Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-di­hydro­pyrimidin-1-ium 3-hy­droxy­pyridine-2-carboxyl­ate

Karthikeyan, A.; Thomas Muthiah, P.; Perdih, F.

doi:10.1107/S1600536814021898

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ISSN: 2056-9890

Volume 70| Part 11| November 2014| Pages 328-330

doi:10.1107/S1600536814021898

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Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium 3-hydroxypyridine-2-carboxylate

Ammasai Karthikeyan,^a Packianathan Thomas Muthiah ^a ^* and Franc Perdih ^b,^c

^aSchool of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India, ^bFaculty of Chemistry and Chemical Technology, University of Ljubljana, Vecna pot 113, PO Box 537, SI-1000 Ljubljana, Slovenia, and ^cCO EN-FIST, Trg Osvobodilne fronte 13, SI-1000 Ljubljana, Slovenia
^*Correspondence e-mail: tommtrichy@yahoo.co.in

Edited by E. R. T. Tiekink, University of Malaya, Malaysia (Received 30 September 2014; accepted 4 October 2014; online 11 October 2014)

The asymmetric unit of the title salt, C₄H₅FN₃O⁺·C₆H₄NO₃⁻, contains one 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium (5-fluorocytosinium, 5FC) cation and a 3-hydroxypicolinate (3HAP) anion. The 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidine molecule is protonated at one of the pyrimidine N atoms. The typical intramolecular N—H⋯F and O—H⋯O S(5) and S(6) hydrogen-bond ring motifs are observed in the cations and anions. The protonated N atom and 2-amine group of the 5FC cation interact with the 3HPA anion through a pair of nearly parallel N—H⋯O hydrogen bonds, forming a robust R₂²(8) ring motif. The ions are further linked by N—H⋯N, O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds, generating R₂²(7), R₃³(12) and R₆⁵(18) ring motifs, respectively, leading to supramolecular wave-like sheets parallel to (010). The crystal structure is further stabilized by C—H⋯π interactions, generating a three-dimensional architecture.

Keywords: crystal structure; antifungal drug; 5-fluorocytosine; hydrogen bonding; supramolecular structure; hydrogen-bond ring motifs; crystal structure.

CCDC reference: 1027535

1. Chemical context

Fluorinated pyrimidine and purine derivatives have received much interest because of their wide range of biological applications (Giner-Sorolla & Bendich, 1958 ). 5-Fuorocytosine is a fluorinated pyrimidine derivative anti-metabolite drug and is also extensively used as an anti-fungal agent for the treatment of Candida and Cryptococcus (Vermes et al., 2000 ). 5-Fluorocytosine is a versatile molecule that plays essential roles in many biological applications, such as anti-tumour, potential gene therapy and gene-directed prodrug therapy (GDEPT) in the treatment of cancer (Kohila et al., 2012 ). The crystal structures of 5-fluorocytosine monohydrate, 5-fluorocytosine co-crystals and salts have also been reported (Louis et al., 1982 ; Tutughamiarso et al., 2012 ; Perumalla & Sun, 2014 ; Prabakaran et al., 2001 ). The crystal structures of various salts and complexes of 3-hydroxypicolinic acid have also been reported (Quintal et al., 2000 ; Soares-Santos et al., 2003 ; Betz and Gerber, 2011 ; Nirmalram et al., 2011 ).

We report herein the molecular structure of the title salt, formed from the reaction of 5-fluorocytosine with 3-hydroxypicoinic acid, namely 5-fluorocytosinium 3-hydroxypicolinate.

2. Structural commentary

The asymmetric unit contains a 5-fluorocytosinium cation and a 3-hydroxypicolinate anion (Fig. 1). The 5-fluorocytosine molecule is protonated at N3, as is evident from the increase in the internal angle at N3 from 120.8 (5) in neutral 5-fluorocytosine (Louis et al., 1982) to 124.85 (15)°. There is an intramolecular N—H⋯F hydrogen bond with an S(5) ring motif between the N4 amino group and the F atom of the 5-fluorocytosinum cation. These hydrogen-bonding parameters are similar to those observed in 5-fluorocytosinium salicylate (Prabakaran et al., 2001). An intramolecular O—H⋯O interaction forms an S(6) motif between the phenolic OH and carboxylate group, which is also observed in 3-hydroxypyridinium-2-carboxylate (Betz & Gerber, 2011).

