Methyl 4-(4-fluoro­anilino)-1,2,6-tris­(4-fluoro­phen­yl)-1,2,5,6-tetra­hydro­pyri­dine-3-carboxyl­ate

Sumati Anthal; Goutam Brahmachari; Suvankar Das; Rajni Kant; Vivek K Gupta

doi:10.1107/S160053681300370X

. 2013 Feb 9;69(Pt 3):o373–o374. doi: 10.1107/S160053681300370X

Methyl 4-(4-fluoroanilino)-1,2,6-tris(4-fluorophenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate

Sumati Anthal ^a, Goutam Brahmachari ^b, Suvankar Das ^b, Rajni Kant ^a, Vivek K Gupta ^a,^*

PMCID: PMC3588473 PMID: 23476561

Abstract

In the title molecule, C₃₁H₂₄F₄N₂O₂, the tetrahydropyridine ring adopts a distorted boat conformation. An intramolecular N—H⋯O hydrogen bond is formed by the amino group and ccarboxyl C=O atom. The crystal structure features weak C—H⋯F and C—H⋯O interactions.

Related literature

For biological activity of functionalized piperidine derivatives, see: Zhou et al. (2007 ▶); Misra et al. (2009 ▶); Bin et al. (2001 ▶); Agrawal & Somani (2009 ▶); Jaen et al. (1988 ▶). For general background to functionalized piperidines, see: Kamei et al. (2005 ▶). For related structures, see: Sambyal et al. (2011 ▶); Brahmachari & Das (2012 ▶); Khan et al. (2010 ▶); Anthal et al. (2013 ▶). For asymmetry parameters, see: Duax et al. (1975 ▶).

Experimental

Crystal data

C₃₁H₂₄F₄N₂O₂
M _r = 532.52
Triclinic,
a = 9.7990 (2) Å
b = 10.7316 (4) Å
c = 13.7395 (4) Å
α = 110.797 (3)°
β = 100.338 (2)°
γ = 96.323 (2)°
V = 1304.81 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 293 K
0.30 × 0.20 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire3 diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2010 ▶) T _min = 0.899, T _max = 1.000
42990 measured reflections
5413 independent reflections
3730 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.046
wR(F ²) = 0.118
S = 1.05
5413 reflections
353 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CrysAlis PRO (Oxford Diffraction, 2010 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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, 2012 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(33.7KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681300370X/gk2551sup1.cif

e-69-0o373-sup1.cif^{(33.7KB, cif)}

Click here for additional data file.^{(259.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681300370X/gk2551Isup2.hkl

e-69-0o373-Isup2.hkl^{(259.7KB, hkl)}

Click here for additional data file.^{(9.7KB, cml)}

Supplementary material file. DOI: 10.1107/S160053681300370X/gk2551Isup3.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
N9—H9⋯O1	0.86	2.05	2.695 (2)	131
C20—H20⋯F2ⁱ	0.93	2.54	3.384 (2)	152
C32—H32⋯O1ⁱⁱ	0.93	2.47	3.311 (3)	151

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

Acknowledgments

RK acknowledges the Department of Science & Technology for a single-crystal X-ray diffractometer sanctioned as a National Facility under project No. SR/S2/CMP-47/2003. GB is thankful to the CSIR, New Delhi, for financial support [grant No. 02 (110)/12/EMR-II]. VKG thanks the University of Jammu for financial support.

supplementary crystallographic information

Comment

Functionalized piperidines, very particularly 1,4-disubstituted piperidine scaffolds, are found to be useful in designing a variety of medicinal entities exhibiting a broad spectrum of pharmacological activities that include antibacterial (Zhou et al., 2007), antimalarial (Misra et al., 2009), anti-hypertensive, anticonvulsant, anti-inflammatory (Bin et al., 2001), and enzyme inhibitory activity (Agrawal & Somani, 2009; Jaen et al., 1988). Moreover, a large number of compounds bearing piperidine scaffold have already entered into preclinical and clinical trials over the last few years (Kamei et al., 2005). Hence, investigation of the structural features of biologically relevant piperidine derivatives is demanding. In continuation of our structural studies of densely functionalized piperidines (Sambyal et al., 2011; Brahmachari & Das, 2012) we present here the crystal structure of the title compound. The molecular structure of the title compound is illustrated in Fig.1. The bond lengths and angles of the title compound are normal and correspond to those observed in related structures (Khan et al., 2010; Anthal et al., 2013). In the title molecule, tetrahydropyridine ring adopts a distorted boat conformation with asymmetry parameters [ΔC_s(C2)=10.10] and [ΔC_s(C3-C4)=15.48] (Duax et al., 1975). In the crystal, an intramolecular hydrogen bond N9-H9···O1 is found. This intramolecular interaction leads to the formation of a pseudo-six membered ring comprising atoms O1, C7, C3, C4, N9 and H9. The molecular structure is stablized by N—H···O intramolecular interaction and crystal packing is stablized by C—H···F and C—H···O intermolecular interactions (Table 1). Molecules are linked via C—H···F and C—H···O hydrogen bonds to form chains along [010](Fig. 2).

Experimental

An oven-dried screw cap reaction tube was charged with a magnetic stir bar, 4-fluoroaniline (2 mmol), methyl acetoacetate (1 mmol) and Bi(NO₃)₃.5H₂O (10 mol%) in 4 ml ethanol; the mixture was stirred at room temperature for 20 min, and then 4-fluorobenzaldehyde (2 mmol) was added to the reaction mixture and stirring was continued up to 12 h to complete the reaction (monitored by TLC). On completion of the reaction, a thick white precipitate was obtained. The solid residue was filtered off and washed with cold ethanol–water. The solid mass was dissolved in hot ethyl acetate–ethanol mixture and filtered off when bismuth salt separated out; the filtrate on standing afforded white crystals of the title compound, characterized by elemental analyses and spectral studies including FT—IR, ¹H-NMR, and ¹³C-NMR. For X-ray study, single crystals were prepared by further recrystallization by slow evaporation from ethanol-ethyl acetate-water solution. Methyl 1,2,6-tris(4-fluorophenyl)-4-((4-fluorophenyl)amino)-1,2,5,6- tetrahydropyridine-3-carboxylate : white crystals; mp 452–454 K. Anal. Calcd for C₃₁H₂₄F₄N₂O₂: C 69.92, H 4.54, N 5.26; found: C 69.95, H 4.52, N 5.28.