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Acta Cryst. (2008). E64, o1737    [ doi:10.1107/S1600536808024835 ]

3-Ethyl 5-methyl 2-hydroxy-6-methyl-4-(4-nitrophenyl)-2-trifluoromethyl-1,2,3,4-tetrahydropyridine-3,5-dicarboxylate

C.-X. Yu, P.-L. Qian, J.-J. Ping and C.-S. Yao

Abstract top

In the title compound, C18H19F3N2O7, the tetrahydropyridine ring adopts a half-chair conformation. The nitro group is disordered over two sites with occupancies of 0.780 (15) and 0.220 (15). An intramolecular N-H...F hydrogen bond is observed in the molecular structure. The molecules are linked into a two-dimensional network parallel to (100) by O-H...O, N-H...O and C-H...O hydrogen bonds.

Comment top

1,4-Dihydropyridines are well known compounds as a consequence of their pharmacological profile as the most important calcium channel modulators (Achiwa & Kato, 1999). 4-Aryl-2,6-dimethyl-1,4-dihydropyridine -3,5-dicarboxylate derivatives are widely used for the treatment of cardiovascular diseases such as hypertension, angina pectoris and infarction (Dubur et al., 1989). In addition, compounds that contain fluorine have special bioactivity, for example, flumioxazin is a widely used herbicide (Hermann et al., 2003; Ulrich,2004). This led us to pay much attention to the synthesis and bioactivity of these fluoro-compounds. During the synthesis of trifluoromethylated 1,4-dihydropyridine derivatives, an intermediate, the title compound, was isolated. We report here the crystal structure of the title compound.

In the title molecule (Fig.1), the pyridine ring adopts a half-chair conformation, with atoms C10 and C11 deviating from the N2/C7/C8/C9 plane by 0.261 (4) Å and -0.544 (4)Å, respectively. The dihedral angle between the N2/C7/C8/C9 and C1-C6 planes is 72.30 (9)°. The N atom of the nitro group adopts a planar configuration in the major disorder component, while pyramidal configuration in the minor disorder component. An intramolecular N2—H2···F2 hydrogen bond is observed in the molecular structure.

The crystal packing is stabilized by O—H···O, N—H···O and C—H···O intermolecular hydrogen bonds (Table 1) which link the molecules into a two-dimensional network parallel to the (1 0 0) (Fig. 2).

Related literature top

For related literature, see: Achiwa & Kato (1999); Dubur et al. (1989); Hermann et al. (2003); Ulrich (2004).

Experimental top

The title compound was synthesized by the reaction of 4-nitrobenzaldehyde (1 mmol), methyl 3-amino-but-2-enoate (1 mmol) and ethyl 4,4,4-trifluoro-3-oxobutanoate (1 mmol) catalyzed by triethylbenzylaminium chloride (0.02 g) in water (10 ml) at 363 K. After cooling, the reaction mixture was washed with water and recrystallized from ethanol, to obtain single crystals suitable for X-ray diffraction.

Refinement top

All H atoms were placed in calculated positions (C-H = 0.93–0.98 Å, O-H = 0.82 Å and N-H = 0.86 Å) and included in the final cycles of refinement using a riding model, with Uiso(H) = 1.2Ueq(parent atom). Atom O1 is disordered over two positions with site-occupancy factors of 0.220 (15) and 0.780 (15), respectively. The Uij components of disordered atoms were restrained to an approximate isotropic behaviour. The N1—O1 and N1—O1' bond lengths were restrained to 1.22 (2) Å.

