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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o2852.
Published online 2010 October 20. doi:  10.1107/S1600536810041085
PMCID: PMC3009001

6-Hy­droxy-4-(pyridin-3-yl)-5-(2-thienyl­carbon­yl)-6-trifluoro­meth­yl-3,4,5,6-tetra­hydro­pyrimidin-2(1H)-one

Abstract

In the title compound, C15H12F3N3O3S, the pyrimidine ring adopts a half-chair conformation with the mean plane formed by the ring atoms excluding the C atom bonded to thio­phene-2-carbonyl group lying nearly perpendicular to the pyridine and thio­phene rings, making dihedral angles of 84.91 (4) and 87.40 (5)°, respectively. The dihedral angle between the pyridine and thio­phene rings is 54.44 (5)°. The crystal structure is stabilized by inter­molecular O—H(...)O and N—H(...)N hydrogen bonds and weak C—H(...)O inter­actions further consolidate the structure.

Related literature

For the bioactivity of dihydro­pyrimidines, see: Cochran et al. (2005 [triangle]); Moran et al. (2007 [triangle]); Zorkun et al. (2006 [triangle]). For the bioactivity of organofluorine compounds, see: Ulrich (2004 [triangle]). For a related stucture, see: Yang et al. (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o2852-scheme1.jpg

Experimental

Crystal data

  • C15H12F3N3O3S
  • M r = 371.34
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2852-efi1.jpg
  • a = 29.694 (3) Å
  • b = 5.9710 (8) Å
  • c = 17.6910 (16) Å
  • β = 95.223 (8)°
  • V = 3123.6 (6) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.26 mm−1
  • T = 113 K
  • 0.26 × 0.22 × 0.20 mm

Data collection

  • Rigaku Saturn724 CCD diffractometer
  • Absorption correction: multi-scan (CrystalClear-SM Expert; Rigaku/MSC, 2009 [triangle]) T min = 0.935, T max = 0.950
  • 15077 measured reflections
  • 3707 independent reflections
  • 2888 reflections with I > 2.0 σ(I)
  • R int = 0.056

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.098
  • S = 1.04
  • 3707 reflections
  • 238 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.36 e Å−3
  • Δρmin = −0.23 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810041085/pv2334sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810041085/pv2334Isup2.hkl

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

Acknowledgments

This work was supported by the Natural Science Foundation of Henan Province (grant No. 082300420110) and the Natural Science Foundation of Henan Province Education Department (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 (a member of the Kinesin-5 subclass of kinesins) for treating cancer (Cochran et al., 2005) and as TRPA1 (Transient Receptor Potential cation channel, subfamily A, member 1) modulators for treating pain (Moran et al., 2007). In addition, compounds that contain fluorine have special bioactivity, for example flumioxazin is a widely used herbicide (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 (I) was isolated and its structure established by X-ray diffraction method, in order to elucidate the reaction mechanism.

In the structure of the title molecule, the dihydropyrimidine ring adopts a half-chair conformation; the atoms C1/C2/C3/N1/N2 are nearly coplanar and the plane is nearly perpendicular with pyridine and thiophene rings with dihedral angles 84.91 (4) and 87.40 (5)°, respectively. The dihedral angle between the pyridine ring and the thiophene ring is 54.44 (5)°. The crystal structure is stabilized by intermolecular hydrogen bonds of the types O—H···O and N—H···N; there are also weak hydrogen bonding interactions of the type C—H···O present in the structure (Table 1). For a crystal structure related to the title compound, see: Yang et al., (2009).

Experimental

The title compound was synthesized by refluxing for 3 h a stirred solution of 3-pyridinaldehyde (0.22 g, 2 mmol), 4,4,4-trifluoro-1-(thiophen-2-yl)butane- 1,3-dione (0.51 g, 2.3 mmol) and urea (0.18 g, 3 mmol) in 3 ml of anhydrous ethanol; the reaction was catalyzed by sulfamic acid (0.06 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 of (I) were obtained by slow evaporation.

