Ethyl 4-(4-hydroxy­phen­yl)-6-methyl-2-oxo-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate monohydrate

Ushati Das; Shardul B Chheda; Suhas R Pednekar; Narendra P Karambelkar; T N Guru Row

doi:10.1107/S1600536808039548

. 2008 Nov 29;64(Pt 12):o2488–o2489. doi: 10.1107/S1600536808039548

Ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate monohydrate

Ushati Das ^a, Shardul B Chheda ^b, Suhas R Pednekar ^b, Narendra P Karambelkar ^c, T N Guru Row ^a,^*

PMCID: PMC2960136 PMID: 21581452

Abstract

There are three formula units in the asymmetric unit of the title compound, C₁₄H₁₆N₂O₄·H₂O. Molecules are linked by N—H⋯O hydrogen bonds into dimers with the common R ₂ ²(8) graph-set motif. Between dimers, single N—H⋯O hydrogen bonds are formed between the other N—H group of each pyrimidine ring and the hydroxyl groups. The water molecules accept O—H⋯O hydrogen bonds from the hydroxyl groups and donate hydrogen bonds to the ester groups.

Related literature

For background literature concerning pyrimidine compounds and for synthesis details, see: Kappe (2000 ▶); Biginelli (1891 ▶); List (2006 ▶); Mabry & Ganem (2006 ▶).

Experimental

Crystal data

C₁₄H₁₆N₂O₄·H₂O
M _r = 294.30
Monoclinic,
a = 11.1583 (15) Å
b = 17.773 (2) Å
c = 21.686 (3) Å
β = 91.448 (2)°
V = 4299.3 (10) Å³
Z = 12
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 292 (2) K
0.50 × 0.20 × 0.10 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.906, T _max = 0.990
33204 measured reflections
8419 independent reflections
3947 reflections with I > 2σ(I)
R _int = 0.083

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.138
S = 0.90
8419 reflections
601 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.23 e Å⁻³

Data collection: SMART (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1999 ▶) and CAMERON (Watkin et al., 1993 ▶); software used to prepare material for publication: PLATON (Spek, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808039548/bi2319sup1.cif

e-64-o2488-sup1.cif^{(44.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808039548/bi2319Isup2.hkl

e-64-o2488-Isup2.hkl^{(403.5KB, 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—H11⋯O5	0.86	2.14	3.002 (3)	176
N2—H2⋯O2ⁱ	0.86	2.05	2.882 (3)	162
N3—H3⋯O9	0.86	2.25	3.079 (3)	161
N4—H4⋯O10ⁱⁱ	0.86	1.99	2.854 (3)	177
N5—H511⋯O1ⁱⁱⁱ	0.86	2.47	3.278 (3)	158
N6—H6⋯O6^iv	0.86	2.05	2.862 (3)	157
O1—H1⋯O14	0.82	1.84	2.657 (3)	171
O5—H5⋯O13	0.82	1.82	2.633 (3)	172
O9—H9A⋯O15	0.82	1.81	2.627 (3)	174
O13—H13A⋯O3^v	0.89 (3)	1.91 (3)	2.789 (3)	172 (3)
O13—H13B⋯O2	0.86 (3)	2.02 (3)	2.834 (3)	158 (3)
O14—H14A⋯O10^vi	0.93 (4)	1.88 (4)	2.752 (3)	156 (4)
O14—H14B⋯O11^vii	0.86 (3)	2.02 (3)	2.856 (3)	164 (3)
O15—H15A⋯O6	1.03 (4)	1.78 (4)	2.747 (3)	155 (3)
O15—H15B⋯O7^viii	0.88 (3)	1.93 (3)	2.809 (3)	173 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) ; (vii) ; (viii) .

Acknowledgments

We thank the Department of Science and Technology, India, for use of the CCD facility set up under the IRHPA–DST program at IISc.

supplementary crystallographic information

Comment

Heterocyclic compounds containing the pyrimidine subunit have been found to have strong bioactivity especially as calcium antagonists. In addition, some of these compounds have also been found to exhibit antihypertensive, antiviral, anti-tumor, antibacterial and anti-inflammatory activity. They can also be potentially used in prevention of coronary artery spasm (Kappe, 2000). The title compound has been synthesized using a Biginelli reaction (Biginelli, 1891), a century-old multi-component reaction (MCR) used to design alkaloids with dihydropyrimidine cores (List, 2006; Mabry & Ganem, 2006).

The compound crystallizes in space group P2₁/c with an unusual Z value of 12. A search of the Cambridge Structural Database (CSD) yielded only 275 structures having Z = 12, which is less than 0.5% of the 75,822 P2₁/c structures. In each molecule in the asymmetric unit (Fig. 1), the tetrahydropyrimidine ring adopts a twist boat conformation [C29—N2—C30—C24 = -13.09°, C8—N4—C23—C32 = -14.55°, C38—N6—C33—C37 = 14.90°, C29—N1—C9—C24 = -21.8°, C8—N3—C34—C32 = -31.09°, C38—N5—C52—C37 = 28.07°]. The C—N bond lengths in the tetrahydropyrimidine ring (1.327 (3) to 1.473 (3) Å) are in accordance with those in similar structures. The mean plane of the pyrimidine ring is nearly perpendicular to the phenyl ring [C37—C52—N5 = 110.05°, C14—C34—N3 = 110.25°, C18—C9—N1 = 110.38°].

The structure contains extensive intermolecular N—H···O hydrogen bonding (see Table). Atom N2 acts as a hydrogen-bond donor to O2 to form a centrosymmetric dimer centered at (1/2,1/2,1/2) with the common R₂²(8) graph-set motif. Atom N6 acts as a hydrogen-bond donor to O6 and N4 acts as a donor to O10 to form another dimeric R₂²(8) motif. However, such R₂²(8) motifs are not generated via N1, N3 and N5. Instead, these N atoms form single N—H···O hydrogen bonds to hydroxyl groups: N1 to O5, N3 to O9 and N5 to O1.

Experimental

4-Hydroxybenzaldehyde (0.01 mol), ethyl acetoacetate (0.01 mol), urea (0.02 mol) and p-TSA (0.002 mol) were ground for 4-5 min using a mortar and pestle. The initial syrupy reaction mixture solidified within 15 min. The solid was filtered, washed and recrystallized from a water-acetic acid mixture (yield 95%, m.p. 509–511 K).

¹H NMR (DMSO):δ 6.66 (d, 2H), 7.02 (d, 2H), 1.07 (t, 2H), 3.98 (q, 2 H), 2.23 (s, 3 H), 5.08 (s, 1 H), 7.58 (s, 1H), 9.08 (s, 1H), 9.30 (s, 1H).