Figure 1
The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids. Dashed lines represent hydrogen bonds.

3. Supramolecular features

In the crystal structure, the carboxylate group of the 3-hydroxypicolinate anion (O3 and O4) interacts with the protonated N3 atom and the 4-amino group of the 5-fluorocytosinium moiety through a pair of N—H⋯O hydrogen bonds, forming a robust $[R_{2}^{2}]$ (8) motif (Etter, 1990 ; Bernstein et al., 1995 ). The 3-hydroxypicolinate (N2 and C12) atoms interact with the N1 atom and the exocyclic oxygen O2 atom of the 5-fluorocytosinium moiety through a pair of N—H⋯N and C—H⋯O hydrogen bonds, forming an $[R_{2}^{2}]$ (7) motif. This type of motif rarely occurs in cytosinium carboxylate interactions (Benali-Cherif et al., 2009 ). The motif is further connected on the other side by R₃³(12) and R₅⁶(18) motifs formed (Bernstein et al., 1995) through C—H⋯O and N—H⋯O hydrogen bonds involving the O2 and N4 atoms of the 5-fluorocytosinium cation and the symmetry-related C6 atom of the another cytosinium cation and O1 atoms of 3-hydroxypicolinate anions, generating a wavy sheet-like structure parallel to (010) (Fig. 2). These wavy sheets are interconnected via C10—H10⋯O2 hydrogen bonds (Fig. 3). The crystal structure is further stabilized by C—H⋯π interactions between 3-hydroxypicolinate anions, Table 1, Fig. 4.

Table 1
Hydrogen-bond geometry (Å, °)

Cg is the centroid of the N2/C8–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N2ⁱ	0.86	2.04	2.873 (2)	163
N3—H3⋯O4	0.86	1.85	2.6665 (18)	158
N4—H4A⋯O3	0.86	1.98	2.830 (2)	169
N4—H4B⋯O1ⁱⁱ	0.86	2.26	3.076 (2)	159
N4—H4B⋯F1	0.86	2.43	2.7312 (18)	101
O1—H1A⋯O3	0.82	1.83	2.5542 (18)	146
C6—H6⋯O2ⁱ	0.93	2.29	3.127 (2)	150
C10—H10⋯O3ⁱⁱⁱ	0.93	2.54	3.272 (2)	136
C12—H12⋯O2^iv	0.93	2.39	3.129 (2)	137
Cll—H11⋯Cg1^v	0.93	2.88	3.426 (2)	119
Symmetry codes: (i) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (ii) $[x-{\script{1\over 2}}, y, -z+{\script{1\over 2}}]$ ; (iii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iv) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+1]$ ; (v) $[-x+{\script{3\over 2}}, y-{\script{1\over 2}}, z]$ .

Figure 2
A view of the supramolecular wavy sheet-like structure formed by N—H⋯F, O—H⋯O, N—H⋯O, N—H⋯N and C—H⋯O hydrogen bonds. Symmetry codes are given in Table 1

. Dashed lines represent hydrogen bonds.

Figure 3
The wavy sheets interlinked by C—H⋯O hydrogen bonds. Dashed lines represent hydrogen bonds (see Table 1

for details).

Figure 4
A view of the C—H⋯π interactions shown as dashed lines. Symmetry codes are given in Table 1

4. Synthesis and crystallization

Hot aqueous solutions of 5-fluorocytosine (32 mg, Alfa Aesar) and 3-hydroxypicolinic acid (37 mg, Alfa Aesar) were mixed in a 1:1 molar ratio. The resulting solution was warmed over a water bath for half an hour and then kept at room temperature for crystallization. After a week, colourless prismatic crystals were obtained.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms were initially located in difference Fourier maps and were subsequently treated as riding atoms in geometrically idealized positions, with C—H = 0.93, N—H = 0.86 and O—H = 0.83 Å, and with U_iso(H) = 1.2U_eq(C,N) and U_iso(H) = 1.5U_eq(O).

