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Acta Crystallogr Sect E Struct Rep Online. 2008 September 1; 64(Pt 9): o1752.
Published online 2008 August 13. doi:  10.1107/S1600536808025610
PMCID: PMC2960668

Ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Abstract

The title compound, C14H16N2O3, belongs to a group of esters of 2-oxo- and 1,2,3,4-tetra­hydro­pyrimidine-5-carboxylic acids, which exhibit a wide spectrum of biological activities. The dihydro­pyrimidine ring adopts a screw-boat conformation. The crystal packing is stabilized by strong N—H(...)O and weak C—H(...)O inter­molecular hydrogen bonds. An intra­molecular C—H(...)O hydrogen bond is also present.

Related literature

For related literature, see: Atwal et al. (1991 [triangle]); Broughton et al. (1975 [triangle]); Cremer & Pople (1975 [triangle]); Kappe et al. (1997 [triangle]); Li et al. (2005 [triangle]); Nardelli (1983 [triangle]); Overman et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o1752-scheme1.jpg

Experimental

Crystal data

  • C14H16N2O3
  • M r = 260.29
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1752-efi1.jpg
  • a = 7.5495 (2) Å
  • b = 8.9797 (3) Å
  • c = 11.0812 (3) Å
  • α = 107.843 (2)°
  • β = 108.603 (1)°
  • γ = 98.244 (2)°
  • V = 653.07 (4) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 (2) K
  • 0.3 × 0.2 × 0.2 mm

Data collection

  • Bruker APEXII CCD area-detector diffractometer
  • Absorption correction: none
  • 16135 measured reflections
  • 3710 independent reflections
  • 2972 reflections with I > 2σ(I)
  • R int = 0.023

Refinement

  • R[F 2 > 2σ(F 2)] = 0.047
  • wR(F 2) = 0.159
  • S = 1.00
  • 3710 reflections
  • 174 parameters
  • H-atom parameters constrained
  • Δρmax = 0.34 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; 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/S1600536808025610/bt2758sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808025610/bt2758Isup2.hkl

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

Acknowledgments

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

supplementary crystallographic information

Comment

The title compound belongs to the group of esters of 2-oxo and -1,2,3,4-tetrahydropyrimidine-5-carboxylic acids, which are known as `Biginelli compounds' (Kappe et al., 1997). It has been suggested that the substituent effect may be attributable to intramolecular hydrogen bonding between the alkoxy oxygen and the proton of the pyrimidine ring NH group (Broughton et al., 1975). Several marine alkaloids having the dihydropyrimidine core unit have been found to show interesting biological activities, such as antiviral, antibacterial and anti-inflammatory (Overman et al., 1995). Many functionalized derivatives are used as calcium channel blockers and antihypertensive agents (Atwal et al., 1991). Against this background and in order to obtain detailed information on its molecular conformation, the structure of the title compound has been determined and the results are presented here.

The bond lengths and angles are comparable with the similar structure reported in the literature (Li et al., 2005). The six membered ring (atoms N1, N2, C7, C8, C9, C10) of the dihydropyrimidine group adopts a screw boat conformation; the puckering parameters are q2 = 0.257 (1) Å and [var phi] = 211.7 (2)° (Cremer & Pople, 1975), and the lowest displacement asymmetry parameters ΔS(N1) is 14.4 (1)° (Nardelli, 1983), with atom O1 deviating by -0.116 (1) Å from the least squares plane of the ring.

The dihedral angle between the pyrimidine and benzene rings is 86.5 (1)°, close to the value of 82.8 (6)° found in ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5- carboxylate.

The crystal packing is stabilized by strong N—H···O and C—H···O intermolecular hydrogen bonds (Table 1).

Experimental

A mixture of benzaldehyde (0.106 g, 1 mmol), ethyl acetoacetate (0.130 g, 1 mmol) and urea (0.070 g, 1.17 mmol) was ground with four drops of ortho phosphoric acid for about 30 minutes. The reaction mixture was cooled for 15 minutes and poured into a beaker containing 50 ml of cold water. The precipitate obtained was filtered, washed with water and ethanol to get white solid. Single crystals of the title compound suitable for X-ray diffraction were obtained by slow evaporation of a solution in ethanol (0.26 g, 92% yield; mp 203–204).

