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

N Anuradha; A Thiruvalluvar; K Pandiarajan; S Chitra; R J Butcher

doi:10.1107/S1600536809047187

. 2009 Nov 14;65(Pt 12):o3068. doi: 10.1107/S1600536809047187

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

N Anuradha ^a, A Thiruvalluvar ^a,^*, K Pandiarajan ^b, S Chitra ^b, R J Butcher ^c

PMCID: PMC2972027 PMID: 21578798

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 ▶); Kappe (1993 ▶, 2000 ▶); Kappe et al. (2000 ▶); Rovnyak et al. (1995 ▶); Sadanandam et al. (1992 ▶). For related crystal structures, see: Anuradha et al. (2008 ▶, 2009 ▶); Chitra et al. (2009 ▶). graphic file with name e-65-o3068-scheme1.jpg

Experimental

Crystal data

C₁₃H₁₃ClN₂OS
M _r = 280.77
Monoclinic,
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 ▶) 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
Δρ_max = 1.19 e Å⁻³
Δρ_min = −0.39 e Å⁻³

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

Supplementary Material

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

e-65-o3068-sup1.cif^{(21.1KB, cif)}

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

e-65-o3068-Isup2.hkl^{(120.2KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O15ⁱ	0.83 (4)	2.20 (4)	2.957 (4)	152 (4)
N3—H3⋯S2ⁱⁱ	0.89 (5)	2.48 (5)	3.355 (3)	170 (4)
C46—H46⋯S2ⁱⁱⁱ	0.95	2.84	3.761 (4)	165
C16—H16A⋯Cg1^iv	0.98	2.86	3.660 (4)	139

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) . Cg1 is the centroid of the benzene ring.

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).