N-(2-Amino-4,6-dihydroxypyrimidin-5-yl)acetamide dihydrate

Abstract

The title compound, C₆H₈N₄O₃·2H₂O, which crystallized as a dihydrate, has two almost planar segments viz. the pyrimidine ring and the C—N—C(=O)—C group [maxmum deviations of 0.020 (2) and 0.014 (2) Å, respectively], with a dihedral angle of 87.45°. In the crystal, the components are linked by O—H⋯O and N—H⋯O hydrogen bonds.

Related literature

For the biological properties of pyrimidine compounds see: Marchal et al. (2010 ▶); Giandinoto et al. (1996 ▶); Sun et al. (2006 ▶). For related structures, see: Glidewell et al. (2003 ▶); Nakayama et al. (2004 ▶); Quesada et al. (2004 ▶); Hockova et al. (2003 ▶).

Experimental

Crystal data

• C₆H₈N₄O₃·2H₂O

• M _r = 220.20

• Monoclinic,

• a = 9.5501 (12) Å

• b = 12.2161 (13) Å

• c = 8.5324 (8) Å

• β = 98.708 (1)°

• V = 983.96 (19) ų

• Z = 4

• Mo Kα radiation

• μ = 0.13 mm⁻¹

• T = 298 K

• 0.23 × 0.15 × 0.10 mm

Data collection

• Bruker SMART CCD area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2002 ▶) T _min = 0.971, T _max = 0.987

• 5002 measured reflections

• 1727 independent reflections

• 1082 reflections with I > 2σ(I)

• R _int = 0.039

Refinement

• R[F ² > 2σ(F ²)] = 0.042

• wR(F ²) = 0.120

• S = 0.85

• 1727 reflections

• 136 parameters

• H-atom parameters constrained

• Δρ_max = 0.20 e Å⁻³

• Δρ_min = −0.26 e Å⁻³

Data collection: SMART (Bruker, 2002 ▶); cell refinement: SMART; 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.

Supplementary Material

Supplementary material file. DOI: 10.1107/S1600536811034441/fl2354Isup3.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—H1⋯O1i	0.86	1.98	2.810 (2)	164
N2—H2⋯O2ii	0.86	2.00	2.836 (2)	163
N3—H3A⋯O5ii	0.86	1.95	2.803 (2)	172
N3—H3B⋯O4i	0.86	1.98	2.843 (2)	178
N4—H4⋯O2iii	0.86	2.27	3.115 (2)	170
O4—H4A⋯O1	0.85	1.90	2.717 (2)	159
O4—H4B⋯O3iv	0.85	1.96	2.812 (2)	176
O5—H5A⋯O2	0.85	1.95	2.716 (2)	150
O5—H5B⋯O3iii	0.85	1.97	2.814 (2)	174

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .

supplementary crystallographic information

Comment

Pyrimidine and its derivatives are important targets for drug discovery having attracted much attention for their biological activities and molecular structures (Sun et al., (2006)). Research findings indicate that the pyrimidine derivatives are associated with diverse pharmacological activities, such as antifungal, antibacterial, pesticidal, analgesic, and antitumor (Giandinoto et al.; (1996); Nakayama et al., (2004); Hockova et al., (2003)). The present X-ray crystal structure analysis was undertaken in order to study the stereochemistry and crystal packing of the title compound (I).

As shown in Fig 1, the title compound which crystallized as a dihydrate is composed of two planar segments. One segment is a pyrimidine ring, which (C1, N2, C2, C3, C4, N1), and the other segment contains C3, N4, C6, C5 and O3. The dihedral angle between the two planar segments is 87.45 °. (I)crystallized in the keto form.

The molecule exhibits O..H···O hydrogen bonding with the water molecules and intermoleculer N-H···O hydrogen bonding between the pyrimidine moieties (Table 1). The chains formed by the the N—H···O hydrogen bonds can be seen in Fig. 2. The crystal structure is also aggregated into a three-dimensional framework via further N—H···O interactions (Fig.3).

Experimental

A mixture of guanidine hydrochloride (2.04 g, 4 mmol) and diethyl acetylaminomalonate (5.0 g, 2 mmol) were reacted in 36 ml sodium ethylate at 358 K for 5 h. Then the product was disolved in water with proper pH adjustment (3–4) by HCl. After filtering and drying, the crystalline product of the title compound was collected by recrystallization at room temperature in 10% HCl(10 ml).

Refinement

All the H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with O—H distances of 0.85 Å, N—-H distances of 0.86 Å, C—H distances of 0.93–0.97 Å and U_iso(H) = 1.2–1.5U_eq of the parent atom.

Figures

Fig. 1.

The molecular structure of the title compound, showing 30% displacement ellipsoids for the non-hydrogen atoms. Hydrogen atoms are drawn as spheres of arbitrary radius.

Fig. 2.

One-dimensional chain of the title compound. Hydrogen bonds are shown as dashed lines.

Fig. 3.