Computing details top

Data collection: CrystalClear (Rigaku/MSC, 2002); cell refinement: CrystalClear (Rigaku/MSC, 2002); data reduction: CrystalClear (Rigaku/MSC, 2002); 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 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. Both disorder components are shown. The dashed line indicates a hydrogen bond.
[Figure 2] Fig. 2. The packing diagram of the title compound. Intermolecular hydrogen bonds are shown as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity.
3-Ethyl 5-methyl 2-hydroxy-6-methyl-4-(4-nitrophenyl)-2-trifluoromethyl- 1,2,3,4-tetrahydropyridine-3,5-dicarboxylate top
Crystal data top
C18H19F3N2O7F000 = 1792
Mr = 432.35Dx = 1.475 Mg m−3
Monoclinic, C2/cMo Kα radiation
λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 3562 reflections
a = 28.678 (6) Åθ = 2.2–25.0º
b = 9.6678 (19) ŵ = 0.13 mm−1
c = 14.120 (3) ÅT = 293 (2) K
β = 95.72 (3)ºPrism, colourless
V = 3895.1 (13) Å30.16 × 0.16 × 0.04 mm
Z = 8
Data collection top
Rigaku Saturn
diffractometer		3438 independent reflections
Radiation source: rotating anode2572 reflections with I > 2σ(I)
Monochromator: confocalRint = 0.043
Detector resolution: 7.31 pixels mm-1θmax = 25.0º
T = 293(2) Kθmin = 2.2º
ω scansh = −33→34
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2002)		k = −11→11
Tmin = 0.979, Tmax = 0.995l = −16→12
11673 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.150  w = 1/[σ2(Fo2) + (0.0873P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
3438 reflectionsΔρmax = 0.22 e Å−3
284 parametersΔρmin = −0.20 e Å−3
14 restraintsExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C18H19F3N2O7V = 3895.1 (13) Å3
Mr = 432.35Z = 8
Monoclinic, C2/cMo Kα
a = 28.678 (6) ŵ = 0.13 mm−1
b = 9.6678 (19) ÅT = 293 (2) K
c = 14.120 (3) Å0.16 × 0.16 × 0.04 mm
β = 95.72 (3)º
Data collection top
Rigaku Saturn
diffractometer		3438 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku/MSC, 2002)		2572 reflections with I > 2σ(I)
Tmin = 0.979, Tmax = 0.995Rint = 0.043
11673 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.05214 restraints
wR(F2) = 0.150H-atom parameters constrained
S = 1.06Δρmax = 0.22 e Å−3
3438 reflectionsΔρmin = −0.20 e Å−3
284 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
F10.08689 (6)0.58977 (17)0.93658 (13)0.0775 (5)
F20.15032 (7)0.70065 (15)0.97856 (12)0.0800 (6)
F30.12464 (6)0.68534 (15)0.83137 (11)0.0725 (5)
O10.0452 (7)−0.100 (2)0.5112 (8)0.086 (6)0.220 (15)
O1'0.06713 (19)−0.1837 (7)0.5322 (3)0.090 (2)0.780 (15)
O20.01478 (8)−0.1793 (3)0.63009 (19)0.0972 (9)
O30.13847 (6)0.44788 (18)0.67834 (12)0.0545 (5)
O40.06795 (6)0.44145 (19)0.73469 (12)0.0594 (5)
O50.21673 (6)0.00503 (18)1.01751 (13)0.0546 (5)
O60.21490 (6)0.01870 (17)0.85947 (12)0.0512 (5)
