Ethyl 4-hy­droxy-6-(4-hy­droxy­phen­yl)-4-trifluoro­methyl-2-sulfanyl­idene-1,3-diazinane-5-carboxyl­ate ethanol monosolvate

Feng-Ling Yang; Wen-Jun Fa

doi:10.1107/S1600536811015376

. 2011 Apr 29;67(Pt 5):o1280–o1281. doi: 10.1107/S1600536811015376

Ethyl 4-hydroxy-6-(4-hydroxyphenyl)-4-trifluoromethyl-2-sulfanylidene-1,3-diazinane-5-carboxylate ethanol monosolvate

Feng-Ling Yang ^a,^*, Wen-Jun Fa ^b

PMCID: PMC3089211 PMID: 21754562

Abstract

The title compound, C₁₄H₁₅F₃N₂O₄S·C₂H₅OH, was prepared by reaction of 4-hydroxybenzaldehyde, ethyl 4,4,4-trifluoro-3-oxobutanoate and thiourea. 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 0.0333 Å, and the dihedral angle between this plane and the benzene ring is 56.76 (5)°. The molecular conformation is stabilized by an intramolecular O—H⋯O hydrogen bond, generating an S(6) ring. The crystal structure is stabilized by intermolecular O—H⋯O, O—H⋯S, N—H⋯O and N—H⋯S hydrogen bonds. The ethyl group of the ester unit is disordered over two positions, with an occupancy ratio of 0.757 (10):0.243 (10).

Related literature

For the bioactivity of dihydropyrimidines, see: Brier et al. (2004 ▶); Cochran et al. (2005 ▶); Moran et al. (2007 ▶); Zorkun et al. (2006 ▶). For the bioactivity of organofluorine compounds, see: Hermann et al. (2003 ▶); Ulrich (2004 ▶). For a related structure, see: Song et al. (2010 ▶).

Experimental

Crystal data

C₁₄H₁₅F₃N₂O₄S·C₂H₆O
M _r = 410.41
Monoclinic,
a = 14.7204 (14) Å
b = 9.9772 (12) Å
c = 14.7357 (15) Å
β = 119.716 (11)°
V = 1879.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 113 K
0.20 × 0.16 × 0.10 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2009 ▶) T _min = 0.955, T _max = 0.977
23471 measured reflections
4486 independent reflections
3815 reflections with I > 2σ(I)
R _int = 0.047

Refinement

R[F ² > 2σ(F ²)] = 0.036
wR(F ²) = 0.092
S = 1.03
4486 reflections
280 parameters
24 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.47 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: CrystalClear (Rigaku, 2009 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811015376/om2424sup1.cif

e-67-o1280-sup1.cif^{(22.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811015376/om2424Isup2.hkl

e-67-o1280-Isup2.hkl^{(219.8KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811015376/om2424Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2	0.853 (19)	1.987 (19)	2.7383 (13)	146.3 (17)
O1—H1⋯S1ⁱ	0.853 (19)	3.029 (19)	3.4858 (11)	115.8 (15)
O4—H4⋯O5ⁱⁱ	0.835 (18)	1.873 (19)	2.7066 (14)	175.6 (19)
O5—H5⋯S1ⁱⁱⁱ	0.84	2.36	3.1970 (11)	175
N1—H1A⋯S1ⁱⁱⁱ	0.855 (17)	2.583 (18)	3.4307 (12)	171.5 (14)
N2—H2A⋯O1^iv	0.814 (14)	2.368 (15)	3.1701 (15)	168.7 (14)

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

Acknowledgments

This work was supported by the Natural Science Foundation of Henan Province, China (grant No. 082300420110) and the Natural Science Foundation of Henan Province Education Department, China (grant No. 2007150036).

supplementary crystallographic information

Comment

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 C₁₄H₁₅F₃N₂O₄S.C₂H₅OH was isolated and the structure confirmed by X-ray diffraction.

In the structure of the title molecule, the 1,3-diazinane 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 0.0333 Å, the dihedral angle between the mean plane and benzene ring is 56.76 (5)°. The molecular conformation is stabilized by intramolecular O—H···O hydrogen bond, generating an S(6) ring. The crystal structure is stabilized by intermolecular hydrogen bonds (O—H···O, O—H···S, N—H···O and N—H···S). The ethyl group of the ester unit is disordered over two positions, with a site-occupancy ratio of 0.757 (10):0.243 (10). For a crystal structure related to the title compound, see: Song et al., 2010.

Experimental

The title compound was synthesized by refluxing for 3 h a stirred solution of 4-hydroxybenzaldehyde (2.45 g, 20 mmol), ethyl 4,4,4-trifluoro-3-oxobutanoate (4.42 g, 24 mmol) and thiourea (2.28 g, 30 mmol) in 20 ml of anhydrous ethanol. The reaction was catalyzed by sulfamic acid (0.6 g). The solvent was evaporated in vacuo and the residue was washed with water. The title compound was recrystallized by slow evaporation of a 50% aqueous ethanol solution.