r-2,c-6-Bis(4-chloro­phen­yl)-c-3,t-3-dimethyl­piperidin-4-one

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

doi:10.1107/S1600536808036325

. 2008 Nov 13;64(Pt 12):o2312. doi: 10.1107/S1600536808036325

r-2,c-6-Bis(4-chlorophenyl)-c-3,t-3-dimethylpiperidin-4-one

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

PMCID: PMC2960012 PMID: 21581289

Abstract

In the title molecule, C₁₉H₁₉Cl₂NO, the piperidine ring adopts a chair conformation and the dihedral angle between the two benzene rings is 77.23 (7)°. In the crystal structure, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, and a weak C—H⋯π interaction is also observed.

Related literature

For a related crystal structure, see: Gayathri et al. (2008 ▶). For background on the biological activities of piperidones, see: Dimmock et al. (2001 ▶); Perumal et al. (2001 ▶). For the synthesis and stereodynamics of piperidin-4-ones and their derivatives, see: Ponnuswamy et al. (2002 ▶). For the synthesis, see: Noller & Baliah (1948 ▶).

Experimental

Crystal data

C₁₉H₁₉Cl₂NO
M _r = 348.25
Orthorhombic,
a = 13.1627 (5) Å
b = 22.4739 (7) Å
c = 5.8794 (2) Å
V = 1739.23 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.38 mm⁻¹
T = 200 (2) K
0.44 × 0.31 × 0.22 mm

Data collection

Oxford Diffraction Gemini R diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008 ▶) T _min = 0.950, T _max = 1.000 (expected range = 0.874–0.920)
19147 measured reflections
5694 independent reflections
2460 reflections with I > 2σ(I)
R _int = 0.051

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.083
S = 0.82
5694 reflections
212 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.34 e Å⁻³
Δρ_min = −0.31 e Å⁻³
Absolute structure: Flack (1983 ▶), 2278 Friedel pairs
Flack parameter: −0.03 (5)

Data collection: CrysAlis CCD (Oxford Diffraction, 2008 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2008 ▶); data reduction: CrysAlis RED; 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, 2003 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808036325/hb2832sup1.cif

e-64-o2312-sup1.cif^{(20.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808036325/hb2832Isup2.hkl

e-64-o2312-Isup2.hkl^{(273.2KB, 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	0.853 (17)	2.312 (17)	3.092 (2)	152.3 (15)
C23—H23⋯O4ⁱⁱ	0.95	2.56	3.377 (2)	144
C31—H31B⋯Cg1ⁱⁱⁱ	0.98	2.96	3.7265 (15)	136

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) . Cg1 is the centroid of the C61–C66 ring.

Acknowledgments

AT thanks the UGC, India, for the award of a Minor Research Project [File No. MRP-2355/06(UGC-SERO), Link No. 2355, 10/01/2007]. RJB acknowledges the NSF–MRI program for funding the purchase of the X-ray CCD diffractometer.

supplementary crystallographic information

Comment

Piperidones are an important group of heterocyclic compounds in the field of medicinal chemistry due to their biological activities, including cytotoxic and anticancer properties (Dimmock et al., 2001). Piperidones were also reported to possess analgesic, anti-inflammatory, central nervous system (CNS), local anaesthetic, anticancer and antimicrobial activity (Perumal et al., 2001). The design and synthesis of conformationally anchored molecules is an important approach towards improving potency and selectivity. One such class of compounds constitutes piperidin-4-ones and their derivatives, whose synthesis and stereodynamics are well investigated (Ponnuswamy et al., 2002). The crystal structure of r-2,c-6-Bis(4-chlorophenyl)-t-3-isopropyl-1-nitrosopiperidin-4-one has been reported, wherein the piperidine ring adopts a chair conformation (Gayathri et al., 2008).

In the title molecule, C₁₉H₁₉Cl₂NO (Fig. 1), the piperidine ring adopts a chair conformation. The phenyl 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 phenyl rings is 77.23 (7)°. In the crystal, the molecules are linked by N1—H1···O4 (x - 1/2, 1/2 - y, z) and C23—H23···O4(x - 1/2, -y + 1/2, z - 1) hydrogen bonds (Table 1). Further, a C31—H31B···π interaction involving the phenyl ring (C61—C66) at position 6 also present in the crystal structure.

Experimental

The procedure adopted for the preparation of the title heterocyclic compound is similar to that of Noller & Baliah (1948). Ammonium acetate (7.7 g, 0.1 mol), 4-chlorobenzaldehyde (28.1 g, 0.2 mol) and 3-methyl-2-butanone (10.7 ml, 0.1 mol) were dissolved in 70 ml of rectified spirit. The resulting solution was heated to boiling and set aside for a day. The oily base obtained was converted into its hydrochloride by the addition of concentrated hydrochloric acid and the separated solid was filtered. Then the hydrochloride was neutralized with liquid ammonia. The resulting solid was filtered and purified by recrystallization from ethanol to yield colourless plates of (I). The yield of the product obtained was 28.65 g (82%).