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

C14H16N2O3Z = 2
Mr = 260.29F000 = 276
Triclinic, P1Dx = 1.324 Mg m3
Hall symbol: -P 1Mo Kα radiation λ = 0.71073 Å
a = 7.5495 (2) ÅCell parameters from 5321 reflections
b = 8.9797 (3) Åθ = 2.5–24.1º
c = 11.0812 (3) ŵ = 0.09 mm1
α = 107.843 (2)ºT = 293 (2) K
β = 108.603 (1)ºNeedle, colourless
γ = 98.244 (2)º0.3 × 0.2 × 0.2 mm
V = 653.07 (4) Å3

Data collection

Bruker APEXII CCD area-detector diffractometer2972 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.023
Monochromator: graphiteθmax = 29.7º
T = 293(2) Kθmin = 2.5º
ω and [var phi] scansh = −9→10
Absorption correction: Nonek = −12→12
16135 measured reflectionsl = −15→15
3710 independent reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.047H-atom parameters constrained
wR(F2) = 0.159  w = 1/[σ2(Fo2) + (0.0959P)2 + 0.106P] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
3710 reflectionsΔρmax = 0.34 e Å3
174 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
O1−0.18468 (12)0.90274 (12)0.54481 (10)0.0472 (2)
O20.51966 (14)0.59340 (12)0.67258 (11)0.0546 (3)
O30.30937 (13)0.47104 (11)0.73822 (10)0.0473 (2)
N1−0.09885 (13)0.70875 (12)0.62494 (10)0.0389 (2)
H1−0.21650.66510.61070.047*
N20.10294 (14)0.85056 (13)0.55737 (11)0.0413 (2)
H20.12880.92640.52850.050*
C10.2277 (2)0.89996 (17)0.91862 (15)0.0542 (3)
H1A0.27820.94950.86990.065*
C20.2660 (3)0.9866 (2)1.05616 (17)0.0711 (5)
H2A0.33981.09421.09820.085*
C30.1961 (3)0.9148 (3)1.12917 (17)0.0757 (5)
H30.22260.97261.22120.091*
C40.0872 (4)0.7575 (3)1.0669 (2)0.0860 (6)
H40.04000.70791.11700.103*
C50.0461 (3)0.6709 (2)0.93002 (18)0.0663 (4)
H5−0.02920.56380.88850.080*
C60.11595 (16)0.74226 (14)0.85451 (12)0.0380 (2)
C70.05617 (15)0.65119 (13)0.70151 (12)0.0351 (2)
H70.00320.53600.68080.042*
C8−0.06779 (16)0.82505 (14)0.57613 (12)0.0363 (2)
C90.23610 (16)0.76219 (13)0.58195 (12)0.0371 (2)
C100.22084 (15)0.66550 (13)0.65175 (11)0.0353 (2)
C110.3835 (2)0.7861 (2)0.52121 (17)0.0556 (4)
H11A0.50170.86120.59180.083*
H11B0.33540.82860.45110.083*
H11C0.40800.68390.48170.083*
C120.36538 (16)0.57600 (13)0.68571 (12)0.0387 (2)
C130.4443 (2)0.37945 (18)0.77957 (16)0.0533 (3)
H13A0.56860.45260.84610.064*
H13B0.46380.31160.70060.064*
C140.3605 (3)0.2774 (2)0.8412 (2)0.0736 (5)
H14A0.33730.34550.91710.110*
H14B0.44950.21850.87290.110*
H14C0.24030.20230.77330.110*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0364 (4)0.0620 (5)0.0619 (5)0.0227 (4)0.0271 (4)0.0348 (5)
O20.0412 (5)0.0638 (6)0.0791 (7)0.0260 (4)0.0348 (5)0.0359 (5)
O30.0454 (5)0.0496 (5)0.0621 (6)0.0229 (4)0.0290 (4)0.0276 (4)
N10.0265 (4)0.0462 (5)0.0487 (5)0.0090 (4)0.0175 (4)0.0211 (4)
N20.0337 (5)0.0488 (5)0.0569 (6)0.0163 (4)0.0268 (4)0.0281 (5)
C10.0591 (8)0.0482 (7)0.0481 (7)0.0069 (6)0.0199 (6)0.0127 (6)
C20.0693 (11)0.0669 (9)0.0531 (8)0.0156 (8)0.0146 (7)0.0016 (7)
C30.0706 (11)0.1122 (15)0.0470 (8)0.0445 (11)0.0283 (8)0.0187 (9)
C40.1003 (15)0.1211 (18)0.0684 (11)0.0388 (14)0.0585 (11)0.0462 (12)
C50.0736 (10)0.0732 (10)0.0667 (9)0.0123 (8)0.0443 (8)0.0307 (8)
C60.0327 (5)0.0453 (6)0.0446 (6)0.0160 (4)0.0208 (4)0.0195 (5)
C70.0300 (5)0.0336 (5)0.0453 (6)0.0088 (4)0.0185 (4)0.0152 (4)
C80.0290 (5)0.0425 (5)0.0397 (5)0.0100 (4)0.0162 (4)0.0150 (4)
C90.0304 (5)0.0407 (5)0.0434 (6)0.0112 (4)0.0194 (4)0.0138 (4)
C100.0306 (5)0.0357 (5)0.0410 (5)0.0109 (4)0.0182 (4)0.0109 (4)
C110.0466 (7)0.0753 (9)0.0742 (9)0.0281 (7)0.0421 (7)0.0416 (8)
C120.0353 (5)0.0382 (5)0.0436 (6)0.0133 (4)0.0184 (4)0.0116 (4)
C130.0531 (8)0.0576 (7)0.0645 (8)0.0292 (6)0.0289 (7)0.0302 (7)
C140.0817 (12)0.0773 (11)0.0928 (13)0.0373 (9)0.0446 (10)0.0539 (10)

