rac-Ethyl 4-hy-droxy-4-trifluoro-methyl-6-(2,4,5-trimeth-oxy-phen-yl)-2-thio-1,3-diazinane-5-carboxyl-ate.

In the title compound, C(17)H(21)F(3)N(2)O(6)S, the hexa-hydro-pyrimidine ring adopts a half-chair conformation: the mean plane formed by the ring atoms excluding the C atom bonded to the eth-oxy-carbonyl 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 mol-ecular conformation is stabilized by an intra-molecular hydroxyl O-H⋯O(carbox-yl) 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.

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 = 438.42

Triclinic,

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[F 2 > 2σ(F 2)] = 0.033

wR(F 2) = 0.080

S = 0.90

5290 reflections

279 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.33 e Å−3

Δρmin = −0.26 e Å−3

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.

Click here for additional data file.

Crystal structure: contains datablock(s) shelxl, I. DOI: 10.1107/S1600536812041013/zs2236sup1.cif

Click here for additional data file.

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

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536812041013/zs2236Isup3.cml

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

C17H21F3N2O6S	Z = 2
Mr = 438.42	F(000) = 456
Triclinic, P1	Dx = 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

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

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(Fo2) + (0.0266P)2 + ] where P = (Fo2 + 2Fc2)/3
S = 0.90	(Δ/σ)max = 0.001
5290 reflections	Δρmax = 0.33 e Å−3
279 parameters	Δρmin = −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)

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.

	x	y	z	Uiso*/Ueq
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)*

	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)

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)

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)

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) ; (ii) .