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

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

doi:10.1107/S1600536808039366

. 2008 Nov 29;64(Pt 12):o2474–o2475. doi: 10.1107/S1600536808039366

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

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

PMCID: PMC2960013 PMID: 21581440

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 ▶); Kappe (1993 ▶, 2000 ▶); Kappe et al. (1997 ▶); Rovnyak et al. (1992 ▶, 1995 ▶); Shivarama Holla et al. (2004 ▶).

Experimental

Crystal data

C₁₃H₁₃ClN₂O₂
M _r = 264.70
Orthorhombic,
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 ▶) 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
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ▶), 1654 Friedel pairs
Flack parameter: 0.01 (6)

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2; 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 ▶).

Supplementary Material

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

e-64-o2474-sup1.cif^{(22.1KB, cif)}

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

e-64-o2474-Isup2.hkl^{(174.7KB, 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⋯O2ⁱ	0.80 (2)	2.05 (2)	2.8386 (18)	170.6 (19)
N3—H3⋯Cl1	0.83 (2)	2.748 (18)	3.2005 (15)	116.2 (14)
N3—H3⋯O2ⁱⁱ	0.83 (2)	2.18 (2)	2.9627 (18)	158.6 (16)
C4—H4⋯O15	0.98	2.35	2.712 (2)	101
C16—H16A⋯O2ⁱⁱⁱ	0.96	2.51	3.421 (2)	159
C45—H45⋯O15^iv	0.93	2.55	3.257 (3)	133
C16—H16C⋯Cgⁱⁱⁱ	0.96	2.86	3.699 (2)	147

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) . Cg is the centroid of the C41–C46 ring.

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%).