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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3068.
Published online 2009 November 14. doi:  10.1107/S1600536809047187
PMCID: PMC2972027

5-Acetyl-4-(2-chloro­phen­yl)-6-methyl-3,4-dihydro­pyrimidine-2(1H)-thione

Abstract

In the title mol­ecule, C13H13ClN2OS, the heterocyclic ring adopts a flattened boat conformation with the plane through the four coplanar atoms making a dihedral angle of 85.6 (1)° with the benzene ring, which adopts an axial orientation. The thionyl, acetyl and methyl groups all have equatorial orientations. Inter­molecular N—H(...)O, N—H(...)S and C—H(...)S hydrogen bonds are found in the crystal structure. A weak C—H(...)π inter­action involving the benzene ring also occurs.

Related literature

For chemical and biological applications of dihydro­pyrimidinones, see: Atwal et al. (1990 [triangle]); Kappe (1993 [triangle], 2000 [triangle]); Kappe et al. (2000 [triangle]); Rovnyak et al. (1995 [triangle]); Sadanandam et al. (1992 [triangle]). For related crystal structures, see: Anuradha et al. (2008 [triangle], 2009 [triangle]); Chitra et al. (2009 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3068-scheme1.jpg

Experimental

Crystal data

  • C13H13ClN2OS
  • M r = 280.77
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3068-efi1.jpg
  • a = 7.2346 (12) Å
  • b = 22.585 (3) Å
  • c = 8.0941 (15) Å
  • β = 106.177 (17)°
  • V = 1270.2 (4) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 4.11 mm−1
  • T = 110 K
  • 0.45 × 0.43 × 0.12 mm

Data collection

  • Oxford Diffraction Xcalibur Ruby Gemini diffractometer
  • Absorption correction: multi-scan (CrysAlis Pro; Oxford Diffraction, 2009 [triangle]) T min = 0.451, T max = 1.000
  • 4641 measured reflections
  • 2497 independent reflections
  • 2246 reflections with I > 2σ(I)
  • R int = 0.035

Refinement

  • R[F 2 > 2σ(F 2)] = 0.062
  • wR(F 2) = 0.184
  • S = 1.13
  • 2497 reflections
  • 173 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 1.19 e Å−3
  • Δρmin = −0.39 e Å−3

Data collection: CrysAlis Pro (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis Pro; data reduction: CrysAlis Pro; 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, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809047187/wn2366sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809047187/wn2366Isup2.hkl

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

Acknowledgments

RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

supplementary crystallographic information

Comment

5-Ethoxycarbonyl-4-(3-hydroxyphenyl)-6-methyl-3,4-dihydropyrimidine- 2(1H)-thione can be used as an anticancer drug (Kappe et al., 2000). Dihydropyrimidinones can be used as analgesic agents (Sadanandam et al., 1992). Dihydropyrimidinones have attracted increasing attention due to their various therapeutic and pharmacological properties, such as antiviral, antibacterial, antihypertensive and antitumor effects (Kappe, 1993; Kappe, 2000). More recently they have emerged as integral backbones of several calcium blockers, antihypertensive agents, α-1a-antagonists and neuropeptide Y (NPY) antagonists (Atwal et al., 1990; Rovnyak et al., 1995). The crystal structures of three very closely related compounds have recently been reported [Anuradha et al., (2008, 2009); Chitra et al., (2009)]. This study of the title compound, was undertaken to compare the biological activity and structure of dihydropyrimidin-2(1H)-thione and its corresponding 2(1H)-one (Anuradha et al., 2008).

In the title molecule, C13H13ClN2OS (Fig. 1) the heterocyclic ring adopts a flattened boat conformation with the plane through the four coplanar atoms (C2,N3,C5,C6) making a dihedral angle of 85.6 (1)° with the benzene ring, which adopts an axial orientation. The thionyl, acetyl and methyl groups all have equatorial orientations. Intermolecular N1—H1···O15(1 + x, y, z), N3—H3···S2(1 - x, -y, 1 - z) and C46—H46···S2(-1 + x, y, z) hydrogen bonds are found in the crystal structure. Furthermore, a weak C16—H16A···π(x, y, 1 + z) interaction involving the benzene ring (C41—C46) is also found.

