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Acta Cryst. (2009). E65, o23    [ doi:10.1107/S1600536808040270 ]

5-Acetyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one

S. Chitra, K. Pandiarajan, N. Anuradha and A. Thiruvalluvar

Abstract top

In the title molecule, C14H16N2O3, the heterocyclic ring adopts a flattened boat conformation, and the plane through its four coplanar atoms makes a dihedral angle of 89.65 (7)° with the benzene ring. The non-H atoms of the carbonyl, acetyl and methyl groups are nearly coplanar with the attached heterocyclic ring. Intermolecular N-H...O and C-H...O hydrogen bonds are present in the crystal structure.

Comment top

Dihydropyrimidinone derivatives exhibit a wide range of biological effects including antifungal, antiviral, anticancer, antibacterial, anti-inflammatory and antihypertensive effects (Kappe, 2000; Ghorab et al., 2000; Shivarama Holla et al., 2004). It also exhibit a biological activity of antitumour property (Kappe, 1993). Dihydropyrimidinones used as an anticancer drug capable of inhibiting Kinesin motor protein (Kappe et al., 2000). Many dihydropyrimidinones and their derivatives are pharmacologically important as calcium channel blockers, antihypertensive agents and α-1a-antagonists (Atwal et al., 1989; Kappe et al., 1997). Dihydropyrimidin-2(1H)-ones can be used as an antioxidant agents (Stefani et al., 2006).

In the title molecule, (I) (Fig. 1), the heterocyclic ring adopts a flattened boat conformation, and the plane through the four coplanar atoms(C2, N3, C5 and C6) makes a dihedral angle of 89.65 (7)° with the benzene ring. The carbonyl, acetyl and methyl groups, except for the H atoms, are nearly coplanar with the attached heterocyclic ring. A network of hydrogen bonds (Table 1) help to establish the packing (Fig. 2, Table 1).

Related literature top

For chemical and medicinal background, see: Atwal et al. (1989); Ghorab et al. (2000); Kappe (1993, 2000); Kappe et al. (1997, 2000); Shivarama Holla et al. (2004); Stefani et al. (2006).

Experimental top

A solution of acetylacetone (1.00 g, 0.01 mol), anisaldehyde (1.36 g, 0.01 mol) and urea (0.90 g, 0.015 mol) in EtOH (20 ml) was heated under reflux in the presence of calcium chloride (0.11 g, 0.001 mol) for 3 h (monitored by TLC). After completion of the reaction, the reaction mixture was cooled to room temperature and the reaction mixture was poured into crushed ice and the resulting solid was filtered under suction and purified by column chromatography on silica gel. Elution of 1:1 (benzene:ethyl acetate v/v) gave the product in the pure form. Yield 0.86 g (96%).

Refinement top

Atoms H1 and H3 were located in a difference map and refined isotropically. The C-bound H atoms were positioned geometrically (C—H = 0.93–0.98 Å) and refined as riding with Uiso(H)= 1.2Ueq(C) or 1.5Ueq(methyl C).

Computing details top

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

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) with displacement ellipsoids drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radius.
[Figure 2] Fig. 2. The packing of (I), viewed down the b axis. Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonding have been omitted.
5-Acetyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydropyrimidin-2(1H)-one top
Crystal data top
C14H16N2O3F(000) = 1104
Mr = 260.29Dx = 1.323 Mg m−3
Monoclinic, C2/cMelting point: 474.5 K
Hall symbol: -C 2ycMo Kα radiation, λ = 0.71073 Å
a = 23.7948 (12) ÅCell parameters from 5096 reflections
b = 7.9905 (3) Åθ = 2.7–26.4°
c = 14.4757 (7) ŵ = 0.09 mm−1
β = 108.305 (5)°T = 293 K
V = 2613.0 (2) Å3Block, colourless
Z = 80.3 × 0.2 × 0.2 mm
Data collection top
Bruker Kappa APEXII CCD
diffractometer		2960 independent reflections
Radiation source: fine-focus sealed tube2226 reflections with I > 2σ(I)
graphiteRint = 0.045
ω and φ scansθmax = 27.5°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		h = −30→30
Tmin = 0.837, Tmax = 1.000k = −10→10
26518 measured reflectionsl = −18→18
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.046Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.149H atoms treated by a mixture of independent and constrained refinement
S = 1.10 w = 1/[σ2(Fo2) + (0.0771P)2 + 1.0144P]
where P = (Fo2 + 2Fc2)/3
2960 reflections(Δ/σ)max = 0.001
183 parametersΔρmax = 0.27 e Å−3
0 restraintsΔρmin = −0.24 e Å−3
Crystal data top
C14H16N2O3V = 2613.0 (2) Å3
Mr = 260.29Z = 8
Monoclinic, C2/cMo Kα radiation
a = 23.7948 (12) ŵ = 0.09 mm−1
b = 7.9905 (3) ÅT = 293 K
c = 14.4757 (7) Å0.3 × 0.2 × 0.2 mm
β = 108.305 (5)°
Data collection top
Bruker Kappa APEXII CCD
diffractometer		2960 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2004)		2226 reflections with I > 2σ(I)
Tmin = 0.837, Tmax = 1.000Rint = 0.045
26518 measured reflectionsθmax = 27.5°
Refinement top
R[F2 > 2σ(F2)] = 0.046H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.149Δρmax = 0.27 e Å−3
S = 1.10Δρmin = −0.24 e Å−3
2960 reflectionsAbsolute structure: ?
183 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

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 > 2σ(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) top
xyzUiso*/Ueq
O20.03463 (6)0.62339 (16)−0.06612 (9)0.0448 (4)
O150.06948 (6)0.98745 (15)0.31847 (8)0.0430 (4)
O440.27417 (7)0.4726 (2)0.44596 (12)0.0748 (6)
N10.07453 (7)0.86574 (18)0.00570 (10)0.0358 (4)
N30.04449 (7)0.66399 (18)0.09271 (10)0.0351 (4)
C20.05037 (7)0.7104 (2)0.00812 (11)0.0319 (5)
C40.06651 (7)0.75657 (19)0.18405 (11)0.0297 (4)
C50.07616 (7)0.93953 (19)0.16471 (11)0.0294 (5)
C60.08211 (7)0.98438 (19)0.07810 (11)0.0303 (5)
C140.27926 (12)0.4564 (4)0.54607 (19)0.0879 (11)
C150.07743 (7)1.0494 (2)0.24592 (11)0.0332 (5)
C160.08710 (11)1.2339 (2)0.24595 (14)0.0558 (7)
C410.12158 (7)0.67712 (19)0.25352 (11)0.0320 (5)
C420.17355 (9)0.6594 (3)0.23045 (14)0.0514 (7)
C430.22307 (10)0.5896 (3)0.29545 (17)0.0624 (8)
C440.22238 (9)0.5391 (3)0.38624 (14)0.0493 (6)
C450.17137 (9)0.5551 (2)0.41034 (13)0.0436 (6)
C460.12122 (8)0.6231 (2)0.34341 (12)0.0362 (5)
C610.09756 (9)1.1526 (2)0.04681 (13)0.0424 (6)
H10.0736 (9)0.901 (3)−0.0548 (16)0.048 (6)*
H30.0231 (9)0.572 (3)0.0913 (14)0.046 (6)*
H40.035590.752560.215530.0356*
H14A0.272760.563250.571240.1316*
H14B0.318180.416850.581480.1316*
H14C0.250290.378000.553090.1316*
H16A0.083241.281400.304560.0837*
H16B0.058211.282960.190640.0837*
H16C0.126081.256010.242650.0837*
H420.174930.695340.170100.0616*
H430.257280.576300.278120.0749*
H450.170300.520540.471120.0523*
H460.086580.632270.359880.0434*
H61A0.065701.229430.041720.0636*
H61B0.103881.14266−0.015280.0636*
H61C0.132991.193460.093970.0636*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O20.0622 (9)0.0433 (7)0.0320 (7)−0.0143 (6)0.0191 (6)−0.0122 (5)
O150.0643 (9)0.0401 (7)0.0261 (6)0.0044 (6)0.0164 (6)−0.0015 (5)
O440.0478 (9)0.0956 (13)0.0681 (11)0.0106 (9)−0.0003 (8)0.0305 (10)
N10.0501 (9)0.0354 (7)0.0249 (7)−0.0069 (6)0.0160 (6)−0.0019 (6)
N30.0469 (9)0.0314 (7)0.0264 (7)−0.0105 (6)0.0108 (6)−0.0029 (5)
C20.0358 (9)0.0334 (8)0.0263 (8)−0.0038 (7)0.0094 (7)−0.0037 (6)
C40.0380 (9)0.0294 (7)0.0233 (7)−0.0033 (6)0.0119 (7)−0.0004 (6)
C50.0339 (9)0.0279 (7)0.0251 (8)0.0007 (6)0.0074 (6)0.0002 (6)
C60.0331 (9)0.0297 (8)0.0266 (8)0.0002 (6)0.0074 (6)−0.0003 (6)
C140.0716 (18)0.102 (2)0.0639 (17)−0.0019 (16)−0.0163 (13)0.0314 (15)
C150.0388 (9)0.0335 (8)0.0240 (8)0.0044 (7)0.0051 (7)−0.0013 (6)
C160.0959 (18)0.0337 (9)0.0369 (10)−0.0012 (10)0.0196 (11)−0.0053 (8)
C410.0396 (9)0.0275 (7)0.0288 (8)−0.0036 (7)0.0108 (7)−0.0002 (6)
C420.0474 (12)0.0697 (13)0.0400 (10)0.0058 (10)0.0181 (9)0.0166 (9)
C430.0406 (12)0.0861 (17)0.0623 (14)0.0084 (11)0.0188 (10)0.0201 (12)
C440.0436 (11)0.0487 (11)0.0469 (11)0.0012 (9)0.0017 (9)0.0111 (9)
C450.0548 (12)0.0399 (9)0.0329 (9)0.0014 (9)0.0090 (8)0.0082 (8)
C460.0454 (10)0.0330 (8)0.0314 (9)0.0005 (7)0.0139 (7)0.0022 (7)
C610.0613 (12)0.0324 (8)0.0360 (9)−0.0030 (8)0.0188 (9)0.0029 (7)
Geometric parameters (Å, °) top
O2—C21.235 (2)C42—C431.374 (3)
O15—C151.228 (2)C43—C441.380 (3)
O44—C141.422 (3)C44—C451.370 (3)
O44—C441.371 (3)C45—C461.390 (3)
N1—C21.373 (2)C4—H40.9800
N1—C61.382 (2)C14—H14A0.9600
N3—C21.328 (2)C14—H14B0.9600
N3—C41.461 (2)C14—H14C0.9600
N1—H10.91 (2)C16—H16A0.9600