The molecular packing of the title compound, viewed along the b axis. Intermolecular hydrogen bonds are indicated by dashed lines.

Crystal data

C6H8N4O3·2H2O	F(000) = 464
Mr = 220.20	Dx = 1.486 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 9.5501 (12) Å	Cell parameters from 1089 reflections
b = 12.2161 (13) Å	θ = 2.7–26.2°
c = 8.5324 (8) Å	µ = 0.13 mm−1
β = 98.708 (1)°	T = 298 K
V = 983.96 (19) Å3	Cuboid, colorless
Z = 4	0.23 × 0.15 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer	1727 independent reflections
Radiation source: fine-focus sealed tube	1082 reflections with I > 2σ(I)
graphite	Rint = 0.039
Detector resolution: 0 pixels mm-1	θmax = 25.0°, θmin = 2.2°
φ and ω scans	h = −11→11
Absorption correction: multi-scan (SADABS; Bruker, 2002)	k = −14→13
Tmin = 0.971, Tmax = 0.987	l = −9→10
5002 measured reflections

Refinement

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.120	H-atom parameters constrained
S = 0.85	w = 1/[σ2(Fo2) + (0.0641P)2 + 0.2581P] where P = (Fo2 + 2Fc2)/3
1727 reflections	(Δ/σ)max < 0.001
136 parameters	Δρmax = 0.20 e Å−3
0 restraints	Δρmin = −0.26 e Å−3

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
O4	0.21459 (17)	0.66228 (13)	0.37653 (19)	0.0498 (5)
N1	0.51891 (18)	0.27137 (14)	0.8076 (2)	0.0336 (5)
H1	0.5490	0.2108	0.8520	0.040*
N2	0.53066 (18)	0.45908 (14)	0.7961 (2)	0.0350 (5)
H2	0.5664	0.5196	0.8351	0.042*
N3	0.68269 (19)	0.36480 (15)	0.9877 (2)	0.0403 (5)
H3A	0.7194	0.4256	1.0247	0.048*
H3B	0.7129	0.3038	1.0305	0.048*
N4	0.25806 (19)	0.36468 (14)	0.4697 (2)	0.0364 (5)
H4	0.2839	0.3634	0.3774	0.044*
O1	0.38963 (16)	0.55753 (12)	0.60969 (18)	0.0443 (5)
O2	0.35840 (16)	0.17282 (12)	0.64300 (17)	0.0408 (4)
O3	0.07419 (17)	0.37021 (14)	0.60637 (19)	0.0526 (5)
H4A	0.2598	0.6153	0.4382	0.063*
H4B	0.1272	0.6500	0.3778	0.063*
O5	0.1825 (2)	0.06285 (14)	0.4167 (2)	0.0641 (6)
H5A	0.2207	0.1168	0.4697	0.077*
H5B	0.1527	0.0876	0.3245	0.077*
C1	0.5807 (2)	0.36517 (17)	0.8661 (2)	0.0313 (5)
C2	0.4238 (2)	0.46472 (18)	0.6633 (2)	0.0327 (5)
C3	0.3655 (2)	0.36483 (17)	0.6053 (2)	0.0320 (5)
C4	0.4087 (2)	0.26646 (18)	0.6789 (2)	0.0314 (5)
C5	0.1185 (2)	0.36648 (18)	0.4780 (3)	0.0377 (6)
C6	0.0201 (3)	0.3621 (2)	0.3226 (3)	0.0566 (8)
H6A	−0.0314	0.2944	0.3152	0.085*
H6B	0.0743	0.3670	0.2367	0.085*
H6C	−0.0452	0.4222	0.3166	0.085*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O4	0.0423 (10)	0.0475 (11)	0.0557 (11)	−0.0018 (8)	−0.0048 (8)	0.0086 (8)
N1	0.0395 (11)	0.0234 (10)	0.0348 (10)	0.0006 (8)	−0.0042 (9)	0.0052 (8)
N2	0.0390 (11)	0.0231 (10)	0.0398 (11)	−0.0015 (8)	−0.0039 (9)	−0.0026 (8)
N3	0.0443 (12)	0.0300 (10)	0.0418 (11)	0.0004 (9)	−0.0090 (9)	−0.0010 (9)
N4	0.0418 (12)	0.0348 (11)	0.0312 (10)	0.0005 (9)	0.0009 (8)	−0.0002 (8)
O1	0.0548 (11)	0.0217 (9)	0.0508 (10)	0.0016 (7)	−0.0104 (8)	0.0031 (7)
O2	0.0472 (10)	0.0251 (9)	0.0452 (9)	−0.0033 (7)	−0.0092 (7)	0.0004 (7)
O3	0.0398 (10)	0.0727 (13)	0.0433 (10)	−0.0004 (9)	−0.0004 (8)	−0.0034 (9)
O5	0.0867 (14)	0.0427 (11)	0.0521 (11)	−0.0023 (10)	−0.0241 (10)	−0.0001 (9)
C1	0.0329 (12)	0.0273 (12)	0.0328 (11)	0.0001 (10)	0.0020 (10)	−0.0005 (10)
C2	0.0335 (12)	0.0301 (13)	0.0336 (12)	0.0022 (10)	0.0019 (10)	0.0008 (10)
C3	0.0344 (12)	0.0277 (12)	0.0319 (12)	0.0004 (10)	−0.0017 (10)	−0.0008 (10)
C4	0.0316 (12)	0.0290 (13)	0.0331 (12)	−0.0020 (10)	0.0029 (10)	−0.0036 (10)
C5	0.0427 (15)	0.0293 (12)	0.0385 (13)	0.0016 (11)	−0.0025 (11)	−0.0034 (10)
C6	0.0507 (16)	0.0645 (19)	0.0473 (15)	0.0095 (13)	−0.0159 (13)	−0.0124 (13)

