Ethyl 4-(2-bromo-5-fluoro­phen­yl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Hoong-Kun Fun; Samuel Robinson Jebas; M Babu; P S Patil; B Kalluraya; S M Dharmaprakash

doi:10.1107/S1600536808021685

. 2008 Jul 19;64(Pt 8):o1526–o1527. doi: 10.1107/S1600536808021685

Ethyl 4-(2-bromo-5-fluorophenyl)-6-methyl-1-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Hoong-Kun Fun ^a,^*, Samuel Robinson Jebas ^a,^‡, M Babu ^b, P S Patil ^c, B Kalluraya ^b, S M Dharmaprakash ^c

PMCID: PMC2962151 PMID: 21203233

Abstract

In the title molecule, C₂₀H₁₈BrFN₂O₂S, the pyrimidine ring adopts a flattened envelope conformation. The halogenated benzene ring is orthogonal to the planar part of the pyrimidine ring [dihedral angle = 89.05 (4)°], while the other phenyl ring is oriented at an angle of 85.14 (5)°. The ethoxy group is disordered over two orientations with site occpancies of ca 0.869 (4) and 0.131 (4). Intramolecular C—H⋯Br and C—H⋯O hydrogen bonds generate S(5) and S(6) ring motifs. The crystal structure is stabilized by intermolecular N—H⋯S, C—H⋯F, C—H⋯O and C—H⋯Br hydrogen bonds.

Related literature

For the biological activity of pyrimidinone derivatives, see: Atwal (1990 ▶); Matsuda & Hirao (1965 ▶); Sadanandam et al. (1992 ▶). For the synthetic procedure, see: Steele et al. (1998 ▶); Manjual et al. (2004 ▶); Kappe (1993 ▶); Wipf & Cunningham (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₂₀H₁₈BrFN₂O₂S
M _r = 449.33
Triclinic,
a = 10.0455 (1) Å
b = 10.2969 (1) Å
c = 10.3714 (1) Å
α = 64.286 (1)°
β = 83.110 (1)°
γ = 78.796 (1)°
V = 947.36 (2) Å³
Z = 2
Mo Kα radiation
μ = 2.31 mm⁻¹
T = 100 (2) K
0.41 × 0.35 × 0.22 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.451, T _max = 0.631
30132 measured reflections
5490 independent reflections
4895 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.084
S = 1.04
5490 reflections
267 parameters
15 restraints
H-atom parameters constrained
Δρ_max = 1.01 e Å⁻³
Δρ_min = −0.66 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005 ▶); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808021685/ci2628sup1.cif

e-64-o1526-sup1.cif^{(21KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808021685/ci2628Isup2.hkl

e-64-o1526-Isup2.hkl^{(263.3KB, 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—H1N1⋯S1ⁱ	0.85	2.51	3.327 (2)	162
C1—H1⋯F1ⁱⁱ	0.95	2.52	3.370 (2)	148
C7—H7⋯Br1	1.00	2.69	3.265 (2)	117
C20—H20⋯O1ⁱⁱⁱ	0.95	2.44	3.368 (3)	164
C21—H21A⋯O2	0.98	2.11	2.737 (3)	120
C21—H21B⋯Br1ⁱⁱⁱ	0.98	2.91	3.886 (2)	171

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

Acknowledgments

HKF and SRJ thank the Malaysian Government and Universiti Sains Malaysia for the Science Fund grant No. 305/PFIZIK/613312. SRJ thanks the Universiti Sains Malaysia for a postdoctoral research fellowship.

supplementary crystallographic information

Comment

3,4-Dihydropyrimidinones have drawn wide-spread attention due to their pharmaceutical applications. A variety of these derivatives have been screened for antihypertension (Atwal, 1990), antibacterial (Matsuda & Hirao, 1965) and anti-inflammatory activities (Sadanandam et al., 1992). The common synthetic routes to these compounds generally involve multi step transformations, which are essentially based on the Biginelli condensation methodology (Steele et al., 1998). These pyrimidinones are also associated with calcium channel blocking activity (Manjual et al., 2004). In 1893, Biginelli reported the first synthesis of dihydropyrimidines by a simple one-pot condensation reaction of ethyl acetoacetate, benzaldehyde and urea. In the following decades the original cyclo-condensation reaction has been extended widely to include variations in all three components, allowing access to a large number of muti functionalized dihydropyrimidinone derivatives (Kappe, 1993). Biginelli reaction has recently attracted a great deal of attention and several improved procedures for the preparation of dihydropyrimidinones have been reported within the past few years. Several solid-phase modifications of the Biginelli reaction suitable for the combinatorial chemistry have also been described (Wipf & Cunningham, 1995).

Bond lengths and angles in the title molecule (Fig. 1) are found to have normal values (Allen et al., 1987). The pyrimidine ring adopts a flattened envelope conformation, with puckering parameters (Cremer & Pople, 1975) Q = 0.067 (2) Å, θ = 132.5 (16)° and φ = 237 (2)°. The C1-C6 and C15-C20 phenyl rings form dihedral angles of 89.05 (4)° and 85.14 (5)°, respectively, with the N1/N2/C7/C8/C13/C14 plane. Intramolecular C—H···Br and C—H···O hydrogen bonds generate S(5) and S(6) ring motifs (Bernstein et al., 1995), respectively.

The crystal structure is stabilized by intermolecular N—H···S, C—H···F, C—H···O and C—H···Br hydrogen bonds (Table 1 and Fig.2).

Experimental

A mixture of 2-bromo-5-fluorobenzaldehyde (0.01 mol, 2.0301 g), ethyl acetoacetate [0.015 mol, 2 g (2 ml)], phenylthiourea (0.01 mol, 1.5215 g) and concentrated H₂SO₄ (2 drops) in absolute alcohol (10 ml) taken in a beaker (100 ml) was put inside a microwave oven for 4 minutes at 160 Watts (25% MW power). The reaction mixture was then allowed to stand at room temperature and the product formed was filtered, washed with ethanol followed by water and dried. Further purification was done by recrystallization from ethanol (yield = 77%, m.p = 442–445 K). Composition calculated (found): C 53.45 (53.34), H 4.008 (3.92), N 6.236 (6.15), S 7.1269 (7.03)%.