rac-Ethyl 4-hydroxy-4-trifluoromethyl-6-(2,4,5-trimethoxyphenyl)-2-thio-1,3-diazinane-5-carboxylate

In the title compound, C17H21F3N2O6S, the hexahydropyrimidine ring adopts a half-chair conformation: the mean plane formed by the ring atoms excluding the C atom bonded to the ethoxycarbonyl group has an r.m.s. deviation of 0.0427 Å and forms a dihedral angle of 66.41 (5)° with the benzene ring. The molecular conformation is stabilized by an intramolecular hydroxyl O—H⋯Ocarboxyl hydrogen bond, generating an S(6) ring. In the crystal, pairs of N—H⋯S and N–H⋯O hydrogen bonds give rise to the formation of two-dimensional networks lying parallel to the ab plane, which incorporate graph-set motifs R 2 2(8) and R 2 2(16), respectively.

In the title compound, C 17 H 21 F 3 N 2 O 6 S, the hexahydropyrimidine ring adopts a half-chair conformation: the mean plane formed by the ring atoms excluding the C atom bonded to the ethoxycarbonyl group has an r.m.s. deviation of 0.0427 Å and forms a dihedral angle of 66.41 (5) with the benzene ring. The molecular conformation is stabilized by an intramolecular hydroxyl O-HÁ Á ÁO carboxyl hydrogen bond, generating an S(6) ring. In the crystal, pairs of N-HÁ Á ÁS and N-HÁ Á ÁO hydrogen bonds give rise to the formation of twodimensional networks lying parallel to the ab plane, which incorporate graph-set motifs R 2 2 (8) and R 2 2 (16), respectively.

Yong-Qiang Li and Zhi-Yu Ju Comment
The Biginelli reaction, the direct synthesis of dihydropyrimidinones by the one-pot condensation of aldehydes, urea or thiourea, was first reported more than a century ago (Biginelli, 1893). Dihydropyrimidine (DHPM) derivatives can be used as potential calcium channel blockers (Zorkun et al., 2006), inhibitors of mitotic kinesin Eg5 for treating cancer (Cochran et al., 2005;Brier et al., 2004) and as TRPA1 modulators for treating pain (Moran et al., 2007). In addition, compounds that contain fluorine have special bioactivity, e.g. flumioxazin is a widely used herbicide (Hermann et al., 2003;Ulrich, 2004). This led us to focus our attention on the synthesis and bioactivity of these important fused perfluoroalkylated heterocyclic compounds. During the synthesis of DHPM derivatives, the title compound, an intermediate C 17 H 21 F 3 N 2 O 6 S was isolated and the structure confirmed by X-ray diffraction.
In the structure of the title molecule, the hexahydropyrimidine ring adopts a half-chair conformation, the mean plane formed by the ring atoms excluding the C atom bonded to the ethoxy carbonyl group has an r.m.s. deviation of 0.0427 Å, with a dihedral angle of 66.41 (5)° between the this plane and the benzene ring. The molecular conformation is stabilized by an intramolecular hydroxyl O-H···O carboxyl hydrogen bond (Table 1), generating an S(6) ring. In the crystal structure, intermolecular cyclic N-H···S, and N-H···O hydrogen-bonding interactions [graph sets R 2 2 (8) and R 2 2 (16), respectively (Bernstein et al., 1995)], together with a short hydroxyl O-H···O interaction give a two-dimensional structure (Fig. 2).
For the crystal structure of a compound related to the title compound, see Li et al. (2011).

Experimental
The title compound was synthesized by refluxing for 3 h a stirred solution of 2,4,5-trimethoxybenzaldehyde (0.98 g, 5 mmol), ethyl 4,4,4-trifluoro-3-oxobutanoate (1.11 g, 6 mmol) and thiourea (0.57 g, 7.5 mmol) in 5 ml of anhydrous ethanol, the reaction catalyzed by sulfamic acid (0.15 g). The solvent was evaporated in vacuo and the residue was washed with water. The title compound was recrystallized from 50% aqueous ethanol and single crystals were obtained by slow room-temperature evaporation of the solution.

Refinement
Hydrogen atoms involved in hydrogen-bonding interactions were located by difference methods and their positional and isotropic displacement parameters were refined. Other H atoms were placed in calculated positions, with C-H(aromatic) = 0.95 Å and C-H(aliphatic) = 0.98 Å, 0.99 Å or 1.00 Å and treated as riding, with U iso (H) = 1.2U eq (C).   The packing of the title compound in the unit cell viewed down the c axis, with hydrogen bonds shown as dashed lines.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.