Experimental

A solution of acetylacetone (1.001 g, 0.01 mol), 2-chlorobenzaldehyde (1.406 g, 0.01 mol) and thiourea (1.149 g, 0.015 mol) was heated under reflux in the presence of calcium fluoride (0.078 g, 0.001 mol) for 1.5 h (monitored by TLC). After completion of the reaction, the reaction mixture was cooled to room temperature and poured into crushed ice. The crude product, containing also the catalyst, was collected on a Buchner funnel by filtration. The mixture of the product and the catalyst was digested in methanol (40 ml). The undissolved catalyst was removed by filtration. The crude product was obtained by evaporation of the methanol and further purified by recrystallization from hot ethanol to afford the pure title compound. Yield 84% (1.86 g).

Refinement

H1 at N1 was located in a difference Fourier map and the N1—H1 distance was restrained to be 0.83 (4) Å. H3 at N3 was located in a difference Fourier map and refined freely; N3—H3 = 0.89 (5) Å. The remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H = 0.95 - 1.00 Å; Uiso(H) = kUeq(C), where k = 1.5 for methyl and 1.2 for all other H atoms. The maximum residual electron density peak is located 0.86 Å from C42.

Figures

Fig. 1.
The molecular structure of the title compound, showing the atom-numbering scheme and displacement ellipsoids drawn at the 40% probability level. H atoms are shown as small spheres of arbitrary radius.
Fig. 2.
The packing of the title compound, viewed down the a axis. Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonding have been omitted.

Crystal data

C13H13ClN2OSF(000) = 584
Mr = 280.77Dx = 1.468 Mg m3
Monoclinic, P21/cMelting point: 484.5 K
Hall symbol: -P 2ybcCu Kα radiation, λ = 1.54184 Å
a = 7.2346 (12) ÅCell parameters from 3483 reflections
b = 22.585 (3) Åθ = 5.7–73.8°
c = 8.0941 (15) ŵ = 4.11 mm1
β = 106.177 (17)°T = 110 K
V = 1270.2 (4) Å3Triangular-plate, colourless
Z = 40.45 × 0.43 × 0.12 mm

Data collection

Oxford Diffraction Xcalibur Ruby Gemini diffractometer2497 independent reflections
Radiation source: Enhance (Cu) X-ray Source2246 reflections with I > 2σ(I)
graphiteRint = 0.035
Detector resolution: 10.5081 pixels mm-1θmax = 74.1°, θmin = 6.0°
ω scansh = −8→8
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)k = −27→16
Tmin = 0.451, Tmax = 1.000l = −9→8
4641 measured reflections

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)] = 0.062Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.184H atoms treated by a mixture of independent and constrained refinement
S = 1.13w = 1/[σ2(Fo2) + (0.1043P)2 + 2.5484P] where P = (Fo2 + 2Fc2)/3
2497 reflections(Δ/σ)max = 0.001
173 parametersΔρmax = 1.19 e Å3
1 restraintΔρmin = −0.38 e Å3

