Ethyl 4-[3,5-bis­(trifluoro­meth­yl)phen­yl]-6-methyl-2-oxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

Hoong-Kun Fun; Ching Kheng Quah; M Babu; B Kalluraya

doi:10.1107/S1600536809019035

. 2009 May 29;65(Pt 6):o1404–o1405. doi: 10.1107/S1600536809019035

Ethyl 4-[3,5-bis(trifluoromethyl)phenyl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Hoong-Kun Fun ^a,^*,^‡, Ching Kheng Quah ^a,^§, M Babu ^b, B Kalluraya ^b

PMCID: PMC2969686 PMID: 21583249

Abstract

In the title compound, C₁₆H₁₄F₆N₂O₃, the dihydropyrimidinone ring adopts an envelope conformation. In the crystal, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds into a ribbon-like structure along the b axis. In the ribbon, a pair of bifurcated acceptor N—H⋯O and C—H⋯O bonds generate an R ₂ ¹(6) ring motif. Adjacent ribbons are linked via C—H⋯F hydrogen bonds.

Related literature

For general background and the pharmaceutical applications of pyrimidinones, see: Kalluraya & Rai (2003 ▶); Atwal (1990 ▶); Steele et al. (1998 ▶); Manjula et al. (2004 ▶); Matsuda & Hirao (1965 ▶). For a related structure, see: Fun et al. (2009 ▶). For ring conformations, see: Cremer & Pople (1975 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶). For bond-length data, see: Allen et al. (1987 ▶). For the stability of the temperature controller used for the data collection, see: Cosier & Glazer (1986 ▶).

Experimental

Crystal data

C₁₆H₁₄F₆N₂O₃
M _r = 396.29
Monoclinic,
a = 12.6876 (2) Å
b = 7.3073 (1) Å
c = 19.9547 (3) Å
β = 114.443 (1)°
V = 1684.23 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 110 K
0.45 × 0.25 × 0.22 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ▶) T _min = 0.908, T _max = 0.967
22326 measured reflections
7151 independent reflections
5660 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.134
S = 1.04
7151 reflections
254 parameters
36 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.45 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); data reduction: SAINT; 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, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809019035/ci2801sup1.cif

e-65-o1404-sup1.cif^{(20.8KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809019035/ci2801Isup2.hkl

e-65-o1404-Isup2.hkl^{(349.9KB, 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⋯O1ⁱ	0.86 (2)	2.05 (2)	2.8641 (13)	157 (1)
N2—H1N2⋯O3ⁱⁱ	0.86 (2)	2.13 (2)	2.9796 (12)	166 (1)
C5—H5⋯O1ⁱⁱⁱ	0.95	2.46	3.3797 (14)	162
C14—H14B⋯O3ⁱⁱ	0.98	2.46	3.3571 (13)	153
C12—H12B⋯F3^iv	0.99	2.47	3.2308 (15)	133

Open in a new tab

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

Acknowledgments

HKF and CKQ thank Universiti Sains Malaysia (USM) for the Research University Golden Goose Grant (No. 1001/PFIZIK/811012). CKQ also thanks USM for a Research Fellowship.

supplementary crystallographic information

Comment

3,4-Dihydropyrimidinones are compounds that have been drawn wide-spread attention due to their pharmaceutical applications. A variety of dihydropyrimidinone derivatives have been screened for antihypertension (Atwal, 1990) and antibacterial (Matsuda & Hirao, 1965) activities. Michael addition followed by aldol condensation known as the Robinson's annulation is synthetically a very useful reaction for the construction of six-membered cyclic compounds (Kalluraya & Rai, 2003). The common synthetic routes to these compounds generally involve multi-step transformations that are essentially based on the Biginelli condensation methodology (Steele et al., 1998). These pyrimidinones are also associated with activities like calcium channel blocking (Manjula et al., 2004). We report here the crystal structure of the title compound which was synthesized by means of Robinson's annulation employing microwave technique.

The bond lengths (Allen et al., 1987) and angles in the molecule (Fig. 1) are within normal ranges, and are comparable to those observed in a closely related structure (Fun et al., 2009). The dihydropyrimidinone ring adopts an envelope conformation with atom C7 as the flap. The puckering parameters (Cremer & Pople, 1975) are Q = 0.288 (1) Å; Θ = 72.0 (2)° and φ = 52.3 (2)°. The dihedral angle formed by benzene ring (C1—C6) and the N1/C8/N2/C9-/C10 plane is 89.33 (3)°.

In the solid state, the molecules are linked into a ribbon-like structure (Fig. 2) along the [010] by N–H···O and C–H···O hydrogen bonds (Table 1). In the ribbon, C14–H14B···O3 and N2–H1N2···O3 interactions form a pair of bifurcated acceptor bonds, generating an R₂¹(6) ring motif (Bernstein et al., 1995). The adjacent ribbons are linked via C—H···F hydrogen bonds (Fig. 3).

Experimental

A mixture of 3,5-bis(trifluoromethyl)benzaldehyde (0.01 mol), ethyl acetoacetate (0.015 mol), thiourea (0.01 mol) and conc. H₂SO₄ (2 drops) in absolute alcohol (10 ml) taken in a beaker (100 ml) was zapped inside a MW oven for a duration of 3 minutes (at 160 Watt i.e, 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. Single crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution.