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

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

doi:10.1107/S1600536809005029

. 2009 Feb 21;65(Pt 3):o564–o565. doi: 10.1107/S1600536809005029

5-Acetyl-4-(4-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: PMC2968427 PMID: 21582221

Abstract

In the title molecule, C₁₃H₁₃ClN₂OS, the heterocyclic ring adopts a flattened boat conformation, and the plane through the four coplanar atoms makes a dihedral angle of 87.92 (10)° with the benzene ring. The thione, acetyl and methyl groups have equatorial orientations with respect to the attached heterocyclic ring. The chlorophenyl group has an axial orientation. Intermolecular N—H⋯O, N—H⋯S and C—H⋯O hydrogen bonds are found in the crystal structure.

Related literature

For dihydropyrimidin-2(1H)-ones as anti-oxidant agents, see: Stefani et al. (2006 ▶), and for their biological activity, see: Patil et al. (1995 ▶). For dihydropyrimidinones as calcium channel blockers, see: Rovnyak et al. (1995 ▶); Atwal et al. (1990 ▶) and as antihypertensive agents, see: Atwal et al. (1991 ▶); Grover et al. (1995 ▶). For the biological activity of marine alkaloids possessing a dihydropyrimidine-5-carboxylate core, see: Patil et al. (1995 ▶). For the biological activity of dihydropyrimidin-2(1H)-thiones, see: Kappe (1993 ▶).

Experimental

Crystal data

C₁₃H₁₃ClN₂OS
M _r = 280.77
Triclinic,
a = 7.2389 (6) Å
b = 8.2304 (7) Å
c = 12.9038 (11) Å
α = 73.366 (7)°
β = 89.373 (7)°
γ = 72.613 (7)°
V = 700.62 (11) Å³
Z = 2
Cu Kα radiation
μ = 3.72 mm⁻¹
T = 295 K
0.42 × 0.25 × 0.22 mm

Data collection

Oxford Diffraction Gemini R diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008 ▶) T _min = 0.182, T _max = 1.000 (expected range = 0.080–0.441)
6666 measured reflections
2878 independent reflections
2105 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.071
wR(F ²) = 0.202
S = 1.03
2878 reflections
173 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.53 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2008 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2008 ▶); data reduction: CrysAlis RED; 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/S1600536809005029/hg2476sup1.cif

e-65-0o564-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809005029/hg2476Isup2.hkl

e-65-0o564-Isup2.hkl^{(138.4KB, 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)	2.06 (4)	2.882 (3)	175 (4)
N3—H3⋯S2ⁱⁱ	0.90 (4)	2.43 (4)	3.328 (3)	172 (3)
C61—H61B⋯O15ⁱ	0.96	2.58	3.405 (4)	144

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Symmetry codes: (i) Inline graphic ; (ii) .

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 (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

supplementary crystallographic information

Comment

Dihydropyrimidin-2(1H)-ones are pharmacologically acitive as antioxidant agents (Stefani et al., 2006). In recent years, much research has been focused on the synthesis of dihydropyrimidinones, which are important compounds due to their therapeutic and pharmacological properties. For example, they can serve as the integral of several calcium channel blockers (Rovnyak et al., 1995; Atwal et al., 1990), antihypertensive agents (Atwal et al., 1991; Grover et al., 1995). Recently, some marine alkaloids possessing dihydropyrimidine-5-carboxylate core have been shown to exhibit interesting biological activities such as potent HIV-gp-120-CD4 inhibitors as well as anti-HIV agents (Patil et al., 1995). Dihydropyrimidin-2(1H)-thiones are also of much interest with regard to biological activity (Kappe, 1993).

In the title molecule, C₁₃H₁₃ClN₂OS, 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 87.92 (10)° with the benzene ring. The thione, acetyl and methyl groups have equatorial orientation, with the attached heterocyclic ring. The chlorophenyl group has an axial orientation. N1—H1···O15(1 + x, y, z), N3—H3···S2(2 - x, 1 - y, 1 - z) and C61—H61B···O15(1 + x, y, z) intermolecular hydrogen bonds are found in the crystal structure(Fig.2., Table 1).

Experimental

A solution of acetylacetone (1.0012 g, 0.01 mol), 4-chlorobenzaldehyde (1.40 g, 0.01 mol) and thiourea (1.14 g, 0.015 mol) was heated under reflux in the presence of calcium fluoride (0.07 g, 0.001 mol) for 2 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 recrystallization from hot methanol to gave the product in the pure form. Yield 1.02 g (90%).