Refinement

Hydrogen atoms involved in hydrogen-bonding inetractions were located from a difference Fourier map and their positional and isotropic displacement parameters were refined. The other H atoms were placed in calculated positions, with C—H(aromatic) = 0.95 Å and C—H(aliphatic) = 1.00 Å, and treated as riding, with Uiso(H) = 1.2Ueq(C).

Figures

Fig. 1.
Molecular configuration and atom numbering scheme for (I), with displacement ellipsoids drawn at the 30% probability level.
Fig. 2.
The packing diagram of the title compound.

Crystal data

C15H12F3N3O3SF(000) = 1520
Mr = 371.34Dx = 1.579 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71075 Å
Hall symbol: -C 2ycCell parameters from 5438 reflections
a = 29.694 (3) Åθ = 1.7–28.0°
b = 5.9710 (8) ŵ = 0.26 mm1
c = 17.6910 (16) ÅT = 113 K
β = 95.223 (8)°Prism, colorless
V = 3123.6 (6) Å30.26 × 0.22 × 0.20 mm
Z = 8

Data collection

Rigaku Saturn724 CCD diffractometer3707 independent reflections
Radiation source: rotating anode2888 reflections with I > 2.0 σ(I)
multilayerRint = 0.056
Detector resolution: 14.222 pixels mm-1θmax = 27.9°, θmin = 2.3°
ω scansh = −38→37
Absorption correction: multi-scan (CrystalClear-SM Expert; Rigaku/MSC, 2009)k = −7→7
Tmin = 0.935, Tmax = 0.950l = −23→23
15077 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.036Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.098H atoms treated by a mixture of independent and constrained refinement
S = 1.04w = 1/[σ2(Fo2) + (0.0496P)2] where P = (Fo2 + 2Fc2)/3
3707 reflections(Δ/σ)max = 0.001
238 parametersΔρmax = 0.36 e Å3
0 restraintsΔρmin = −0.23 e Å3

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 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)

