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Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2518.
Published online 2009 September 26. doi:  10.1107/S1600536809037453
PMCID: PMC2970428

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

Abstract

In the title compound, C14H15ClN2O2S, the tetra­hydro­pyrimidine ring adopts a twisted boat conformation with the carbonyl group in an s-trans conformation with respect to the C=C double bond of the six-membered tetra­hydro­pyrimidine ring. The mol­ecular conformation is determined by an intra­molecular C—H(...)π inter­action. The crystal structure is further stabilized by inter­molecular N—H(...)O mol­ecular chains and centrosymmetric N—H(...)S dimers.

Related literature

For background to the applications of poly-functionalized dihydro­pyrimidines, see: Corey & Cheng (1995 [triangle]); Hurst & Hull (1961 [triangle]); Jauk et al. (2000 [triangle]); Kappe (2000 [triangle]); Mayer et al. (1999 [triangle]). For ring puckering parameters, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2518-scheme1.jpg

Experimental

Crystal data

  • C14H15ClN2O2S
  • M r = 310.80
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2518-efi1.jpg
  • a = 7.3420 (3) Å
  • b = 9.4895 (4) Å
  • c = 12.0425 (5) Å
  • α = 73.823 (4)°
  • β = 88.512 (3)°
  • γ = 70.264 (4)°
  • V = 756.32 (6) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.39 mm−1
  • T = 292 K
  • 0.24 × 0.22 × 0.18 mm

Data collection

  • Oxford Diffraction Xcalibur diffractometer with Eos (Nova) detector
  • Absorption correction: multi-scan (CrysAlis Pro; Oxford Diffraction, 2009 [triangle]) T min = 0.902, T max = 0.933
  • 16944 measured reflections
  • 2960 independent reflections
  • 2232 reflections with I > 2σ(I)
  • R int = 0.040

Refinement

  • R[F 2 > 2σ(F 2)] = 0.053
  • wR(F 2) = 0.161
  • S = 1.09
  • 2960 reflections
  • 183 parameters
  • H-atom parameters constrained
  • Δρmax = 0.48 e Å−3
  • Δρmin = −0.37 e Å−3

Data collection: CrysAlis Pro (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis Pro; data reduction: CrysAlis Pro; program(s) used to solve structure: SHELXL97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]) and CAMERON (Watkin et al., 1993 [triangle]); software used to prepare material for publication: PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809037453/sj2653sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809037453/sj2653Isup2.hkl

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

Acknowledgments

We are grateful for funding under DST–FIST (Level II) for the Oxford Diffraction facility at SSCU. SKN thanks CSIR (SRF), India, for financial support.

supplementary crystallographic information

Comment

The logic of chemical reactivity (Corey & Cheng, 1995) has found application in the rational design of a variety of drug molecules. One such class of compounds is the "Bignelli compounds". These are poly-functionalized dihydropyrimidine (DHPM's) exhibiting a broad range of therapeutic and pharmacological properties (Kappe, 2000) namely, antiviral (Hurst et al., 1961), antimimotic (Mayer et al.,1999) and calcium channel modulators (Jauk et al., 2000). In view of immense range of applications of this class of compounds we have undertaken a single-crystal determination of the title compound.

The tetrahydropyrimidine ring adopts a twist boat conformation. The puckering parameters (Cremer & Pople 1975) are Q = 0.277 (3) Å, θ(2) = 108.1 (3)° and [var phi](2) = 349.1 (6)° respectively. The orientation of the chloro-phenyl moiety is such that it bisects the twist boat conformation of the tetrahydropyrimidine ring, the C9—C4—C3—C5 torsion angle being 77.4 (3)°. The molecular conformation is stabilized by an intramolecular C—H···π interaction (2.67 Å, 113°) wherein the aryl hydrogen H14 is oriented towards the π electrons of the C2=C3 double bond (Figure 1). The crystal structure is further stabilized by centrosymmetric N—H···S dimers and N—H···O hydrogen bonds forming molecular chains along the crystallographic a axis (Figure 2).

Experimental

A mixture of ethylacetoacetate (0.1 mol), para chlorosubstituted benzaldehyde (0.1 mol) and thiourea was refluxed in 50.0 mL of ethanol for 2.0 hrs in presence of concentrated hydrochloric acid as catalyst. The reaction completion was monitored through thin layer chromatography and and, on completion, the products were poured into ice cold water. The precipitate obtained was filtered, dried and crystallized from methanol to obtain the title compound.

