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

Li, Y.-Q.; Ju, Z.-Y.

doi:10.1107/S1600536812041013

organic compounds

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ISSN: 2056-9890

Volume 68| Part 11| November 2012| Pages o3092-o3093

doi:10.1107/S1600536812041013

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

Yong-Qiang Li ^a ^* and Zhi-Yu Ju ^b

^aState Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, People's Republic of China, and ^bCollege of Chemistry and Chemical Engineering, Xuchang University, Xuchang, Henan Province, 461000, People's Republic of China
^*Correspondence e-mail: chinarenbeijing@126.com

(Received 15 September 2012; accepted 29 September 2012; online 10 October 2012)

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⋯O_carboxyl 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 R²₂(8) and R²₂(16), respectively.

Related literature

For the bioactivity of dihydropyrimidines, see: Brier et al. (2004 ); Cochran et al. (2005 ); Moran et al. (2007 ); Zorkun et al. (2006 ) and for the bioactivity of organofluorine compounds, see: Hermann et al. (2003 ); Ulrich (2004 ). For the original Biginelli synthesis, see: Biginelli (1893 ). For a related structure, see: Li et al. (2011 ). For graph-set analysis, see: Bernstein et al. (1995 ).

Experimental

Crystal data

C₁₇H₂₁F₃N₂O₆S
M_r = 438.42
Triclinic, $[P \overline 1]$
a = 9.5070 (8) Å
b = 9.9040 (8) Å
c = 11.4710 (13) Å
α = 71.582 (13)°
β = 76.740 (16)°
γ = 79.743 (15)°
V = 990.89 (19) Å³
Z = 2
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 113 K
0.28 × 0.22 × 0.20 mm

Data collection

Rigaku Saturn724 CCD-detector diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998) T_min = 0.939, T_max = 0.956
13891 measured reflections
5290 independent reflections
3175 reflections with I > 2σ(I)
R_int = 0.049

Refinement

R[F² > 2σ(F²)] = 0.033
wR(F²) = 0.080
S = 0.90
5290 reflections
279 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2	0.820 (15)	2.103 (16)	2.8055 (15)	143.5 (15)
N2—H2⋯O5ⁱ	0.824 (15)	2.129 (15)	2.9521 (15)	176.6 (15)
N1—H1A⋯S1ⁱⁱ	0.834 (15)	2.526 (16)	3.3427 (13)	166.3 (15)
Symmetry codes: (i) -x+1, -y, -z+1; (ii) -x+2, -y+1, -z+1.

Data collection: CrystalClear (Rigaku/MSC, 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: CrystalStructure (Rigaku/MSC, 2009); software used to prepare material for publication: CrystalStructure.

Supporting information

Crystal structure: contains datablocks shelxl, I. DOI: 10.1107/S1600536812041013/zs2236sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536812041013/zs2236Isup2.hkl

Supporting information file. DOI: 10.1107/S1600536812041013/zs2236Isup3.cml

checkCIF report

Comment top

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 C₁₇H₂₁F₃N₂O₆S 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 R²₂(8) and R²₂(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).

Related literature top

For the bioactivity of dihydropyrimidines, see: Brier et al. (2004); Cochran et al. (2005); Moran et al. (2007); Zorkun et al. (2006) and for the bioactivity of organofluorine compounds, see: Hermann et al. (2003); Ulrich (2004). For the original Biginelli synthesis, see: Biginelli (1893). For a related structure, see: Li et al. (2011). For graph-set analysis, see: Bernstein et al. (1995).

Experimental top

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.

Computing details top

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

Figures top

	Fig. 1. Molecular conformation and atom numbering scheme for the title compound, with displacement ellipsoids drawn at the 30% probability level.
	Fig. 2. The packing of the title compound in the unit cell viewed down the c axis, with hydrogen bonds shown as dashed lines.

