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Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1812.
Published online 2008 August 23. doi:  10.1107/S1600536808026664
PMCID: PMC2960718

Ethyl 2-allylsulfanyl-4-(4-methoxyphenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate

Abstract

In the title compound, C18H22N2O3S, the pyrimidine ring is not planar. It adopts a half-chair conformation The crystal structure is characterized by classical N—H(...)O and C—H(...)O inter- and intra­molecular hydrogen bonds, respectively. The title compound exhibits a wide spectrum of biological activities.

Related literature

For related literature, see: Allen et al. (1987 [triangle]); Biginelli (1893 [triangle]); Cremer & Pople (1975 [triangle]); Gurskaya et al. (2003a [triangle],b [triangle]); Kappe (1993 [triangle]); Kappe et al. (1997 [triangle]); Li (2006 [triangle]); Nardelli (1983 [triangle]); Nizam Mohideen et al. (2008 [triangle]); Overman et al. (1995 [triangle]); Snider et al. (1996 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1812-scheme1.jpg

Experimental

Crystal data

  • C18H22N2O3S
  • M r = 346.44
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1812-efi1.jpg
  • a = 28.325 (5) Å
  • b = 7.410 (2) Å
  • c = 20.202 (4) Å
  • β = 121.61 (3)°
  • V = 3610.9 (18) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.20 mm−1
  • T = 293 (2) K
  • 0.4 × 0.2 × 0.1 mm

Data collection

  • Bruker Kappa APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2004 [triangle]) T min = 0.954, T max = 0.983
  • 16675 measured reflections
  • 3183 independent reflections
  • 2722 reflections with I > 2σ(I)
  • R int = 0.025

Refinement

  • R[F 2 > 2σ(F 2)] = 0.045
  • wR(F 2) = 0.140
  • S = 1.04
  • 3183 reflections
  • 220 parameters
  • H-atom parameters constrained
  • Δρmax = 0.47 e Å−3
  • Δρmin = −0.33 e Å−3

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: APEX2 and SAINT (Bruker, 2004 [triangle]); data reduction: SAINT and XPREP (Bruker, 2004 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808026664/pv2100sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808026664/pv2100Isup2.hkl

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

Acknowledgments

MNM, AR, and CAMAH thank the Management of The New College, Chennai, India, for providing the necessary facilities.

supplementary crystallographic information

Comment

The title compound, (I), belongs to the class of 5-substituted 1,2,3,4-tetrahydropyrimidin-2-ones, which are known as `Biginelli compounds' (Kappe, 1993). The Biginelli reaction is a classic multicomponent reaction (Biginelli, 1893). The biological activity of some isolated alkaloids has been attributed to the presence of the dihydropyrimidinone moiety in the molecules (Overman et al., 1995) and the conformation of the pyrimidine ring (Kappe et al., 1997; Gurskaya et al., 2003a,b). Most important among them are batzelladine alkaloids, which have been found to be potent HIVgp-120-CD4 inhibitors (Snider et al., 1996). The aim of the present work was to study classical and extended Biginelli reactions. As part of our ongoing investigation of pyrimidine derivatives, the title compound, (I), has been prepared and its crystal structure is presented here.

The bond lengths and angles in the title compound (Fig. 1) are comparable with ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenylpyrimidine-5-carboxylate, a structure closely related to (I) (Nizam Mohideen et al., 2008). The torsion angles [C1—C6—C7—C10 = 153.1 (2), C5—C6—C7—C10 = -31.5 (2), C9—C10—C12—O2 = 171.3 (2), C7—C10—C12—O2 = -11.6 (3), C9—C10—C12—O3 = -10.1 (1) and C7—C10—C12—O3 = 167.1 (2) °] differs from the torsion angles [47.6 (2), -137.1 (2), 10.1 (2), -167.8 (2) -171.5 (2) and 10.5 (2) °] in the reported structure mentioned above.

