino-1,3-dimethyl-2,4(1H,3H)-dione-derived Schiff-base ligands (Booysen et al., 2011b; Booysen et al., 2011c) is apparent in the literature.

Protonation of the neutral organic ligand took place on the nitrogen atom of the pyridine moiety. The C=N bond is (E)-configured. Intracyclic angles in the protonated pyridine moiety cover a range of 117.73 (16)–123.66 (16) ° with the biggest angle on the protonated nitrogen atom and the smallest angle on the carbon atom bonded to the exocyclic substituent. The organic cation is essentially planar (r.m.s. for all its fitted non-hydrogen atoms = 0.0373 Å). The low puckering amplitude (τ = 2.2 °, r.m.s. for all its fitted and bonded non-hydrogen atoms = 0.0373 Å) of the non-aromatic heterocycle precludes a conformational analysis (Cremer & Pople, 1975) (Fig. 1).

In the crystal, hydrogen bonds as well as C–H···O and C–H···Cl contacs are observed whose range fall by about and more than 0.1 Å below the sum of van-der-Waals radii of the atoms participating for the latter two types of interaction. The classical hydrogen bonds are supported by the protons of the water molecule as well as the amino group and have the chloride ion, the oxygen atom of the water molecule and the oxygen atom of the keto group located between the two methylated nitrogen atoms as acceptor. Two C–H···O contacts can be observed: the first one stemming from the C–H group in ortho-position to the protonated nitrogen atom in the pyridyl moiety and the keto group not acting as acceptor for a classical hydrogen bond and the second one between the C–H group in para position to the protonated nitrogen atom of the pyridyl moiety and the keto group that is already acting as acceptor for one of the classical hydrogen bonds. The two C–H···Cl contacts apply the vinylic hydrogen atom as well as one of the C–H groups present in the pyridyl moiety as donors. The chloride anion thus is pentacoordinate. A description of the classical hydrogen bonds in terms of graph-set analysis (Etter et al., 1990; Bernstein et al., 1995) necessitates a DDDDD descriptor on the unitary level while the C–H···O as well as the C–H···Cl contacts can be described by means of a DDC¹₁(9)C¹₁(11) descriptor on the same level. In total, the entities of the title compound are connected to a three-dimensional network. The shortest intercentroid distance between two centers of gravity was found at 3.6364 (9) Å (Fig. 2).

The packing of the title compound in the crystal structure is shown in Figure 3.

Experimental

The title compound was prepared by the reaction of (E)-6-amino-1,3- dimethyl-5-(pyridin-2-ylmethyleneamino)pyrimidine-2,4(1H,3H)- dione and trans-[ReOCl₃(PPh₃)₂] in acetonitrile. The solution was filtered and single crystals suitable for the X-ray analysis were obtained from the mother liquor which was left in a fridge over several days.