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Acta Crystallogr Sect E Struct Rep Online. 2008 January 1; 64(Pt 1): o261.
Published online 2007 December 12. doi:  10.1107/S1600536807065737
PMCID: PMC2915317

Ethyl 4-(4-hydroxy­phen­yl)-6-methyl-2-thioxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate monohydrate

Abstract

In the organic mol­ecule of the title compound, C14H16N2O3S·H2O, the two rings are oriented at a dihedral angle of 84.31 (2)°. In the crystal structure, intra­molecular O—H(...)O and inter­molecular O—H(...)O, N—H(...)O, O—H(...)S and N—H(...)S hydrogen bonds are found.

Related literature

For general background, see: Atwal et al. (1991 [triangle]); Mayer et al. (1999 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]).

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Object name is e-64-0o261-scheme1.jpg

Experimental

Crystal data

  • C14H16N2O3S·H2O
  • M r = 310.36
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-0o261-efi1.jpg
  • a = 5.6702 (17) Å
  • b = 11.212 (3) Å
  • c = 12.343 (4) Å
  • α = 90.406 (5)°
  • β = 95.251 (5)°
  • γ = 104.393 (5)°
  • V = 756.5 (4) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.23 mm−1
  • T = 294 (2) K
  • 0.22 × 0.16 × 0.16 mm

Data collection

  • Bruker SMART CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 1996 [triangle]) T min = 0.951, T max = 0.964
  • 3958 measured reflections
  • 2655 independent reflections
  • 1741 reflections with I > 2σ(I)
  • R int = 0.025

Refinement

  • R[F 2 > 2σ(F 2)] = 0.044
  • wR(F 2) = 0.117
  • S = 1.01
  • 2655 reflections
  • 209 parameters
  • 5 restraints
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.21 e Å−3

Data collection: SMART (Bruker, 1997 [triangle]); cell refinement: SAINT (Bruker, 1997 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 [triangle]); molecular graphics: SHELXTL (Bruker, 1997 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807065737/hk2363sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807065737/hk2363Isup2.hkl

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

supplementary crystallographic information

Comment

The title compound, (I), is a kind of polyfunctionalized dihydropyrimidines (DHPMs), which represents a heterocyclic system of remarkable pharmacological efficiency and may exhibit antiviral, antitumor, antibacterial, and anti inflammatory properties (Atwal et al., 1991). It is the only cell-permeable molecule currently known to specifically inhibit mitotic kinesis Eg5 and is considered a lead for the development of new anticancer drugs (Mayer et al., 1999).

In the molecule of the title compound, (I), (Fig.1) the bond lengths and angles are within normal ranges (Allen et al., 1987). Rings A (N1/N2/C1—C4) and B (C9—C14) are, of course, planar and they are oriented at a dihedral angle of A/B = 84.31 (2)°.

In the crystal structure, intramolecular O—H···O and intermolecular O—H···O, N—H···O, O—H···S and N—H···S hydrogen bonds (Table 1) link the molecules (Fig. 2), in which they seem to be effective in the stabilization of the structure.

Experimental

For the preparation of the title compound, a solution of ethyl acetoacetate (1.44 g, 10 mmol), 4-hydroxybenzaldehyde (1.38 g, 10 mmol) and thiourea (0.86 g, 10 mmol) in ethanol (5 ml) was heated under reflux in the presence of HCl (three drops) for 2.5 h. After being cooled to room temperature, the reaction mixture was poured onto crushed ice (30 g) and stirred for 5–10 min. The separated solid was filtered under suction (water aspirator), washed with ice-cold water (50 ml), and then recrystallized from hot ethanol to afford the pure product.

Refinement

H atoms (for H2O and NH) were located in difference synthesis and refined isotropicaly [O—H = 0.864 (10) and 0.855 (10) Å, Uiso(H) = 0.088 (13) and 0.096 (14) Å2; N—H = 0.895 (10) and 0.892 (10) Å, Uiso(H) = 0.047 (8) and 0.061 (9) Å2]. The remaining H atoms were positioned geometrically, with O—H = 0.82 Å (for OH) and C—H = 0.93, 0.98, 0.97 and 0.96 Å, for aromatic, methine, methylene and methyl H atoms and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C,O), where x = 1.5 for OH H and methyl H, and x = 1.2 for all other H atoms.

Figures

Fig. 1.
The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bond is shown as dashed lines.
Fig. 2.
A packing diagram of (I). Hydrogen bonds are shown as dashed lines.