In (I), the heterocyclic ring (atoms N1, N2, C7, C8, C9, C10) of the dihydropyrimidine group is not planar, as indicated by the displacement of atom C7 from the least-squares plane [0.212 (1) Å] and by the C8—N1—C7—C10 torsion angle [31.1 (1) °]. Atom C11 deviating by -0.204 (1) Å from the least squares plane of the pyrimidine ring. The pyrimidine ring adopts half chair conformation; the puckering parameters are q2 = 0.312 (1) Å, [var phi] = 236.3 (2)°, and θ = 104.2 (1)° (Cremer & Pople, 1975), and the lowest displacement asymmetry parameters ΔS(C7) is 2.3 (1)°, Δ2(C10) is 22.4 (1)° (Nardelli, 1983).

The benzene ring is planar, the larget displacement observed being -0.008 (1) Å for atom C6. The dihedral angle between the pyrimidine and benzene rings is 89.5 (1)°, close to the value of 86.5 (1)° found in ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenylpyrimidine-5-carboxylate.

The crystal packing is characterized by classical N—H···O and C—H···O inter and intramolecular hydrogen bonds (Table 1).

Experimental

To a suspension of NaH (0.100 g, 2 mmol, 50% dispersion in mineral oil washed with hexane) in dry THF (25 ml) was added a solution of dihydropyrimidone, (0.594 g, 2 mmol) in dry THF (10 ml) and stirred in an atmosphere of N2 for one hour. Then a solution of allyl bromide (0.2 ml, 2.5 mmol) in dry THF (5 ml) was added drop wise and stirred for futher four hours. (TLC control, silica, ethyl acetate: hexane 1:9 as eluent). Evaporation of solvent under reduced pressure, followed by purification of the residue by column chromatography gave a yellow solid. Single crystals of the title compound suitable for X-ray diffraction were obtained by slow evaporation of a solution in ethanol (mp 368–369 K).

Refinement

All H atoms were positioned geometrically and allowed to ride on their parent C atoms, with C—H distances fixed in the range 0.93–0.98 Å and N—H distance of 0.86 Å, with Uiso(H) = 1.5Ueq(C) for methyl H atoms and Uiso(H) = 1.2Ueq(C, N) for other H atoms.

Figures

Fig. 1.
The molecular configuration and atom-numbering scheme for (I). Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C18H22N2O3SF000 = 1472
Mr = 346.44Dx = 1.275 Mg m3
Monoclinic, C2/cMo Kα radiation λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 7889 reflections
a = 28.325 (5) Åθ = 2.6–25º
b = 7.410 (2) ŵ = 0.20 mm1
c = 20.202 (4) ÅT = 293 (2) K
β = 121.61 (3)ºNeedle, yellow
V = 3610.9 (18) Å30.4 × 0.2 × 0.1 mm
Z = 8

Data collection

Bruker Kappa APEXII CCD diffractometer'3183 independent reflections
Radiation source: fine-focus sealed tube2722 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.026
T = 293(2) Kθmax = 25.0º
ω and [var phi] scanθmin = 1.7º
Absorption correction: Multi-scan(SADABS; Bruker, 2004)h = −33→33
Tmin = 0.954, Tmax = 0.983k = −8→8
16675 measured reflectionsl = −24→24

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045H-atom parameters constrained
wR(F2) = 0.140  w = 1/[σ2(Fo2) + (0.0785P)2 + 3.5811P] where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.002
3183 reflectionsΔρmax = 0.48 e Å3
220 parametersΔρmin = −0.33 e Å3
Primary atom site location: structure-invariant direct methodsExtinction correction: none

