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

Zhang, X.-M.; Zhou, H.-L.; Hu, Q.-L.

doi:10.1107/S1600536811034441

organic compounds

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ISSN: 2056-9890

Volume 67| Part 9| September 2011| Page o2526

doi:10.1107/S1600536811034441

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

Xiao-Min Zhang,^a Hui-Liang Zhou ^a and Qi-Lin Hu ^a ^*

^aCollege of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021, Ninxia, People's Republic of China
^*Correspondence e-mail: huqilin@nxu.edu.cn

(Received 21 July 2011; accepted 22 August 2011; online 31 August 2011)

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, P 2₁ /c
a = 9.5501 (12) Å
b = 12.2161 (13) Å
c = 8.5324 (8) Å
β = 98.708 (1)°
V = 983.96 (19) Å³
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[F² > 2σ(F²)] = 0.042
wR(F²) = 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

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⋯O3^iv	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) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (ii) $[-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iii) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (iv) -x, -y+1, -z+1.

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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811034441/fl2354sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536811034441/fl2354Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536811034441/fl2354Isup3.cml

checkCIF report

Comment top

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).

Related literature top

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 top

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).

Computing details top

Data collection: SMART (Bruker, 2002); cell refinement: SMART (Bruker, 2002); 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 (Sheldrick, 2008).

Figures top

	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.

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

Crystal data top

C₆H₈N₄O₃·2H₂O	F(000) = 464
M_r = 220.20	D_x = 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 top

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

Refinement top

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(F_o²) + (0.0641P)² + 0.2581P] where P = (F_o² + 2F_c²)/3
1727 reflections	(Δ/σ)_max < 0.001
136 parameters	Δρ_max = 0.20 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₆H₈N₄O₃·2H₂O	V = 983.96 (19) Å³
M_r = 220.20	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 9.5501 (12) Å	µ = 0.13 mm⁻¹
b = 12.2161 (13) Å	T = 298 K
c = 8.5324 (8) Å	0.23 × 0.15 × 0.10 mm
β = 98.708 (1)°

Data collection top

Bruker SMART CCD area-detector diffractometer	1727 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2002)	1082 reflections with I > 2σ(I)
T_min = 0.971, T_max = 0.987	R_int = 0.039
5002 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.120	H-atom parameters constrained
S = 0.85	Δρ_max = 0.20 e Å⁻³
1727 reflections	Δρ_min = −0.26 e Å⁻³
136 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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, º) top

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, º) top

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···O3^iv	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.

Experimental details

Crystal data
Chemical formula	C₆H₈N₄O₃·2H₂O
M_r	220.20
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	298
a, b, c (Å)	9.5501 (12), 12.2161 (13), 8.5324 (8)
β (°)	98.708 (1)
V (Å³)	983.96 (19)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.13
Crystal size (mm)	0.23 × 0.15 × 0.10

Data collection
Diffractometer	Bruker SMART CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2002)
T_min, T_max	0.971, 0.987
No. of measured, independent and observed [I > 2σ(I)] reflections	5002, 1727, 1082
R_int	0.039
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.120, 0.85
No. of reflections	1727
No. of parameters	136
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.26

Computer programs: SMART (Bruker, 2002), SAINT (Bruker, 2002), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1ⁱ	0.86	1.98	2.810 (2)	163.6
N2—H2···O2ⁱⁱ	0.86	2.00	2.836 (2)	162.7
N3—H3A···O5ⁱⁱ	0.86	1.95	2.803 (2)	171.8
N3—H3B···O4ⁱ	0.86	1.98	2.843 (2)	178.3
N4—H4···O2ⁱⁱⁱ	0.86	2.27	3.115 (2)	169.6
O4—H4A···O1	0.85	1.90	2.717 (2)	159.3
O4—H4B···O3^iv	0.85	1.96	2.812 (2)	175.7
O5—H5A···O2	0.85	1.95	2.716 (2)	149.6
O5—H5B···O3ⁱⁱⁱ	0.85	1.97	2.814 (2)	174.0

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.

Acknowledgements

The authors thank the Instrumental Analysis Center of LiaoCheng University for the data collection.

References

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