Redetermination of orotic acid monohydrate

Portalone, G.

doi:10.1107/S160053680800562X

organic compounds

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Volume 64| Part 4| April 2008| Page o656

doi:10.1107/S160053680800562X

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Redetermination of orotic acid monohydrate

Gustavo Portalone ^a ^*

^aChemistry Department, `Sapienza' University of Rome, P. le A. Moro 5, I-00185 Rome, Italy
^*Correspondence e-mail: g.portalone@caspur.it

(Received 26 February 2008; accepted 27 February 2008; online 5 March 2008)

The crystal structure of the title compound, which is also known as vitamin B₁₃ (systematic name: 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid monohydrate), C₅H₄N₂O₄·H₂O, was reported for the first time by Takusagawa & Shimada [Bull. Chem. Soc. Jpn (1973 ), 46, 2011–2019]. The present redetermination provides more precise values of the molecular geometry. The asymmetric unit comprises a planar diketo tautomer and a solvent water molecule. In the crystal structure, molecules are connected by O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds involving NH groups, two carbonyl O atoms and the solvent water molecule.

Related literature

For the previous structure determination, see: Takusagawa & Shimada (1973). For a general approach to the use of multiple hydrogen-bonding DNA/RNA nucleobases as potential supramolecular reagents, see: Portalone et al. (1999 ); Brunetti et al. (2000 , 2002 ); Portalone & Colapietro (2007 and references therein). For the computation of ring patterns formed by hydrogen bonds in crystal structures, see: Etter et al. (1990 ); Bernstein et al. (1995 ); Motherwell et al. (1999 ).

Experimental

Crystal data

C₅H₄N₂O₄·H₂O
M_r = 174.12
Triclinic, $[P \overline 1]$
a = 5.89854 (14) Å
b = 6.92921 (15) Å
c = 9.59160 (18) Å
α = 74.6778 (12)°
β = 72.3232 (16)°
γ = 68.447 (2)°
V = 342.21 (1) Å³
Z = 2
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 298 (2) K
0.20 × 0.15 × 0.15 mm

Data collection

Oxford Diffraction Xcalibur S CCD diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.32.3. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ) T_min = 0.977, T_max = 0.985
64781 measured reflections
2340 independent reflections
2048 reflections with I > 2σ(I)
R_int = 0.017

Refinement

R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.133
S = 1.08
2340 reflections
133 parameters
All H-atom parameters refined
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯O5	0.89 (3)	1.65 (3)	2.5231 (11)	166 (2)
N1—H1⋯O1ⁱ	0.85 (2)	2.03 (2)	2.8824 (11)	175.2 (19)
N3—H3⋯O2ⁱⁱ	0.94 (2)	1.87 (2)	2.8112 (11)	174.6 (18)
O5—H51⋯O2ⁱⁱⁱ	0.81 (3)	2.00 (3)	2.7786 (12)	161 (3)
O5—H52⋯O3^iv	0.82 (3)	1.98 (3)	2.7787 (12)	164 (2)
C5—H5⋯O4ⁱⁱⁱ	0.879 (19)	2.740 (19)	3.5922 (13)	163.7 (15)
Symmetry codes: (i) -x, -y, -z+2; (ii) -x, -y+1, -z+1; (iii) -x+2, -y, -z+1; (iv) -x+2, -y-1, -z+2.

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.32.3. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); cell refinement: CrysAlis RED (Oxford Diffraction, 2006 $[Oxford Diffraction (2006). CrysAlis CCD and CrysAlis RED. Versions 1.171.32.3. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]$ ); data reduction: CrysAlis RED; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEP3 (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053680800562X/kp2160sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053680800562X/kp2160Isup2.hkl