xyzUiso*/Ueq
S10.026595 (14)0.12707 (8)0.92814 (2)0.03528 (14)
F10.10963 (3)−0.11784 (17)0.62064 (4)0.0313 (2)
F20.06951 (3)−0.11496 (17)0.71617 (5)0.0298 (2)
F30.09202 (3)0.19531 (16)0.67005 (5)0.0302 (2)
O10.15452 (3)−0.25213 (17)0.75794 (5)0.0181 (2)
O20.25389 (3)0.21588 (17)0.70458 (5)0.0176 (2)
O30.10702 (3)−0.12933 (18)0.89515 (5)0.0238 (2)
N10.18320 (4)0.0743 (2)0.70261 (6)0.0155 (3)
N20.21958 (4)0.2166 (2)0.81451 (6)0.0153 (3)
N30.19968 (4)0.2310 (2)1.07057 (6)0.0179 (3)
C10.14728 (4)−0.0243 (2)0.74123 (7)0.0146 (3)
C20.22112 (4)0.1687 (2)0.74020 (7)0.0143 (3)
C30.18652 (4)0.1181 (2)0.86052 (7)0.0136 (3)
H30.1952−0.04100.87190.016*
C40.14098 (4)0.1215 (2)0.81197 (7)0.0141 (3)
H40.13450.27880.79490.017*
C50.10424 (5)−0.0160 (3)0.68637 (7)0.0211 (3)
C60.18514 (4)0.2436 (2)0.93467 (7)0.0144 (3)
C70.16718 (4)0.4565 (3)0.93907 (7)0.0178 (3)
H70.15650.53490.89430.021*
C80.16500 (5)0.5540 (3)1.01013 (7)0.0208 (3)
H80.15240.69901.01480.025*
C90.18153 (5)0.4355 (3)1.07377 (7)0.0201 (3)
H90.17990.50251.12220.024*
C100.20114 (4)0.1383 (2)1.00190 (7)0.0153 (3)
H100.2138−0.00720.99900.018*
C110.10371 (4)0.0461 (3)0.85989 (7)0.0168 (3)
C120.06578 (5)0.1986 (3)0.86639 (7)0.0206 (3)
C130.05608 (5)0.4038 (3)0.83352 (9)0.0255 (3)
H130.07380.47230.79780.031*
C140.01670 (5)0.5012 (3)0.85897 (10)0.0372 (4)
H140.00490.64250.84230.045*
C15−0.00227 (5)0.3696 (3)0.90984 (10)0.0404 (5)
H15−0.02890.40880.93280.048*
H10.1888 (5)0.007 (3)0.6611 (9)0.024 (4)*
H20.2439 (5)0.260 (3)0.8390 (9)0.020 (4)*
H50.1814 (6)−0.273 (3)0.7674 (10)0.031 (5)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0254 (2)0.0467 (3)0.0363 (2)−0.00599 (19)0.01643 (16)−0.00842 (19)
F10.0228 (4)0.0510 (7)0.0189 (4)0.0021 (4)−0.0042 (3)−0.0141 (4)
F20.0159 (4)0.0449 (7)0.0283 (5)−0.0080 (4)0.0001 (3)−0.0047 (4)
F30.0265 (5)0.0355 (6)0.0266 (4)0.0091 (4)−0.0088 (3)0.0028 (4)
O10.0159 (5)0.0168 (6)0.0216 (5)−0.0013 (4)0.0015 (4)−0.0016 (4)
O20.0170 (5)0.0202 (6)0.0161 (4)−0.0023 (4)0.0039 (3)0.0002 (4)
O30.0260 (5)0.0226 (6)0.0233 (5)−0.0020 (4)0.0059 (4)0.0052 (4)
N10.0154 (5)0.0206 (7)0.0107 (5)−0.0008 (5)0.0019 (4)−0.0017 (4)
N20.0140 (6)0.0198 (7)0.0121 (5)−0.0037 (5)0.0005 (4)−0.0012 (4)
N30.0187 (6)0.0215 (7)0.0133 (5)−0.0030 (5)0.0008 (4)0.0005 (5)
C10.0137 (6)0.0152 (8)0.0147 (6)0.0003 (5)0.0002 (4)−0.0008 (5)
C20.0163 (6)0.0119 (7)0.0146 (6)0.0006 (5)0.0005 (5)0.0010 (5)
C30.0150 (6)0.0140 (7)0.0119 (6)−0.0006 (5)0.0013 (4)0.0006 (5)
C40.0135 (6)0.0150 (8)0.0137 (6)0.0001 (5)0.0011 (5)0.0003 (5)
C50.0180 (7)0.0274 (9)0.0176 (6)0.0000 (6)−0.0003 (5)−0.0035 (6)
C60.0143 (6)0.0151 (8)0.0137 (6)−0.0026 (6)0.0016 (4)−0.0005 (5)
C70.0209 (7)0.0178 (8)0.0146 (6)−0.0008 (6)0.0011 (5)0.0015 (5)
C80.0257 (7)0.0166 (8)0.0201 (6)−0.0006 (6)0.0031 (5)−0.0027 (5)
C90.0237 (7)0.0222 (9)0.0146 (6)−0.0025 (6)0.0029 (5)−0.0033 (5)
C100.0144 (6)0.0162 (8)0.0155 (6)−0.0013 (5)0.0024 (5)0.0008 (5)
C110.0165 (6)0.0191 (8)0.0147 (6)−0.0028 (6)0.0009 (5)−0.0023 (5)
C120.0152 (7)0.0270 (9)0.0197 (6)−0.0026 (6)0.0024 (5)−0.0057 (6)
C130.0197 (7)0.0257 (9)0.0307 (8)0.0054 (7)0.0006 (6)−0.0044 (6)
C140.0235 (8)0.0365 (12)0.0499 (10)0.0109 (8)−0.0060 (7)−0.0172 (8)
C150.0178 (8)0.0559 (14)0.0483 (10)−0.0007 (8)0.0075 (7)−0.0310 (9)