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
S10.15041 (3)0.63300 (8)0.44134 (3)0.0551 (2)
O10.33272 (7)1.1779 (2)0.34204 (10)0.0580 (4)
O20.06407 (7)1.4020 (2)0.24877 (9)0.0522 (4)
O30.01426 (7)1.2100 (2)0.15153 (9)0.0617 (5)
N10.14728 (7)0.9848 (2)0.40787 (9)0.0385 (4)
N20.09759 (7)0.7816 (2)0.30377 (10)0.0387 (4)
H20.09540.67150.28890.046*
C10.23063 (8)1.2512 (3)0.39532 (11)0.0399 (5)
H10.22801.31710.43250.048*
C20.27875 (9)1.2591 (3)0.39437 (13)0.0456 (5)
H2A0.30821.32920.43080.055*
C30.28341 (8)1.1622 (3)0.33898 (12)0.0406 (5)
C40.23922 (9)1.0596 (3)0.28488 (12)0.0424 (5)
H40.24180.99510.24740.051*
C50.19079 (8)1.0533 (3)0.28672 (11)0.0387 (5)
H50.16110.98440.24990.046*
C60.18558 (8)1.1467 (2)0.34195 (11)0.0331 (4)
C70.13489 (8)1.1274 (2)0.34918 (11)0.0334 (4)
H70.12981.24150.36920.040*
C80.13171 (8)0.8265 (3)0.38169 (11)0.0359 (4)
C90.06696 (8)0.9154 (3)0.25004 (11)0.0355 (4)
C100.08227 (8)1.0897 (3)0.27177 (11)0.0341 (4)
C110.02055 (9)0.8432 (3)0.17415 (13)0.0484 (5)
H11A−0.01170.91730.15620.073*
H11B0.01230.72170.18130.073*
H11C0.03150.84440.13650.073*
C120.05336 (8)1.2485 (3)0.22475 (12)0.0382 (5)
C13−0.01773 (13)1.3590 (4)0.10104 (16)0.0718 (8)
H13A0.00671.44730.09890.086*
H13B−0.03871.41780.12040.086*
C14−0.05525 (19)1.2832 (6)0.0238 (2)0.1255 (18)
H14A−0.03411.21910.00660.188*
H14B−0.07551.3789−0.01200.188*
H14C−0.08071.20170.02610.188*
C150.33997 (12)1.0703 (4)0.28976 (19)0.0700 (8)
H15A0.33270.94620.29490.105*
H15B0.37741.08230.30160.105*
H15C0.31471.10980.23740.105*
C160.19334 (12)0.7289 (4)0.53535 (15)0.0662 (7)
H16A0.22150.64100.56760.079*
H16B0.21220.83240.53040.079*
C170.16579 (19)0.7873 (5)0.57661 (19)0.0867 (10)
H170.18910.81740.62870.104*
C180.1139 (2)0.8017 (6)0.5498 (3)0.1070 (13)
H18A0.08840.77360.49810.128*
H18B0.10150.84040.58200.128*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0785 (5)0.0335 (3)0.0492 (4)−0.0010 (3)0.0305 (3)0.0058 (2)
O10.0468 (9)0.0614 (11)0.0707 (11)−0.0059 (8)0.0342 (8)−0.0012 (9)
O20.0615 (10)0.0249 (8)0.0522 (9)0.0007 (7)0.0174 (8)−0.0004 (7)
O30.0692 (11)0.0348 (9)0.0446 (9)0.0068 (8)0.0045 (8)0.0012 (7)
N10.0498 (10)0.0318 (9)0.0347 (9)−0.0012 (7)0.0226 (8)0.0015 (7)
N20.0510 (10)0.0219 (8)0.0409 (9)0.0009 (7)0.0224 (8)−0.0030 (7)
C10.0456 (11)0.0325 (11)0.0356 (10)−0.0020 (8)0.0171 (9)−0.0050 (8)
C20.0414 (11)0.0391 (12)0.0444 (11)−0.0100 (9)0.0142 (9)−0.0054 (9)
C30.0393 (11)0.0361 (11)0.0454 (11)0.0010 (8)0.0215 (9)0.0083 (9)
C40.0521 (12)0.0385 (11)0.0400 (11)−0.0019 (9)0.0264 (10)−0.0029 (9)
C50.0419 (11)0.0337 (11)0.0358 (10)−0.0082 (8)0.0171 (9)−0.0065 (8)
C60.0395 (10)0.0237 (9)0.0313 (9)0.0004 (7)0.0151 (8)0.0028 (7)
C70.0415 (10)0.0240 (9)0.0331 (9)−0.0002 (8)0.0184 (8)−0.0013 (7)
C80.0436 (11)0.0294 (10)0.0383 (10)0.0022 (8)0.0239 (9)0.0033 (8)
C90.0372 (10)0.0307 (10)0.0387 (10)−0.0005 (8)0.0200 (9)−0.0024 (8)
C100.0376 (10)0.0270 (10)0.0359 (10)0.0006 (8)0.0180 (8)−0.0002 (8)
C110.0488 (13)0.0345 (12)0.0484 (12)−0.0045 (9)0.0161 (10)−0.0061 (9)
C120.0380 (10)0.0333 (11)0.0405 (11)0.0007 (8)0.0187 (9)0.0004 (8)
C130.0752 (18)0.0447 (15)0.0550 (15)0.0156 (13)0.0063 (13)0.0100 (12)
C140.133 (3)0.085 (3)0.065 (2)0.022 (2)−0.013 (2)0.0010 (19)
C150.0728 (17)0.0696 (18)0.094 (2)0.0004 (14)0.0614 (17)0.0047 (16)
C160.0784 (18)0.0486 (15)0.0485 (14)−0.0047 (13)0.0173 (13)0.0134 (11)
C170.129 (3)0.067 (2)0.0587 (17)−0.014 (2)0.045 (2)−0.0015 (15)
C180.141 (4)0.098 (3)0.103 (3)0.017 (3)0.078 (3)0.004 (2)