checkCIF report

Comment top

Orotic acid monohydrate, the only effective precursor in the biosynthesis of pyrimidine nucleobases, was determined some 35 years ago (Takusagawa & Shimada, 1973). In this study, 1488 unique reflections were collected at an ambient temperature by photographic techniques using Cu Kα radiation. 1344 of these, having values significantly above background, were estimated visually and no absorption correction was applied [µ(Cu Kα) = 15.4 cm^-1]. The final refinement led to R = 0.058 with standard deviations of 0.005Å in C—C bond lengths, As a part of a more general study of multiple hydrogen-bonded DNA/RNA-nucleobases as potential supramolecular reagents (Brunetti et al., 2000, 2002; Portalone et al., 1999; Portalone & Colapietro, 2007), this paper reports a redetermination of the crystal structure of the title compound, (I), with greater precision and accuracy. The asymmetric unit of (I) (Fig. 1) comprises a planar diketo tautomer and a crystal water molecule. The analysis of the crystal packing of (I) shows five N—H···O and O—H···O intermolecular hydrogen bonds (Table 1) which link the molecules into planar layers (Fig. 2). Two kinds of inversion-related N—H···O hydrogen bonds with graph-set motifs R²₂(8) (Etter et al., 1990; Bernstein et al., 1995; Motherwell et al., 1999) (Table 1) are formed between NH groups and two carbonyl O atoms (O1ⁱ and O2ⁱⁱ) [symmetry code: (i) -x, -y, z + 2; (ii) -x, -y + 1, -z + 1] to give a zigzag chain. Each chain is joined by three O—H···O intermolecular hydrogen bonds to form rings of descriptor R⁴₄(12), R⁴₃(13) and R⁴₄(18) through a water molecule (O4—H4···O5, O5—H51···O2ⁱⁱⁱ and O5—H52···O2^iv; symmetry code: (iii) -x + 2, -y, -z + 1; (iv) -x + 2, -y - 1, -z + 2). The hydrogen-bonded two-dimensional array involves the C5—H5···O4ⁱⁱⁱ intermolecular interaction.

Related literature top

For the previous structure determination, see: Takusagawa & Shimada (1973). For a general approach to the use of multiple hydrogen-bonding DNA/RNA nucleobases as potential supramolecular reagents, see: Portalone et al. (1999); Brunetti et al. (2000, 2002); Portalone & Colapietro (2007 and references therein). For the computation of ring patterns formed by hydrogen bonds in crystal structures, see: Etter et al. (1990); Bernstein et al. (1995); Motherwell et al. (1999).

Experimental top

The title compound (0.1 mmol, Sigma Aldrich of 98% purity) was dissolved in water (9 ml) and heated under reflux for 2 h. After cooling the solution to ambient temperature, crystals suitable for single-crystal X-ray diffraction were grown by slow evaporation.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: WinGX (Farrugia, 1999); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Displacements ellipsoids are at the 50% probability level. Hydrogen bonding is indicated by dashed lines.
	Fig. 2. Crystal packing diagram of (I). All atoms are shown as small spheres of arbitrary radii. Hydrogen bonding is indicated by dashed lines.

2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid monohydrate top

Crystal data top

C₅H₄N₂O₄·H₂O	Z = 2
M_r = 174.12	F(000) = 180
Triclinic, P1	D_x = 1.690 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 5.89854 (14) Å	Cell parameters from 64781 reflections
b = 6.92921 (15) Å	θ = 3.2–32.0°
c = 9.59160 (18) Å	µ = 0.15 mm⁻¹
α = 74.6778 (12)°	T = 298 K
β = 72.3232 (16)°	Plate, colourless
γ = 68.447 (2)°	0.20 × 0.15 × 0.15 mm
V = 342.21 (1) Å³

Data collection top

Oxford Diffraction Xcalibur S CCD diffractometer	2340 independent reflections
Radiation source: Enhance (Mo) X-ray source	2048 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.017
Detector resolution: 16.0696 pixels mm^-1	θ_max = 32.0°, θ_min = 3.2°
ω and ϕ scans	h = −8→8
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	k = −10→10
T_min = 0.977, T_max = 0.985	l = −14→14
64781 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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.133	All H-atom parameters refined
S = 1.08	w = 1/[σ²(F_o²) + (0.0846P)² + 0.0376P] where P = (F_o² + 2F_c²)/3
2340 reflections	(Δ/σ)_max < 0.001
133 parameters	Δρ_max = 0.19 e Å⁻³
0 restraints	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₅H₄N₂O₄·H₂O	γ = 68.447 (2)°
M_r = 174.12	V = 342.21 (1) Å³
Triclinic, P1	Z = 2
a = 5.89854 (14) Å	Mo Kα radiation
b = 6.92921 (15) Å	µ = 0.15 mm⁻¹
c = 9.59160 (18) Å	T = 298 K
α = 74.6778 (12)°	0.20 × 0.15 × 0.15 mm
β = 72.3232 (16)°