Refinement

All H atoms were positioned geometrically, C—H = 0.93 Å, 0.96 Å, 0.97 Å, 0.98Å for aromatic, methyl, methylene and methine hydrogen respectively and N—H = 0.86 Å and all refined using a riding model with Uiso(H)= 1.2 Ueq(C, N) for aromatic and amine hydrogen and 1.5 Ueq(C) for methyl, methylene and methine H atoms respectively.

Figures

Fig. 1.
: The structure of the title compound showing the atom labelling Scheme with displacement ellipsoids for non-H atoms at the 50% probability level. The dotted line shows the C—H···π intramolecular interactions. Cg1 ...
Fig. 2.
: The crystal packing showing the molecular chains of N—H···O hydrogen bonds and N—H···S centrosymmetric dimers. Molecules at # and * have the symmetry codes (- x + 1, - y + 1, - z + 1) and ...

Crystal data

C14H15ClN2O2SZ = 2
Mr = 310.80F(000) = 324
Triclinic, P1Dx = 1.365 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.7107 Å
a = 7.3420 (3) ÅCell parameters from 340 reflections
b = 9.4895 (4) Åθ = 1.0–28.0°
c = 12.0425 (5) ŵ = 0.39 mm1
α = 73.823 (4)°T = 292 K
β = 88.512 (3)°Block, colorless
γ = 70.264 (4)°0.24 × 0.22 × 0.18 mm
V = 756.32 (6) Å3

Data collection

Oxford Diffraction Xcalibur with Eos (Nova) detector diffractometer2960 independent reflections
Radiation source: Enhance (Mo) X-ray Source2232 reflections with I > 2σ(I)
graphiteRint = 0.040
Detector resolution: 16.0839 pixels mm-1θmax = 26.0°, θmin = 3.3°
ω scansh = −9→9
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)k = −11→11
Tmin = 0.902, Tmax = 0.933l = −14→14
16944 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)] = 0.053Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.161H-atom parameters constrained
S = 1.09w = 1/[σ2(Fo2) + (0.094P)2 + 0.1394P] where P = (Fo2 + 2Fc2)/3
2960 reflections(Δ/σ)max < 0.001
183 parametersΔρmax = 0.48 e Å3
0 restraintsΔρmin = −0.37 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
S10.19746 (10)0.59669 (9)0.54217 (7)0.0474 (3)
Cl10.98420 (16)0.22640 (13)1.09156 (8)0.0841 (4)
N20.5115 (3)0.6617 (3)0.57987 (18)0.0368 (5)
H20.56870.60380.53680.044*
C30.5079 (4)0.8759 (3)0.6529 (2)0.0337 (6)
N10.2287 (3)0.8143 (3)0.6307 (2)0.0395 (5)
H10.10990.82880.64630.047*
C40.6301 (4)0.7183 (3)0.6403 (2)0.0343 (6)
H40.73600.73200.59220.041*
O20.5259 (3)1.0762 (3)0.7252 (2)0.0562 (6)