Table 2
Experimental details

Crystal data
Chemical formula	C₄H₅FN₃O⁺·C₆H₄NO₃⁻
M_r	268.21
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	293
a, b, c (Å)	12.6487 (4), 7.0786 (2), 23.7200 (6)
V (Å³)	2123.77 (10)
Z	8
Radiation type	Mo Kα
μ (mm⁻¹)	0.14
Crystal size (mm)	0.15 × 0.05 × 0.05

Data collection
Diffractometer	Agilent SuperNova (Dual, Cu at zero, Atlas)
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011 )
T_min, T_max	0.979, 0.993
No. of measured, independent and observed [I > 2σ(I)] reflections	8914, 2437, 1955
R_int	0.027

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.111, 1.08
No. of reflections	2437
No. of parameters	173
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.19
Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 and SHELXL97 (Sheldrick, 2008 ) and PLATON (Spek, 2009 ).

Supporting information

CCDC reference: 1027535

Crystal structure: contains datablock I. DOI: 10.1107/S1600536814021898/tk5344sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536814021898/tk5344Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536814021898/tk5344Isup3.cml

checkCIF report

Chemical context top

Fluorinated pyrimidine and purine derivatives have received much interest because of their wide range of biological applications (Giner-Sorolla & Bendich, 1958). 5-Fuorocytosine is a fluorinated pyrimidine derivative anti-metabolite drug and is also extensively used as an anti-fungal agent for the treatment of Candida and Cryptococcus (Vermes et al., 2000). 5-Flurocytosine is a versatile molecule that plays essential roles in many biological applications, such as anti-tumour, potential gene therapy and gene-directed prodrug therapy (GDEPT) in the treatment of cancer (Kohila et al., 2012). The crystal structures of 5-fluorocytosine monohydrate, 5-flurocytosine co-crystals and salts have also been reported (Louis et al., 1982; Tutughamiarso et al., 2012; Perumalla & Sun, 2014; Prabakaran et al., 2001). The crystal structures of various salts and complexes of 3-hydroxypicolinc acid have also been reported (Quintal et al., 2000; Soares-Santos et al., 2003; Betz and Gerber, 2011; Nirmalram et al., 2011). We report here the molecular structure of a salt, (I), formed from the reaction of 5-fluorocytosine with 3-hydroxypicoinic acid, namely 5-fluorocytosinium 3-hydroxypicolinate.

Structural commentary top

The asymmetric unit of (I) contains an 5-fluorocytosinium molecule and a 3-hydroxypicolininate anion (Fig. 1). The 5-fluorocytosine molecule is protonated at N3, as is evident from the increase in the internal angle at N3 from 120.8 (5) neutral 5-fluorocytosine (Louis et al., 1982) to 124.85 (15)°. There is an intramolecular N—H···F hydrogen bond with an S(5) ring motif between the N4 amino group and the F atom of the 5-fluorocytosinum cation. These hydrogen-bonding parameters are in agreement those in with 5-fluorocytosinium salicylate (Prabakaran et al., 2001). An intramolecular O—H···O interaction forms an S(6) motif between the phenolic OH and carboxylate groups, which is also observed in 3-hydroxypyridinium-2-carboxylate (Betz & Gerber, 2011).

Supramolecular features top

In the crystal structure, the carboxylate group of the 3-hydroxypicolinate anion (O3 and O4) interacts with the protonated N3 atom and the 4-amino group of the 5-fluorocytosinium moiety through a pair of N—H···O hydrogen bonds, forming a robust R₂²(8) motif (Etter, 1990; Bernstein et al., 1995). The 3-hydroxypicolinate (N2 and C12) atoms interact with the N1 atom and the exocyclic oxygen O2 atom of the 5-fluorocytosinium moiety through a pair of N—H···N and C—H···O hydrogen bonds, forming an R₂²(7) motif. This type of motif rarely occurs in cytosinium carboxylate interactions (Benali-Cherif et al., 2009). The motif is further connected on the other side by R₃³(12) and R₅⁶(18) motifs (Bernstein et al., 1995) formed through C—H···O and N—H···O hydrogen bonds involving the O2 and N4 atoms of the 5-fluorocytosinium cation and the symmetry-related C6 atom of the another cytosine cation and O1 atoms of 3-hydroxypicolinate anions, generating a wavy sheet-like structure parallel to (010) [OK?] (Fig. 2). These wavy sheets are interconnected via C10—H10···O2 hydrogen bonds (Fig. 3). The crystal structure is further stabilized by C—H···π interactions between 3-hydroxypicolinate anions, Table 1.