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*/Ueq
Cl20.66371 (12)0.18610 (4)0.75112 (12)0.0277 (3)
S20.80912 (11)0.01280 (4)0.64291 (10)0.0198 (3)
O150.1673 (3)0.10482 (11)1.0187 (3)0.0216 (7)
N10.7634 (4)0.06358 (13)0.9244 (3)0.0185 (8)
N30.4871 (4)0.05026 (12)0.7069 (3)0.0162 (8)
C20.6750 (5)0.04420 (15)0.7613 (4)0.0164 (9)
C40.3680 (4)0.08463 (14)0.7922 (4)0.0150 (8)
C50.4719 (5)0.09279 (14)0.9816 (4)0.0156 (9)
C60.6658 (5)0.08508 (15)1.0377 (4)0.0168 (9)
C150.3405 (5)0.10641 (14)1.0875 (4)0.0164 (9)
C160.4118 (5)0.12310 (17)1.2760 (4)0.0228 (10)
C410.2962 (5)0.14262 (14)0.6951 (4)0.0170 (9)
C420.4137 (5)0.18851 (15)0.6678 (4)0.0200 (10)
C430.3389 (6)0.23843 (16)0.5701 (5)0.0246 (10)
C440.1437 (6)0.24424 (16)0.5040 (5)0.0257 (11)
C450.0217 (5)0.20019 (17)0.5320 (5)0.0247 (10)
C460.0963 (5)0.15024 (15)0.6247 (4)0.0207 (10)
C610.7992 (5)0.09730 (19)1.2130 (4)0.0269 (10)
H10.882 (5)0.0629 (17)0.962 (5)0.012 (9)*
H30.422 (7)0.032 (2)0.611 (7)0.029 (11)*
H40.251210.060160.786650.0180*
H16A0.301670.131961.319970.0342*
H16B0.494800.158081.288720.0342*
H16C0.485170.090051.341080.0342*
H430.422790.268150.549710.0295*
H440.091680.278370.438900.0309*
H45−0.113640.204510.487130.0297*
H460.011110.120310.641560.0249*
H61A0.787060.138861.243300.0406*
H61B0.932140.089371.212230.0406*
H61C0.765440.071661.297900.0406*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl20.0192 (5)0.0300 (5)0.0347 (5)−0.0063 (3)0.0090 (4)0.0031 (3)
S20.0184 (4)0.0252 (5)0.0188 (4)−0.0016 (3)0.0102 (3)−0.0050 (3)
O150.0169 (13)0.0327 (13)0.0173 (12)−0.0004 (9)0.0084 (9)0.0002 (9)
N10.0148 (14)0.0282 (15)0.0131 (13)−0.0005 (11)0.0051 (11)−0.0036 (10)
N30.0190 (14)0.0206 (13)0.0112 (12)−0.0020 (11)0.0077 (10)−0.0052 (10)
C20.0192 (16)0.0209 (15)0.0111 (14)−0.0027 (12)0.0074 (12)0.0005 (11)
C40.0131 (15)0.0205 (15)0.0132 (14)−0.0014 (12)0.0066 (12)−0.0016 (11)
C50.0178 (16)0.0187 (15)0.0111 (14)−0.0008 (12)0.0055 (12)−0.0017 (11)
C60.0159 (16)0.0241 (16)0.0106 (14)−0.0018 (12)0.0039 (12)−0.0006 (12)
C150.0187 (17)0.0182 (15)0.0150 (15)−0.0010 (12)0.0092 (13)0.0025 (11)
C160.0264 (18)0.0319 (18)0.0132 (16)−0.0021 (14)0.0107 (13)−0.0041 (13)
C410.0213 (16)0.0211 (16)0.0101 (14)−0.0030 (12)0.0069 (12)−0.0036 (12)
C420.0221 (17)0.0250 (17)0.0152 (16)−0.0026 (13)0.0091 (13)−0.0016 (12)
C430.035 (2)0.0221 (17)0.0201 (17)−0.0056 (14)0.0131 (15)−0.0015 (13)
C440.034 (2)0.0243 (17)0.0194 (18)0.0016 (15)0.0087 (15)0.0035 (13)
C450.0230 (18)0.0310 (18)0.0186 (17)0.0003 (14)0.0032 (13)−0.0010 (14)
C460.0294 (19)0.0229 (16)0.0120 (15)−0.0033 (13)0.0092 (13)−0.0019 (12)
C610.0188 (17)0.045 (2)0.0155 (17)0.0003 (15)0.0024 (13)−0.0052 (14)

Geometric parameters (Å, °)