Geometric parameters (Å, °)

S1—C151.699 (2)C3—C41.5345 (17)
S1—C121.7208 (15)C3—H31.0000
F1—C51.3347 (15)C4—C111.5222 (17)
F2—C51.3379 (16)C4—H41.0000
F3—C51.3370 (18)C6—C71.383 (2)
O1—C11.4047 (17)C6—C101.3902 (17)
O1—H50.81 (2)C7—C81.3922 (18)
O2—C21.2390 (16)C7—H70.9500
O3—C111.2187 (17)C8—C91.3813 (19)
N1—C21.3753 (17)C8—H80.9500
N1—C11.4435 (17)C9—H90.9500
N1—H10.87 (2)C10—H100.9500
N2—C21.3501 (16)C11—C121.461 (2)
N2—C31.4553 (16)C12—C131.375 (2)
N2—H20.85 (2)C13—C141.416 (2)
N3—C91.3379 (19)C13—H130.9500
N3—C101.3393 (16)C14—C151.355 (3)
C1—C51.5337 (18)C14—H140.9500
C1—C41.5495 (17)C15—H150.9500
C3—C61.5145 (17)
C15—S1—C1291.49 (9)F1—C5—C1112.19 (11)
C1—O1—H5108.7 (13)F3—C5—C1111.18 (12)
C2—N1—C1123.09 (10)F2—C5—C1111.36 (11)
C2—N1—H1112.9 (10)C7—C6—C10118.08 (12)
C1—N1—H1114.8 (11)C7—C6—C3122.98 (11)
C2—N2—C3122.91 (11)C10—C6—C3118.90 (12)
C2—N2—H2117.3 (11)C6—C7—C8119.02 (12)
C3—N2—H2115.1 (11)C6—C7—H7120.5
C9—N3—C10117.51 (11)C8—C7—H7120.5
O1—C1—N1112.90 (10)C9—C8—C7118.65 (14)
O1—C1—C5105.49 (11)C9—C8—H8120.7
N1—C1—C5107.24 (10)C7—C8—H8120.7
O1—C1—C4113.67 (10)N3—C9—C8123.19 (12)
N1—C1—C4107.58 (11)N3—C9—H9118.4
C5—C1—C4109.76 (11)C8—C9—H9118.4
O2—C2—N2123.02 (12)N3—C10—C6123.54 (13)
O2—C2—N1119.57 (11)N3—C10—H10118.2
N2—C2—N1117.31 (12)C6—C10—H10118.2
N2—C3—C6110.93 (11)O3—C11—C12121.48 (13)
N2—C3—C4106.64 (10)O3—C11—C4120.69 (12)
C6—C3—C4112.73 (11)C12—C11—C4117.68 (13)
N2—C3—H3108.8C13—C12—C11130.93 (13)
C6—C3—H3108.8C13—C12—S1111.21 (11)
C4—C3—H3108.8C11—C12—S1117.77 (11)
C11—C4—C3109.42 (10)C12—C13—C14112.26 (16)
C11—C4—C1115.54 (11)C12—C13—H13123.9
C3—C4—C1106.24 (10)C14—C13—H13123.9
C11—C4—H4108.5C15—C14—C13112.22 (17)
C3—C4—H4108.5C15—C14—H14123.9
C1—C4—H4108.5C13—C14—H14123.9
F1—C5—F3107.07 (11)C14—C15—S1112.82 (13)
F1—C5—F2107.45 (12)C14—C15—H15123.6
F3—C5—F2107.35 (11)S1—C15—H15123.6
C2—N1—C1—O1−88.51 (15)N2—C3—C6—C771.30 (16)
C2—N1—C1—C5155.73 (13)C4—C3—C6—C7−48.22 (17)
C2—N1—C1—C437.72 (17)N2—C3—C6—C10−111.02 (13)
C3—N2—C2—O2−165.46 (13)C4—C3—C6—C10129.46 (13)
C3—N2—C2—N118.18 (19)C10—C6—C7—C8−1.32 (19)
C1—N1—C2—O2167.89 (12)C3—C6—C7—C8176.37 (12)
C1—N1—C2—N2−15.6 (2)C6—C7—C8—C91.0 (2)