O70.19972 (6)0.52220 (18)0.86560 (12)0.0512 (5)
H70.22180.51890.90710.077*
N10.05038 (9)−0.1349 (3)0.6024 (2)0.0738 (8)
N20.16656 (7)0.42268 (18)0.99703 (13)0.0432 (5)
H20.16300.47251.04630.052*
C10.13495 (7)0.1409 (2)0.77500 (16)0.0353 (5)
C20.14347 (8)0.1173 (2)0.68116 (16)0.0424 (6)
H2A0.16830.16210.65650.051*
C30.11549 (9)0.0281 (2)0.62409 (18)0.0485 (6)
H30.12100.01320.56110.058*
C40.07957 (8)−0.0378 (2)0.66212 (18)0.0469 (6)
C50.07026 (9)−0.0190 (3)0.75489 (19)0.0502 (6)
H50.0458−0.06590.77930.060*
C60.09829 (8)0.0715 (2)0.81067 (17)0.0446 (6)
H60.09240.08600.87350.053*
C70.16340 (7)0.2485 (2)0.83367 (15)0.0365 (5)
H7A0.19020.27470.79960.044*
C80.18168 (7)0.2018 (2)0.93315 (15)0.0354 (5)
C90.18004 (7)0.2873 (2)1.00940 (15)0.0368 (5)
C100.15830 (8)0.4834 (2)0.90448 (17)0.0427 (6)
C110.13175 (8)0.3763 (2)0.83985 (16)0.0373 (5)
H110.10440.34730.87110.045*
C120.11414 (9)0.4275 (2)0.74130 (17)0.0418 (6)
C130.04231 (12)0.4735 (4)0.6429 (2)0.0755 (9)
H13A0.06370.50900.59970.091*
H13B0.01890.54390.65090.091*
C140.01957 (13)0.3484 (4)0.6032 (2)0.0918 (11)
H14A0.04300.28300.58840.138*
H14B−0.00010.37120.54620.138*
H14C0.00080.30860.64880.138*
C150.20522 (8)0.0677 (2)0.94376 (17)0.0396 (5)
C160.23732 (10)−0.1148 (3)0.8569 (2)0.0651 (8)
H16A0.2607−0.12310.91010.098*
H16B0.2518−0.12370.79870.098*
H16C0.2143−0.18640.86010.098*
C170.19319 (8)0.2520 (2)1.11186 (15)0.0460 (6)
H17A0.19070.33311.15020.069*
H17B0.22490.21841.11980.069*
H17C0.17250.18181.13130.069*
C180.12955 (10)0.6156 (2)0.91287 (19)0.0543 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0761 (12)0.0770 (11)0.0819 (13)0.0222 (9)0.0199 (10)−0.0030 (9)
F20.1242 (15)0.0509 (9)0.0612 (11)0.0076 (9)−0.0094 (10)−0.0176 (8)
F30.1081 (13)0.0524 (9)0.0544 (10)0.0161 (8)−0.0046 (9)0.0094 (7)
O10.085 (8)0.118 (10)0.055 (7)−0.032 (7)0.008 (5)−0.026 (6)
O1'0.093 (3)0.111 (4)0.069 (2)−0.038 (3)0.023 (2)−0.052 (2)
O20.0728 (14)0.1166 (18)0.1066 (19)−0.0437 (14)0.0303 (14)−0.0568 (16)
O30.0674 (11)0.0622 (11)0.0344 (10)−0.0019 (8)0.0074 (9)0.0101 (8)
O40.0528 (11)0.0799 (12)0.0425 (11)0.0022 (9)−0.0094 (9)0.0098 (9)
O50.0621 (11)0.0555 (10)0.0458 (11)0.0078 (8)0.0028 (9)0.0114 (9)
O60.0595 (11)0.0521 (10)0.0420 (10)0.0109 (8)0.0042 (9)−0.0055 (8)
O70.0536 (10)0.0592 (10)0.0403 (10)−0.0162 (9)0.0018 (8)0.0045 (8)
N10.0681 (16)0.0885 (18)0.0668 (18)−0.0311 (14)0.0167 (14)−0.0349 (15)
N20.0620 (13)0.0418 (10)0.0254 (10)0.0000 (9)0.0027 (9)−0.0041 (8)
C10.0372 (12)0.0379 (11)0.0307 (12)0.0012 (9)0.0025 (10)−0.0011 (9)
C20.0468 (13)0.0470 (13)0.0348 (13)−0.0064 (11)0.0109 (11)−0.0042 (11)
C30.0543 (15)0.0555 (14)0.0368 (14)−0.0044 (12)0.0099 (12)−0.0133 (11)
C40.0476 (14)0.0504 (13)0.0425 (14)−0.0070 (11)0.0032 (12)−0.0148 (11)
C50.0478 (14)0.0553 (14)0.0487 (15)−0.0135 (12)0.0103 (12)−0.0045 (12)