Cl2—C421.746 (4)C41—C421.397 (5)
S2—C21.697 (4)C42—C431.397 (5)
O15—C151.222 (4)C43—C441.370 (6)
N1—C21.369 (4)C44—C451.390 (6)
N1—C61.392 (4)C45—C461.379 (5)
N3—C21.314 (5)C4—H41.0000
N3—C41.467 (4)C16—H16A0.9800
N1—H10.83 (4)C16—H16B0.9800
N3—H30.89 (5)C16—H16C0.9800
C4—C411.541 (4)C43—H430.9500
C4—C51.519 (4)C44—H440.9500
C5—C61.360 (5)C45—H450.9500
C5—C151.479 (5)C46—H460.9500
C6—C611.503 (5)C61—H61A0.9800
C15—C161.516 (4)C61—H61B0.9800
C41—C461.410 (5)C61—H61C0.9800
Cl2···N13.095 (3)C6···H16C3.0900
Cl2···N33.304 (3)C15···H43viii2.9300
Cl2···C23.206 (4)C16···H61A2.8200
Cl2···C53.360 (4)C16···H61C2.7700
Cl2···C63.251 (3)C16···H43viii3.0800
Cl2···C45i3.538 (4)C41···H16Av3.0600
Cl2···C46i3.644 (4)C42···H16Av2.9900
Cl2···H45i3.0400C43···H16Bx2.9600
Cl2···H44ii3.1500C45···H61Axi2.8400
S2···C16iii3.604 (4)C46···H44viii3.0200
S2···N3iv3.355 (3)C61···H16B2.8000
S2···H61Cv3.0300C61···H16C2.7500
S2···H46i2.8400H1···O15i2.20 (4)
S2···H3iv2.48 (5)H1···H61B2.0400
S2···H16Ciii3.1800H3···S2iv2.48 (5)
S2···H61Bvi3.0000H4···O152.3600
O15···N1vii2.957 (4)H4···H462.2600
O15···C413.134 (4)H16A···C41ix3.0600
O15···C463.252 (4)H16A···C42ix2.9900
O15···C44viii3.414 (4)H16B···C612.8000
O15···H42.3600H16B···H61A2.2900
O15···H61Bvii2.6400H16B···C43viii2.9600
O15···H1vii2.20 (4)H16B···H43viii2.5000
O15···H44viii2.7300H16C···C63.0900
N1···Cl23.095 (3)H16C···C612.7500
N1···O15i2.957 (4)H16C···H61C2.1900
N3···Cl23.304 (3)H16C···S2iii3.1800
N3···S2iv3.355 (3)H43···C15x2.9300
C2···Cl23.206 (4)H43···C16x3.0800
C5···Cl23.360 (4)H43···H16Bx2.5000
C6···Cl23.251 (3)H44···Cl2xiii3.1500
C15···C43viii3.507 (5)H44···O15x2.7300
C16···S2iii3.604 (4)H44···C46x3.0200
C16···C43viii3.514 (5)H45···Cl2vii3.0400
C16···C42ix3.495 (5)H45···H61Axi2.4100
C16···C613.042 (5)H46···S2vii2.8400
C41···O153.134 (4)H46···H42.2600
C42···C16v3.495 (5)H61A···C162.8200
C43···C15x3.507 (5)H61A···C45xii2.8400
C43···C16x3.514 (5)H61A···H16B2.2900
C44···O15x3.414 (4)H61A···H45xii2.4100
C45···C61xi3.513 (5)H61B···O15i2.6400
C45···Cl2vii3.538 (4)H61B···H12.0400
C46···Cl2vii3.644 (4)H61B···S2vi3.0000
C46···O153.252 (4)H61C···S2ix3.0300
C61···C163.042 (5)H61C···C162.7700
C61···C45xii3.513 (5)H61C···H16C2.1900
C2—N1—C6124.1 (3)C42—C43—C44119.5 (4)
