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Acta Crystallogr Sect E Struct Rep Online. 2008 December 1; 64(Pt 12): o2474–o2475.
Published online 2008 November 29. doi:  10.1107/S1600536808039366
PMCID: PMC2960013

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

Abstract

In the title mol­ecule, C13H13ClN2O2, the heterocyclic ring adopts a flattened boat conformation with the plane through the four coplanar atoms making a dihedral angle of 89.16 (5)° with the benzene ring, which adopts an axial orientation. The carbonyl, acetyl and methyl groups each have an equatorial orientation. In the crystal structure, inter­molecular N—H(...)O hydrogen bonds lead to a tape motif. The H atoms of the methyl group at position 6 are disordered over two positions of opposite orientation.

Related literature

For the biological applications of dihydro­pyrimidinone derivatives, see: Ghorab et al. (2000 [triangle]); Kappe (1993 [triangle], 2000 [triangle]); Kappe et al. (1997 [triangle]); Rovnyak et al. (1992 [triangle], 1995 [triangle]); Shivarama Holla et al. (2004 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-64-o2474-scheme1.jpg

Experimental

Crystal data

  • C13H13ClN2O2
  • M r = 264.70
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-64-o2474-efi1.jpg
  • a = 14.5364 (8) Å
  • b = 12.1587 (5) Å
  • c = 7.0780 (4) Å
  • V = 1250.99 (11) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.30 mm−1
  • T = 296 (2) K
  • 0.58 × 0.22 × 0.16 mm

Data collection

  • Bruker APEXII CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2004 [triangle]) T min = 0.845, T max = 0.954
  • 22043 measured reflections
  • 3637 independent reflections
  • 3087 reflections with I > 2σ(I)
  • R int = 0.043

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037
  • wR(F 2) = 0.090
  • S = 1.03
  • 3637 reflections
  • 172 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.20 e Å−3
  • Δρmin = −0.22 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1654 Friedel pairs
  • Flack parameter: 0.01 (6)

Data collection: APEX2 (Bruker, 2004 [triangle]); cell refinement: APEX2; data reduction: SAINT-NT (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 (Farrugia, 1997 [triangle]); software used to prepare material for publication: PLATON (Spek, 2003 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808039366/tk2333sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808039366/tk2333Isup2.hkl

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

Acknowledgments

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]. RJB acknowledges the NSF–MRI program for funding to purchase the X-ray CCD diffractometer.

supplementary crystallographic information

Comment

Dihydropyrimidinone derivatives exhibit a wide range of biological effects including anti-fungal, anti-viral, anti-cancer, anti-bacterial, and anti-inflammatory activities (Kappe, 2000; Ghorab et al., 2000; Shivarama Holla et al., 2004). Some dihydropyrimidinones exhibit anti-tumour properties (Kappe, 1993). In addition, these compounds have emerged as the integral backbones of several calcium channel blockers (Rovnyak et al., 1995), antagonists (Kappe et al., 1997) and anti-hypertensive agents (Rovnyak et al., 1992).

In the title molecule, C13H13ClN2O2, (I) & Fig. 1, the heterocyclic ring adopts a flattened boat conformation with the plane through the four co- planar atoms (N3, C2, C5 and C6) forming a dihedral angle of 89.16 (5)° with the benzene ring, which is in an axial orientation. The carbonyl, acetyl and methyl groups are each in an equatorial orientation. Intermolecular N1—H1···O2, N3—H3···O2, C16—H16A···O2 and C45—H45···O15 interactions, and N3—H3···Cl1 and C4—H4···O15 intramolecular contacts are found, Table 1. The N—H···O hydrogen bonding leads to the formation of tapes. Further, a C16—H16C···π interaction is also found involving the benzene (C41—C46) ring. Fig. 2 shows a view of the unit-cell contents.

Experimental

A solution of acetylacetone (1.0012 g, 0.01 mol), 2-chlorobenzaldehyde (1.4057 g, 0.01 mol) and urea (0.90 g, 0.015 mol) was heated under reflux in the presence of calcium chloride (0.1109 g, 0.001 mol) for 5 h (monitored by TLC). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into crushed ice. The solid product was filtered under suction and purified by column chromatography on silica gel. Elution with 1:1 (benzene:ethyl acetate v/v) gave the product in the pure form. Yield 0.79 g (88%).

Refinement

The N-bound H atoms were located in a difference Fourier map and refined isotropically, see Table 1 for bond distances. The remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H = 0.93 - 0.98 Å and Uiso(H) = 1.2 - 1.5 times Ueq(C). The H atoms bound to the C6-methyl group were found to be disordered over two positions with equal weight.

Figures

Fig. 1.
The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radius.
Fig. 2.
The crystal packing of (I), viewed down the c axis. Dashed lines indicate intermolecular contacts. H atoms not involved in hydrogen bonding have been omitted.

Crystal data

C13H13ClN2O2Dx = 1.406 Mg m3
Mr = 264.70Melting point: 555.5 K
Orthorhombic, Pna21Mo Kα radiation λ = 0.71073 Å
Hall symbol: P 2c -2nCell parameters from 6857 reflections
a = 14.5364 (8) Åθ = 2.8–25.4º
b = 12.1587 (5) ŵ = 0.30 mm1
c = 7.0780 (4) ÅT = 296 (2) K
V = 1250.99 (11) Å3Needle, colourless
Z = 40.58 × 0.22 × 0.16 mm
F000 = 552

Data collection

Bruker APEXII CCD diffractometer3637 independent reflections
Radiation source: fine-focus sealed tube3087 reflections with I > 2σ(I)
Monochromator: graphiteRint = 0.043
T = 296(2) Kθmax = 30.1º
[var phi] and ω scansθmin = 2.2º
Absorption correction: multi-scan(SADABS; Bruker, 2004)h = −20→20
Tmin = 0.845, Tmax = 0.954k = −17→16
22043 measured reflectionsl = −9→9

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.037  w = 1/[σ2(Fo2) + (0.0429P)2 + 0.1683P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.090(Δ/σ)max = 0.001
S = 1.03Δρmax = 0.20 e Å3
3637 reflectionsΔρmin = −0.22 e Å3
172 parametersExtinction correction: none
1 restraintAbsolute structure: Flack (1983), 1654 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.01 (6)
Secondary atom site location: difference Fourier map

Special details

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)

xyzUiso*/UeqOcc. (<1)
Cl10.55079 (4)0.22136 (5)1.08117 (7)0.0597 (2)
O20.50642 (8)0.51312 (9)0.62182 (16)0.0343 (3)
O150.27723 (11)0.09996 (13)0.7672 (3)0.0774 (6)
N10.42438 (10)0.38746 (11)0.4557 (2)0.0317 (4)
N30.44410 (10)0.36578 (10)0.7731 (2)0.0307 (4)
C20.46183 (10)0.42625 (12)0.6203 (2)0.0272 (4)
C40.41461 (11)0.25076 (12)0.7555 (2)0.0287 (4)
C50.34298 (9)0.24351 (12)0.6009 (2)0.0292 (4)
C60.35395 (10)0.31050 (12)0.4495 (2)0.0292 (4)
C150.27134 (12)0.16018 (14)0.6294 (3)0.0411 (5)
C160.19130 (12)0.14572 (17)0.4994 (4)0.0527 (7)
C410.49732 (11)0.17499 (12)0.7223 (2)0.0289 (4)
C420.56389 (12)0.15910 (13)0.8612 (3)0.0375 (5)
C430.64096 (14)0.09425 (16)0.8322 (3)0.0486 (6)
C440.65258 (14)0.04277 (16)0.6600 (3)0.0484 (6)
C450.58767 (13)0.05448 (15)0.5208 (3)0.0430 (5)
C460.51081 (12)0.11989 (13)0.5529 (2)0.0351 (5)
C610.30143 (13)0.31541 (15)0.2672 (3)0.0423 (5)
H10.4383 (13)0.4194 (16)0.362 (3)0.039 (5)*
H30.4662 (12)0.3844 (14)0.876 (3)0.028 (5)*
H40.385480.229090.874710.0345*
H16A0.151910.088740.547080.0791*
H16B0.213070.125730.376080.0791*
H16C0.157490.213390.491640.0791*
H430.684350.085510.927540.0584*
H440.704570.000020.638360.0581*
H450.595050.018820.405580.0516*
H460.467060.126940.457760.0421*
H61A0.326560.372310.188610.0635*0.500
H61B0.237930.331070.293040.0635*0.500
H61C0.306190.245990.203330.0635*0.500
H61D0.253890.260600.268040.0635*0.500
H61E0.342520.301850.163610.0635*0.500
H61F0.274260.386920.253320.0635*0.500