Geometric parameters (Å, °)

S1—C81.766 (2)C7—H70.9800
S1—C161.780 (3)C9—C101.359 (3)
O1—C31.370 (3)C9—C111.501 (3)
O1—C151.421 (3)C10—C121.464 (3)
O2—C121.211 (2)C11—H11A0.9600
O3—C121.334 (3)C11—H11B0.9600
O3—C131.453 (3)C11—H11C0.9600
N1—C81.267 (3)C12—O21.211 (2)
N1—C71.486 (2)C13—C141.464 (4)
N2—C81.388 (3)C13—H13A0.9700
N2—C91.389 (3)C13—H13B0.9700
N2—H20.8600C14—H14A0.9600
C1—C21.374 (3)C14—H14B0.9600
C1—C61.395 (3)C14—H14C0.9600
C1—H10.9300C15—H15A0.9600
C2—C31.393 (3)C15—H15B0.9600
C2—H2A0.9300C15—H15C0.9600
C3—C41.380 (3)C16—C171.474 (5)
C4—C51.392 (3)C16—H16A0.9700
C4—H40.9300C16—H16B0.9700
C5—C61.385 (3)C17—C181.277 (5)
C5—H50.9300C17—H170.9300
C6—C71.524 (3)C18—H18A0.9300
C7—C101.517 (3)C18—H18B0.9300
C8—S1—C16101.35 (11)C9—C11—H11B109.5
C3—O1—C15117.37 (19)H11A—C11—H11B109.5
C12—O3—C13117.77 (18)C9—C11—H11C109.5
C8—N1—C7116.11 (16)H11A—C11—H11C109.5
C8—N2—C9119.55 (16)H11B—C11—H11C109.5
C8—N2—H2120.2O2—C12—O3122.22 (18)
C9—N2—H2120.2O2—C12—O3122.22 (18)
C2—C1—C6121.64 (19)O2—C12—C10123.91 (19)
C2—C1—H1119.2O2—C12—C10123.91 (19)
C6—C1—H1119.2O3—C12—C10113.86 (17)
C1—C2—C3120.11 (19)O3—C13—C14107.1 (2)
C1—C2—H2A119.9O3—C13—H13A110.3
C3—C2—H2A119.9C14—C13—H13A110.3
O1—C3—C4124.2 (2)O3—C13—H13B110.3
O1—C3—C2116.34 (19)C14—C13—H13B110.3
C4—C3—C2119.44 (19)H13A—C13—H13B108.5
C3—C4—C5119.65 (19)C13—C14—H14A109.5
C3—C4—H4120.2C13—C14—H14B109.5
C5—C4—H4120.2H14A—C14—H14B109.5
C6—C5—C4121.81 (18)C13—C14—H14C109.5
C6—C5—H5119.1H14A—C14—H14C109.5
C4—C5—H5119.1H14B—C14—H14C109.5
C5—C6—C1117.34 (18)O1—C15—H15A109.5
C5—C6—C7122.25 (17)O1—C15—H15B109.5
C1—C6—C7120.26 (17)H15A—C15—H15B109.5
N1—C7—C10112.63 (15)O1—C15—H15C109.5
N1—C7—C6107.63 (15)H15A—C15—H15C109.5
C10—C7—C6112.61 (15)H15B—C15—H15C109.5
