Crystal structure of ethyl 6-methyl-2-oxo-4-(3,4,5-tri­meth­oxy­phen­yl)-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

J J Novina; G Vasuki; M Suresh; M Syed Ali Padusha

doi:10.1107/S2056989015003576

. 2015 Feb 25;71(Pt 3):o206–o207. doi: 10.1107/S2056989015003576

Crystal structure of ethyl 6-methyl-2-oxo-4-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydropyrimidine-5-carboxylate

J J Novina ^a, G Vasuki ^b,^*, M Suresh ^c, M Syed Ali Padusha ^c

PMCID: PMC4350754 PMID: 25844251

Abstract

In the title compound, C₁₇H₂₂N₂O₆, the dihydropyrimidine ring adopts a flattened boat conformation. The dihedral angle between the benzene ring and the mean plane of the dihydropyrimidine ring is 75.25 (6)°. In the crystal, molecules are linked via pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R ₂ ²(8) ring motif which are linked through N—H⋯O and weak C—H⋯O hydrogen bonds. These, together with π–π ring interactions [centroid–centroid distance = 3.7965 (10) Å], give an overall three-dimensional structure.

Keywords: crystal structure, pyrimidine, hydrogen bonds, centrosymmetric dimer

Related literature

For general background and the biological activity of dihydropyrimidinones, see: Jawale et al. (2011 ▸); Beşoluk et al. (2010 ▸); Karade et al. (2007 ▸). graphic file with name e-71-0o206-scheme1.jpg

Experimental

Crystal data

C₁₇H₂₂N₂O₆
M _r = 350.37
Triclinic,
a = 10.1447 (3) Å
b = 10.1919 (2) Å
c = 10.8724 (2) Å
α = 117.882 (1)°
β = 101.371 (1)°
γ = 105.498 (1)°
V = 886.40 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.20 × 0.15 × 0.10 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▸) T _min = 0.970, T _max = 0.995
13060 measured reflections
3659 independent reflections
3009 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.154
S = 1.06
3659 reflections
228 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.60 e Å⁻³
Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▸); cell refinement: APEX2 and SAINT (Bruker, 2008 ▸); data reduction: SAINT and XPREP (Bruker, 2008 ▸); program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▸); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▸); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▸) and Mercury (Macrae et al., 2008 ▸); software used to prepare material for publication: PLATON (Spek, 2009 ▸).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989015003576/zs2327sup1.cif

e-71-0o206-sup1.cif^{(26.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989015003576/zs2327Isup2.hkl

e-71-0o206-Isup2.hkl^{(179.4KB, hkl)}

Click here for additional data file.^{(7.2KB, cml)}

Supporting information file. DOI: 10.1107/S2056989015003576/zs2327Isup3.cml

Click here for additional data file.^{(1.3MB, tif)}

. DOI: 10.1107/S2056989015003576/zs2327fig1.tif

The molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level.

Click here for additional data file.^{(1.2MB, tif)}

a . DOI: 10.1107/S2056989015003576/zs2327fig2.tif

Cystal packing of the title compound viewed along the a axis. Hydrogen bonds are shown as dashed lines (Table 1). For clarity only the H atoms participating in these interactions are shown.

Click here for additional data file.^{(1.2MB, tif)}

. DOI: 10.1107/S2056989015003576/zs2327fig3.tif

A view showing the π–π interactions. The H atoms are omitted for the sake of clarity.

CCDC reference: 1050728

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N1H1NO6ⁱ	0.86	2.01	2.867(2)	171
N2H2NO4ⁱⁱ	0.86	2.39	3.1331(19)	145
C8H8AO1ⁱⁱⁱ	0.96	2.46	3.325(3)	149
C9H9AO1^iv	0.96	2.56	3.491(3)	163

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

Acknowledgments

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection.

supplementary crystallographic information

S1. Comment

Dihydropyrimidinones (DHPMs) occupy a special place in the areas of natural and synthetic organic chemistry, because of their therapeutic and pharmacological properties. The dihydropyrimidinone scaffold has emerged as an integral backbone for several drugs used as calcium channel blockers as well as anti-hypertensive and anti-cancer agents. DHPMs also exhibit anti-diabetic activity (Jawale et al., 2011). Furthermore, the 2-oxodihydropyrimidine-5-carboxylate core unit is also found in many marine natural products, including the batzelladine alkaloids, which were found to be potent HIV gp-120-CD4 inhibitors (Karade et al., 2007; Beşoluk et al., 2010). Because of this background and in order to obtain detailed information on its molecular conformation, the X-ray structure of the title compound, C₁₇H₂₂N₂O₂ has been determined and is presented herein.

In the racemic title compound (Fig. 1) the dihydropyrimidone ring adopts a flattened boat conformation with the atom C13 and N2 deviating by -0.1218 (11) and 0.1432 (12) Å, respectively from the least squares plane defined by the remaining atoms N1/C11/C12/C14 in the ring. The puckering parameters are q2 = 0.207 Å, q3 = -0.074 Å, Q = 0.220 Å, Θ = 109.7° and Φ = 35.0°. The C1—C6 benzene ring is twisted with respect to the dihydropyrimidinone ring, with an inter-ring dihedral angle of 75.25 (9)°. The ethyl acetate group attached to the pyrimidine ring shows an extended conformation [torsion angle C12—C15—O2—C16 = -177.55 (20)°]. The methoxy two substituent groups at C3 and C5 are almost coplanar with the benzene ring [torsion angles C2—C3—O3—C7 = 7.7 (3)° and C6—C5—O5—C9 = -5.1 (3)°] whereas the central group at C4 deviates significantly from the benzene plane [C3—C4—O4—C8 = 102.7 (2)°].

In the crystal, molecules are linked via a pair of N—H···O hydrogen bonds (Table 1) forming a centrosymmetric cyclic dimer with an R₂²(8) ring motif. The inter-dimer N2—H···O3ⁱⁱ and N2—H···O4ⁱⁱ interactions constitute a bifurcated association generating an asymmetric R²₁(5) ring motif. The one-dimensional chain structures extend across [101] (Fig. 2) while the crystal structure is further stabilized by weak C—H···O hydrogen bonds and by π–π stacking interactions between inversion-related benzene rings [ring centroid–centroid distance = 3.7965 (10)Å] (Fig. 3), giving an overall three-dimensional structure.

S2. Experimental

A mixture of ethyl acetoacetate (0.13 ml, 1 mmol), 3,4,5-trimethoxybenzaldehyde (0.196 g, 1 mmol), and urea (0.18 g, 3 mmol) in ethanol (5 ml) was heated under reflux in the presence of cerium chloride heptahydrate (25%) for 1 h (monitored by TLC). After the completion of the reaction, the reaction mixture was cooled to room temperature and poured onto crushed ice and stirred for 5–10 min. The solid was separated and filtered under suction, washed with ice-cold water (50 ml) and then recrystallized from hot ethanol to afford the pure product [m.p. 445 K; yield 96%].