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0743 (3)0.0725 (3)0.0323 (2)0.0214 (3)−0.0192 (2)−0.0082 (2)
O20.0433 (6)0.0301 (5)0.0294 (6)−0.0071 (4)−0.0026 (5)0.0000 (4)
O150.0606 (9)0.0728 (10)0.0989 (14)−0.0278 (8)−0.0217 (9)0.0522 (10)
N10.0394 (7)0.0341 (6)0.0216 (6)−0.0083 (5)−0.0014 (6)0.0039 (5)
N30.0430 (8)0.0278 (6)0.0212 (6)−0.0006 (5)−0.0028 (6)−0.0001 (5)
C20.0303 (7)0.0269 (6)0.0244 (7)0.0021 (5)0.0006 (5)0.0002 (5)
C40.0333 (7)0.0282 (6)0.0247 (7)−0.0022 (6)0.0018 (6)0.0040 (5)
C50.0250 (6)0.0306 (7)0.0321 (8)−0.0014 (5)0.0002 (6)0.0029 (6)
C60.0276 (7)0.0312 (7)0.0289 (8)0.0005 (6)−0.0009 (6)−0.0001 (6)
C150.0309 (8)0.0366 (8)0.0558 (12)−0.0015 (6)−0.0004 (8)0.0099 (8)
C160.0332 (9)0.0493 (10)0.0757 (15)−0.0123 (8)−0.0068 (9)0.0098 (10)
C410.0307 (8)0.0268 (6)0.0292 (8)−0.0029 (5)−0.0010 (6)0.0044 (5)
C420.0436 (9)0.0360 (8)0.0328 (8)0.0025 (7)−0.0059 (7)0.0011 (7)
C430.0448 (10)0.0489 (10)0.0522 (11)0.0116 (8)−0.0135 (9)0.0044 (9)
C440.0428 (10)0.0409 (9)0.0616 (13)0.0128 (8)0.0011 (9)−0.0012 (9)
C450.0459 (10)0.0367 (8)0.0465 (10)0.0027 (7)0.0052 (8)−0.0087 (7)
C460.0381 (8)0.0338 (7)0.0334 (9)−0.0009 (6)−0.0031 (7)−0.0031 (6)
C610.0423 (9)0.0493 (10)0.0354 (8)−0.0078 (8)−0.0091 (8)0.0036 (8)

Geometric parameters (Å, °)

