Crystal structure of 5-(dibenzofuran-4-yl)-2′-deoxyuridine

Deoxyuridine substituted by dibenzofuranyl at the carbon atom in base position C5 was synthesized and structurally characterized. The coupling was achieved by a Suzuki–Miyaura reaction utilizing the PTABS ligand and palladium(II) acetate.

The molecule of the title compound, C 21 H 18 N 2 O 6 , has a bent rather than a linear conformation supported by three intramolecular C-HÁ Á ÁO hydrogen bonds. The packing in the crystal lattice is largely determined by interactions between hydrogen atoms with oxygen atom lone pairs with one molecule interacting with neigbouring molecules via O-HÁ Á ÁO, N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds. The title compound crystallizes in the chiral orthorhombic space group P2 1 2 1 2 1 . Its absolute structure could not be determined crystallographically and was assumed with reference to that of the reactant 5-iodo-2 0 -deoxyuridine.

Chemical context
As a result of their numerous applications, synthetically modified nucleoside analogues have attracted much attention in recent years. Many of these modified nucleosides show potential activity as drug candidates, biological probes etc (Huryn & Okabe, 1992). Modern trends in this field of research consider palladium complexes to be active catalysts for the efficient modification of nucleosides because of their greater ability to perform such catalytic processes in aqueous media (Agrofoglio et al., 2003;Kapdi et al., 2014). Base modification in purine and pyrimidine nucleosides, resulting in a new class of compounds with better fluorescence properties, enhancing their chances of being employed as biological probes for studying biological environments such as DNA damage, protein-DNA interactions and DNA probes is of great interest to chemical biologists as well as bio-organic chemists (Tanpure et al., 2013). Structural elucidation of such compounds is an important task in order to understand the mechanistic pathways. Herein we present the synthesis and the crystal structure of the title compound, 5-(dibenzofuran-4-yl)-2 0 -deoxyuridine. ISSN 2056-9890

Structural commentary
The title compound crystallizes in the orthorhombic space group P2 1 2 1 2 1 with four molecules in the unit cell. The two aromatic systems (pyrimidine and dibenzofuranyl), which are connected by a C-C bond [C7-C10 = 1.489 (6) Å ] subtend a dihedral angle of 30.7 (2) (Fig. 1). All bond lengths or angles are comparable to those in related compounds. Fifty two entries can be found in the Cambridge Crystallographic Database (ConQuest Version 1.19; Groom et al., 2016) for deoxyuridine with a substituent only in the C 5 position of the base (i.e. C7 here) and neither substituents nor protecting groups anywhere else, nine of which are for compounds that had already been characterized (i.e. repeats, polymorphs, present/absent solvent). The bond lengths of the pyrimidine moiety observed for the title compound are very close to the average values found for related structures (see Table S1 in the Supporting information). As is typical for this class of compounds, the bond usually assigned to be a double bond within the six-membered ring (here C6 C7) is the shortest for the pyrimidine ring at 1.353 (6) Å and the bond between the second carbonyl carbon atom and the substituted carbon (here C7-C8) is the longest at 1.447 (6) Å . All four other ring atom-to-ring atom distances (N-C and C-C bonds) are shorter than 1.393 Å , indicating significant -electron delocalization throughout the pyrimidine base. All this, however, is in accordance with the majority of previously reported structures.
The relative orientation between sugar and base moieties in the title compound is also comparable with compounds in the database. The hydrogen-bonding interaction (or distance) between the C 6 -H function (here C6) and the ring oxygen atom of the sugar (here O3) and/or the -CH 3 -OH group (here O1) is useful for evaluation in this context. The C-HÁ Á ÁO hydrogen-to-oxygen distances for the interaction with the alcohol range from 2.29 to 5.98 Å (when the -CH 3 -OH moiety is pointing directly towards the C-H or completely turned away, respectively; Moore et al., 1989;Basnak et al., 1996). The C-HÁ Á ÁO hydrogen-to-oxygen distances for the interaction with the furane ring oxygen atom (here O3) range from 2.26 to 3.43 Å (Greco & Tor, 2007;Basnak et al., 1996) with the vast majority of orientations allowing at least weak hydrogen bonding between this oxygen and the C 6 -H hydrogen atom. No systematic dependency between these two groups of distances was found, i.e. a very short or long hydrogen bond with the ring oxygen atom does neither lead to particularly short nor long distances of the hydrogen atom to the methanoyl oxygen atom.
Only five of the related archived structures bear directly attached aromatic -systems. In all five cases, the orientation of the sugar and the pyrimidine moieties are relatively similar in which the C 6 -H moiety points to some extent towards the methanoyl oxygen atom of the sugar, forming a weak intramolecular hydrogen bond and resulting in comparable molecular bends. The dihedral angles between the two aromatic systems do vary and range from 11.9 for a ferrocene substituent (Song et al., 2006) to 37.2 for a para-biphenyl substituent , indicating that the extent of delocalization of the -systems depends on the actual type of aromatic substituent but is not particularly strong in any case.

Synthesis and crystallization
The title compound was synthesized according to our recently reported method (Bhilare et al., 2016). This involves the crosscoupling reaction of 5-iodo-2 0 -deoxyuridine and 4-(dibenzofuranyl)boronic acid in the presence of Pd(OAc) 2 and PTBS (phospha-triaza-adamantyl propane sulfonate) in water. Synthesis of 5-(dibenzofuran-4-yl)-2 0 0 0 -deoxyuridine: To a solution of palladium acetate (1.12 mg, 1.0 mol %) and PTABS ligand (2.93 mg, 2.0 mol %) in degassed water (1.0 ml) at ambient temperature under N 2 were added 5-iodo-2 0 -deoxyuridine (0.5 mmol) and the solution stirred for 5 min at 353 K. After that, the reaction mixture was allowed to cool to room temperature and then 4-(dibenzofuranyl)boronic acid (0.75 mmol) was added along with triethylamine (0.14 ml, 1.0 mmol) and degassed water (2.0 ml). The resulting solution was then stirred at 353 K for 3 h. The reaction progress was monitored by TLC. After the completion of reaction, the solvent was removed in vacuo and the resultant residue obtained was purified using column chromatography in CH 2 Cl 2 :MeOH solvent system (96:4) to afford the desired product as a white solid (162 mg, 82% yield).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The two protons on oxygen (O1, O2) and the one on nitrogen (N2) were located and refined with a constraint for the atom-H distance (SHELXL instruction: SADI 0.05 O1 H1O O2 H2O N2 H2N), as otherwise the N-H distance became rather short and the O-H distances rather long. The respective orientations, i.e. the directions the hydrogen atoms are pointing to (particularly important for the alcohol functions), were refined without any restraints or constraints. The C-bound H atoms were included The crystal packing (Mercury; Macrae et al., 2006) viewed along the a axis showing the classical hydrogen bonds which lead to a two-dimensional network parallel to (010).  SHELXL2013 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2006); software used to prepare material for publication: CIFTAB (Sheldrick, 2008) and PLATON (Spek, 2009).

5-(Dibenzofuran-4-yl)-2′-deoxyuridine
Crystal data C 21 H 18 N 2 O 6 M r = 394.37 Orthorhombic, P2 1 2 1 2 1 a = 6.2899 (13)  Special details Experimental. The reaction was carried out in a Schlenk tube using Schlenk techniques under a nitrogen atmosphere. All other reagents and solvents were purchased commercially and used without any further purification. A UV-visible spectrum of the title compound (10 µM) was measured in methanol using a UV-visible spectrophotometer with a cell of 1 cm path length. A fluorescence spectrum of the same solution was obtained using a fluorescence spectrophotometer at 298 K using a 1 cm path-length cell. The reaction was monitored by thin layer chromatography using TLC silica gel 60 F254 precoated plates (Merck). Visualization was accomplished by irradiation with UV light. C, H, and N analyses was carried out locally. NMR data ( 1 H, 13 C) of the synthesized compound were recorded locally on 500 MHz spectrometers. Mass spectroscopic analysis was carried out with a mass spectrometer from Varian Inc, US: 10 Prostar Binary LC with 500 MS IT PDA detectors. Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.