Crystal structure of 5,5′-[(4-fluoro­phen­yl)methyl­ene]bis­[6-amino-1,3-di­methyl­pyrimidine-2,4(1H,3H)-dione]

Naresh Sharma; Goutam Brahmachari; Bubun Banerjee; Rajni Kant; Vivek K Gupta

doi:10.1107/S1600536814019886

. 2014 Sep 10;70(Pt 10):o1098–o1099. doi: 10.1107/S1600536814019886

Crystal structure of 5,5′-[(4-fluorophenyl)methylene]bis[6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione]

Naresh Sharma ^a, Goutam Brahmachari ^b, Bubun Banerjee ^b, Rajni Kant ^a, Vivek K Gupta ^a,^*

PMCID: PMC4257154 PMID: 25484692

Abstract

In the title molecule, C₁₉H₂₁FN₆O₄, the dihedral angles between the benzene ring and essentially planar pyrimidine rings [maximum deviations of 0.036 (2) and 0.056 (2) Å] are 73.32 (7) and 63.81 (8)°. The dihedral angle between the mean planes of the pyrimidine rings is 61.43 (6)°. In the crystal, N—H⋯O hydrogen bonds link molecules, forming a two-dimensional network parallel to (001) and in combination with weak C—H⋯O hydrogen bonds, a three-dimensional network is formed. Weak C—H⋯π interactions and π–π interactions, with a centroid–centroid distance of 3.599 (2) Å are also observed.

Keywords: crystal structure, uracil derivatives, biological activity, pyrimidine scaffolds, bis-uracil derivatives

Related literature

For the biological activity of uracil derivatives, see: Muller et al. (1993 ▶); Buckle et al. (1994 ▶). For drugs containing purine moieties, see: Zhi et al. (2003 ▶); Devi & Bhuyan (2005 ▶). For the biological activity of pyrimidine scaffolds, see: Makarov et al. (2005 ▶); Deshmukh et al. (2009 ▶); Ibrahim & El-Metwally (2010 ▶). For the synthesis of bis-uracil derivatives, see: Karimi et al. (2013 ▶). For a related structure, see: Das et al. (2009 ▶). graphic file with name e-70-o1098-scheme1.jpg

Experimental

Crystal data

C₁₉H₂₁FN₆O₄
M _r = 416.42
Orthorhombic,
a = 14.6208 (6) Å
b = 11.3324 (7) Å
c = 22.6410 (12) Å
V = 3751.4 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire3 diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.862, T _max = 1.000
9655 measured reflections
3665 independent reflections
2208 reflections with I > 2σ(I)
R _int = 0.047

Refinement

R[F ² > 2σ(F ²)] = 0.052
wR(F ²) = 0.130
S = 1.04
3665 reflections
291 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S1600536814019886/lh5725sup1.cif

e-70-o1098-sup1.cif^{(29.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814019886/lh5725Isup2.hkl

e-70-o1098-Isup2.hkl^{(176.1KB, hkl)}

Click here for additional data file.^{(8.2KB, cml)}

Supporting information file. DOI: 10.1107/S1600536814019886/lh5725Isup3.cml

Click here for additional data file.^{(1.6MB, tif)}

. DOI: 10.1107/S1600536814019886/lh5725fig1.tif

The molecular structure with displacement ellipsoids drawn at the 40% probability level. H atoms are shown as small spheres of arbitrary radii.

Click here for additional data file.^{(2.5MB, tif)}

a . DOI: 10.1107/S1600536814019886/lh5725fig2.tif

Part of the crystal structure viewed along the a axis. Hydrogen bonds are shown as dashed lines.

CCDC reference: 973485

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg is the centroid of the C7–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N15—H40⋯O3A′	0.96 (3)	1.96 (3)	2.916 (3)	174 (2)
N18—H50⋯O3A	0.93 (3)	1.88 (3)	2.803 (3)	170 (2)
N15—H30⋯O3A ⁱ	0.86 (3)	2.26 (3)	3.083 (3)	161 (3)
N18—H60⋯O3A′ⁱⁱ	0.91 (3)	2.14 (3)	3.007 (3)	159 (2)
C13—H13A⋯O3A ⁱ	0.96	2.41	3.154 (3)	134
C13—H13A⋯Cg ⁱⁱⁱ	0.96	2.98	3.744 (3)	138

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

Acknowledgments

RK acknowledges the Department of Science & Technology for the single-crystal X-ray diffractometer sanctioned as a National Facility under project No. SR/S2/CMP-47/2003. GB is thankful to the CSIR, New Delhi, for financial support [grant No. 02 (110)/12/EMR-II]. BB is grateful to the UGC, New Delhi, for the award of a Senior Research Fellowship.