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

Crystal data top

C₁₇H₂₁F₃N₂O₆S	Z = 2
M_r = 438.42	F(000) = 456
Triclinic, P1	D_x = 1.469 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71075 Å
a = 9.5070 (8) Å	Cell parameters from 3446 reflections
b = 9.9040 (8) Å	θ = 1.9–29.2°
c = 11.4710 (13) Å	µ = 0.23 mm⁻¹
α = 71.582 (13)°	T = 113 K
β = 76.740 (16)°	Prism, colorless
γ = 79.743 (15)°	0.28 × 0.22 × 0.20 mm
V = 990.89 (19) Å³

Data collection top

Rigaku Saturn724 CCD-detector diffractometer	5290 independent reflections
Radiation source: rotating anode	3175 reflections with I > 2σ(I)
Multilayer monochromator	R_int = 0.049
Detector resolution: 14.222 pixels mm^-1	θ_max = 29.1°, θ_min = 1.9°
ω scans	h = −12→13
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	k = −13→13
T_min = 0.939, T_max = 0.956	l = −15→15
13891 measured reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.033	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.080	w = 1/[σ²(F_o²) + (0.0266P)² + ] where P = (F_o² + 2F_c²)/3
S = 0.90	(Δ/σ)_max = 0.001
5290 reflections	Δρ_max = 0.33 e Å⁻³
279 parameters	Δρ_min = −0.26 e Å⁻³
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0101 (11)

Crystal data top

C₁₇H₂₁F₃N₂O₆S	γ = 79.743 (15)°
M_r = 438.42	V = 990.89 (19) Å³
Triclinic, P1	Z = 2
a = 9.5070 (8) Å	Mo Kα radiation
b = 9.9040 (8) Å	µ = 0.23 mm⁻¹
c = 11.4710 (13) Å	T = 113 K
α = 71.582 (13)°	0.28 × 0.22 × 0.20 mm
β = 76.740 (16)°

Data collection top

Rigaku Saturn724 CCD-detector diffractometer	5290 independent reflections
Absorption correction: multi-scan (REQAB; Jacobson, 1998)	3175 reflections with I > 2σ(I)
T_min = 0.939, T_max = 0.956	R_int = 0.049
13891 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.033	0 restraints
wR(F²) = 0.080	H atoms treated by a mixture of independent and constrained refinement
S = 0.90	Δρ_max = 0.33 e Å⁻³
5290 reflections	Δρ_min = −0.26 e Å⁻³
279 parameters