Synthesis and crystallization top

Hot aqueous solutions of 5-fluorocytosine (32 mg, Alfa Aesar) and 3-hydroxypicolinicacid (37 mg, Alfa Aesar) were mixed in a 1:1 molar ratio. The resulting solution was warmed over a water bath for half an hour and then kept at room temperature for crystallization. After a week, colourless prismatic crystals were obtained.

Refinement top

Related literature top

For applications of 5-flurocytosine, see: Vermes et al. (2000); Kohila et al. (2012). For applications and crystal structures of 3-hydroxypicolinic acid derivatives, see: Quintal et al. (2000); Soares-Santos et al. (2003); Betz and Gerber (2011); Nirmalram et al. (2011). For related structures, see: Louis et al. (1982); Prabakaran et al. (2001); Tutughamiarso et al. (2012); Perumalla et al. (2014); Benali-Cherif et al. (2009). For hydrogen-bond graph-set notation, see: Etter et al. (1990); Bernstein et al. (1995).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top

The asymmetric unit of the title compound, showing 30% probability displacement ellipsoids. Dashed lines represent hydrogen bonds.

A view of the supramolecular wavy sheet-like structure formed by N—H···F, O—H···O, N—H···O, N—H···N and C—H···O hydrogen bonds. Symmetry codes are given in Table 1. Dashed lines represent hydrogen bonds.

The wavy sheets interlinked by C—H···O hydrogen bonds. Dashed lines represent hydrogen bonds.

A view of the C—H···π interactions shown as dashed lines. Symmetry codes are given in Table 1.

4-Amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium 3-hydroxypicolinate top

Crystal data top

C₄H₅FN₃O⁺·C₆H₄NO₃⁻	F(000) = 1104
M_r = 268.21	D_x = 1.678 Mg m⁻³
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 3551 reflections
a = 12.6487 (4) Å	θ = 3.7–29.7°
b = 7.0786 (2) Å	µ = 0.14 mm⁻¹
c = 23.7200 (6) Å	T = 293 K
V = 2123.77 (10) Å³	Needle, colourless
Z = 8	0.15 × 0.05 × 0.05 mm

Data collection top

Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer	2437 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	1955 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.027
Detector resolution: 10.4933 pixels mm^-1	θ_max = 27.5°, θ_min = 3.2°
ω scans	h = −16→11
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	k = −9→6
T_min = 0.979, T_max = 0.993	l = −30→30
8914 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) = 0.111	H-atom parameters constrained
S = 1.08	w = 1/[σ²(F_o²) + (0.0458P)² + 0.8599P] where P = (F_o² + 2F_c²)/3
2437 reflections	(Δ/σ)_max < 0.001
173 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³

Crystal data top

C₄H₅FN₃O⁺·C₆H₄NO₃⁻	V = 2123.77 (10) Å³
M_r = 268.21	Z = 8
Orthorhombic, Pbca	Mo Kα radiation
a = 12.6487 (4) Å	µ = 0.14 mm⁻¹
b = 7.0786 (2) Å	T = 293 K
c = 23.7200 (6) Å	0.15 × 0.05 × 0.05 mm

Data collection top

Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer	2437 independent reflections
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2011)	1955 reflections with I > 2σ(I)
T_min = 0.979, T_max = 0.993	R_int = 0.027
8914 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.042	0 restraints
wR(F²) = 0.111	H-atom parameters constrained
S = 1.08	Δρ_max = 0.24 e Å⁻³
2437 reflections	Δρ_min = −0.19 e Å⁻³
173 parameters

Special details top

Experimental. 185 frames in 5 runs of ω scans. Crystal-detector distance = 55.0 mm.

