Crystal structures of 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(3-nitrophenyl)acetamide monohydrate and N-(2-chlorophenyl)-2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide

In the title 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamides, both compounds have a folded conformation about the methylene C atom of the thioacetamide bridge, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6) and 67.84 (6)°. In both molecules, there is an intramolecular N—H⋯N hydrogen bond stabilizing the folded conformation.

The title compounds, C 12 H 12 N 6 O 3 SÁH 2 O, (I), and C 12 H 12 ClN 5 OS, (II), are 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamides. Compound (I) crystallized as a monohydrate. In both compounds, the molecules have a folded conformation, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6) in (I) and by 67.84 (6) in (II). In both molecules, there is an intramolecular N-HÁ Á ÁN hydrogen bond stabilizing the folded conformation. In (I), there is also a C-HÁ Á ÁO intramolecular short contact, and in (II) an intramolecular N-HÁ Á ÁCl hydrogen bond is present. In the crystal of (I), molecules are linked by a series of N-HÁ Á ÁO, O-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds, forming undulating sheets parallel to the (100). The sheets are linked via an N-HÁ Á ÁO water hydrogen bond, forming a three-dimensional network. In the crystal of (II), molecules are linked by a series of N-HÁ Á ÁO, N-HÁ Á ÁN and C-HÁ Á ÁO hydrogen bonds, forming slabs parallel to (001).

Chemical context
Recent studies have shown that diamino substituted pyrimidines are active inhibitors of human dihydrofolate reductase (hDHFR) and also possess inhibitory potency against tyrosine kinase (Gangjee et al., 2006). 2,4-diamino pyrimidine derivatives have anti-retro viral activity (Hocková et al., 2004) and also anti-trypanosoma brucei activity (Perales et al., 2011). A series of 2,4-diaminopyrimidines have as also been prepared to study their immuno-suppressant activity (Blumenkopf et al., 2003). Pyrimidines are also potent antiviral agents and a series of N-benzyl-2-(4,6-diaminopyrimidin-2-ylsulfanyl)acetamides have been designed to fight Dengue Virus Protease (Timiri et al., 2016). A series 5-substituted benzyl-2,4-diamino pyrimidine derivatives have also been synthesized as c-Fms kinase inhibitors (Xu et al., 2010). As part of our studies in this area, we now describe the syntheses and crystal structures of the title compounds.

Structural commentary
The molecular structures of compounds (I) and (II) are illustrated in Figs. 1 and 2, respectively. In compound (I), the pyrimidine ring makes a dihedral angle of 56.18 (6) with the benzene ring (C7-C12). The nitro group is inclined by 16.3 (3) to the benzene ring to which it is attached. The amine nitrogen atoms, N1 and N2, are displaced from the pyrimidine ring by 0.028 (2) and 0.026 (2) Å , respectively.
In both the compounds, the folded conformation is reinforced by an intramolecular N-HÁ Á ÁO hydrogen bond [ Fig. 1

Supramolecular features
In the crystal of compound (I), molecules are linked by a series of N-HÁ Á ÁO, O-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds, forming undulating sheets parallel to the bc plane (Table 1 and Fig. 3). The sheets are linked via an N-HÁ Á ÁO water hydrogen bond, forming a three-dimensional network (Table 1 and  The molecular structure of compound (I), with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. Intramolecular hydrogen bonds are shown as dashed lines (see Table 1).

Synthesis and crystallization
Compound (I): To a solution of 4,6-diamino-pyrimidine-2thiol (0.5 g; 3.52 mmol) in 25 ml of ethanol in a round-bottom flask, potassium hydroxide (0.2 g; 3.52 mmol) was added and the mixture was refluxed for half an hour and to it 3.52 mmol The crystal packing of compound (I), viewed along the b axis. Hydrogen bonds are shown as dashed lines (see Table 1). C-bound H atoms have been excluded for clarity.

Figure 4
A view of the hydrogen-bonded ring motifs in the crystal of compound (I). Details of the hydrogen bonding are given in Table 1.

Figure 5
The crystal packing of compound (II), viewed along the a axis. Hydrogen bonds are shown as dashed lines (see Table 2)ÁC-bound H atoms have been excluded for clarity.

Figure 6
A view of the hydrogen-bonded ring motifs in the crystal of compound (II). Details of the hydrogen bonding are given in Table 2. of 3-nitro phenylacetamide was added and refluxed for 4 h. At the end of the reaction (observed by TLC), ethanol was evaporated under vacuum and cold water was added and the precipitate filtered and dried to give compound (I) as a crystalline powder (yield 88-96%). After purification, the compound was recrystallized from ethyl acetate solution by slow evaporation of the solvent.
Compound (II): To a solution of 4,6-diamino-pyrimidine-2thiol (0.5 g; 3.52 mmol) in 25 ml of ethanol in a round-bottom flask potassium hydroxide (0.2 g; 3.52 mmol) was added and refluxed for half an hour and to it 3.52 mmol of 2-chlorophenylacetamide was added and the mixture was refluxed for 3 h. At the end of the reaction (observed by TLC), ethanol was evaporated under vacuum and cold water was added, and the precipitate was filtered and dried to give compound (II) as a crystalline powder (yield 88-96%). After purification, the compound was recrystallized from ethanol solution by slow evaporation of the solvent.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. For both compounds, the NH 2 and NH H atoms, and the water H atoms for (I), were located in difference Fourier maps. The N-bound H atoms were freely refined, while the water H atoms were initially freely refined and in the final cycles of refinement as riding atoms. The Cbound H atoms were placed in calculated positions and refined as riding: C-H = 0.93-0.97 Å with U iso (H) = 1.2U eq (C).   For both compounds, data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009).

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.