Geometric parameters (Å, °)

O1—C81.2310 (14)C5—C61.3793 (18)
O2—C121.2133 (14)C5—H50.9300
O3—C121.3359 (15)C6—C71.5176 (16)
O3—C131.4481 (15)C7—C101.5168 (14)
N1—C81.3398 (15)C7—H70.9800
N1—C71.4716 (15)C9—C101.3436 (16)
N1—H10.8600C9—C111.4950 (15)
N2—C81.3684 (14)C10—C121.4673 (15)
N2—C91.3788 (14)C11—H11A0.9600
N2—H20.8600C11—H11B0.9600
C1—C61.3712 (18)C11—H11C0.9600
C1—C21.393 (2)C12—O21.2133 (14)
C1—H1A0.9300C13—C141.483 (2)
C2—C31.357 (3)C13—H13A0.9700
C2—H2A0.9300C13—H13B0.9700
C3—C41.362 (3)C14—H14A0.9600
C3—H30.9300C14—H14B0.9600
C4—C51.382 (3)C14—H14C0.9600
C4—H40.9300
C12—O3—C13116.09 (10)O1—C8—N2120.40 (10)
C8—N1—C7123.94 (9)N1—C8—N2115.72 (10)
C8—N1—H1118.0C10—C9—N2119.72 (10)
C7—N1—H1118.0C10—C9—C11127.49 (11)
C8—N2—C9124.03 (10)N2—C9—C11112.77 (10)
C8—N2—H2118.0C9—C10—C12121.18 (10)
C9—N2—H2118.0C9—C10—C7120.31 (10)
C6—C1—C2120.50 (14)C12—C10—C7118.47 (10)
C6—C1—H1A119.8C9—C11—H11A109.5
C2—C1—H1A119.8C9—C11—H11B109.5
C3—C2—C1120.33 (17)H11A—C11—H11B109.5
C3—C2—H2A119.8C9—C11—H11C109.5
C1—C2—H2A119.8H11A—C11—H11C109.5
C2—C3—C4119.62 (15)H11B—C11—H11C109.5
C2—C3—H3120.2O2—C12—O3122.18 (11)
C4—C3—H3120.2O2—C12—O3122.18 (11)
C3—C4—C5120.60 (17)O2—C12—C10126.44 (11)
C3—C4—H4119.7O2—C12—C10126.44 (11)
C5—C4—H4119.7O3—C12—C10111.36 (9)
C6—C5—C4120.44 (17)O3—C13—C14107.69 (12)
C6—C5—H5119.8O3—C13—H13A110.2
C4—C5—H5119.8C14—C13—H13A110.2
C1—C6—C5118.50 (13)O3—C13—H13B110.2
C1—C6—C7121.28 (11)C14—C13—H13B110.2
C5—C6—C7120.04 (12)H13A—C13—H13B108.5
N1—C7—C10109.36 (9)C13—C14—H14A109.5
N1—C7—C6109.37 (9)C13—C14—H14B109.5
C10—C7—C6114.22 (9)H14A—C14—H14B109.5
N1—C7—H7107.9C13—C14—H14C109.5
C10—C7—H7107.9H14A—C14—H14C109.5
C6—C7—H7107.9H14B—C14—H14C109.5
O1—C8—N1123.84 (10)
C6—C1—C2—C31.3 (3)C8—N2—C9—C11165.78 (12)
C1—C2—C3—C4−0.4 (3)N2—C9—C10—C12−176.93 (10)
C2—C3—C4—C5−0.4 (3)C11—C9—C10—C124.52 (19)
C3—C4—C5—C60.4 (3)N2—C9—C10—C70.98 (17)
C2—C1—C6—C5−1.3 (2)C11—C9—C10—C7−177.57 (12)