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
F1	−0.04979 (8)	0.58078 (18)	0.39473 (5)	0.0483 (3)
N1	0.10109 (11)	0.8014 (2)	0.50442 (6)	0.0335 (3)
H1	0.0909	0.8491	0.5373	0.040*
N3	0.21136 (11)	0.7249 (2)	0.42943 (6)	0.0312 (3)
H3	0.2733	0.7239	0.4145	0.037*
N4	0.14821 (12)	0.5828 (2)	0.34880 (6)	0.0392 (4)
H4A	0.2108	0.5846	0.3347	0.047*
H4B	0.0966	0.5360	0.3298	0.047*
O2	0.27785 (10)	0.8667 (2)	0.50714 (5)	0.0446 (4)
C2	0.20128 (14)	0.8021 (3)	0.48270 (7)	0.0317 (4)
C4	0.13147 (14)	0.6513 (2)	0.39922 (7)	0.0296 (4)
C5	0.03071 (13)	0.6548 (3)	0.42474 (7)	0.0332 (4)
C6	0.01722 (14)	0.7286 (3)	0.47624 (7)	0.0346 (4)
H6	−0.0496	0.7299	0.4926	0.041*
O1	0.49981 (11)	0.4529 (2)	0.24635 (5)	0.0430 (4)
H1A	0.4410	0.4833	0.2578	0.064*
O3	0.36400 (10)	0.5738 (2)	0.31741 (5)	0.0408 (3)
O4	0.41321 (10)	0.6570 (2)	0.40413 (5)	0.0416 (3)
N2	0.61308 (11)	0.5297 (2)	0.38561 (6)	0.0296 (3)
C7	0.43231 (13)	0.5915 (3)	0.35634 (7)	0.0301 (4)
C8	0.54219 (13)	0.5251 (2)	0.34318 (7)	0.0274 (4)
C9	0.56959 (14)	0.4572 (3)	0.28970 (7)	0.0306 (4)
C10	0.67182 (14)	0.3927 (3)	0.28059 (7)	0.0347 (4)
H10	0.6918	0.3464	0.2455	0.042*
C11	0.74279 (14)	0.3982 (3)	0.32407 (7)	0.0339 (4)
H11	0.8118	0.3565	0.3189	0.041*
C12	0.71035 (14)	0.4669 (3)	0.37608 (7)	0.0332 (4)
H12	0.7589	0.4690	0.4055	0.040*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0265 (6)	0.0690 (8)	0.0494 (7)	−0.0079 (5)	−0.0027 (5)	−0.0139 (6)
N1	0.0293 (8)	0.0439 (9)	0.0272 (7)	0.0025 (7)	0.0027 (6)	−0.0036 (6)
N3	0.0221 (7)	0.0427 (8)	0.0288 (7)	−0.0005 (6)	0.0025 (5)	−0.0008 (6)
N4	0.0295 (8)	0.0552 (10)	0.0330 (8)	−0.0036 (8)	0.0024 (6)	−0.0086 (7)
O2	0.0291 (7)	0.0668 (9)	0.0379 (7)	−0.0048 (7)	−0.0022 (5)	−0.0131 (7)
C2	0.0278 (9)	0.0392 (9)	0.0280 (8)	0.0024 (8)	0.0003 (7)	0.0009 (7)
C4	0.0278 (9)	0.0330 (9)	0.0280 (8)	0.0017 (7)	−0.0008 (6)	0.0039 (7)
C5	0.0238 (8)	0.0406 (10)	0.0351 (9)	−0.0010 (8)	−0.0034 (7)	−0.0001 (8)
C6	0.0249 (8)	0.0426 (10)	0.0362 (9)	0.0019 (8)	0.0043 (7)	0.0038 (8)
O1	0.0331 (7)	0.0677 (9)	0.0280 (6)	0.0063 (7)	−0.0043 (5)	−0.0070 (6)
O3	0.0251 (6)	0.0644 (9)	0.0329 (7)	0.0030 (6)	−0.0020 (5)	0.0009 (6)
O4	0.0275 (7)	0.0623 (9)	0.0349 (7)	0.0053 (6)	0.0032 (5)	−0.0091 (6)
N2	0.0244 (7)	0.0380 (8)	0.0265 (7)	−0.0016 (6)	0.0002 (5)	0.0011 (6)
C7	0.0247 (8)	0.0361 (9)	0.0294 (8)	−0.0013 (7)	0.0015 (7)	0.0045 (7)
C8	0.0238 (8)	0.0326 (9)	0.0258 (8)	−0.0020 (7)	0.0014 (6)	0.0024 (7)
C9	0.0292 (9)	0.0367 (9)	0.0258 (8)	−0.0007 (8)	−0.0012 (6)	0.0007 (7)
C10	0.0357 (10)	0.0394 (10)	0.0290 (8)	0.0047 (8)	0.0048 (7)	−0.0026 (7)
C11	0.0257 (9)	0.0375 (9)	0.0386 (9)	0.0058 (8)	0.0028 (7)	0.0011 (8)
C12	0.0267 (9)	0.0411 (10)	0.0319 (9)	0.0005 (8)	−0.0030 (7)	0.0012 (8)