Data collection top

Oxford Diffraction Xcalibur S CCD diffractometer	2340 independent reflections
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006)	2048 reflections with I > 2σ(I)
T_min = 0.977, T_max = 0.985	R_int = 0.017
64781 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.044	0 restraints
wR(F²) = 0.133	All H-atom parameters refined
S = 1.08	Δρ_max = 0.19 e Å⁻³
2340 reflections	Δρ_min = −0.22 e Å⁻³
133 parameters

Special details top

Experimental. Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

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
O1	−0.14403 (15)	0.19593 (14)	0.87497 (9)	0.0437 (2)
O2	0.33017 (14)	0.40869 (13)	0.43298 (8)	0.0402 (2)
O3	0.67729 (18)	−0.25757 (17)	0.92057 (11)	0.0575 (3)
O4	0.94015 (16)	−0.17721 (14)	0.70790 (10)	0.0430 (2)
H4	1.045 (5)	−0.276 (4)	0.759 (3)	0.072 (6)*
N1	0.27952 (15)	0.03091 (13)	0.83018 (9)	0.03108 (19)
H1	0.248 (4)	−0.038 (3)	0.918 (2)	0.052 (4)*
C2	0.06502 (18)	0.17428 (15)	0.79307 (10)	0.0302 (2)
N3	0.09988 (15)	0.29328 (13)	0.65310 (8)	0.03059 (19)
H3	−0.050 (4)	0.391 (3)	0.630 (2)	0.054 (5)*
C4	0.32531 (17)	0.28849 (14)	0.55477 (10)	0.0284 (2)
C5	0.54286 (17)	0.13666 (14)	0.60218 (10)	0.0295 (2)
H5	0.689 (3)	0.127 (3)	0.540 (2)	0.042 (4)*
C6	0.51057 (17)	0.01317 (13)	0.73716 (9)	0.02706 (19)
C7	0.72006 (19)	−0.15575 (15)	0.79814 (11)	0.0325 (2)
O5	1.28887 (17)	−0.45822 (16)	0.81521 (11)	0.0523 (3)
H51	1.421 (5)	−0.460 (4)	0.757 (3)	0.080 (7)*
H52	1.313 (5)	−0.528 (4)	0.896 (3)	0.082 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0285 (4)	0.0499 (5)	0.0329 (4)	−0.0054 (3)	−0.0022 (3)	0.0094 (3)
O2	0.0291 (4)	0.0447 (4)	0.0298 (4)	−0.0065 (3)	−0.0079 (3)	0.0154 (3)
O3	0.0390 (5)	0.0612 (6)	0.0449 (5)	−0.0062 (4)	−0.0138 (4)	0.0266 (4)
O4	0.0302 (4)	0.0449 (4)	0.0385 (4)	−0.0003 (3)	−0.0112 (3)	0.0054 (3)
N1	0.0289 (4)	0.0311 (4)	0.0247 (3)	−0.0063 (3)	−0.0080 (3)	0.0067 (3)
C2	0.0277 (4)	0.0308 (4)	0.0252 (4)	−0.0071 (3)	−0.0065 (3)	0.0037 (3)
N3	0.0245 (4)	0.0319 (4)	0.0258 (3)	−0.0047 (3)	−0.0077 (3)	0.0070 (3)
C4	0.0260 (4)	0.0289 (4)	0.0244 (4)	−0.0064 (3)	−0.0078 (3)	0.0041 (3)
C5	0.0243 (4)	0.0308 (4)	0.0258 (4)	−0.0045 (3)	−0.0072 (3)	0.0029 (3)
C6	0.0268 (4)	0.0251 (4)	0.0257 (4)	−0.0045 (3)	−0.0106 (3)	0.0014 (3)
C7	0.0306 (4)	0.0297 (4)	0.0322 (4)	−0.0049 (3)	−0.0137 (3)	0.0038 (3)
O5	0.0287 (4)	0.0598 (6)	0.0426 (5)	0.0010 (4)	−0.0082 (3)	0.0118 (4)

Geometric parameters (Å, º) top

O1—C2	1.2241 (12)	N3—C4	1.3716 (12)
O2—C4	1.2418 (10)	N3—H3	0.94 (2)
O3—C7	1.2056 (13)	C4—C5	1.4387 (12)
O4—C7	1.3040 (13)	C5—C6	1.3525 (12)
O4—H4	0.89 (3)	C5—H5	0.879 (19)
N1—C6	1.3656 (12)	C6—C7	1.5012 (12)
N1—C2	1.3702 (12)	O5—H51	0.81 (3)
N1—H1	0.85 (2)	O5—H52	0.82 (3)
C2—N3	1.3772 (11)