Special details top

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 F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.92027 (4)	0.42289 (4)	0.38162 (3)	0.02116 (10)
F1	0.81454 (9)	0.32810 (9)	0.86049 (8)	0.0272 (2)
F2	0.79020 (9)	0.55959 (9)	0.79756 (8)	0.0284 (2)
F3	0.61189 (9)	0.44824 (10)	0.91797 (8)	0.0276 (2)
O1	0.56858 (11)	0.56726 (10)	0.67450 (10)	0.0200 (2)
O2	0.35960 (10)	0.39204 (11)	0.83456 (10)	0.0237 (2)
O3	0.46465 (10)	0.17323 (11)	0.92763 (9)	0.0221 (2)
O4	0.72397 (10)	0.03795 (10)	0.63698 (9)	0.0195 (2)
O5	0.31176 (10)	−0.21345 (10)	0.69741 (9)	0.0183 (2)
O6	0.13106 (10)	0.03586 (10)	0.68092 (10)	0.0196 (2)
N1	0.78623 (12)	0.44308 (13)	0.60651 (11)	0.0160 (3)
N2	0.67147 (12)	0.33257 (13)	0.51166 (11)	0.0148 (3)
C1	0.78416 (14)	0.39765 (14)	0.50737 (12)	0.0144 (3)
C2	0.66487 (14)	0.44157 (14)	0.70770 (13)	0.0154 (3)
C3	0.59354 (14)	0.30412 (14)	0.73587 (12)	0.0143 (3)
H3	0.6653	0.2186	0.7617	0.017*
C4	0.54789 (14)	0.30384 (14)	0.61551 (12)	0.0139 (3)
H4	0.4682	0.3838	0.5970	0.017*
C5	0.72143 (15)	0.44432 (16)	0.82155 (13)	0.0194 (3)
C6	0.45866 (15)	0.29678 (15)	0.83747 (13)	0.0177 (3)
C7	0.34010 (16)	0.15335 (18)	1.03094 (14)	0.0295 (4)
H7A	0.3011	0.2466	1.0472	0.035*
H7B	0.3722	0.0874	1.1075	0.035*
C8	0.22227 (18)	0.0932 (2)	1.00195 (17)	0.0471 (5)
H8A	0.1833	0.1628	0.9315	0.057*
H8B	0.1441	0.0732	1.0754	0.057*
H8C	0.2624	0.0043	0.9801	0.057*
C9	0.48928 (14)	0.16512 (14)	0.63245 (12)	0.0139 (3)
C10	0.57798 (14)	0.03450 (15)	0.64410 (12)	0.0148 (3)
C11	0.51657 (14)	−0.09063 (14)	0.66579 (12)	0.0156 (3)
H11	0.5770	−0.1790	0.6717	0.019*
C12	0.36760 (14)	−0.08670 (14)	0.67880 (13)	0.0154 (3)
C13	0.27734 (14)	0.04244 (15)	0.66821 (12)	0.0150 (3)
C14	0.33970 (14)	0.16737 (15)	0.64445 (12)	0.0152 (3)
H14	0.2792	0.2560	0.6362	0.018*
C15	0.81956 (14)	−0.09137 (15)	0.63483 (14)	0.0202 (3)
H15A	0.7976	−0.1643	0.7152	0.024*
H15B	0.9207	−0.0719	0.6201	0.024*
H15C	0.8057	−0.1261	0.5677	0.024*
C16	0.21996 (16)	−0.26397 (16)	0.81787 (13)	0.0259 (4)
H16A	0.2755	−0.2799	0.8841	0.031*
H16B	0.1859	−0.3540	0.8236	0.031*
H16C	0.1361	−0.1922	0.8276	0.031*
C17	0.03752 (14)	0.16588 (16)	0.68146 (15)	0.0240 (4)
H17A	0.0532	0.2022	0.7471	0.029*
H17B	−0.0641	0.1473	0.6976	0.029*
H17C	0.0594	0.2372	0.6001	0.029*