C2—N3—C4125.9 (3)C43—C44—C45120.0 (3)
C2—N1—H1121 (3)C44—C45—C46120.3 (4)
C6—N1—H1115 (3)C41—C46—C45121.5 (3)
C2—N3—H3119 (3)N3—C4—H4107.00
C4—N3—H3115 (3)C5—C4—H4107.00
S2—C2—N3123.7 (2)C41—C4—H4107.00
N1—C2—N3116.9 (3)C15—C16—H16A109.00
S2—C2—N1119.4 (3)C15—C16—H16B109.00
N3—C4—C5110.4 (3)C15—C16—H16C109.00
N3—C4—C41111.6 (3)H16A—C16—H16B109.00
C5—C4—C41114.4 (3)H16A—C16—H16C110.00
C4—C5—C15113.1 (3)H16B—C16—H16C109.00
C6—C5—C15127.1 (3)C42—C43—H43120.00
C4—C5—C6119.7 (3)C44—C43—H43120.00
N1—C6—C5119.4 (3)C43—C44—H44120.00
N1—C6—C61112.1 (3)C45—C44—H44120.00
C5—C6—C61128.6 (3)C44—C45—H45120.00
C5—C15—C16122.8 (3)C46—C45—H45120.00
O15—C15—C5118.2 (3)C41—C46—H46119.00
O15—C15—C16119.0 (3)C45—C46—H46119.00
C4—C41—C46118.2 (3)C6—C61—H61A109.00
C42—C41—C46116.5 (3)C6—C61—H61B109.00
C4—C41—C42125.3 (3)C6—C61—H61C109.00
Cl2—C42—C41121.8 (3)H61A—C61—H61B109.00
Cl2—C42—C43116.1 (3)H61A—C61—H61C109.00
C41—C42—C43122.1 (3)H61B—C61—H61C109.00
C6—N1—C2—S2−174.1 (3)C15—C5—C6—N1170.2 (3)
C6—N1—C2—N34.6 (5)C15—C5—C6—C61−10.3 (6)
C2—N1—C6—C5−6.2 (5)C4—C5—C15—O156.0 (4)
C2—N1—C6—C61174.3 (3)C4—C5—C15—C16−173.0 (3)
C4—N3—C2—S2−170.3 (2)C6—C5—C15—O15−171.3 (3)
C4—N3—C2—N111.1 (5)C6—C5—C15—C169.7 (5)
C2—N3—C4—C5−22.0 (4)C4—C41—C42—Cl2−2.6 (5)
C2—N3—C4—C41106.5 (3)C4—C41—C42—C43176.3 (3)
N3—C4—C5—C618.9 (4)C46—C41—C42—Cl2178.6 (2)
N3—C4—C5—C15−158.6 (3)C46—C41—C42—C43−2.5 (5)
C41—C4—C5—C6−108.0 (4)C4—C41—C46—C45−178.1 (3)
C41—C4—C5—C1574.5 (4)C42—C41—C46—C450.8 (5)
N3—C4—C41—C42−61.9 (4)Cl2—C42—C43—C44−178.4 (3)
N3—C4—C41—C46117.0 (3)C41—C42—C43—C442.7 (5)
C5—C4—C41—C4264.4 (4)C42—C43—C44—C45−1.0 (6)
C5—C4—C41—C46−116.8 (3)C43—C44—C45—C46−0.7 (6)
C4—C5—C6—N1−6.9 (5)C44—C45—C46—C410.8 (5)
C4—C5—C6—C61172.5 (3)

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

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O15i0.83 (4)2.20 (4)2.957 (4)152 (4)
N3—H3···S2iv0.89 (5)2.48 (5)3.355 (3)170 (4)
C46—H46···S2vii0.952.843.761 (4)165
C16—H16A···Cg1ix0.982.863.660 (4)139

Symmetry codes: (i) x+1, y, z; (iv) −x+1, −y, −z+1; (vii) x−1, y, z; (ix) x, y, z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: WN2366).

References

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