O10.7882 (3)0.9466 (2)0.64949 (19)0.0501 (5)
C10.3222 (4)0.6937 (3)0.5869 (2)0.0352 (6)
C90.7198 (3)0.5977 (3)0.7561 (2)0.0330 (6)
C20.3137 (4)0.9158 (3)0.6519 (2)0.0352 (6)
C50.6218 (4)0.9691 (3)0.6732 (2)0.0373 (6)
C140.6506 (4)0.6140 (4)0.8616 (2)0.0467 (7)
H140.54690.70270.86330.056*
C60.6261 (5)1.1724 (4)0.7526 (3)0.0571 (8)
H6A0.75281.10730.79160.069*
H6B0.64341.24520.68210.069*
C80.1693 (4)1.0610 (4)0.6676 (3)0.0520 (8)
H8A0.21701.14610.63950.078*
H8B0.14881.04680.74850.078*
H8C0.04901.08400.62510.078*
C100.8750 (4)0.4642 (4)0.7572 (3)0.0472 (7)
H100.92470.45230.68730.057*
C120.8839 (4)0.3695 (4)0.9625 (3)0.0499 (7)
C110.9569 (4)0.3507 (4)0.8560 (3)0.0489 (7)
H111.05970.26170.85390.059*
C130.7329 (5)0.5008 (4)0.9644 (3)0.0532 (8)
H130.68560.51401.03450.064*
C70.5083 (6)1.2561 (6)0.8271 (5)0.1004 (17)
H7A0.50771.18390.90090.151*
H7B0.37811.30840.79220.151*
H7C0.56081.33170.83790.151*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0396 (4)0.0547 (5)0.0629 (5)−0.0215 (3)0.0076 (3)−0.0340 (4)
Cl10.0859 (7)0.0806 (7)0.0595 (6)−0.0202 (6)−0.0165 (5)0.0120 (5)
N20.0311 (12)0.0444 (13)0.0402 (11)−0.0104 (10)0.0019 (9)−0.0236 (10)
C30.0304 (13)0.0358 (14)0.0366 (13)−0.0117 (11)0.0014 (10)−0.0124 (11)
N10.0330 (12)0.0468 (13)0.0508 (13)−0.0190 (10)0.0131 (10)−0.0271 (11)
C40.0300 (13)0.0409 (14)0.0386 (13)−0.0156 (11)0.0079 (10)−0.0179 (11)
O20.0448 (12)0.0589 (14)0.0878 (16)−0.0276 (10)0.0155 (11)−0.0453 (13)
O10.0322 (11)0.0551 (13)0.0722 (14)−0.0202 (9)0.0073 (9)−0.0265 (11)
C10.0369 (14)0.0388 (14)0.0316 (12)−0.0127 (11)0.0040 (10)−0.0134 (11)
C90.0277 (13)0.0393 (14)0.0378 (13)−0.0141 (11)0.0041 (10)−0.0171 (11)
C20.0341 (14)0.0353 (14)0.0376 (13)−0.0123 (11)0.0015 (10)−0.0121 (11)
C50.0404 (16)0.0338 (14)0.0371 (13)−0.0120 (12)0.0017 (11)−0.0098 (11)
C140.0449 (17)0.0473 (16)0.0463 (16)−0.0090 (13)0.0060 (13)−0.0195 (14)
C60.056 (2)0.0570 (19)0.079 (2)−0.0327 (16)0.0092 (17)−0.0356 (18)
C80.0314 (15)0.0469 (17)0.082 (2)−0.0096 (13)0.0046 (14)−0.0304 (17)
C100.0379 (15)0.0524 (18)0.0508 (17)−0.0091 (13)0.0088 (13)−0.0224 (15)
C120.0429 (16)0.0570 (18)0.0457 (16)−0.0185 (14)−0.0079 (13)−0.0056 (14)
C110.0324 (15)0.0459 (17)0.0593 (18)−0.0023 (13)0.0021 (13)−0.0147 (15)
C130.060 (2)0.062 (2)0.0397 (16)−0.0214 (16)0.0062 (14)−0.0179 (15)
C70.079 (3)0.130 (4)0.152 (4)−0.063 (3)0.045 (3)−0.103 (4)