Crystal data

C14H16N2O3S·H2OZ = 2
Mr = 310.36F000 = 328
Triclinic, P1Dx = 1.362 Mg m3
Hall symbol: -P 1Mo Kα radiation λ = 0.71073 Å
a = 5.6702 (17) ÅCell parameters from 1137 reflections
b = 11.212 (3) Åθ = 3.3–25.0º
c = 12.343 (4) ŵ = 0.23 mm1
α = 90.406 (5)ºT = 294 (2) K
β = 95.251 (5)ºPlate, colorless
γ = 104.393 (5)º0.22 × 0.16 × 0.16 mm
V = 756.5 (4) Å3

Data collection

Bruker SMART CCD area-detector diffractometer2655 independent reflections
Radiation source: fine-focus sealed tube1741 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.025
T = 294(2) Kθmax = 25.0º
[var phi] and ω scansθmin = 2.5º
Absorption correction: multi-scan(SADABS; Sheldrick, 1996)h = −6→6
Tmin = 0.951, Tmax = 0.964k = −10→13
3958 measured reflectionsl = −14→14

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.117  w = 1/[σ2(Fo2) + (0.0529P)2 + 0.1375P] where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max = 0.003
2655 reflectionsΔρmax = 0.20 e Å3
209 parametersΔρmin = −0.20 e Å3
5 restraintsExtinction correction: none
Primary atom site location: structure-invariant direct methods

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
S10.30417 (14)0.38411 (6)0.11066 (6)0.0509 (3)
O10.1221 (4)0.95058 (17)0.15444 (17)0.0588 (6)
O2−0.2131 (3)0.83224 (15)0.21777 (15)0.0464 (5)
O30.1542 (4)0.70709 (18)0.67773 (14)0.0520 (5)
H30.29770.74380.69340.078*
O40.6317 (5)0.8288 (2)0.72788 (18)0.0688 (7)
H4A0.700 (6)0.7722 (19)0.753 (3)0.088 (13)*
H4B0.681 (6)0.8966 (17)0.765 (2)0.096 (14)*
N10.2842 (4)0.61232 (19)0.06966 (18)0.0417 (6)
H1A0.385 (4)0.602 (2)0.0205 (16)0.047 (8)*
N20.0298 (4)0.51470 (18)0.19204 (17)0.0376 (5)
H2A−0.020 (5)0.4483 (17)0.231 (2)0.061 (9)*
C10.1972 (5)0.5103 (2)0.12598 (19)0.0343 (6)
C2−0.0549 (5)0.6237 (2)0.2218 (2)0.0351 (6)
H2−0.23270.60500.20440.042*
C30.0627 (4)0.7321 (2)0.1543 (2)0.0334 (6)
C40.2179 (5)0.7224 (2)0.0817 (2)0.0378 (6)
C50.3300 (6)0.8169 (2)0.0035 (2)0.0521 (8)
H5A0.24370.8805−0.00100.078*
H5B0.31970.7784−0.06710.078*
H5C0.49860.85210.02860.078*
C6−0.0012 (5)0.8494 (2)0.1737 (2)0.0401 (6)
C7−0.2762 (6)0.9417 (2)0.2582 (3)0.0563 (8)
