Crystal structure of 4,6-dimethyl-2-[(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)sulfanyl]pyrimidine

In the title compound, the S atom is attached equatorially to the sugar ring. The C—S bond lengths are unequal. In the crystal, a system of three weak hydrogen bonds, sharing an oxygen acceptor, links the molecules to form chains propagating parallel to the b-axis direction.


Chemical context
Nucleosides are building blocks of biological systems and display a wide range of biological activities (Ding et al., 2003). Pyrimidine nucleoside analogues provide diverse and novel moieties for pharmacological targets, and they play basic and comprehensive roles in the field of medicinal chemistry (Xu et al., 2017). Different strategies for the synthesis of many pyrimidine nucleoside analogues have been developed to access new and potent pharmacological agents (Cao et al., 2011). Many such derivatives are manufactured as potential chemotherapeutic agents and have a significant impact on current medicinal research (Ohkubo et al., 2012). Recently, thioglycosides have proved to be important in the production of medically important carbohydrate compounds, because of their ease of preparation and chemical stability (Gourdain et al., 2011).
We have recently described the preparation of various pyrimidine and pyridine thioglycosides that displayed antagonistic activity (Hammad et al., 2018;Elgemeie et al., 2010). We have also reported the use of dihydropyridine thioglycosides as substrates or inhibitors of protein glycosylation (Scale et al., 1997;Elgemeie et al., 2015Elgemeie et al., , 2016 and the use of pyrimidine thioglycosides as antihepatocellular carcinoma agents (Elgemeie & Farag, 2017). Continuing our efforts to develop simple and cost-effective methodologies for the synthesis of pyrimidine thioglycosides, we report here the onestep synthesis of a pyrimidine-2-thiogalactoside derivative by the reaction of 4,6-dimethylpyrimidine-2(1H)-thione (1) with 2,3,4,6-tetra-O-acetyl--d-galactopyranosyl bromide (2). This reaction in NaH/DMF at room temperature gave a product for which two isomeric structures seemed possible, corresponding to two possible modes of glysosylation to give the pyrimidine-N-galactoside (3) or its regioisomer pyrimidine-2-thiogalactoside 4 (see Scheme). Spectroscopic data cannot differentiate between these structures. It has been suggested that 1 reacts with 2 via a simple S N 2 reaction to give the -glycoside product 4 (Davis, 2000). ISSN 2056-9890

Structural commentary
The crystal structure determination indicated unambiguously the formation of the pyrimidine-2-thiogalactoside, 4, as the only product in the solid state.
The molecular structure of 4 is shown in Fig. 1 (for selected torsion angles, see Table 1) and the S atom is attached equatorially to the sugar ring. Similar to the structure of a related glucose derivative (Masoud et al., 2017), the C-S bond lengths are unequal, with S-C s = 1.8018 (13) Å and S-C p = 1.7662 (13) Å (s = sugar and p = pyrimidyl). The relative orientation of the pyridyl ring and the sugar moiety is defined by the torsion angles N2-C1-S1-C11 [À7.85 (12) ] and C1-S1-C11-C12 [165.01 (9) ]. All the acetyl groups show extended conformations, with absolute C-O-C-C torsion angles in the range 173-179 .

Supramolecular features
Some short C-HÁ Á ÁO and C-HÁ Á ÁS contacts are listed in Table 2, but these are at best borderline 'weak' hydrogen bonds, particularly in view of their narrow angles. The molecular packing is thus rather featureless. However, a motif of three sugar-ring C-H groups (C13-H13, C14-H14 and C15-H15) sharing a common acceptor (O8) can be recog-nized (Fig. 2). Neighbouring molecules are connected via the 2 1 operator, leading to chains of molecules propagating parallel to the b-axis direction.

Figure 1
The molecular structure of the title compound, 4, in the crystal. Displacement ellipsoids represent 50% probability levels.
temperature until the reaction was judged complete by thinlayer chromatography (3-6 h). The mixture was evaporated under reduced pressure at 333 K and the residue was washed with distilled water to remove potassium bromide. The crude solid was collected by filtration and purified using column chromatography (

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Methyl groups were refined as idealized rigid groups allowed to rotate but not tip (    Special details 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.