C7—O4—H4	104.3 (16)	N3—C4—C5	115.74 (8)
C6—N1—C2	122.36 (8)	C6—C5—C4	118.56 (8)
C6—N1—H1	126.4 (14)	C6—C5—H5	124.1 (11)
C2—N1—H1	111.2 (14)	C4—C5—H5	117.3 (11)
O1—C2—N1	123.81 (8)	C5—C6—N1	122.13 (8)
O1—C2—N3	121.35 (8)	C5—C6—C7	124.03 (9)
N1—C2—N3	114.83 (8)	N1—C6—C7	113.84 (8)
C4—N3—C2	126.29 (7)	O3—C7—O4	125.70 (9)
C4—N3—H3	120.3 (12)	O3—C7—C6	120.28 (10)
C2—N3—H3	113.3 (12)	O4—C7—C6	114.02 (8)
O2—C4—N3	119.61 (8)	H51—O5—H52	110 (2)
O2—C4—C5	124.64 (9)

C6—N1—C2—O1	−178.86 (10)	C4—C5—C6—N1	−1.20 (15)
C6—N1—C2—N3	2.20 (15)	C4—C5—C6—C7	178.02 (9)
O1—C2—N3—C4	177.12 (10)	C2—N1—C6—C5	0.18 (16)
N1—C2—N3—C4	−3.91 (15)	C2—N1—C6—C7	−179.11 (9)
C2—N3—C4—O2	−178.17 (10)	C5—C6—C7—O3	178.85 (12)
C2—N3—C4—C5	2.97 (15)	N1—C6—C7—O3	−1.87 (15)
O2—C4—C5—C6	−179.05 (10)	C5—C6—C7—O4	−1.13 (15)
N3—C4—C5—C6	−0.26 (14)	N1—C6—C7—O4	178.15 (9)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O5	0.89 (3)	1.65 (3)	2.5231 (11)	166 (2)
N1—H1···O1ⁱ	0.85 (2)	2.03 (2)	2.8824 (11)	175.2 (19)
N3—H3···O2ⁱⁱ	0.94 (2)	1.87 (2)	2.8112 (11)	174.6 (18)
O5—H51···O2ⁱⁱⁱ	0.81 (3)	2.00 (3)	2.7786 (12)	161 (3)
O5—H52···O3^iv	0.82 (3)	1.98 (3)	2.7787 (12)	164 (2)
C5—H5···O4ⁱⁱⁱ	0.879 (19)	2.740 (19)	3.5922 (13)	163.7 (15)

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

Experimental details

Crystal data
Chemical formula	C₅H₄N₂O₄·H₂O
M_r	174.12
Crystal system, space group	Triclinic, P1
Temperature (K)	298
a, b, c (Å)	5.89854 (14), 6.92921 (15), 9.59160 (18)
α, β, γ (°)	74.6778 (12), 72.3232 (16), 68.447 (2)
V (Å³)	342.21 (1)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.15
Crystal size (mm)	0.20 × 0.15 × 0.15

Data collection
Diffractometer	Oxford Diffraction Xcalibur S CCD diffractometer
Absorption correction	Multi-scan (CrysAlis RED; Oxford Diffraction, 2006)
T_min, T_max	0.977, 0.985
No. of measured, independent and observed [I > 2σ(I)] reflections	64781, 2340, 2048
R_int	0.017
(sin θ/λ)_max (Å⁻¹)	0.745

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.133, 1.08
No. of reflections	2340
No. of parameters	133
H-atom treatment	All H-atom parameters refined
Δρ_max, Δρ_min (e Å⁻³)	0.19, −0.22

Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···O5	0.89 (3)	1.65 (3)	2.5231 (11)	166 (2)
N1—H1···O1ⁱ	0.85 (2)	2.03 (2)	2.8824 (11)	175.2 (19)
N3—H3···O2ⁱⁱ	0.94 (2)	1.87 (2)	2.8112 (11)	174.6 (18)
O5—H51···O2ⁱⁱⁱ	0.81 (3)	2.00 (3)	2.7786 (12)	161 (3)
O5—H52···O3^iv	0.82 (3)	1.98 (3)	2.7787 (12)	164 (2)
C5—H5···O4ⁱⁱⁱ	0.879 (19)	2.740 (19)	3.5922 (13)	163.7 (15)

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

Acknowledgements

The author thanks MIUR (Rome) for financial support in 2006 of the project `X-ray diffractometry and spectrometry'.

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