supplementary crystallographic information

S1. Chemical context

S2. Structural commentary

Uracil derivatives represent a "privileged" structural motif in a wide variety of natural and synthetic compounds with a broad spectrum of significant biological activities (Muller et al., 1993). 6-Aminouracils are the important starting compounds for the synthesis of medicinally useful xanthines and theophyllines, which are now routinely used as a phosphodiesterase inhibitor for the treatment of asthma (Buckle et al., 1994). 6-Aminouracils are regarded as the key intermediates for the synthesis of purine-based drugs, such as penciclovir, caffeine, theophylline, and theobromine (Zhi et al., (2003); Devi & Bhuyan, 2005). In addition, pyrimidine scaffolds are reported to exhibit diverse biological and pharmaceutical activities (Ibrahim & El-Metwally, 2010; Deshmukh et al., 2009), Makarov et al., 2005). Herein, we report the synthesis and crystal structure of a new arylmethylene-bis uracil derivative, namely 5,5'-((4-fluorophenyl)methylene) bis(6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) synthesized via one-pot pseudo multicomponent reaction at room temperature using iodine as inexpensive and eco-friendly catalyst.

The molecular structure of the title compound is shown in Fig. 1. The distances are in the normal ranges and correspond to those observed in a related structure (Das et al., 2009). The pyrimidine rings are essentially planar with maximum deviations of 0.036 (2) and 0.056 (2) Å for C6 and N1', respectively. The dihedral angle between the mean plane of benzene ring [C7—C12] and pyrimidine rings-A and B are 73.32 (7) ° and 63.81 (8) ° respectively. The dihedral angle between the two pyrimidine rings is 61.43 (6) °. The planarity of the phenyl group confirms its aromatic character. From the least-squares plane calculations of the phenyl moiety, the maximum deviation observed is 0.014 (2) Å for atom C8. The double bond distances C2—O2 = 1.220 (4) Å, C3—O3A = 1.257 (3) Å (ring-A) and C2'- O2' = 1.217 (4) Å, C3A'- O3A' = 1.261 (4) Å (ring-B), are significantly larger than the standard value for carbonyl group (1.192 Å) and lengthening of the C═O double bond is due their involvment in N—H···O and C—H···O hydrogen bonds. In the crystal, N—H···O hydrogen bonds link molecules forming a two-dimensional network parallel to (001) (Fig. 2) and in combination with weak C—H···O hydrogen bonds a three-dimensional network is formed. Weak C—H···π interactions and π–π interactions with a centroid–centroid distance of 3.599 (2) Å between pyrimidine ring-B and benzene ring-C at (1/2 - x, -1/2 + y, z) are also observed.

S3. Supramolecular features

S4. Database survey

S5. Synthesis and crystallization

An oven-dried screw cap test tube was charged with a magnetic stir bar, 6-amino-1,3-dimethyluracil (0.155 g, 1.0 mmol), 4-fluorobenzaldehyde (0.062 g, 0.5 mmol), iodine (0.025 g, 10 mol % as catalyst), and EtOH:H₂O (1:1 v/v; 4 ml) in a sequential manner. The reaction mixture was then stirred vigorously at room temperature and the stirring was continued for 4 h; the progress of the reaction was monitored by TLC. On completion of the reaction, a solid mass precipitated out, which was filtered, and washed with aqueous ethanol to obtain the crude product that was purified just by recrystallization from ethanol without carrying out column chromatography (72% yield). The title compound forms as a White solid. Yield 72%. Mp: 537–539 K. IR (KBr) ν_max cm^-1: 3430, 3104, 2956, 1690, 1603, 1498, 1247, 1216, 1142, 1070, 870, 789, 756. ¹H NMR (400 MHz, DMSO-d₆) δ/p.p.m.: 7.42 (4H, s, –NH₂), 7.11 (2H, dd, J = 8.4 & 5.6 Hz, aromatic H), 6.99 (2H, t, J = 8.8 Hz, aromatic H), 5.56 (1H, s, –CH–), 3.32 (6H, s, 2 × NCH₃), 3.14 (6H, s, 2 × NCH₃). TOF-MS: 439.1513 [M+Na]⁺. The structure of 5,5'-((4-fluorophenyl)methylene)bis(6-amino-1, 3-dimethylpyrimidine-2,4(1H,3H)-dione) was characterized by means of spectral studies including FT—IR, ¹H NMR, and TOF-MS. Crystals suitable for X-ray diffraction were grown by dissolving 50 mg of the title compound in 5 ml DMSO and after several days at ambient temperature colourless block-shaped crystals were formed.

S6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. Atoms H30, H40 attached to N15 and H50, H60 attached to N18 were located in a difference Fourier map and refined isotropically. All the remaining H atoms were geometrically fixed and allowed to ride on their parent C atoms, with C—H distances of 0.93–0.98 Å; and with U_iso(H) = 1.2U_eq(C), except for the methyl group where U_iso(H) = 1.5U_eq(C).