H1	0.4866 (17)	0.5528 (17)	0.7147 (15)	0.037 (6)*
H1A	0.8556 (17)	0.4884 (18)	0.5985 (16)	0.040 (5)*
H2	0.6770 (15)	0.2958 (16)	0.4553 (14)	0.025 (5)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0211 (2)	0.0299 (2)	0.01504 (19)	−0.01212 (17)	0.00076 (15)	−0.00803 (16)
F1	0.0276 (5)	0.0317 (5)	0.0234 (5)	0.0066 (4)	−0.0116 (4)	−0.0100 (4)
F2	0.0321 (5)	0.0333 (5)	0.0273 (5)	−0.0162 (4)	−0.0006 (4)	−0.0159 (4)
F3	0.0227 (5)	0.0429 (6)	0.0209 (5)	−0.0075 (4)	0.0038 (4)	−0.0179 (4)
O1	0.0177 (6)	0.0143 (5)	0.0266 (6)	0.0009 (4)	−0.0044 (5)	−0.0052 (4)
O2	0.0185 (6)	0.0235 (6)	0.0266 (6)	0.0010 (5)	−0.0002 (5)	−0.0084 (5)
O3	0.0244 (6)	0.0220 (6)	0.0160 (5)	−0.0049 (5)	0.0024 (4)	−0.0030 (4)
O4	0.0115 (5)	0.0170 (5)	0.0301 (6)	−0.0007 (4)	−0.0038 (4)	−0.0077 (5)
O5	0.0183 (5)	0.0175 (5)	0.0205 (6)	−0.0078 (4)	0.0026 (4)	−0.0088 (4)
O6	0.0119 (5)	0.0169 (5)	0.0300 (6)	−0.0012 (4)	−0.0047 (4)	−0.0062 (5)
N1	0.0140 (6)	0.0199 (7)	0.0161 (6)	−0.0065 (5)	−0.0006 (5)	−0.0072 (5)
N2	0.0160 (6)	0.0169 (6)	0.0127 (6)	−0.0054 (5)	−0.0009 (5)	−0.0053 (5)
C1	0.0166 (7)	0.0116 (7)	0.0157 (7)	−0.0017 (6)	−0.0060 (6)	−0.0027 (6)
C2	0.0160 (7)	0.0155 (7)	0.0151 (7)	−0.0025 (6)	−0.0016 (6)	−0.0053 (6)
C3	0.0134 (7)	0.0143 (7)	0.0157 (7)	−0.0011 (6)	−0.0026 (6)	−0.0052 (6)
C4	0.0123 (7)	0.0135 (7)	0.0155 (7)	−0.0001 (6)	−0.0022 (6)	−0.0043 (6)
C5	0.0174 (7)	0.0210 (8)	0.0201 (8)	−0.0030 (6)	0.0004 (6)	−0.0086 (6)
C6	0.0197 (8)	0.0185 (8)	0.0173 (7)	−0.0047 (6)	−0.0030 (6)	−0.0077 (6)
C7	0.0302 (9)	0.0356 (10)	0.0165 (8)	−0.0071 (8)	0.0065 (7)	−0.0050 (7)
C8	0.0394 (11)	0.0665 (14)	0.0341 (11)	−0.0269 (10)	0.0071 (9)	−0.0112 (10)
C9	0.0158 (7)	0.0144 (7)	0.0114 (7)	−0.0033 (6)	−0.0014 (5)	−0.0034 (6)
C10	0.0117 (7)	0.0191 (8)	0.0140 (7)	−0.0027 (6)	−0.0012 (6)	−0.0055 (6)
C11	0.0159 (7)	0.0142 (7)	0.0165 (7)	0.0016 (6)	−0.0026 (6)	−0.0062 (6)
C12	0.0173 (7)	0.0162 (7)	0.0142 (7)	−0.0059 (6)	−0.0006 (6)	−0.0059 (6)
C13	0.0116 (7)	0.0187 (7)	0.0151 (7)	−0.0032 (6)	−0.0014 (5)	−0.0055 (6)
C14	0.0158 (7)	0.0149 (7)	0.0149 (7)	0.0000 (6)	−0.0031 (6)	−0.0049 (6)
C15	0.0148 (7)	0.0203 (8)	0.0245 (8)	0.0015 (6)	−0.0027 (6)	−0.0078 (6)
C16	0.0362 (9)	0.0217 (8)	0.0180 (8)	−0.0105 (7)	0.0011 (7)	−0.0035 (6)
C17	0.0134 (7)	0.0235 (9)	0.0345 (9)	0.0012 (6)	−0.0035 (7)	−0.0102 (7)

