3-Amino-5-methyl-5-(4-pyrid­yl)hydantoin

Hristo Varbanov; Rossen Buyukliev; Adriana Bakalova; Alexander Roller

doi:10.1107/S1600536809011404

. 2009 Apr 2;65(Pt 5):o953. doi: 10.1107/S1600536809011404

3-Amino-5-methyl-5-(4-pyridyl)hydantoin

Hristo Varbanov ^a,^*, Rossen Buyukliev ^b, Adriana Bakalova ^c, Alexander Roller ^a

PMCID: PMC2977653 PMID: 21583996

Abstract

The title compound, 3-amino-5-methyl-5-(4-pyridyl)imidazolidine-2,4-dione, C₉H₁₀N₄O₂, was obtained by reaction of 5-methyl-5-(4-pyridyl)hydantoin with hydrazine. It crystallizes as a racemate in the tetragonal space group I4₁/a with one molecule in the asymmetric unit. The dihedral angle between the pyridine ring and the five-membered hydantoin ring is 47.99 (3)° In the crystal structure, molecules are joined in a three-dimensional hydrogen-bonded network by N—H⋯N and N—H⋯O links.

Related literature

For the biological activity of hydantoin derivatives and their metal complexes, see: Rajic et al. (2006 ▶); Bazil et al. (1998 ▶); Bakalova et al. (2005 ▶, 2008 ▶, 2009 ▶). For crystal structures of other 3-amino substituted hydantoins and their metal complexes, see: Shivachev et al. (2005 ▶); Bakalova et al. (2007 ▶). For the synthesis of 5-methyl-5-(4-pyridyl)-hydantoin, see: Chu & Teague (1958 ▶). For the preparation of 3-aminohydantoins, see: Davidson (1964 ▶).

Experimental

Crystal data

C₉H₁₀N₄O₂
M _r = 206.21
Tetragonal,
a = 12.8282 (5) Å
c = 22.9016 (17) Å
V = 3768.8 (3) Å³
Z = 16
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 100 K
0.50 × 0.50 × 0.50 mm

Data collection

Bruker X8 APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.948, T _max = 0.948
51879 measured reflections
2765 independent reflections
2179 reflections with I > 2σ(I)
R _int = 0.076

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.127
S = 1.03
2765 reflections
144 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.56 e Å⁻³
Δρ_min = −0.44 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809011404/at2752sup1.cif

e-65-0o953-sup1.cif^{(16.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809011404/at2752Isup2.hkl

e-65-0o953-Isup2.hkl^{(136.1KB, hkl)}

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
N2—H2⋯N4ⁱ	0.88	2.69	3.526	159
N2—H2⋯O2ⁱ	0.88	2.26	2.9184 (15)	131
N4—H4A⋯O1ⁱⁱ	0.977 (19)	2.139 (19)	3.0676 (16)	158.07
N4—H4B⋯O1ⁱⁱⁱ	0.96 (2)	2.17 (2)	3.1003 (16)	162.23

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

Acknowledgments

The authors are indebted to Professor V. Arion of the Institute of Inorganic Chemistry of the University of Vienna for discussions about the X-ray data.

supplementary crystallographic information

Comment

Some hydantoin derivatives are biologically active molecules with anticonvulsive, antiarythmic, antimicrobial, antiviral or cytostatic activitiy (Rajic et al., 2006; Bazil et al., 1998). 5-Methyl-5-(4-pyridyl)hydantoin was synthesized by Chu (Chu et al. 1958). This compound was used as starting material for preparation of new 3-amino-5-methyl-5-(4-pyridyl)hydantoin (AMPH). These hydantoin derivatives were utilized as carrier ligands for synthesis of new platinum and palladium complexes with potential cytotoxic activity. (Bakalova et al., 2008, 2009). In the recent work we synthesized AMPH (I) by the method of Davidson (Davidson, 1964) with some modifications. The new compound was characterized by elemental analysis, IR, ¹H and ¹³C NMR spectroscopy and molar conductivity. Suitable crystals of AMPH for X-ray diffraction analysis have been isolated and its structure was determined. The result of X-ray diffraction study of 3-amino-5-methyl-5-(4-pyridyl)hydantoin is shown in Fig. 1. The racemic compound crystallizes in the tetragonal space group I4₁/a with one molecule in the asymmetric unit. The presence of the sp³-hybridized chiral carbon atom C1 is responsible for the dihedral angle between the pyridine ring and five-membered C₃N₂ ring of ca 48°. The sum of the angles around N4 is clearly smaller than 360° (327.0°), indicating its trigonal-pyramidal configuration. The lone-pair region at N4 is directed towards adjacent atom O1. The secondary amine nitrogen N2 acts as a proton donor in an intermolecular bifurcated hydrogen bonding interactions with the nitrogen atom N4 and oxygen atom O2 of the neighbouring molecule of AMPH (Fig. 2) The hydrazinic atom N4 is involved in two intermolecular H bonds with the atoms O1ⁱⁱ and O1ⁱⁱⁱ of the two different neighbouring molecules (Table 1).

Experimental

3-Amino-5-methyl-5-(4-pyridyl)hydantoin was synthesized by dissolving 5-methyl-5(4-pyridyl)hydantoin (1.91 g, 10 mmol) in 98% N₂H₄.H₂O (5 cm³) and refluxing the solution for 2 h. The reaction mixture was cooled to room temperature and water (15 cm³) was added. The solution was placed in refrigerator for 24 h. The white product was filtered off, recrystallized from ethanol and dried at 373 K for 5 h. The purity was checked by TLC. The substance is soluble in DMSO and weakly soluble in water and ethanol. Yield: 1.26 g, 61%, m.p. = 523.2–524.7 K. Crystals, suitable for X-ray data collection were grown by slow evaporation from ethanol solution at 277 K. Analysis calculated for C₉H₁₀N₄O₂: C 52.42, H 4.89, N 27.17%. Found: C 52.23, H 4.46, N 26.83%. λ_M = 0.979 S.cm².mol^-1; IR(pellets KBr)/cm^-1: 3314.0, 3276.0, 1766.9, 1713.0, 1597.2 and 1411.1. ¹H NMR (250 MHz; DMSO-d⁶): 8.95 (1H, s, N(1)—H), 8.59 (2H, d, J=7 Hz, H-2, H-6), 7.50 (2H, d, J=7 Hz, H-3, H-5), 4.80 (2H, s, NH2), 1.66 (3H, s, CH₃). ¹³C NMR (62.5 MHz; DMSO-d⁶): 172.7 (C=O-4`), 155.5 (C=O-2`), 150.0 (C-2,C-6), 148.4 (C-4), 120.6 (C-3, C-5), 60.8 (C-5`), 24.7 (CH₃).