Cl1—C421.742 (2)C43—C441.381 (3)
O2—C21.2393 (18)C44—C451.372 (3)
O15—C151.223 (3)C45—C461.390 (3)
N1—C21.370 (2)C4—H40.9800
N1—C61.388 (2)C16—H16A0.9600
N3—C21.333 (2)C16—H16B0.9600
N3—C41.4680 (19)C16—H16C0.9600
N1—H10.80 (2)C43—H430.9300
N3—H30.83 (2)C44—H440.9300
C4—C411.533 (2)C45—H450.9300
C4—C51.513 (2)C46—H460.9300
C5—C61.355 (2)C61—H61A0.9600
C5—C151.467 (2)C61—H61B0.9600
C6—C611.501 (3)C61—H61C0.9600
C15—C161.494 (3)C61—H61D0.9600
C41—C461.387 (2)C61—H61E0.9600
C41—C421.393 (2)C61—H61F0.9600
C42—C431.385 (3)
Cl1···N33.2005 (15)C46···H16Cv2.9700
Cl1···C46i3.6067 (15)C61···H16B2.7500
Cl1···O2ii3.3462 (13)C61···H16C2.9100
Cl1···H42.8100H1···H61A2.1100
Cl1···H46i3.1500H1···H61E2.4400
Cl1···H32.748 (18)H1···H61F2.5400
O2···Cl1iii3.3462 (13)H1···O2iii2.05 (2)
O2···N1ii2.8386 (18)H1···C2iii2.93 (2)
O2···N3iii2.9627 (18)H3···Cl12.748 (18)
O15···C45iv3.257 (3)H3···C423.087 (17)
O15···C413.342 (2)H3···O2ii2.18 (2)
O2···H61Aii2.8400H3···C2ii3.064 (19)
O2···H1ii2.05 (2)H4···Cl12.8100
O2···H3iii2.18 (2)H4···O152.3500
O2···H16Av2.5100H4···H61Ei2.3100
O15···H42.3500H16A···O2vii2.5100
O15···H44iv2.9100H16A···C2vii2.8200
O15···H45iv2.5500H16B···C63.0800
O15···H61Fvi2.7000H16B···C612.7500
N1···C413.370 (2)H16B···H61B2.5900
N1···O2iii2.8386 (18)H16B···H61C2.3400
N3···Cl13.2005 (15)H16B···H61D1.9000
N3···O2ii2.9627 (18)H16B···H44viii2.5700
C2···C16v3.553 (2)H16C···C612.9100
C6···C463.333 (2)H16C···H61B2.3200
C15···C463.557 (2)H16C···H61D2.1900
C16···C2vii3.553 (2)H16C···C45vii3.0100
C16···C613.086 (3)H16C···C46vii2.9700
C41···O153.342 (2)H44···O15viii2.9100
C41···N13.370 (2)H44···H16Biv2.5700
C42···C45iv3.588 (3)H45···O15viii2.5500
C45···C42viii3.588 (3)H45···C41viii3.0100
C45···O15viii3.257 (3)H46···Cl1ix3.1500
C46···Cl1ix3.6067 (15)H46···C52.5100
C46···C153.557 (2)H46···C62.7700
C46···C63.333 (2)H61A···H12.1100
C61···C163.086 (3)H61A···O2iii2.8400
C2···H16Av2.8200H61B···C162.7700
C2···H1ii2.93 (2)H61B···H16B2.5900
C2···H3iii3.064 (19)H61B···H16C2.3200
C5···H462.5100H61B···C45vii3.0500
C6···H462.7700H61C···C162.9400
C6···H16B3.0800H61C···H16B2.3400
C15···H61D2.8500H61D···C152.8500
C16···H61C2.9400H61D···C162.3400
C16···H61D2.3400H61D···H16B1.9000
C16···H61B2.7700H61D···H16C2.1900
C41···H45iv3.0100H61E···H12.4400
C42···H33.087 (17)H61E···H4ix2.3100
C45···H61Bv3.0500H61F···H12.5400
C45···H16Cv3.0100H61F···O15x2.7000
C2—N1—C6123.53 (13)C15—C16—H16B109.00
C2—N3—C4120.87 (13)C15—C16—H16C109.00
C2—N1—H1116.1 (14)H16A—C16—H16B109.00
C6—N1—H1119.4 (14)H16A—C16—H16C109.00
C2—N3—H3119.2 (12)H16B—C16—H16C110.00
C4—N3—H3116.7 (12)C42—C43—H43120.00
O2—C2—N3124.35 (14)C44—C43—H43120.00