Geometric parameters (Å, º) top

F1—C5	1.348 (2)	O1—C9	1.355 (2)
N1—C6	1.356 (2)	O1—H1A	0.8200
N1—C2	1.368 (2)	O3—C7	1.271 (2)
N1—H1	0.8600	O4—C7	1.248 (2)
N3—C4	1.344 (2)	N2—C12	1.328 (2)
N3—C2	1.383 (2)	N2—C8	1.348 (2)
N3—H3	0.8600	C7—C8	1.500 (2)
N4—C4	1.308 (2)	C8—C9	1.400 (2)
N4—H4A	0.8600	C9—C10	1.388 (2)
N4—H4B	0.8600	C10—C11	1.368 (2)
O2—C2	1.218 (2)	C10—H10	0.9300
C4—C5	1.411 (2)	C11—C12	1.388 (2)
C5—C6	1.340 (2)	C11—H11	0.9300
C6—H6	0.9300	C12—H12	0.9300

C6—N1—C2	122.73 (15)	C9—O1—H1A	109.5
C6—N1—H1	118.6	C12—N2—C8	118.75 (14)
C2—N1—H1	118.6	O4—C7—O3	124.40 (16)
C4—N3—C2	124.84 (15)	O4—C7—C8	118.99 (15)
C4—N3—H3	117.6	O3—C7—C8	116.60 (15)
C2—N3—H3	117.6	N2—C8—C9	121.32 (15)
C4—N4—H4A	120.0	N2—C8—C7	116.96 (14)
C4—N4—H4B	120.0	C9—C8—C7	121.70 (15)
H4A—N4—H4B	120.0	O1—C9—C10	118.77 (15)
O2—C2—N1	123.98 (16)	O1—C9—C8	122.25 (16)
O2—C2—N3	120.68 (16)	C10—C9—C8	118.98 (15)
N1—C2—N3	115.34 (15)	C11—C10—C9	118.99 (16)
N4—C4—N3	120.63 (16)	C11—C10—H10	120.5
N4—C4—C5	123.02 (16)	C9—C10—H10	120.5
N3—C4—C5	116.34 (15)	C10—C11—C12	119.08 (16)
C6—C5—F1	122.47 (16)	C10—C11—H11	120.5
C6—C5—C4	120.85 (16)	C12—C11—H11	120.5
F1—C5—C4	116.68 (15)	N2—C12—C11	122.87 (16)
C5—C6—N1	119.89 (16)	N2—C12—H12	118.6
C5—C6—H6	120.1	C11—C12—H12	118.6
N1—C6—H6	120.1

