(3E,5E)-1-Benzyl-3,5-bis­(2-fluoro­benzyl­idene)piperidin-4-one

R S Rathore; N S Karthikeyan; K Sathiyanarayanan; P G Aravindan

doi:10.1107/S1600536809039609

. 2009 Oct 7;65(Pt 11):o2667. doi: 10.1107/S1600536809039609

(3E,5E)-1-Benzyl-3,5-bis(2-fluorobenzylidene)piperidin-4-one

R S Rathore ^a,^*, N S Karthikeyan ^b, K Sathiyanarayanan ^b, P G Aravindan ^c

PMCID: PMC2970975 PMID: 21578277

Abstract

The inversion-related molecules of the title compound, C₂₆H₂₁F₂NO, associate into closed dimeric subunits via co-operative C—H⋯π interactions. Two non-classical C—H⋯O and one C—H⋯N intramolecular hydrogen bonds are also found in the crystal structure. The piperidin-4-one ring adopts a sofa conforamtion with the 1-benzyl group in the equatorial position, and the equiplanar fluorophenyl substituents in the 3- and 5-positions stretched out on either side. The 1-benzyl group is disposed towards the substituent in the 6th position of the piperidin-4-one ring. The 3,5-diene units possess E configurations.

Related literature

For the synthesis of and pharmaceutical studies on 3,5-diarylidene-4-piperidone compounds, see: Krapcho & Turk (1979 ▶); Das et al. (2007 ▶). For a related structure, see: Suresh et al. (2007 ▶). For ring conformations, see: Cremer & Pople (1975 ▶), Duax et al., (1976 ▶). For C—H⋯π interactions, see: Nishio et al. (2009 ▶).

Experimental

Crystal data

C₂₆H₂₁F₂NO
M _r = 401.44
Triclinic,
a = 6.7738 (4) Å
b = 12.5652 (7) Å
c = 12.8535 (7) Å
α = 71.051 (1)°
β = 88.057 (2)°
γ = 89.117 (2)°
V = 1034.12 (10) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 K
0.19 × 0.18 × 0.12 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.966, T _max = 0.984
13326 measured reflections
4281 independent reflections
2531 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.048
wR(F ²) = 0.135
S = 1.12
4281 reflections
271 parameters
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT-Plus (Bruker, 2004 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809039609/rk2161sup1.cif

e-65-o2667-sup1.cif^{(27.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809039609/rk2161Isup2.hkl

e-65-o2667-Isup2.hkl^{(205.5KB, 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
C14—H14⋯O1	0.93	2.40	2.772 (2)	104
C21—H21⋯O1	0.93	2.39	2.768 (2)	104
C7—H7B⋯Cg2ⁱ	0.97	2.78	3.7315 (19)	168
C13—H13⋯N1	0.93	2.56	2.873 (3)	100

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Symmetry code: (i) Inline graphic . Cg2 is the centroid of the C8–C13 ring.

Acknowledgments

RSR thanks the Council for Scientific and Industrial Research, New Delhi, for funding under the scientist’s pool scheme, and the Bioinformatics Infrastructure Facility of the University of Hyderabad, Hyderabad for computational resources.

supplementary crystallographic information

Comment

Derivatives of 3,5-diarylidene-4-piperidones (D4P) are pharmaceutically important compounds (Krapcho & Turk, 1979; Das et al., 2007). During our investigations on D4P, a series of compounds were prepared. The molecular and crystal structure of title compound (3E,5E)-1-benzyl-3,5-bis[(2-fluorophenyl)methylidene]piperidin-4-one, (I), is reported here.

The molecular structure of I with atom numbering scheme is shown in Fig. 1. The 3,5-diene moieties possess E-configuration. The 3,5-difluorophenyl substituents of the piperidinone ring are stretched out on either side with following values of torsion angles: C4–C3–C14–C15 = 175.34 (16)°, C3–C14–C15–C16 = 147.49 (19)°, C4–C5–C21–C22 = -172.85 (15)°, and C5–C21–C22–C23 = -151.13 (17)°. The dihedral angle of 3,5-difluorophenyl units is 3.29 (7)°. The dihedral angles between of benzene rings of 3- and 5-substitutens with respect to the corresponding ring of 1-benzyl substituent are 58.65 (7)° and 56.90 (7)°, respectively.

The sp² hybridized C3, C4 and C5 atoms give rise to a sofa-conformation of the six-membered piperidinone ring as also observed in the structures of related compounds, namely, (R)-3,5-Bis[(E)-benzylidene]-1-(1-phenylethyl)piperidin-4-one, 3,5-bis[(E)-4-chlorobenzylidene]-1-[(R)-1-phenylethyl] piperidin-4-one, and 3,5-bis[(E)-2-chlorobenzylidene]-1-[(R)-1-phenylethyl] piperidin-4-one (Suresh et al., 2007). In the sofa conformation, the N1 atom is -0.781 (1)Å shifted out of the base plane (C2/C3/C4/C5/C6). The deviation of the ring from ideal sofa-conformation, ΔC₂ (Duax et al., 1976) is 3.4°. The Cremer and Pople (Cremer & Pople, 1975) puckering parameters, corresponding to the ring conformation are as follows: q2 = 0.5432 (16)Å, q3 = 0.2577 (17)Å, φ = 3.14 (18)°, θ = 64.62 (16)°, and total puckering amplitude Q = 0.6012 (16)Å. The benzyl substituent is in equatorial position of piperidinone ring and its conformation is described by the following torsion angles: C2–N1–C7–C8 = -162.82 (14)° and N1–C7–C8–C9 = -153.28 (15)°. The N1-benzyl group is disposed towards C6 substituent of the piperidin-4-one ring, a feature that varies among related structures.

The observed inter- and intra-molecular interactions are listed in Table 1. The adjacent H14 and H21 atoms participate in intra-molecular C14–H14···O1···H21–C21 interaction scheme. The crystal packing is characterized by C–H···π hydrogen-bonded dimers. The methylene and aromatic groups of the N1-benzyl substituent participate in the interaction forming C7–H7B···Cg2ⁱ with symmetry code: (i) -x+1, -y+2, -z+2. The Cg2 is the centroid of (C8-C13) ring. The observed geometry of C–H···π interaction in I is in the range, reported by the Nishio and coworkers (Nishio et al., 2009). Crystal packing is shown in Fig. 2.

Experimental

A mixture of 1-benzyl-4-piperidone (0.01 mol) and 2-fluorobenzaldehyde (0.02 mol) was added to a warm solution of ammonium acetate (0.01 mol) in absolute ethanol (15 ml). The mixture was gradually warmed on a water bath until the yellow color changed to orange. The mixture was kept aside overnight at room temperature. Reactions were monitored with TLC for completeness. The solid obtained was separated and the crude compound were purified using silica gel column chromatography with hexane and ethyl acetate as elutant. Final yields: 96.19%; m.p. 415 (2)K. Suitable single crystals for data collection were grown from ethanol, tetrahydrofurane and benzene in (1:1:1) ratio.