H7A−0.45270.92810.25320.068*
H7B−0.21151.01120.21390.068*
C8−0.1728 (7)0.9697 (3)0.3736 (3)0.0710 (10)
H8A−0.21400.89630.41470.106*
H8B−0.23981.03180.40380.106*
H8C0.00180.99900.37660.106*
C90.0011 (4)0.6489 (2)0.34304 (19)0.0319 (6)
C100.2363 (5)0.7051 (2)0.3872 (2)0.0388 (6)
H100.35970.72940.34130.047*
C110.2911 (5)0.7258 (2)0.4978 (2)0.0410 (6)
H110.45010.76390.52590.049*
C120.1096 (5)0.6899 (2)0.5672 (2)0.0371 (6)
C13−0.1259 (5)0.6333 (2)0.5247 (2)0.0428 (7)
H13−0.24880.60880.57080.051*
C14−0.1787 (5)0.6130 (2)0.4140 (2)0.0392 (6)
H14−0.33770.57470.38620.047*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0668 (5)0.0371 (4)0.0559 (5)0.0198 (4)0.0232 (4)0.0093 (3)
O10.0698 (14)0.0296 (11)0.0781 (15)0.0097 (10)0.0198 (12)0.0033 (10)
O20.0440 (11)0.0348 (10)0.0620 (13)0.0132 (9)0.0048 (10)−0.0021 (9)
O30.0695 (14)0.0479 (12)0.0334 (11)0.0024 (11)0.0112 (9)0.0031 (8)
O40.0863 (18)0.0457 (14)0.0663 (16)0.0087 (14)−0.0142 (12)0.0029 (12)
N10.0536 (15)0.0357 (13)0.0396 (14)0.0141 (11)0.0160 (12)0.0062 (10)
N20.0493 (14)0.0279 (12)0.0361 (13)0.0082 (11)0.0112 (11)0.0007 (10)
C10.0404 (15)0.0317 (14)0.0288 (14)0.0062 (12)0.0006 (12)−0.0015 (11)
C20.0342 (14)0.0324 (14)0.0376 (15)0.0064 (12)0.0038 (11)0.0005 (11)
C30.0369 (15)0.0274 (13)0.0339 (14)0.0062 (11)−0.0022 (12)−0.0007 (10)
C40.0474 (17)0.0305 (14)0.0332 (15)0.0077 (12)−0.0014 (12)0.0015 (11)
C50.073 (2)0.0400 (16)0.0440 (17)0.0119 (15)0.0150 (15)0.0102 (13)
C60.0445 (17)0.0357 (16)0.0386 (16)0.0103 (13)−0.0045 (13)0.0004 (12)
C70.058 (2)0.0427 (17)0.075 (2)0.0245 (15)0.0114 (16)0.0012 (15)
C80.090 (3)0.052 (2)0.072 (2)0.0149 (19)0.019 (2)−0.0077 (16)
C90.0351 (15)0.0277 (13)0.0350 (14)0.0106 (11)0.0067 (11)0.0014 (10)
C100.0349 (15)0.0436 (16)0.0366 (15)0.0048 (13)0.0110 (12)0.0047 (12)
C110.0376 (15)0.0446 (16)0.0358 (16)0.0010 (13)0.0032 (12)0.0015 (12)
C120.0518 (18)0.0289 (14)0.0321 (15)0.0098 (13)0.0115 (13)0.0038 (11)
C130.0444 (17)0.0397 (15)0.0460 (17)0.0082 (13)0.0206 (13)0.0061 (12)
C140.0323 (15)0.0397 (15)0.0451 (17)0.0069 (12)0.0076 (12)−0.0018 (12)