C60.0506 (14)0.0524 (13)0.0318 (13)−0.0075 (11)0.0097 (11)−0.0045 (11)
C70.0392 (12)0.0414 (11)0.0291 (11)−0.0038 (9)0.0047 (10)0.0004 (10)
C80.0356 (11)0.0421 (11)0.0286 (12)−0.0036 (9)0.0028 (9)0.0022 (9)
C90.0360 (11)0.0447 (12)0.0294 (12)−0.0058 (10)0.0008 (9)0.0023 (10)
C100.0536 (14)0.0420 (12)0.0320 (13)−0.0026 (10)0.0022 (11)0.0012 (10)
C110.0420 (12)0.0408 (11)0.0291 (12)−0.0032 (10)0.0030 (10)0.0001 (9)
C120.0521 (14)0.0390 (12)0.0338 (13)−0.0027 (10)0.0016 (12)0.0007 (10)
C130.076 (2)0.095 (2)0.0499 (18)0.0053 (18)−0.0195 (16)0.0128 (17)
C140.091 (2)0.114 (3)0.065 (2)−0.019 (2)−0.0149 (19)−0.008 (2)
C150.0373 (12)0.0449 (12)0.0363 (13)−0.0063 (10)0.0015 (10)−0.0001 (11)
C160.0681 (18)0.0536 (15)0.072 (2)0.0125 (13)0.0009 (16)−0.0161 (14)
C170.0544 (14)0.0520 (13)0.0309 (13)−0.0051 (11)0.0000 (11)0.0020 (11)
C180.0761 (19)0.0455 (14)0.0403 (15)0.0047 (13)0.0008 (14)−0.0029 (12)
Geometric parameters (Å, °) top
F1—C181.324 (3)C5—C61.380 (3)
F2—C181.335 (3)C5—H50.93
F3—C181.329 (3)C6—H60.93
O1—N11.325 (13)C7—C81.518 (3)
O1'—N11.237 (4)C7—C111.541 (3)
O2—N11.208 (3)C7—H7A0.98
O3—C121.200 (3)C8—C91.362 (3)
O4—C121.326 (3)C8—C151.462 (3)
O4—C131.458 (3)C9—C171.498 (3)
O5—C151.221 (3)C10—C181.532 (3)
O6—C151.336 (3)C10—C111.532 (3)
O6—C161.444 (3)C11—C121.515 (3)
O7—C101.408 (3)C11—H110.98
O7—H70.82C13—C141.459 (5)
N1—C41.467 (3)C13—H13A0.97
N2—C91.371 (3)C13—H13B0.97
N2—C101.431 (3)C14—H14A0.96
N2—H20.86C14—H14B0.96
C1—C61.384 (3)C14—H14C0.96
C1—C21.390 (3)C16—H16A0.96
C1—C71.516 (3)C16—H16B0.96
C2—C31.381 (3)C16—H16C0.96
C2—H2A0.93C17—H17A0.96
C3—C41.366 (3)C17—H17B0.96
C3—H30.93C17—H17C0.96
C4—C51.375 (4)
C12—O4—C13119.7 (2)N2—C10—C11107.09 (18)
C15—O6—C16118.2 (2)C18—C10—C11111.8 (2)
C10—O7—H7109.5C12—C11—C10115.27 (18)
O2—N1—O1'122.1 (3)C12—C11—C7110.74 (18)
O1'—N1—C4117.4 (2)C10—C11—C7108.39 (18)
O2—N1—C4119.6 (2)C12—C11—H11107.4
O2—N1—O1112.9 (7)C10—C11—H11107.4
O1—N1—C4113.5 (6)C7—C11—H11107.4
C9—N2—C10121.81 (19)O3—C12—O4125.6 (2)
C9—N2—H2119.1O3—C12—C11124.7 (2)
C10—N2—H2119.1O4—C12—C11109.7 (2)
C6—C1—C2118.6 (2)O4—C13—C14109.4 (3)
C6—C1—C7121.39 (19)O4—C13—H13A109.8
C2—C1—C7119.82 (19)C14—C13—H13A109.8
C3—C2—C1120.8 (2)O4—C13—H13B109.8
C3—C2—H2A119.6C14—C13—H13B109.8
C1—C2—H2A119.6H13A—C13—H13B108.2
C4—C3—C2118.6 (2)C13—C14—H14A109.5
C4—C3—H3120.7C13—C14—H14B109.5
C2—C3—H3120.7H14A—C14—H14B109.5
C3—C4—C5122.6 (2)C13—C14—H14C109.5
C3—C4—N1118.8 (2)H14A—C14—H14C109.5
C5—C4—N1118.6 (2)H14B—C14—H14C109.5
C4—C5—C6118.0 (2)O5—C15—O6121.4 (2)
C4—C5—H5121.0O5—C15—C8127.6 (2)
C6—C5—H5121.0O6—C15—C8111.0 (2)
C5—C6—C1121.3 (2)O6—C16—H16A109.5
C5—C6—H6119.3O6—C16—H16B109.5
C1—C6—H6119.3H16A—C16—H16B109.5
C1—C7—C8114.77 (17)O6—C16—H16C109.5
C1—C7—C11107.06 (17)H16A—C16—H16C109.5