Geometric parameters (Å, °)

S1—C11.688 (3)C2—C81.486 (4)
Cl1—C121.735 (3)C14—C131.382 (4)
N2—C11.324 (3)C14—H140.9300
N2—C41.464 (3)C6—C71.441 (5)
N2—H20.8600C6—H6A0.9700
C3—C21.345 (3)C6—H6B0.9700
C3—C51.474 (4)C8—H8A0.9600
C3—C41.510 (3)C8—H8B0.9600
N1—C11.359 (3)C8—H8C0.9600
N1—C21.390 (3)C10—C111.349 (4)
N1—H10.8600C10—H100.9300
C4—C91.528 (4)C12—C131.365 (5)
C4—H40.9800C12—C111.411 (4)
O2—C51.330 (3)C11—H110.9300
O2—C61.455 (3)C13—H130.9300
O1—C51.208 (3)C7—H7A0.9600
C9—C141.386 (4)C7—H7B0.9600
C9—C101.386 (4)C7—H7C0.9600
C1—N2—C4124.5 (2)C7—C6—O2107.4 (3)
C1—N2—H2117.7C7—C6—H6A110.2
C4—N2—H2117.7O2—C6—H6A110.2
C2—C3—C5126.0 (2)C7—C6—H6B110.2
C2—C3—C4119.9 (2)O2—C6—H6B110.2
C5—C3—C4113.9 (2)H6A—C6—H6B108.5
C1—N1—C2123.8 (2)C2—C8—H8A109.5
C1—N1—H1118.1C2—C8—H8B109.5
C2—N1—H1118.1H8A—C8—H8B109.5
N2—C4—C3109.1 (2)C2—C8—H8C109.5
N2—C4—C9110.3 (2)H8A—C8—H8C109.5
C3—C4—C9113.21 (19)H8B—C8—H8C109.5
N2—C4—H4108.0C11—C10—C9122.5 (3)
C3—C4—H4108.0C11—C10—H10118.7
C9—C4—H4108.0C9—C10—H10118.7
C5—O2—C6118.1 (2)C13—C12—C11120.0 (3)
N2—C1—N1116.0 (2)C13—C12—Cl1119.6 (2)
N2—C1—S1123.59 (19)C11—C12—Cl1120.5 (2)
N1—C1—S1120.36 (19)C10—C11—C12118.9 (3)
C14—C9—C10117.7 (3)C10—C11—H11120.6
C14—C9—C4122.9 (2)C12—C11—H11120.6
C10—C9—C4119.5 (2)C12—C13—C14119.8 (3)
C3—C2—N1118.7 (2)C12—C13—H13120.1
C3—C2—C8128.3 (2)C14—C13—H13120.1
N1—C2—C8112.9 (2)C6—C7—H7A109.5
O1—C5—O2123.2 (2)C6—C7—H7B109.5
O1—C5—C3123.5 (2)H7A—C7—H7B109.5
O2—C5—C3113.2 (2)C6—C7—H7C109.5
C13—C14—C9121.2 (3)H7A—C7—H7C109.5
C13—C14—H14119.4H7B—C7—H7C109.5
C9—C14—H14119.4
C1—N2—C4—C3−31.3 (3)C1—N1—C2—C8163.8 (3)
C1—N2—C4—C993.6 (3)C6—O2—C5—O11.1 (4)
C2—C3—C4—N224.4 (3)C6—O2—C5—C3178.3 (2)
C5—C3—C4—N2−159.3 (2)C2—C3—C5—O1−163.6 (3)
C2—C3—C4—C9−98.8 (3)C4—C3—C5—O120.4 (4)
C5—C3—C4—C977.4 (3)C2—C3—C5—O219.2 (4)
C4—N2—C1—N115.8 (4)C4—C3—C5—O2−156.7 (2)
C4—N2—C1—S1−165.7 (2)C10—C9—C14—C13−0.3 (4)
C2—N1—C1—N29.3 (4)C4—C9—C14—C13178.6 (3)
C2—N1—C1—S1−169.2 (2)C5—O2—C6—C7−169.1 (3)
N2—C4—C9—C14−103.7 (3)C14—C9—C10—C111.1 (4)
C3—C4—C9—C1418.9 (3)C4—C9—C10—C11−177.8 (3)
N2—C4—C9—C1075.2 (3)C9—C10—C11—C12−1.0 (5)
C3—C4—C9—C10−162.3 (2)C13—C12—C11—C100.0 (5)
C5—C3—C2—N1179.7 (2)Cl1—C12—C11—C10179.8 (2)
C4—C3—C2—N1−4.6 (4)C11—C12—C13—C140.8 (5)
C5—C3—C2—C81.6 (5)Cl1—C12—C13—C14−179.0 (2)
C4—C3—C2—C8177.3 (3)C9—C14—C13—C12−0.7 (5)
C1—N1—C2—C3−14.6 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.862.253.077 (3)161
N2—H2···S1ii0.862.493.323 (3)164
C14—H14···Cg10.932.673.146 (4)113

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SJ2653).

References

  • Corey, E. J. & Cheng, X.-M. (1995). The Logic of Chemical Synthesis New York: John Wiley & Sons Australia Ltd.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Hurst, E. W. & Hull, R. (1961). J. Med. Pharm. Chem.3, 215–229. [PubMed]
  • Jauk, B., Pernat, T. & Kappe, C. O. (2000). Molecules, 5, 227–239 and references therein.
  • Kappe, C. O. (2000). Eur. J. Med. Chem.4835, 1043–1052. [PubMed]
  • Mayer, T. U., Kapoor, T. M., Haggarty, S. J., King, R. W., Schreiber, S. I. & Mitchison, T. J. (1999). Science, 286, 971–974. [PubMed]
  • Oxford Diffraction (2009). CrysAlis Pro Oxford Diffraction Ltd, Yarnton, England.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Watkin, D. M., Pearce, L. & Prout, C. K. (1993). CAMERON Chemical Crystallography Laboratory, University of Oxford, England.

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