C2—N2—C3—C6−165.76 (12)C10—N3—C9—C8−0.8 (2)
C2—N2—C3—C4−42.66 (17)C7—C8—C9—N30.1 (2)
N2—C3—C4—C11−173.34 (11)C9—N3—C10—C60.38 (19)
C6—C3—C4—C11−51.37 (15)C7—C6—C10—N30.7 (2)
N2—C3—C4—C161.28 (13)C3—C6—C10—N3−177.13 (12)
C6—C3—C4—C1−176.75 (11)C3—C4—C11—O3−52.53 (17)
O1—C1—C4—C11−55.20 (14)C1—C4—C11—O367.28 (16)
N1—C1—C4—C11179.03 (10)C3—C4—C11—C12123.10 (12)
C5—C1—C4—C1162.66 (15)C1—C4—C11—C12−117.09 (13)
O1—C1—C4—C366.33 (13)O3—C11—C12—C13178.48 (14)
N1—C1—C4—C3−59.43 (13)C4—C11—C12—C132.9 (2)
C5—C1—C4—C3−175.80 (11)O3—C11—C12—S12.12 (18)
O1—C1—C5—F1−64.29 (14)C4—C11—C12—S1−173.47 (9)
N1—C1—C5—F156.29 (16)C15—S1—C12—C130.00 (12)
C4—C1—C5—F1172.87 (12)C15—S1—C12—C11177.05 (11)
O1—C1—C5—F3175.84 (10)C11—C12—C13—C14−176.56 (14)
N1—C1—C5—F3−63.58 (14)S1—C12—C13—C14−0.02 (16)
C4—C1—C5—F353.01 (15)C12—C13—C14—C150.03 (19)
O1—C1—C5—F256.18 (14)C13—C14—C15—S1−0.04 (18)
N1—C1—C5—F2176.76 (11)C12—S1—C15—C140.02 (13)
C4—C1—C5—F2−66.65 (15)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O1—H5···O2i0.81 (2)1.94 (2)2.7466 (14)173 (2)
N2—H2···N3ii0.85 (2)2.21 (2)3.0153 (15)159 (2)
N1—H1···N3iii0.87 (2)2.19 (2)3.0378 (16)167 (2)
C3—H3···O11.002.582.961 (2)102
C3—H3···O2i1.002.573.255 (2)126
C7—H7···O3iv0.952.493.108 (2)123

Symmetry codes: (i) −x+1/2, y−1/2, −z+3/2; (ii) −x+1/2, −y+1/2, −z+2; (iii) x, −y, z−1/2; (iv) x, y+1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2334).

References

  • Cochran, J. C., Gatial, J. E., Kapoor, T. M. & Gilbert, S. P. (2005). J. Biol. Chem.280, 12658–12667. [PMC free article] [PubMed]
  • Moran, M. M., Fanger, C., Chong, J. A., McNamara, C., Zhen, X. G. & Mandel-Brehm, J. (2007). WO Patent No. 2 007 073 505.
  • Rigaku/MSC (2009). CrystalClear-SM Expert and CrystalStructure Rigaku/MSC, The Woodlands, Texas, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Ulrich, H. (2004). US Patent No. 2 004 033 897.
  • Yang, F.-L., Zhang, J. & Yao, C.-S. (2009). Acta Cryst. E65, o87–o88. [PMC free article] [PubMed]
  • Zorkun, I. S., Sarac, S., Celebi, S. & Erol, K. (2006). Bioorg. Med. Chem.14, 8582–8589. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography