PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 June 1; 65(Pt 6): o1229.
Published online 2009 May 7. doi:  10.1107/S1600536809016365
PMCID: PMC2969568

Ethyl 4-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-6-methyl-2-oxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Abstract

In the title compound, C18H19ClN4O3, the dihydro­pyrimidin­one ring adopts a flattened boat conformation. The dihedral angle between the phenyl and pyrazole rings is 43.39 (6)°. An intra­molecular C—H(...)O contact generates an S(8) ring motif that stabilizes the mol­ecular conformation and precludes the carbonyl O atom of the ester group from forming inter­molecular inter­actions. Mol­ecules are linked into centrosymmetric dimers by pairs of N—H(...)O hydrogen bonds and the dimers are linked into infinite chains along [101] by N—H(...)N hydrogen bonds.

Related literature

For medicinal applications of pyrimidinone derivatives, see: Atwal (1990 [triangle]); Desai et al. (2006 [triangle]); Wipf & Cunningham (1995 [triangle]); Bedia et al. (2006 [triangle]). For a related structure, see: Fun et al. (2009 [triangle]). For hydrogen-bond motifs, see: Bernstein et al. (1995 [triangle]). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 [triangle]). For reference structural data, see: Allen et al. (1987 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1229-scheme1.jpg

Experimental

Crystal data

  • C18H19ClN4O3
  • M r = 374.82
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1229-efi1.jpg
  • a = 7.9083 (2) Å
  • b = 10.2600 (2) Å
  • c = 10.9075 (3) Å
  • α = 93.394 (1)°
  • β = 99.379 (1)°
  • γ = 90.203 (1)°
  • V = 871.58 (4) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.25 mm−1
  • T = 110 K
  • 0.56 × 0.26 × 0.21 mm

Data collection

  • Bruker SMART APEXII CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2005 [triangle]) T min = 0.875, T max = 0.950
  • 18224 measured reflections
  • 5048 independent reflections
  • 4355 reflections with I > 2σ(I)
  • R int = 0.026

Refinement

  • R[F 2 > 2σ(F 2)] = 0.036
  • wR(F 2) = 0.099
  • S = 1.05
  • 5048 reflections
  • 257 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.48 e Å−3
  • Δρmin = −0.30 e Å−3

Data collection: APEX2 (Bruker, 2005 [triangle]); cell refinement: SAINT (Bruker, 2005 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809016365/tk2442sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809016365/tk2442Isup2.hkl

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

Acknowledgments

HKF thanks Universiti Sains Malaysia for the Research University Golden Goose (grant No. 1001/PFIZIK/811012). CSY thanks the Malaysian government and Universiti Sains Malaysia for the award of the post of Research Officer under Science Fund (grant No. 305/PFIZIK/613312).

supplementary crystallographic information

Comment

Pyrimidinones have drawn widespread attention due to their medicinal applications (Atwal, 1990). A variety of dihydropyrimidinone derivatives have been screened for anti-hypertension (Desai et al., 2006), anti-bacterial and anti-carcinogenic (Wipf & Cunningham, 1995), and anti-tuberculosis activity (Bedia et al., 2006). Prompted by these observations and in continuation of our work in this area, herein we report the crystal structure of the title compound, (I).

In (I), Fig. 1, the dihydropyrimidinone ring adopts a flattened boat conformation. The dihedral angle between the phenyl ring and the pyrazole ring is 43.39 (6)°. Bond lengths and angles are within normal ranges and comparable to a related structure (Fun et al., 2009). An intramolecular C18—H18C···O3 contact generates a S(8) ring motif (Bernstein et al., 1995) which stabilises the molecular conformation and precludes the O3 atom from forming intermolecular contacts. The molecules are linked into centrosymmetric dimers by N—H···O hydrogen bonds (Table 1). The dimers are further linked into infinite chains along [101] by N—H···N hydrogen bonds (Fig. 2).

Experimental

Compound (I) was obtained by refluxing a mixture of 1-phenyl-3-methyl-5-chloropyrazole-4-aldehyde (0.01 mol), ethyl acetoacetate (0.015 mol) and urea (0.01 mol) in ethanol (25 ml). The excess alcohol was removed under reduced pressure. After cooling the reaction mixture to room temperature, the contents were poured into ice-cold water (100 ml). The solid mass separated was collected by filtration and dried. Crystals were obtained from ethanol by slow evaporation (Yield 59%).

Refinement

The N-bound H atoms were located in a difference Fourier map and refined freely. The remaining H atoms were positioned geometrically and refined using a riding model with C—H = 0.93–0.98 Å, and with Uiso(H) = 1.2 or 1.5 Ueq(C). A rotating-group model was applied for the methyl groups.

Figures

Fig. 1.
The molecular structure of (I) with atom labels and 50% probability ellipsoids for non-H atoms. An intramolecular C—H···O contact is shown as dashed lines.
Fig. 2.
A view of the crystal packing in (I), showing an infinite chain along the [101] direction. Intermolecular hydrogen bonds are shown as dashed lines.

Crystal data

C18H19ClN4O3Z = 2
Mr = 374.82F(000) = 392
Triclinic, P1Dx = 1.428 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.9083 (2) ÅCell parameters from 9944 reflections
b = 10.2600 (2) Åθ = 2.6–35.8°
c = 10.9075 (3) ŵ = 0.25 mm1
α = 93.394 (1)°T = 110 K
β = 99.379 (1)°Block, colourless
γ = 90.203 (1)°0.56 × 0.26 × 0.21 mm
V = 871.58 (4) Å3

Data collection

Bruker SMART APEXII CCD area-detector diffractometer5048 independent reflections
Radiation source: fine-focus sealed tube4355 reflections with I > 2σ(I)
graphiteRint = 0.026
[var phi] and ω scansθmax = 30.0°, θmin = 1.9°
Absorption correction: multi-scan (SADABS; Bruker, 2005)h = −11→11
Tmin = 0.875, Tmax = 0.950k = −14→14
18224 measured reflectionsl = −15→15

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) = 0.099H atoms treated by a mixture of independent and constrained refinement
S = 1.05w = 1/[σ2(Fo2) + (0.0515P)2 + 0.3283P] where P = (Fo2 + 2Fc2)/3
5048 reflections(Δ/σ)max < 0.001
257 parametersΔρmax = 0.48 e Å3
0 restraintsΔρmin = −0.30 e Å3

Special details

Experimental. The crystal was placed in the cold stream of an Oxford Cyrosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 110.0 (1) K.
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
Cl10.16502 (4)0.27288 (3)0.28593 (3)0.01867 (8)
O10.09492 (11)0.60474 (9)0.13406 (8)0.01980 (18)
O20.64558 (11)0.20298 (9)0.00629 (8)0.02096 (19)
O30.77714 (11)0.29869 (9)0.18745 (8)0.02079 (19)
N10.40982 (13)0.25693 (10)0.48878 (9)0.01486 (19)
N20.57439 (13)0.29637 (10)0.53670 (9)0.01546 (19)
N30.36526 (13)0.54573 (10)0.21278 (9)0.01470 (19)
N40.21476 (13)0.43462 (10)0.03761 (9)0.0162 (2)
C10.41198 (18)0.06888 (12)0.61334 (11)0.0202 (2)
H1A0.52860.06000.61160.024*
C20.3256 (2)−0.01924 (13)0.67359 (12)0.0253 (3)
H2A0.3844−0.08840.71150.030*
C30.1527 (2)−0.00483 (14)0.67768 (12)0.0265 (3)
H3A0.0951−0.06540.71650.032*
C40.06518 (18)0.09986 (14)0.62404 (12)0.0254 (3)
H4A−0.05030.11060.62890.030*
C50.14923 (16)0.18874 (13)0.56301 (11)0.0202 (2)
H5A0.09100.25940.52760.024*
C60.32146 (16)0.17084 (11)0.55550 (10)0.0161 (2)
C70.36219 (14)0.30274 (11)0.37349 (10)0.0143 (2)
C80.49610 (14)0.37464 (11)0.34481 (10)0.0132 (2)
C90.62520 (14)0.36737 (11)0.45051 (10)0.0144 (2)
C100.50187 (14)0.44856 (11)0.22960 (10)0.0135 (2)
H10A0.61170.49600.24190.016*
C110.21883 (15)0.53209 (11)0.13033 (10)0.0150 (2)
C120.35013 (15)0.35289 (11)0.02438 (10)0.0146 (2)
C130.49312 (14)0.35937 (11)0.11231 (10)0.0140 (2)
C140.65113 (15)0.28596 (11)0.10717 (11)0.0155 (2)
C150.80143 (17)0.13146 (13)−0.00265 (12)0.0223 (3)
H15A0.82430.07160.06350.027*
H15B0.89830.19120.00390.027*
C160.7726 (2)0.05757 (18)−0.12749 (15)0.0387 (4)
H16A0.87460.0112−0.13900.058*
H16B0.74560.1177−0.19180.058*
H16C0.6793−0.0034−0.13140.058*
C170.31577 (17)0.26349 (13)−0.09159 (12)0.0201 (2)
H17A0.207 (3)0.2792 (18)−0.1382 (18)0.034 (5)*
H17B0.316 (3)0.175 (2)−0.0718 (18)0.038 (5)*
H17C0.398 (2)0.2794 (18)−0.1447 (17)0.034 (5)*
C180.79965 (15)0.42889 (12)0.47221 (12)0.0187 (2)
H18A0.85300.41880.55660.028*
H18B0.79020.52010.45750.028*
H18C0.86790.38740.41640.028*
H1N30.367 (2)0.6038 (15)0.2734 (15)0.016 (4)*
H1N40.120 (2)0.4247 (17)−0.0173 (17)0.026 (4)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.01327 (13)0.02560 (15)0.01588 (13)−0.00443 (10)−0.00218 (9)0.00376 (10)
O10.0153 (4)0.0211 (4)0.0210 (4)0.0060 (3)−0.0022 (3)−0.0012 (3)
O20.0159 (4)0.0277 (5)0.0182 (4)0.0091 (3)0.0006 (3)−0.0024 (3)
O30.0145 (4)0.0270 (5)0.0195 (4)0.0048 (3)−0.0011 (3)0.0009 (3)
N10.0128 (4)0.0176 (4)0.0136 (4)−0.0006 (3)−0.0002 (3)0.0026 (3)
N20.0128 (4)0.0175 (4)0.0149 (4)0.0011 (3)−0.0010 (3)0.0006 (3)
N30.0139 (4)0.0149 (4)0.0140 (4)0.0030 (3)−0.0013 (3)0.0004 (3)
N40.0122 (5)0.0200 (5)0.0149 (4)0.0032 (4)−0.0019 (4)−0.0010 (4)
C10.0254 (6)0.0195 (5)0.0158 (5)0.0032 (5)0.0035 (4)0.0025 (4)
C20.0378 (8)0.0200 (6)0.0182 (6)0.0003 (5)0.0033 (5)0.0047 (5)
C30.0361 (8)0.0271 (6)0.0160 (6)−0.0124 (6)0.0031 (5)0.0039 (5)
C40.0224 (6)0.0350 (7)0.0190 (6)−0.0072 (5)0.0037 (5)0.0033 (5)
C50.0192 (6)0.0236 (6)0.0179 (5)−0.0001 (4)0.0027 (4)0.0033 (4)
C60.0201 (6)0.0164 (5)0.0115 (5)−0.0015 (4)0.0021 (4)0.0010 (4)
C70.0132 (5)0.0161 (5)0.0129 (5)0.0009 (4)−0.0002 (4)0.0014 (4)
C80.0110 (5)0.0147 (5)0.0133 (5)0.0017 (4)0.0004 (4)0.0009 (4)
C90.0125 (5)0.0150 (5)0.0147 (5)0.0022 (4)−0.0002 (4)−0.0004 (4)
C100.0100 (5)0.0159 (5)0.0141 (5)0.0011 (4)0.0000 (4)0.0026 (4)
C110.0145 (5)0.0155 (5)0.0147 (5)0.0006 (4)0.0006 (4)0.0030 (4)
C120.0132 (5)0.0168 (5)0.0139 (5)0.0017 (4)0.0023 (4)0.0020 (4)
C130.0125 (5)0.0164 (5)0.0132 (5)0.0019 (4)0.0017 (4)0.0021 (4)
C140.0142 (5)0.0180 (5)0.0148 (5)0.0018 (4)0.0027 (4)0.0044 (4)
C150.0179 (6)0.0280 (6)0.0212 (6)0.0107 (5)0.0032 (5)0.0016 (5)
C160.0343 (8)0.0504 (10)0.0292 (8)0.0220 (7)0.0025 (6)−0.0105 (7)
C170.0182 (6)0.0246 (6)0.0157 (5)0.0029 (5)−0.0008 (4)−0.0031 (4)
C180.0120 (5)0.0226 (6)0.0200 (6)0.0000 (4)−0.0010 (4)0.0007 (4)

Geometric parameters (Å, °)

Cl1—C71.7070 (12)C5—C61.3899 (17)
O1—C111.2378 (14)C5—H5A0.9300
O2—C141.3456 (14)C7—C81.3760 (16)
O2—C151.4505 (14)C8—C91.4158 (15)
O3—C141.2157 (14)C8—C101.5125 (15)
N1—C71.3641 (14)C9—C181.4924 (16)
N1—N21.3712 (13)C10—C131.5202 (15)
N1—C61.4268 (15)C10—H10A0.9800
N2—C91.3334 (15)C12—C131.3570 (15)
N3—C111.3468 (14)C12—C171.5047 (16)
N3—C101.4695 (14)C13—C141.4685 (15)
N3—H1N30.862 (16)C15—C161.5020 (19)
N4—C111.3760 (15)C15—H15A0.9700
N4—C121.3828 (14)C15—H15B0.9700
N4—H1N40.883 (18)C16—H16A0.9600
C1—C21.3886 (18)C16—H16B0.9600
C1—C61.3932 (17)C16—H16C0.9600
C1—H1A0.9300C17—H17A0.95 (2)
C2—C31.383 (2)C17—H17B0.95 (2)
C2—H2A0.9300C17—H17C0.956 (19)
C3—C41.387 (2)C18—H18A0.9600
C3—H3A0.9300C18—H18B0.9600
C4—C51.3887 (18)C18—H18C0.9600
C4—H4A0.9300
C14—O2—C15115.79 (9)C8—C10—C13112.92 (9)
C7—N1—N2110.16 (9)N3—C10—H10A107.5
C7—N1—C6130.02 (10)C8—C10—H10A107.5
N2—N1—C6119.60 (9)C13—C10—H10A107.5
C9—N2—N1105.46 (9)O1—C11—N3122.70 (10)
C11—N3—C10125.12 (9)O1—C11—N4120.82 (10)
C11—N3—H1N3117.1 (10)N3—C11—N4116.45 (10)
C10—N3—H1N3115.4 (10)C13—C12—N4119.61 (10)
C11—N4—C12124.24 (10)C13—C12—C17127.57 (10)
C11—N4—H1N4117.5 (11)N4—C12—C17112.82 (10)
C12—N4—H1N4118.3 (11)C12—C13—C14125.95 (10)
C2—C1—C6119.05 (12)C12—C13—C10120.88 (10)
C2—C1—H1A120.5C14—C13—C10113.16 (9)
C6—C1—H1A120.5O3—C14—O2122.46 (11)
C3—C2—C1120.45 (12)O3—C14—C13122.92 (11)
C3—C2—H2A119.8O2—C14—C13114.63 (10)
C1—C2—H2A119.8O2—C15—C16106.46 (10)
C2—C3—C4120.08 (13)O2—C15—H15A110.4
C2—C3—H3A120.0C16—C15—H15A110.4
C4—C3—H3A120.0O2—C15—H15B110.4
C3—C4—C5120.28 (13)C16—C15—H15B110.4
C3—C4—H4A119.9H15A—C15—H15B108.6
C5—C4—H4A119.9C15—C16—H16A109.5
C4—C5—C6119.22 (12)C15—C16—H16B109.5
C4—C5—H5A120.4H16A—C16—H16B109.5
C6—C5—H5A120.4C15—C16—H16C109.5
C5—C6—C1120.82 (12)H16A—C16—H16C109.5
C5—C6—N1120.71 (11)H16B—C16—H16C109.5
C1—C6—N1118.47 (11)C12—C17—H17A111.0 (11)
N1—C7—C8108.70 (10)C12—C17—H17B111.1 (12)
N1—C7—Cl1123.11 (9)H17A—C17—H17B106.9 (16)
C8—C7—Cl1128.18 (9)C12—C17—H17C110.3 (11)
C7—C8—C9103.79 (10)H17A—C17—H17C106.4 (16)
C7—C8—C10128.17 (10)H17B—C17—H17C111.0 (17)
C9—C8—C10128.00 (10)C9—C18—H18A109.5
N2—C9—C8111.88 (10)C9—C18—H18B109.5
N2—C9—C18120.43 (10)H18A—C18—H18B109.5
C8—C9—C18127.69 (11)C9—C18—H18C109.5
N3—C10—C8111.17 (9)H18A—C18—H18C109.5
N3—C10—C13110.10 (9)H18B—C18—H18C109.5
C7—N1—N2—C90.68 (12)C11—N3—C10—C8−103.04 (12)
C6—N1—N2—C9175.80 (10)C11—N3—C10—C1322.87 (15)
C6—C1—C2—C3−0.95 (19)C7—C8—C10—N357.33 (15)
C1—C2—C3—C4−1.6 (2)C9—C8—C10—N3−120.05 (12)
C2—C3—C4—C51.8 (2)C7—C8—C10—C13−67.00 (15)
C3—C4—C5—C60.54 (19)C9—C8—C10—C13115.62 (12)
C4—C5—C6—C1−3.09 (18)C10—N3—C11—O1166.80 (11)
C4—C5—C6—N1177.20 (11)C10—N3—C11—N4−15.22 (16)
C2—C1—C6—C53.29 (18)C12—N4—C11—O1177.43 (11)
C2—C1—C6—N1−176.99 (11)C12—N4—C11—N3−0.59 (17)
C7—N1—C6—C5−46.54 (17)C11—N4—C12—C135.61 (18)
N2—N1—C6—C5139.45 (11)C11—N4—C12—C17−174.82 (11)
C7—N1—C6—C1133.75 (13)N4—C12—C13—C14−175.52 (11)
N2—N1—C6—C1−40.27 (15)C17—C12—C13—C145.0 (2)
N2—N1—C7—C8−0.59 (13)N4—C12—C13—C104.26 (17)
C6—N1—C7—C8−175.05 (11)C17—C12—C13—C10−175.23 (11)
N2—N1—C7—Cl1−179.88 (8)N3—C10—C13—C12−16.61 (15)
C6—N1—C7—Cl15.67 (17)C8—C10—C13—C12108.30 (12)
N1—C7—C8—C90.25 (12)N3—C10—C13—C14163.20 (9)
Cl1—C7—C8—C9179.49 (9)C8—C10—C13—C14−71.89 (12)
N1—C7—C8—C10−177.62 (10)C15—O2—C14—O3−1.48 (17)
Cl1—C7—C8—C101.62 (18)C15—O2—C14—C13178.58 (10)
N1—N2—C9—C8−0.52 (12)C12—C13—C14—O3177.86 (12)
N1—N2—C9—C18178.99 (10)C10—C13—C14—O3−1.93 (17)
C7—C8—C9—N20.18 (13)C12—C13—C14—O2−2.20 (17)
C10—C8—C9—N2178.06 (10)C10—C13—C14—O2178.00 (10)
C7—C8—C9—C18−179.29 (11)C14—O2—C15—C16−173.84 (12)
C10—C8—C9—C18−1.41 (19)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N3—H1N3···N2i0.863 (16)2.233 (16)3.0601 (14)160.7 (14)
N4—H1N4···O1ii0.882 (17)1.960 (17)2.8418 (13)176.8 (17)
C18—H18C···O30.962.593.2850 (15)129

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2442).

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. (1990). J. Med. Chem.33, 1510–1518. [PubMed]
  • Bedia, K.-K., Elçin, O., Seda, U., Fatma, K., Nathaly, S., Sevim, R. & Dimoglo, A. (2006). Eur. J. Med. Chem.41, 1253–1261. [PubMed]
  • Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl.34, 1555–1573.
  • Bruker (2005). APEX2, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Cosier, J. & Glazer, A. M. (1986). J. Appl. Cryst.19, 105–107.
  • Desai, B., Dallinger, D. & Kappe, C. O. (2006). Tetrahedron, 62, 4651–4664.
  • Fun, H.-K., Yeap, C. S., Babu, M. & Kalluraya, B. (2009). Acta Cryst. E65, o1188–o1189. [PMC free article] [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Wipf, P. & Cunningham, A. (1995). Tetrahedron Lett.36, 7819–7822.

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