Ethyl 6-(4-fluoro­phen­yl)-4-hy­droxy-2-oxo-4-trifluoro­meth­yl-1,3-diazinane-5-carboxyl­ate monohydrate

Gong-Chun Li; Chang-Zeng Wu; Li-Li Guo; Feng-Ling Yang

doi:10.1107/S1600536811021866

. 2011 Jun 18;67(Pt 7):o1704–o1705. doi: 10.1107/S1600536811021866

Ethyl 6-(4-fluorophenyl)-4-hydroxy-2-oxo-4-trifluoromethyl-1,3-diazinane-5-carboxylate monohydrate

Gong-Chun Li ^a, Chang-Zeng Wu ^a, Li-Li Guo ^b, Feng-Ling Yang ^a,^*

PMCID: PMC3151995 PMID: 21837100

Abstract

The asymmetric unit of the title compound, C₁₄H₁₄F₄N₂O₄·H₂O, contains two crystallographically independent organic molecules and two water molecules. The two 1,3-diazinane rings adopt a half-chair conformation and the dihedral angles between their mean planes and those of the benzene rings are 75.65 (4)° and 49.41 (3)° in the two molecules. The crystal structure is stabilized by intermolecular O—H⋯O and N—H⋯O hydrogen bonds.

Related literature

For the bioactivity of dihydropyrimidines, see: Brier et al. (2004 ▶); Cochran et al. (2005 ▶); Moran et al. (2007 ▶); Zorkun et al. (2006 ▶). For the bioactivity of organofluorine compounds, see: Hermann et al. (2003 ▶); Ulrich (2004 ▶). For a related structure, see: Song et al. (2010 ▶).

Experimental

Crystal data

C₁₄H₁₄F₄N₂O₄·H₂O
M _r = 368.29
Triclinic,
a = 10.0196 (9) Å
b = 12.1718 (12) Å
c = 14.3037 (14) Å
α = 98.463 (7)°
β = 103.642 (8)°
γ = 104.400 (9)°
V = 1602.2 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 113 K
0.20 × 0.18 × 0.14 mm

Data collection

Rigaku Saturn CCD area detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku, 2009 ▶) T _min = 0.972, T _max = 0.980
20692 measured reflections
7612 independent reflections
4575 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.072
S = 0.87
7612 reflections
493 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.35 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: CrystalClear (Rigaku, 2009 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811021866/jh2293sup1.cif

e-67-o1704-sup1.cif^{(29.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811021866/jh2293Isup2.hkl

e-67-o1704-Isup2.hkl^{(372.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811021866/jh2293Isup3.cml

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
O2—H2⋯O9ⁱ	0.889 (15)	1.860 (16)	2.7482 (14)	176.2 (15)
O9—H9A⋯O3ⁱⁱ	0.91 (2)	1.90 (2)	2.8026 (15)	169.8 (18)
O6—H6⋯O10ⁱⁱⁱ	0.893 (16)	1.788 (16)	2.6770 (14)	173.5 (15)
N3—H3A⋯O10ⁱⁱⁱ	0.823 (14)	2.583 (15)	3.0737 (16)	119.6 (12)
N4—H4A⋯O5ⁱⁱⁱ	0.904 (14)	1.900 (15)	2.8010 (14)	174.8 (13)
N1—H1A⋯O1^iv	0.828 (14)	2.109 (14)	2.9235 (15)	167.9 (13)
N2—H2A⋯O5^v	0.906 (14)	1.958 (15)	2.8395 (14)	163.8 (13)
O9—H9B⋯O1^vi	0.80 (2)	2.00 (2)	2.7443 (15)	155 (2)
O10—H10A⋯O9^vii	0.861 (17)	1.925 (17)	2.7833 (15)	175.4 (16)
O10—H10B⋯O7^viii	0.82 (2)	2.07 (2)	2.8685 (14)	166 (2)

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

Acknowledgments

This work was supported by the Natural Science Foundation of Henan Province, China (grant No. 082300420110) and the Natural Science Foundation of Henan Province Education Department, China (grant No. 2007150036).

supplementary crystallographic information

Comment

Dihydropyrimidine (DHPM) derivatives can be used as potential calcium channel blockers (Zorkun et al., 2006), inhibitors of mitotic kinesin Eg5 for treating cancer (Cochran et al., 2005; Brier et al., 2004) and as TRPA1 modulators for treating pain (Moran et al., 2007). In addition, compounds that contain fluorine have special bioactivity, e.g. flumioxazin is a widely used herbicide (Hermann et al., 2003; Ulrich, 2004). This led us to focus our attention on the synthesis and bioactivity of these important fused perfluoroalkylated heterocyclic compounds. During the synthesis of DHPM derivatives, the title compound, an intermediate C₁₄H₁₄F₄N₂O₄.H₂O(I) was isolated and the structure confirmed by X-ray diffraction.

The asymmetric unit of the title compound contains two crystallographically independent organic molecules and two water molecules. The two 1,3-diazinane rings adopt half-chair conformation, the mean planes formed by the ring atoms excluding the C atom bonded to the ethoxy carbonyl group have r.m.s. deviations of 0.0202Å and 0.0397 Å, the dihedral angles between the mean planes and benzenes ring are 75.65 (4)° and 49.41 (3)° respectively. The crystal structure is stabilized by intermolecular hydrogen bonds (O—H···O and N—H···O). For a crystal structure related to the title compound, see: Song et al., 2010.

Experimental

The title compound was synthesized refluxing for 3 h a stirred solution of 4-fluorobenzaldehyde (2.50 g, 20 mmol), ethyl ethyl 4,4,4-trifluoroacetoacetate (4.42 g, 24 mmol) and urea (1.80 g, 30 mmol) in 20 ml of anhydrous ethanol. The reaction was catalyzed by sulfamic acid (0.6 g). The solvent was evaporated in vacuo and the residue was washed with water. The title compound was recrystallized from 50% aqueous ethanol and single crystals of the title compound were obtained by slow evaporation of mother liquor.