3,3-Dimethyl-cis-2,6-di-p-tolyl­piperidin-4-one

P Gayathri; S S Ilango; S Ponnuswamy; A Thiruvalluvar; R J Butcher

doi:10.1107/S160053680903579X

. 2009 Sep 12;65(Pt 10):o2445. doi: 10.1107/S160053680903579X

3,3-Dimethyl-cis-2,6-di-p-tolylpiperidin-4-one

P Gayathri ^a, S S Ilango ^b, S Ponnuswamy ^b, A Thiruvalluvar ^a,^*, R J Butcher ^c

PMCID: PMC2970464 PMID: 21577900

Abstract

In the title molecule, C₂₁H₂₅NO, the piperidine ring adopts a chair conformation. The benzene rings and one of the methyl groups attached to the piperidine ring have equatorial orientations. The dihedral angle between the two benzene rings is 72.53 (9)°. In the crystal, molecules are linked by N—H⋯O hydrogen bonds. Weak C—H⋯π interactions involving the benzene rings are also present in the crystal structure.

Related literature

For related crystal structures, see: Gayathri et al. (2008 ▶); Ilango et al. (2008 ▶). For biological activities of piperidones, see: Aridoss et al. (2008 ▶). For the synthesis, see: Noller and Baliah (1948 ▶). For the stereochemistry and ring conformation of piperidin-4-ones and their derivatives, see: Ponnuswamy et al. (2002 ▶).

Experimental

Crystal data

C₂₁H₂₅NO
M _r = 307.42
Orthorhombic,
a = 12.9576 (3) Å
b = 22.6153 (5) Å
c = 5.9600 (1) Å
V = 1746.52 (6) Å³
Z = 4
Cu Kα radiation
μ = 0.55 mm⁻¹
T = 110 K
0.51 × 0.34 × 0.12 mm

Data collection

Oxford Diffraction Xcalibur diffractometer with a Ruby Gemini detector
Absorption correction: multi-scan (CrysAlis Pro; Oxford Diffraction, 2009 ▶) T _min = 0.665, T _max = 1.000
4198 measured reflections
1914 independent reflections
1859 reflections with I > 2σ(I)
R _int = 0.018

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.106
S = 1.04
1914 reflections
216 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: CrysAlis Pro (Oxford Diffraction, 2009 ▶); 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 (Farrugia, 1997 ▶); software used to prepare material for publication: PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680903579X/sj2644sup1.cif

e-65-o2445-sup1.cif^{(24.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053680903579X/sj2644Isup2.hkl

e-65-o2445-Isup2.hkl^{(92.3KB, 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
N1—H1⋯O4ⁱ	0.85 (3)	2.26 (3)	3.057 (2)	157 (2)
C16—H16B⋯Cg1ⁱⁱ	0.98	2.80	3.704 (2)	154
C32—H32A⋯Cg2ⁱⁱⁱ	0.98	2.90	3.659 (2)	135

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 and Cg2 are the centroids of the C21—C26 and C61—C66 rings, respectively.

Acknowledgments

RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

supplementary crystallographic information

Comment

Piperidin-4-ones and their derivatives show a broad spectrum of biological activity which includes antimicrobial, antiviral, anti tuberculosis and anticancer activities (Aridoss et al., 2008). Recent research effort has been devoted to the discovery of potential 2,6-diarylpiperidin-4-one based chemical entities and establishing their stereochemistry, (Ponnuswamy et al., 2002) because, the pharmacological effects of potential drugs depends sensitively on the stereochemistry and ring conformations.

Crystal structures of r-2,c-6-Bis(4-chlorophenyl)-t-3-isopropyl-1-nitrosopiperidin-4-one (Gayathri et al., 2008) and r-2,c-6-Bis(4-chlorophenyl)-c-3,t-3- dimethylpiperidin-4-one(Ilango et al., 2008) have been reported, wherein the piperidine rings adopt chair conformations.

In the title molecule, C₂₁H₂₅NO, Fig.1, the piperidine ring adopts a chair conformation. The benzene rings at position 2,6 and one of the methyl groups attached to the piperidine ring in 3, have equatorial orientations. The dihedral angle between the two benzene rings is 72.53 (9)°. Molecules are linked by intermolecular N1—H1···O4 (-1/2 + x, 1/2 - y, z)hydrogen bonds, forming an infinite one-dimensional chain with base vector [1 0 0]. Further, C16—H16B···π (1/2 - x, 1/2 + y, -1/2 + z) and C32—H32A···π (1/2 + x, 1/2 - y, z) interactions involving the benzene rings at position 2 (C21—C26) and 6 (C61—C66) are also present in the crystal structure.

Experimental

The procedure adopted by Noller & Baliah (1948) was followed for the preparation of the title compound. To the solution of ammonium acetate (3.85 g, 0.05 mol) in dry ethanol, p-tolualdehyde (12.0 g, 0.1 mol) and isopropyl methyl ketone (5.35 ml, 0.05 mol) were added and allowed to reflux on a water bath for 1 h. The resulting solution was kept at room temperature for overnight and the precipitated solid was filtered. The solid was crystallized using benzene - petroleum ether mixture. The yield of the product obtained was 7.36 g (48%).