C8—C7—C11109.70 (17)H16B—C16—H16C109.5
C1—C7—H7A108.4C9—C17—H17A109.5
C8—C7—H7A108.4C9—C17—H17B109.5
C11—C7—H7A108.4H17A—C17—H17B109.5
C9—C8—C15120.6 (2)C9—C17—H17C109.5
C9—C8—C7121.00 (19)H17A—C17—H17C109.5
C15—C8—C7118.15 (19)H17B—C17—H17C109.5
C8—C9—N2120.7 (2)F1—C18—F3107.1 (2)
C8—C9—C17126.9 (2)F1—C18—F2107.5 (2)
N2—C9—C17112.41 (19)F3—C18—F2106.9 (2)
O7—C10—N2113.3 (2)F1—C18—C10112.3 (2)
O7—C10—C18106.83 (19)F3—C18—C10111.6 (2)
N2—C10—C18108.25 (19)F2—C18—C10111.2 (2)
O7—C10—C11109.64 (18)
C6—C1—C2—C31.0 (3)O7—C10—C11—C12−64.1 (3)
C7—C1—C2—C3−174.7 (2)N2—C10—C11—C12172.51 (19)
C1—C2—C3—C4−0.7 (4)C18—C10—C11—C1254.1 (3)
C2—C3—C4—C5−0.2 (4)O7—C10—C11—C760.6 (2)
C2—C3—C4—N1−178.7 (2)N2—C10—C11—C7−62.8 (2)
O2—N1—C4—C3−169.9 (3)C18—C10—C11—C7178.84 (19)
O1'—N1—C4—C320.9 (6)C1—C7—C11—C12−56.5 (2)
O1—N1—C4—C3−32.6 (13)C8—C7—C11—C12178.39 (18)
O2—N1—C4—C511.5 (4)C1—C7—C11—C10176.15 (17)
O1'—N1—C4—C5−157.7 (5)C8—C7—C11—C1051.0 (2)
O1—N1—C4—C5148.8 (12)C13—O4—C12—O35.3 (4)
C3—C4—C5—C60.7 (4)C13—O4—C12—C11−172.6 (2)
N1—C4—C5—C6179.3 (2)C10—C11—C12—O374.1 (3)
C4—C5—C6—C1−0.4 (4)C7—C11—C12—O3−49.4 (3)
C2—C1—C6—C5−0.4 (3)C10—C11—C12—O4−108.0 (2)
C7—C1—C6—C5175.2 (2)C7—C11—C12—O4128.5 (2)
C6—C1—C7—C850.4 (3)C12—O4—C13—C14102.9 (3)
C2—C1—C7—C8−134.0 (2)C16—O6—C15—O53.2 (3)
C6—C1—C7—C11−71.6 (3)C16—O6—C15—C8−178.7 (2)
C2—C1—C7—C11104.0 (2)C9—C8—C15—O516.0 (3)
C1—C7—C8—C9−137.4 (2)C7—C8—C15—O5−169.7 (2)
C11—C7—C8—C9−16.9 (3)C9—C8—C15—O6−161.96 (19)
C1—C7—C8—C1548.4 (2)C7—C8—C15—O612.3 (3)
C11—C7—C8—C15168.92 (18)O7—C10—C18—F1171.4 (2)
C15—C8—C9—N2166.91 (19)N2—C10—C18—F1−66.2 (3)
C7—C8—C9—N2−7.1 (3)C11—C10—C18—F151.5 (3)
C15—C8—C9—C17−11.1 (3)O7—C10—C18—F351.2 (3)
C7—C8—C9—C17174.88 (19)N2—C10—C18—F3173.5 (2)
C10—N2—C9—C8−6.4 (3)C11—C10—C18—F3−68.8 (3)
C10—N2—C9—C17171.9 (2)O7—C10—C18—F2−68.1 (3)
C9—N2—C10—O7−79.4 (3)N2—C10—C18—F254.3 (3)
C9—N2—C10—C18162.2 (2)C11—C10—C18—F2172.0 (2)
C9—N2—C10—C1141.6 (3)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O7—H7···O5i0.821.982.783 (3)166
N2—H2···O3ii0.862.203.030 (3)163
N2—H2···F20.862.422.735 (2)102
C5—H5···O2iii0.932.513.432 (4)171
Symmetry codes: (i) −x+1/2, −y+1/2, −z+2; (ii) x, −y+1, z+1/2; (iii) −x, y, −z+3/2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O7—H7···O5i0.821.982.783 (3)166
N2—H2···O3ii0.862.203.030 (3)163
N2—H2···F20.862.422.735 (2)102
C5—H5···O2iii0.932.513.432 (4)171
Symmetry codes: (i) −x+1/2, −y+1/2, −z+2; (ii) x, −y+1, z+1/2; (iii) −x, y, −z+3/2.
Acknowledgements top

The authors thank the Natural Science Foundation of Xuzhou Normal University (grant No. 06XLB07) and the Natural Science Foundation of Xuzhou City (grant No. XJ07065) for financial support.

references
References top

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