N3—H30.89 (2)C16—H16B0.9600
C4—C411.518 (2)C16—H16C0.9600
C4—C51.520 (2)C42—H420.9300
C5—C61.354 (2)C43—H430.9300
C5—C151.460 (2)C45—H450.9300
C6—C611.501 (2)C46—H460.9300
C15—C161.492 (2)C61—H61A0.9600
C41—C461.374 (2)C61—H61B0.9600
C41—C421.386 (3)C61—H61C0.9600
C14—O44—C44116.75 (19)C41—C46—C45121.59 (18)
C2—N1—C6123.82 (14)N3—C4—H4107.00
C2—N3—C4125.54 (14)C5—C4—H4107.00
C2—N1—H1114.8 (15)C41—C4—H4107.00
C6—N1—H1118.3 (15)O44—C14—H14A109.00
C2—N3—H3115.7 (13)O44—C14—H14B109.00
C4—N3—H3118.6 (13)O44—C14—H14C109.00
O2—C2—N3123.64 (16)H14A—C14—H14B109.00
N1—C2—N3116.24 (14)H14A—C14—H14C109.00
O2—C2—N1120.11 (15)H14B—C14—H14C109.00
N3—C4—C5110.63 (13)C15—C16—H16A109.00
N3—C4—C41112.17 (13)C15—C16—H16B109.00
C5—C4—C41112.06 (13)C15—C16—H16C109.00
C4—C5—C15113.35 (13)H16A—C16—H16B109.00
C6—C5—C15127.23 (14)H16A—C16—H16C109.00
C4—C5—C6119.42 (14)H16B—C16—H16C109.00
N1—C6—C5119.61 (14)C41—C42—H42119.00
N1—C6—C61111.81 (14)C43—C42—H42120.00
C5—C6—C61128.58 (14)C42—C43—H43120.00
C5—C15—C16123.96 (15)C44—C43—H43120.00
O15—C15—C5118.45 (14)C44—C45—H45120.00
O15—C15—C16117.59 (15)C46—C45—H45120.00
C4—C41—C46119.88 (16)C41—C46—H46119.00
C42—C41—C46117.89 (16)C45—C46—H46119.00
C4—C41—C42122.22 (15)C6—C61—H61A109.00
C41—C42—C43120.97 (19)C6—C61—H61B109.00
C42—C43—C44120.4 (2)C6—C61—H61C109.00
O44—C44—C43115.9 (2)H61A—C61—H61B109.00
C43—C44—C45119.5 (2)H61A—C61—H61C109.00
O44—C44—C45124.64 (18)H61B—C61—H61C109.00
C44—C45—C46119.62 (17)
C14—O44—C44—C43165.7 (2)C4—C5—C6—N15.3 (3)
C14—O44—C44—C45−15.5 (3)C4—C5—C6—C61−173.60 (17)
C6—N1—C2—O2166.26 (17)C15—C5—C6—N1−174.25 (17)
C6—N1—C2—N3−12.6 (3)C15—C5—C6—C616.9 (3)
C2—N1—C6—C512.8 (3)C4—C5—C15—O15−1.7 (2)
C2—N1—C6—C61−168.20 (17)C4—C5—C15—C16179.10 (18)
C4—N3—C2—O2174.99 (17)C6—C5—C15—O15177.84 (18)
C4—N3—C2—N1−6.2 (3)C6—C5—C15—C16−1.4 (3)
C2—N3—C4—C521.4 (2)C4—C41—C42—C43178.86 (19)
C2—N3—C4—C41−104.54 (19)C46—C41—C42—C430.2 (3)
N3—C4—C5—C6−20.2 (2)C4—C41—C46—C45−177.71 (15)
N3—C4—C5—C15159.41 (15)C42—C41—C46—C451.0 (3)
C41—C4—C5—C6105.84 (17)C41—C42—C43—C44−1.5 (4)
C41—C4—C5—C15−74.59 (18)C42—C43—C44—O44−179.4 (2)
N3—C4—C41—C4261.2 (2)C42—C43—C44—C451.7 (3)
N3—C4—C41—C46−120.13 (16)O44—C44—C45—C46−179.37 (19)
C5—C4—C41—C42−64.0 (2)C43—C44—C45—C46−0.5 (3)
C5—C4—C41—C46114.72 (17)C44—C45—C46—C41−0.9 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O15i0.91 (2)2.01 (2)2.9209 (18)172 (2)
N3—H3···O2ii0.89 (2)2.04 (2)2.917 (2)170.3 (19)
C16—H16B···O2iii0.962.493.425 (3)165
C61—H61B···O15i0.962.513.352 (2)146
Symmetry codes: (i) x, −y+2, z−1/2; (ii) −x, −y+1, −z; (iii) −x, −y+2, −z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O15i0.91 (2)2.01 (2)2.9209 (18)172 (2)
N3—H3···O2ii0.89 (2)2.04 (2)2.917 (2)170.3 (19)
C16—H16B···O2iii0.962.493.425 (3)165
C61—H61B···O15i0.962.513.352 (2)146
Symmetry codes: (i) x, −y+2, z−1/2; (ii) −x, −y+1, −z; (iii) −x, −y+2, −z.
Acknowledgements top

AT thanks the UGC, India, for the award of a Minor Research Project [File No. MRP-2355/06(UGC-SERO), Link No. 2355, 10/01/2007]. The authors are grateful to Dr A. Babu Vargheese, Sophisticated Analytical Instrument Facility (SAIF), IIT Madras, Chennai, for the X-ray data collection.

references
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