C2—C1—C6—C7173.94 (13)N1—C7—C10—C918.31 (14)
C4—C5—C6—C10.4 (3)C6—C7—C10—C9−104.61 (12)
C4—C5—C6—C7−174.83 (16)N1—C7—C10—C12−163.72 (9)
C8—N1—C7—C10−31.02 (15)C6—C7—C10—C1273.35 (12)
C8—N1—C7—C694.75 (12)C13—O3—C12—O20.36 (18)
C1—C6—C7—N1−75.26 (14)C13—O3—C12—O20.36 (18)
C5—C6—C7—N199.89 (14)C13—O3—C12—C10−178.13 (10)
C1—C6—C7—C1047.66 (15)C9—C10—C12—O210.07 (19)
C5—C6—C7—C10−137.19 (13)C7—C10—C12—O2−167.88 (12)
C7—N1—C8—O1−160.27 (11)C9—C10—C12—O210.07 (19)
C7—N1—C8—N222.03 (16)C7—C10—C12—O2−167.88 (12)
C9—N2—C8—O1−175.96 (11)C9—C10—C12—O3−171.52 (10)
C9—N2—C8—N11.82 (17)C7—C10—C12—O310.53 (14)
C8—N2—C9—C10−12.97 (18)C12—O3—C13—C14177.11 (13)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.862.373.1773 (13)156
N2—H2···O1ii0.862.002.8568 (13)178
C11—H11A···O1iii0.962.583.1785 (16)121
C11—H11C···O20.962.442.8379 (17)105

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT2758).

References

  • Atwal, K. S., Swanson, B. N., Unger, S. E., Floyd, D. M., Moreland, S., Hedberg, A. & O Reilly, B. C. (1991). J. Med. Chem.34, 806–811. [PubMed]
  • Broughton, B. J., Chaplen, P., Knowles, P., Lunt, E., Marshall, S. M., Pain, D. L. & Wooldridge, K. R. H. (1975). J. Med. Chem.18, 1117–1122. [PubMed]
  • Bruker (2004). APEX2 and SAINT Bruker AXS Inc., Madison Wisconsin, USA.
  • Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc.97, 1354–1358.
  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
  • Kappe, C. O., Fabian, W. M. F. & Semones, M. A. (1997). Tetrahedron, 53, 2803–2816.
  • Li, M., Guo, W.-S., Wen, L.-R. & Qi, W.-Y. (2005). Acta Cryst. E61, o531–o533.
  • Nardelli, M. (1983). Acta Cryst. C39, 1141–1142.
  • Overman, L. E., Michael, H., Rabinowitz, M. H. & Renhowe, P. A. (1995). J. Am. Chem. Soc.117, 2657–2658.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2003). J. Appl. Cryst.36, 7–13.

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