N1—C2—N3115.05 (13)C43—C44—H44120.00
O2—C2—N1120.58 (13)C45—C44—H44120.00
N3—C4—C5108.53 (12)C44—C45—H45120.00
N3—C4—C41110.89 (13)C46—C45—H45120.00
C5—C4—C41113.20 (12)C41—C46—H46119.00
C4—C5—C15115.43 (13)C45—C46—H46119.00
C6—C5—C15127.40 (14)C6—C61—H61A109.00
C4—C5—C6117.12 (13)C6—C61—H61B109.00
N1—C6—C5117.84 (13)C6—C61—H61C109.00
N1—C6—C61112.07 (13)C6—C61—H61D109.00
C5—C6—C61130.09 (14)C6—C61—H61E109.00
C5—C15—C16123.34 (17)C6—C61—H61F109.00
O15—C15—C5118.27 (17)H61A—C61—H61B109.00
O15—C15—C16118.39 (17)H61A—C61—H61C109.00
C4—C41—C46122.25 (14)H61A—C61—H61D141.00
C42—C41—C46116.41 (15)H61A—C61—H61E56.00
C4—C41—C42121.34 (13)H61A—C61—H61F56.00
Cl1—C42—C41119.65 (13)H61B—C61—H61C109.00
Cl1—C42—C43117.92 (15)H61B—C61—H61D56.00
C41—C42—C43122.43 (18)H61B—C61—H61E141.00
C42—C43—C44119.20 (19)H61B—C61—H61F56.00
C43—C44—C45120.20 (19)H61C—C61—H61D56.00
C44—C45—C46119.66 (18)H61C—C61—H61E56.00
C41—C46—C45122.08 (16)H61C—C61—H61F141.00
N3—C4—H4108.00H61D—C61—H61E109.00
C5—C4—H4108.00H61D—C61—H61F109.00
C41—C4—H4108.00H61E—C61—H61F109.00
C15—C16—H16A109.00
C6—N1—C2—O2−161.31 (14)C15—C5—C6—N1177.02 (15)
C6—N1—C2—N316.9 (2)C15—C5—C6—C61−3.7 (3)
C2—N1—C6—C5−23.4 (2)C4—C5—C15—O15−3.9 (2)
C2—N1—C6—C61157.25 (15)C4—C5—C15—C16175.71 (16)
C4—N3—C2—O2−162.51 (15)C6—C5—C15—O15173.16 (17)
C4—N3—C2—N119.4 (2)C6—C5—C15—C16−7.3 (3)
C2—N3—C4—C5−44.08 (19)C4—C41—C42—Cl12.9 (2)
C2—N3—C4—C4180.86 (17)C4—C41—C42—C43−177.59 (16)
N3—C4—C5—C635.79 (18)C46—C41—C42—Cl1−177.91 (12)
N3—C4—C5—C15−146.88 (14)C46—C41—C42—C431.6 (2)
C41—C4—C5—C6−87.77 (16)C4—C41—C46—C45177.56 (15)
C41—C4—C5—C1589.56 (16)C42—C41—C46—C45−1.6 (2)
N3—C4—C41—C4266.67 (18)Cl1—C42—C43—C44179.21 (15)
N3—C4—C41—C46−112.46 (16)C41—C42—C43—C44−0.3 (3)
C5—C4—C41—C42−171.08 (14)C42—C43—C44—C45−1.1 (3)
C5—C4—C41—C469.8 (2)C43—C44—C45—C461.0 (3)
C4—C5—C6—N1−6.0 (2)C44—C45—C46—C410.4 (3)
C4—C5—C6—C61173.24 (15)

Symmetry codes: (i) x, y, z+1; (ii) −x+1, −y+1, z+1/2; (iii) −x+1, −y+1, z−1/2; (iv) −x+1, −y, z+1/2; (v) x+1/2, −y+1/2, z; (vi) −x+1/2, y−1/2, z+1/2; (vii) x−1/2, −y+1/2, z; (viii) −x+1, −y, z−1/2; (ix) x, y, z−1; (x) −x+1/2, y+1/2, z−1/2.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O2iii0.80 (2)2.05 (2)2.8386 (18)170.6 (19)
N3—H3···Cl10.83 (2)2.748 (18)3.2005 (15)116.2 (14)
N3—H3···O2ii0.83 (2)2.18 (2)2.9627 (18)158.6 (16)
C4—H4···O150.982.352.712 (2)101
C16—H16A···O2vii0.962.513.421 (2)159
C45—H45···O15viii0.932.553.257 (3)133
C16—H16C···Cgvii0.962.863.699 (2)147

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2333).

References

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