3-Isopropyl-2,6-bis­(4-meth­oxy­phen­yl)­piperidin-4-one

K Ravichandran; S Sethuvasan; K Thirunavukarasu; S Ponnuswamy; M N Ponnuswamy

doi:10.1107/S1600536812030966

. 2012 Jul 14;68(Pt 8):o2453. doi: 10.1107/S1600536812030966

3-Isopropyl-2,6-bis(4-methoxyphenyl)piperidin-4-one

K Ravichandran ^a, S Sethuvasan ^b, K Thirunavukarasu ^b, S Ponnuswamy ^b,^*, M N Ponnuswamy ^a

PMCID: PMC3414364 PMID: 22904897

Abstract

In the title compound, C₂₂H₂₇NO₃, the piperidine ring adopts a slightly distorted chair conformation. The dihedral angle between the two aromatic rings is 60.4 (1)°. In the crystal, the amino group forms a rather long N—H⋯O contact to a methoxy O atom. There are also C—H⋯O interactions present.

Related literature

For the biological activity of piperidine derivatives, see: Bochringer & Soehne (1961 ▶); El-Subbagh et al. (2000 ▶); Ganellin & Spickett (1965 ▶); Hagenbach & Gysin (1952 ▶); Jerom & Spencer (1988 ▶); Katritzky & Fan (1990 ▶); Perumal et al. (2001 ▶); Ravindran et al. (1991 ▶); Severs et al. (1965 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For asymmetry parameters, see: Nardelli (1983 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₂₂H₂₇NO₃
M _r = 353.45
Orthorhombic,
a = 7.5547 (3) Å
b = 11.8792 (6) Å
c = 22.1103 (10) Å
V = 1984.26 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.22 × 0.20 × 0.18 mm

Data collection

Bruker SMART APEX CCD detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.983, T _max = 0.986
10956 measured reflections
2801 independent reflections
1835 reflections with I > 2σ(I)
R _int = 0.038

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.121
S = 1.03
2801 reflections
241 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); 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 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812030966/bt5928sup1.cif

e-68-o2453-sup1.cif^{(27.7KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812030966/bt5928Isup2.hkl

e-68-o2453-Isup2.hkl^{(134.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812030966/bt5928Isup3.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
N1—H1⋯O1ⁱ	0.90 (2)	2.66 (2)	3.538 (2)	167.4 (17)
C16—H16A⋯O1ⁱⁱ	0.96	2.57	3.474 (4)	156

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

Acknowledgments

KR thanks the TBI Consultancy, University of Madras, India, for the data collection and the management of Kandaswami Kandar’s College, Velur, Namakkal, Tamilnadu, India, for the encouragement. SP thanks UGC, New Delhi, for financial assistance in the form of a major research project.

supplementary crystallographic information

Comment

In the family of heterocyclic compounds, piperidin-4-ones possess varied biological properties such as antiviral, antitumour (El-Subbagh et al., 2000), analgesic (Jerom & Spencer, 1988), local anaesthetic (Perumal et al., 2001; Hagenbach & Gysin, 1952), anti-inflammatory and anticancer activities (Katritzky & Fan, 1990). Several 2,6-disubstituted piperidines are found to be useful as tranquillisers (Bochringer & Soehne, 1961) and possess hypotensive activity (Severs et al., 1965), a combination of stimulant and depressant effects on the central nervous system (Ganellin & Spickett, 1965). Also the substitution of methoxy phenyl groups at 2,6-positions is found to be active against CNS subpanels. In addition, the bulkiness of the subtituent in different positons of the piperidine ring leads to the decrease in carcinogenecity (Ravindran et al., 1991). In view of the importance, the crystallographic study of the title compound has been carried out to establish the molecular structure and conformation.

The ORTEP plot of the molecule is shown in Fig. 1. The piperidine ring adopts distorted chair conformation. The puckering (Cremer & Pople, 1975) and the asymmetry parameters (Nardelli, 1983) are: q₂=0.121 (3) Å, q₃ = 0.569 (3) Å, φ₂ = 7.6 (1)° and Δ_s(N1 & C4) = 1.3 (2)°. The sum of the bond angles around the atom N1 [333.5°] is in accordance with sp³ hybridization.

The best plane of the piperidine ring is oriented with respect to the phenyl rings (C9—C14) & (C18—C23) at angles of 82.8 (1)° & 86.2 (1)°, respectively. The two phenyl rings are set apart with an angle of 60.4 (1)°. The methoxy groups substituted at the phenyl rings are coplanar, which can be seen from the torsion angles of [C13—C12—O1—C7=] 4.4 (4)° for (C9—C14) ring and [C20—C21—O3—C8 =] 1.6 (5)° for (C18—C23) ring.

The packing of the molecules is stabilized by a rather long N-H···O contact and by C—H···O interactions in addition to van der Waals forces.

Experimental

Ammonium acetate (100 mmol), anisaldehyde (200 mmol) and isobutylmethylketone (100 mmol) in ethanol (30 ml) were heated on a hot plate at 50–55° C and after the completion of reaction, water was added and extracted with ether, dried and recrystallized from ethanol.