Geometric parameters (Å, º) top

S1—C1	1.6878 (14)	C4—C9	1.5133 (18)
F1—C5	1.3422 (16)	C4—H4	1.0000
F2—C5	1.3384 (16)	C7—C8	1.501 (2)
F3—C5	1.3392 (15)	C7—H7A	0.9900
O1—C2	1.4096 (16)	C7—H7B	0.9900
O1—H1	0.820 (15)	C8—H8A	0.9800
O2—C6	1.2068 (16)	C8—H8B	0.9800
O3—C6	1.3314 (17)	C8—H8C	0.9800
O3—C7	1.4619 (16)	C9—C14	1.3937 (17)
O4—C10	1.3775 (15)	C9—C10	1.3988 (19)
O4—C15	1.4360 (15)	C10—C11	1.3910 (18)
O5—C12	1.3854 (15)	C11—C12	1.3844 (17)
O5—C16	1.4445 (16)	C11—H11	0.9500
O6—C13	1.3758 (15)	C12—C13	1.3949 (19)
O6—C17	1.4296 (16)	C13—C14	1.3895 (19)
N1—C1	1.3538 (17)	C14—H14	0.9500
N1—C2	1.4352 (17)	C15—H15A	0.9800
N1—H1A	0.834 (15)	C15—H15B	0.9800
N2—C1	1.3295 (16)	C15—H15C	0.9800
N2—C4	1.4640 (16)	C16—H16A	0.9800
N2—H2	0.824 (15)	C16—H16B	0.9800
C2—C5	1.5315 (19)	C16—H16C	0.9800
C2—C3	1.5388 (18)	C17—H17A	0.9800
C3—C6	1.5172 (18)	C17—H17B	0.9800
C3—C4	1.5403 (18)	C17—H17C	0.9800
C3—H3	1.0000

C2—O1—H1	109.2 (12)	C8—C7—H7B	109.4
C6—O3—C7	116.46 (11)	H7A—C7—H7B	108.0
C10—O4—C15	117.60 (10)	C7—C8—H8A	109.5
C12—O5—C16	114.69 (11)	C7—C8—H8B	109.5
C13—O6—C17	116.33 (10)	H8A—C8—H8B	109.5
C1—N1—C2	123.14 (12)	C7—C8—H8C	109.5
C1—N1—H1A	115.4 (12)	H8A—C8—H8C	109.5
C2—N1—H1A	120.3 (12)	H8B—C8—H8C	109.5
C1—N2—C4	125.74 (12)	C14—C9—C10	119.20 (12)
C1—N2—H2	116.9 (10)	C14—C9—C4	118.14 (12)
C4—N2—H2	116.8 (10)	C10—C9—C4	122.54 (12)
N2—C1—N1	118.08 (12)	O4—C10—C11	123.52 (12)
N2—C1—S1	120.77 (11)	O4—C10—C9	116.59 (12)
N1—C1—S1	121.16 (10)	C11—C10—C9	119.86 (12)
O1—C2—N1	108.97 (11)	C12—C11—C10	120.18 (13)
O1—C2—C5	107.58 (11)	C12—C11—H11	119.9
N1—C2—C5	108.28 (11)	C10—C11—H11	119.9
O1—C2—C3	112.87 (11)	C11—C12—O5	118.11 (12)
N1—C2—C3	108.27 (11)	C11—C12—C13	120.75 (12)
C5—C2—C3	110.77 (12)	O5—C12—C13	121.09 (12)
C6—C3—C2	112.14 (11)	O6—C13—C14	124.72 (12)
C6—C3—C4	108.08 (11)	O6—C13—C12	116.52 (12)
C2—C3—C4	108.03 (11)	C14—C13—C12	118.76 (12)
C6—C3—H3	109.5	C13—C14—C9	121.24 (13)
C2—C3—H3	109.5	C13—C14—H14	119.4
C4—C3—H3	109.5	C9—C14—H14	119.4
N2—C4—C9	112.66 (11)	O4—C15—H15A	109.5
N2—C4—C3	109.02 (10)	O4—C15—H15B	109.5
C9—C4—C3	111.13 (11)	H15A—C15—H15B	109.5
N2—C4—H4	108.0	O4—C15—H15C	109.5
C9—C4—H4	108.0	H15A—C15—H15C	109.5
C3—C4—H4	108.0	H15B—C15—H15C	109.5
F2—C5—F3	106.90 (11)	O5—C16—H16A	109.5
F2—C5—F1	107.50 (11)	O5—C16—H16B	109.5
F3—C5—F1	107.21 (11)	H16A—C16—H16B	109.5
F2—C5—C2	111.95 (12)	O5—C16—H16C	109.5
F3—C5—C2	110.97 (12)	H16A—C16—H16C	109.5
F1—C5—C2	112.04 (11)	H16B—C16—H16C	109.5
O2—C6—O3	125.39 (13)	O6—C17—H17A	109.5
O2—C6—C3	123.22 (13)	O6—C17—H17B	109.5
O3—C6—C3	111.39 (12)	H17A—C17—H17B	109.5
O3—C7—C8	111.32 (13)	O6—C17—H17C	109.5
O3—C7—H7A	109.4	H17A—C17—H17C	109.5
C8—C7—H7A	109.4	H17B—C17—H17C	109.5
O3—C7—H7B	109.4