C6—N1—C2—O2	179.95 (18)	C12—N2—C8—C7	178.04 (16)
C6—N1—C2—N3	0.7 (3)	O4—C7—C8—N2	4.0 (2)
C4—N3—C2—O2	−179.68 (17)	O3—C7—C8—N2	−174.95 (16)
C4—N3—C2—N1	−0.4 (3)	O4—C7—C8—C9	−177.49 (17)
C2—N3—C4—N4	179.33 (17)	O3—C7—C8—C9	3.6 (3)
C2—N3—C4—C5	0.0 (3)	N2—C8—C9—O1	−179.39 (16)
N4—C4—C5—C6	−179.16 (18)	C7—C8—C9—O1	2.2 (3)
N3—C4—C5—C6	0.2 (3)	N2—C8—C9—C10	0.3 (3)
N4—C4—C5—F1	0.8 (3)	C7—C8—C9—C10	−178.17 (16)
N3—C4—C5—F1	−179.85 (15)	O1—C9—C10—C11	179.43 (17)
F1—C5—C6—N1	−179.86 (16)	C8—C9—C10—C11	−0.3 (3)
C4—C5—C6—N1	0.1 (3)	C9—C10—C11—C12	0.4 (3)
C2—N1—C6—C5	−0.5 (3)	C8—N2—C12—C11	0.7 (3)
C12—N2—C8—C9	−0.5 (3)	C10—C11—C12—N2	−0.7 (3)

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the N2/C8–C12 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.86	2.04	2.873 (2)	163
N3—H3···O4	0.86	1.85	2.6665 (18)	158
N4—H4A···O3	0.86	1.98	2.830 (2)	169
N4—H4B···O1ⁱⁱ	0.86	2.26	3.076 (2)	159
N4—H4B···F1	0.86	2.43	2.7312 (18)	101
O1—H1A···O3	0.82	1.83	2.5542 (18)	146
C6—H6···O2ⁱ	0.93	2.29	3.127 (2)	150
C10—H10···O3ⁱⁱⁱ	0.93	2.54	3.272 (2)	136
C12—H12···O2^iv	0.93	2.39	3.129 (2)	137
Cll—H11···Cg1^v	0.93	2.88	3.426 (2)	119

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

Hydrogen-bond geometry (Å, º) top

Cg is the centroid of the N2/C8–C12 ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N2ⁱ	0.86	2.04	2.873 (2)	163
N3—H3···O4	0.86	1.85	2.6665 (18)	158
N4—H4A···O3	0.86	1.98	2.830 (2)	169
N4—H4B···O1ⁱⁱ	0.86	2.26	3.076 (2)	159
N4—H4B···F1	0.86	2.43	2.7312 (18)	101
O1—H1A···O3	0.82	1.83	2.5542 (18)	146
C6—H6···O2ⁱ	0.93	2.29	3.127 (2)	150
C10—H10···O3ⁱⁱⁱ	0.93	2.54	3.272 (2)	136
C12—H12···O2^iv	0.93	2.39	3.129 (2)	137
Cll—H11···Cg1^v	0.93	2.88	3.426 (2)	119

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

Experimental details

Crystal data
Chemical formula	C₄H₅FN₃O⁺·C₆H₄NO₃⁻
M_r	268.21
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	293
a, b, c (Å)	12.6487 (4), 7.0786 (2), 23.7200 (6)
V (Å³)	2123.77 (10)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.14
Crystal size (mm)	0.15 × 0.05 × 0.05

Data collection
Diffractometer	Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Agilent, 2011)
T_min, T_max	0.979, 0.993
No. of measured, independent and observed [I > 2σ(I)] reflections	8914, 2437, 1955
R_int	0.027

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.111, 1.08
No. of reflections	2437
No. of parameters	173
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.24, −0.19

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Acknowledgements

AK thanks the UGC–SAP, India, for the award of an RFSMS. PTM is thankful to the UGC, New Delhi, for a UGC–BSR one-time grant to Faculty. FP thanks the Slovenian Research Agency for financial support (P1–0230–0175), as well as the EN–FIST Centre of Excellence, Trg Osvobodilne fronte 13, 1000 Ljubljana, Slovenia, for use of the SuperNova diffractometer.

References

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Volume 70| Part 11| November 2014| Pages 328-330

doi:10.1107/S1600536814021898

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research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-di­hydro­pyrimidin-1-ium 3-hy­dr­oxy­pyridine-2-carboxyl­ate

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Synthesis and crystallization

5. Refinement

Supporting information

Acknowledgements

References

research communications

Crystal structure of 4-amino-5-fluoro-2-oxo-2,3-dihydropyrimidin-1-ium 3-hydroxypyridine-2-carboxylate

3. Supramolecular features