Geometric parameters (Å, °)

O4—H4A	0.8504	N4—H4	0.8600
O4—H4B	0.8494	O1—C2	1.247 (2)
N1—C1	1.350 (3)	O2—C4	1.260 (2)
N1—C4	1.403 (2)	O3—C5	1.234 (3)
N1—H1	0.8600	O5—H5A	0.8501
N2—C1	1.347 (3)	O5—H5B	0.8501
N2—C2	1.407 (2)	C2—C3	1.400 (3)
N2—H2	0.8600	C3—C4	1.389 (3)
N3—C1	1.312 (3)	C5—C6	1.505 (3)
N3—H3A	0.8600	C6—H6A	0.9600
N3—H3B	0.8600	C6—H6B	0.9600
N4—C5	1.345 (3)	C6—H6C	0.9600
N4—C3	1.426 (3)
H4A—O4—H4B	106.3	O1—C2—N2	117.21 (19)
C1—N1—C4	124.06 (18)	C3—C2—N2	116.30 (19)
C1—N1—H1	118.0	C4—C3—C2	121.27 (19)
C4—N1—H1	118.0	C4—C3—N4	119.58 (19)
C1—N2—C2	124.33 (18)	C2—C3—N4	119.14 (19)
C1—N2—H2	117.8	O2—C4—C3	126.82 (19)
C2—N2—H2	117.8	O2—C4—N1	116.23 (19)
C1—N3—H3A	120.0	C3—C4—N1	116.95 (19)
C1—N3—H3B	120.0	O3—C5—N4	121.5 (2)
H3A—N3—H3B	120.0	O3—C5—C6	122.1 (2)
C5—N4—C3	123.67 (19)	N4—C5—C6	116.4 (2)
C5—N4—H4	118.2	C5—C6—H6A	109.5
C3—N4—H4	118.2	C5—C6—H6B	109.5
H5A—O5—H5B	105.9	H6A—C6—H6B	109.5
N3—C1—N2	121.66 (19)	C5—C6—H6C	109.5
N3—C1—N1	121.37 (19)	H6A—C6—H6C	109.5
N2—C1—N1	116.96 (17)	H6B—C6—H6C	109.5
O1—C2—C3	126.5 (2)
C2—N2—C1—N3	178.5 (2)	C5—N4—C3—C4	85.7 (3)
C2—N2—C1—N1	−2.9 (3)	C5—N4—C3—C2	−93.2 (3)
C4—N1—C1—N3	179.4 (2)	C2—C3—C4—O2	175.6 (2)
C4—N1—C1—N2	0.9 (3)	N4—C3—C4—O2	−3.3 (3)
C1—N2—C2—O1	−178.93 (19)	C2—C3—C4—N1	−3.7 (3)
C1—N2—C2—C3	1.6 (3)	N4—C3—C4—N1	177.38 (19)
O1—C2—C3—C4	−177.5 (2)	C1—N1—C4—O2	−177.07 (19)
N2—C2—C3—C4	1.9 (3)	C1—N1—C4—C3	2.4 (3)
O1—C2—C3—N4	1.4 (3)	C3—N4—C5—O3	1.2 (3)
N2—C2—C3—N4	−179.17 (18)	C3—N4—C5—C6	−178.0 (2)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1i	0.86	1.98	2.810 (2)	164.
N2—H2···O2ii	0.86	2.00	2.836 (2)	163.
N3—H3A···O5ii	0.86	1.95	2.803 (2)	172.
N3—H3B···O4i	0.86	1.98	2.843 (2)	178.
N4—H4···O2iii	0.86	2.27	3.115 (2)	170.
O4—H4A···O1	0.85	1.90	2.717 (2)	159.
O4—H4B···O3iv	0.85	1.96	2.812 (2)	176.
O5—H5A···O2	0.85	1.95	2.716 (2)	150.
O5—H5B···O3iii	0.85	1.97	2.814 (2)	174.

Symmetry codes: (i) −x+1, y−1/2, −z+3/2; (ii) −x+1, y+1/2, −z+3/2; (iii) x, −y+1/2, z−1/2; (iv) −x, −y+1, −z+1.