C4—N2—C1—N1	−0.5 (2)	C4—C3—C6—O2	−66.66 (17)
C4—N2—C1—S1	179.59 (10)	C2—C3—C6—O3	−127.98 (12)
C2—N1—C1—N2	−8.5 (2)	C4—C3—C6—O3	113.05 (13)
C2—N1—C1—S1	171.37 (10)	C6—O3—C7—C8	86.53 (17)
C1—N1—C2—O1	−84.44 (15)	N2—C4—C9—C14	−131.29 (13)
C1—N1—C2—C5	158.83 (13)	C3—C4—C9—C14	106.04 (14)
C1—N1—C2—C3	38.67 (17)	N2—C4—C9—C10	52.74 (18)
O1—C2—C3—C6	−56.23 (15)	C3—C4—C9—C10	−69.94 (16)
N1—C2—C3—C6	−176.95 (11)	C15—O4—C10—C11	8.80 (19)
C5—C2—C3—C6	64.47 (15)	C15—O4—C10—C9	−173.30 (12)
O1—C2—C3—C4	62.77 (14)	C14—C9—C10—O4	−177.16 (12)
N1—C2—C3—C4	−57.94 (14)	C4—C9—C10—O4	−1.23 (19)
C5—C2—C3—C4	−176.53 (11)	C14—C9—C10—C11	0.8 (2)
C1—N2—C4—C9	−146.08 (13)	C4—C9—C10—C11	176.76 (12)
C1—N2—C4—C3	−22.23 (18)	O4—C10—C11—C12	176.31 (12)
C6—C3—C4—N2	171.55 (11)	C9—C10—C11—C12	−1.5 (2)
C2—C3—C4—N2	50.00 (14)	C10—C11—C12—O5	178.53 (12)
C6—C3—C4—C9	−63.69 (14)	C10—C11—C12—C13	1.2 (2)
C2—C3—C4—C9	174.76 (10)	C16—O5—C12—C11	114.47 (14)
O1—C2—C5—F2	−59.19 (14)	C16—O5—C12—C13	−68.16 (17)
N1—C2—C5—F2	58.44 (15)	C17—O6—C13—C14	−6.35 (19)
C3—C2—C5—F2	177.02 (11)	C17—O6—C13—C12	174.47 (12)
O1—C2—C5—F3	60.15 (14)	C11—C12—C13—O6	179.16 (12)
N1—C2—C5—F3	177.78 (11)	O5—C12—C13—O6	1.86 (19)
C3—C2—C5—F3	−63.64 (15)	C11—C12—C13—C14	−0.1 (2)
O1—C2—C5—F1	179.96 (10)	O5—C12—C13—C14	−177.37 (12)
N1—C2—C5—F1	−62.42 (14)	O6—C13—C14—C9	−179.80 (13)
C3—C2—C5—F1	56.17 (15)	C12—C13—C14—C9	−0.6 (2)
C7—O3—C6—O2	−0.1 (2)	C10—C9—C14—C13	0.3 (2)
C7—O3—C6—C3	−179.80 (11)	C4—C9—C14—C13	−175.86 (12)
C2—C3—C6—O2	52.32 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2	0.820 (15)	2.103 (16)	2.8055 (15)	143.5 (15)
O1—H1···O5ⁱ	0.820 (15)	2.579 (16)	2.9876 (15)	112.2 (13)
N2—H2···O5ⁱⁱ	0.824 (15)	2.129 (15)	2.9521 (15)	176.6 (15)
N1—H1A···S1ⁱⁱⁱ	0.834 (15)	2.526 (16)	3.3427 (13)	166.3 (15)