N1—C7—H7107.9C17—C16—S1116.9 (2)
C10—C7—H7107.9C17—C16—H16A108.1
C6—C7—H7107.9S1—C16—H16A108.1
N1—C8—N2125.34 (17)C17—C16—H16B108.1
N1—C8—S1123.53 (15)S1—C16—H16B108.1
N2—C8—S1111.13 (14)H16A—C16—H16B107.3
C10—C9—N2117.60 (18)C18—C17—C16128.1 (3)
C10—C9—C11128.98 (19)C18—C17—H17115.9
N2—C9—C11113.43 (17)C16—C17—H17115.9
C9—C10—C12125.37 (18)C17—C18—H18A120.0
C9—C10—C7118.86 (17)C17—C18—H18B120.0
C12—C10—C7115.70 (16)H18A—C18—H18B120.0
C9—C11—H11A109.5
C6—C1—C2—C30.3 (3)C16—S1—C8—N2179.62 (16)
C15—O1—C3—C4−5.1 (3)C8—N2—C9—C1017.0 (3)
C15—O1—C3—C2175.6 (2)C8—N2—C9—C11−163.18 (18)
C1—C2—C3—O1179.86 (19)N2—C9—C10—C12−176.65 (17)
C1—C2—C3—C40.5 (3)C11—C9—C10—C123.6 (3)
O1—C3—C4—C5−179.79 (19)N2—C9—C10—C76.3 (3)
C2—C3—C4—C5−0.5 (3)C11—C9—C10—C7−173.39 (19)
C3—C4—C5—C6−0.4 (3)N1—C7—C10—C9−29.8 (2)
C4—C5—C6—C11.2 (3)C6—C7—C10—C992.1 (2)
C4—C5—C6—C7−174.30 (18)N1—C7—C10—C12152.88 (16)
C2—C1—C6—C5−1.2 (3)C6—C7—C10—C12−85.2 (2)
C2—C1—C6—C7174.42 (18)C13—O3—C12—O2−2.9 (3)
C8—N1—C7—C1031.2 (2)C13—O3—C12—O2−2.9 (3)
C8—N1—C7—C6−93.6 (2)C13—O3—C12—C10178.3 (2)
C5—C6—C7—N193.2 (2)C9—C10—C12—O2171.3 (2)
C1—C6—C7—N1−82.1 (2)C7—C10—C12—O2−11.6 (3)
C5—C6—C7—C10−31.5 (2)C9—C10—C12—O2171.3 (2)
C1—C6—C7—C10153.14 (17)C7—C10—C12—O2−11.6 (3)
C7—N1—C8—N2−10.0 (3)C9—C10—C12—O3−10.0 (3)
C7—N1—C8—S1170.98 (14)C7—C10—C12—O3167.10 (17)
C9—N2—C8—N1−16.0 (3)C12—O3—C13—C14177.0 (3)
C9—N2—C8—S1163.17 (14)C8—S1—C16—C1790.0 (2)
C16—S1—C8—N1−1.2 (2)S1—C16—C17—C18−10.8 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N2—H2···O2i0.862.162.990 (2)161
C7—H7···O20.982.462.831 (3)102

Symmetry codes: (i) x, y−1, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: PV2100).

References

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