Geometric parameters (Å, °)

S1—C11.688 (2)C5—H5A0.9600
O1—C61.213 (3)C5—H5B0.9600
O2—C61.335 (3)C5—H5C0.9600
O2—C71.458 (3)C7—C81.489 (4)
O3—C121.368 (3)C7—H7A0.9700
O3—H30.8200C7—H7B0.9700
O4—H4A0.87 (3)C8—H8A0.9600
O4—H4B0.855 (10)C8—H8B0.9600
N1—C11.353 (3)C8—H8C0.9600
N1—C41.387 (3)C9—C101.385 (3)
N1—H1A0.895 (10)C9—C141.390 (3)
N2—C11.316 (3)C10—C111.377 (3)
N2—C21.476 (3)C10—H100.9300
N2—H2A0.892 (10)C11—C121.384 (4)
C2—C91.510 (3)C11—H110.9300
C2—C31.526 (3)C12—C131.381 (4)
C2—H20.9800C13—C141.376 (4)
C3—C41.333 (3)C13—H130.9300
C3—C61.472 (3)C14—H140.9300
C4—C51.500 (4)
C6—O2—C7117.0 (2)O2—C7—C8110.0 (2)
C12—O3—H3109.5O2—C7—H7A109.7
C1—N1—C4124.1 (2)C8—C7—H7A109.7
C1—N1—H1A114.2 (17)O2—C7—H7B109.7
C4—N1—H1A121.6 (17)C8—C7—H7B109.7
C1—N2—C2127.1 (2)H7A—C7—H7B108.2
C1—N2—H2A116.3 (18)C7—C8—H8A109.5
C2—N2—H2A115.7 (18)C7—C8—H8B109.5
N2—C1—N1117.3 (2)H8A—C8—H8B109.5
N2—C1—S1122.54 (19)C7—C8—H8C109.5
N1—C1—S1120.1 (2)H8A—C8—H8C109.5
N2—C2—C9108.85 (18)H8B—C8—H8C109.5
N2—C2—C3109.3 (2)C10—C9—C14117.9 (2)
C9—C2—C3113.4 (2)C10—C9—C2120.7 (2)
N2—C2—H2108.4C14—C9—C2121.4 (2)
C9—C2—H2108.4C11—C10—C9121.3 (2)
C3—C2—H2108.4C11—C10—H10119.3
C4—C3—C6121.1 (2)C9—C10—H10119.3
C4—C3—C2122.1 (2)C10—C11—C12120.0 (2)
C6—C3—C2116.7 (2)C10—C11—H11120.0
C3—C4—N1119.6 (2)C12—C11—H11120.0
C3—C4—C5127.9 (2)O3—C12—C13118.0 (2)
N1—C4—C5112.4 (2)O3—C12—C11122.5 (2)
C4—C5—H5A109.5C13—C12—C11119.5 (2)
C4—C5—H5B109.5C14—C13—C12120.0 (2)
H5A—C5—H5B109.5C14—C13—H13120.0
C4—C5—H5C109.5C12—C13—H13120.0
H5A—C5—H5C109.5C13—C14—C9121.3 (2)
H5B—C5—H5C109.5C13—C14—H14119.4
O1—C6—O2122.9 (2)C9—C14—H14119.4
O1—C6—C3125.3 (3)H4A—O4—H4B112.8 (17)
O2—C6—C3111.7 (2)
C2—N2—C1—N1−7.7 (4)C2—C3—C6—O1156.6 (2)
C2—N2—C1—S1171.99 (18)C4—C3—C6—O2158.4 (2)
C4—N1—C1—N23.7 (4)C2—C3—C6—O2−22.3 (3)
C4—N1—C1—S1−176.06 (19)C6—O2—C7—C8−88.3 (3)
C1—N2—C2—C9−118.3 (3)N2—C2—C9—C1077.4 (3)
C1—N2—C2—C36.0 (3)C3—C2—C9—C10−44.5 (3)
N2—C2—C3—C4−0.5 (3)N2—C2—C9—C14−100.6 (3)
C9—C2—C3—C4121.1 (3)C3—C2—C9—C14137.5 (2)
N2—C2—C3—C6−179.8 (2)C14—C9—C10—C11−0.4 (4)
C9—C2—C3—C6−58.2 (3)C2—C9—C10—C11−178.4 (2)
C6—C3—C4—N1176.6 (2)C9—C10—C11—C120.2 (4)
C2—C3—C4—N1−2.8 (4)C10—C11—C12—O3179.4 (2)
C6—C3—C4—C5−6.3 (4)C10—C11—C12—C130.0 (4)
C2—C3—C4—C5174.4 (2)O3—C12—C13—C14−179.4 (2)
C1—N1—C4—C31.4 (4)C11—C12—C13—C140.0 (4)
C1—N1—C4—C5−176.2 (2)C12—C13—C14—C9−0.2 (4)
C7—O2—C6—O1−9.2 (4)C10—C9—C14—C130.4 (4)
C7—O2—C6—C3169.7 (2)C2—C9—C14—C13178.4 (2)
C4—C3—C6—O1−22.8 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O4—H4B···O1i0.855 (10)1.999 (14)2.835 (3)166 (3)
O4—H4A···S1ii0.87 (3)2.44 (2)3.189 (2)145 (3)
N2—H2A···O3iii0.892 (10)2.097 (11)2.988 (3)177 (3)
N1—H1A···S1iv0.895 (10)2.479 (11)3.363 (2)170 (2)
O3—H3···O40.821.902.724 (3)179

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HK2363).

References

  • Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987). J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
  • Atwal, K. S., Swanson, B. N., Unger, S. E., Floyd, D. M., Moreland, S., Hedberg, A. & Reilly, B. C. (1991). J. Med. Chem.34, 806–811. [PubMed]
  • Bruker (1997). SMART (Version 5.611), SAINT (Version 6.0) and SHELXTL (Version 5.10). Bruker AXS Inc., Madison, Wisconsin, USA.
  • Mayer, T. M., Kapoor, T. M., Haggarty, S. J., King, R. W., Schreiber, S. L. & Mitchison, T. J. (1999). Science, 286, 971–974. [PubMed]
  • Sheldrick, G. M. (1996). SADABS University of Göttingen, Germany.
  • Sheldrick, G. M. (1997). SHELXS97 and SHELXL97 University of Göttingen, Germany.

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