Symmetry codes: (i) x, y+1, z; (ii) −x+1, −y, −z+1; (iii) −x+2, −y+1, −z+1.

Experimental details

Crystal data
Chemical formula	C₁₇H₂₁F₃N₂O₆S
M_r	438.42
Crystal system, space group	Triclinic, P1
Temperature (K)	113
a, b, c (Å)	9.5070 (8), 9.9040 (8), 11.4710 (13)
α, β, γ (°)	71.582 (13), 76.740 (16), 79.743 (15)
V (Å³)	990.89 (19)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.23
Crystal size (mm)	0.28 × 0.22 × 0.20

Data collection
Diffractometer	Rigaku Saturn724 CCD-detector diffractometer
Absorption correction	Multi-scan (REQAB; Jacobson, 1998)
T_min, T_max	0.939, 0.956
No. of measured, independent and observed [I > 2σ(I)] reflections	13891, 5290, 3175
R_int	0.049
(sin θ/λ)_max (Å⁻¹)	0.685

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.033, 0.080, 0.90
No. of reflections	5290
No. of parameters	279
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.26

Computer programs: CrystalClear (Rigaku/MSC, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), CrystalStructure (Rigaku/MSC, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2	0.820 (15)	2.103 (16)	2.8055 (15)	143.5 (15)
N2—H2···O5ⁱ	0.824 (15)	2.129 (15)	2.9521 (15)	176.6 (15)
N1—H1A···S1ⁱⁱ	0.834 (15)	2.526 (16)	3.3427 (13)	166.3 (15)

Symmetry codes: (i) −x+1, −y, −z+1; (ii) −x+2, −y+1, −z+1.

Acknowledgements

The authors thank the Technology Research and Development Program of Henan Province, China (grant No. 122102210426).

References

Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573. CrossRef CAS Web of Science Google Scholar
Biginelli, P. (1893). Gazz. Chim. Ital. 23, 360–413. Google Scholar
Brier, S., Lemaire, D., Debonis, S., Forest, E. & Kozielski, F. (2004). Biochemistry, 43, 13072–13082. Web of Science CrossRef PubMed CAS Google Scholar
Cochran, J. C., Gatial, J. E., Kapoor, T. M. & Gilbert, S. P. (2005). J. Biol. Chem. 280, 12658–12667. Web of Science CrossRef PubMed CAS Google Scholar
Hermann, B., Erwin, H. & Hansjorg, K. (2003). US patent No. 2 003 176 284. Google Scholar
Jacobson, R. (1998). REQAB. Private communication to the Rigaku Corporation, Tokyo, Japan. Google Scholar
Li, G.-C., Wu, C.-Z., Guo, L.-L. & Yang, F.-L. (2011). Acta Cryst. E67, o1704–o1705. Web of Science CSD CrossRef IUCr Journals Google Scholar
Moran, M. M., Fanger, C., Chong, J. A., Mcnamara, C., Zhen, X. G. & Mandel-Brehm, J. (2007). WO Patent No. 2 007 073 505. Google Scholar
Rigaku/MSC (2009). CrystalClear and CrystalStructure. Rigaku/MSC, The Woodlands, Texas, USA. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Ulrich, H. (2004). US patent No. 2 004 033 897. Google Scholar
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Volume 68| Part 11| November 2012| Pages o3092-o3093

doi:10.1107/S1600536812041013

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

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Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

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