1-(2-Chloro­benz­yl)-3,5-dimethyl-2,6-diphenyl­piperidine

Chennan Ramalingan; Seik Weng Ng; Edward R T Tiekink

doi:10.1107/S1600536812029212

. 2012 Jun 30;68(Pt 7):o2301–o2302. doi: 10.1107/S1600536812029212

1-(2-Chlorobenzyl)-3,5-dimethyl-2,6-diphenylpiperidine

Chennan Ramalingan ^a,^‡, Seik Weng Ng ^b,^c, Edward R T Tiekink ^b,^*

PMCID: PMC3394077 PMID: 22798942

Abstract

Two independent molecules (A and B) comprise the asymmetric unit of the title compound, C₂₆H₂₈ClN, with the inverted form of B almost superimposable upon A. Each piperidine ring has a chair conformation and the chloro substituent is anti to the piperidine N atom. Each of two aromatic rings, the benzyl residue and one methyl group substituents occupies an equatorial position, and the second methyl substituent occupies an axial position. The dihedral angle formed between the chlorobenzene ring and the flanking phenyl rings in molecule A are 84.24 (9) and 24.85 (8)°; the equivalent angles for molecule B are 79.97 (9) and 28.33 (9)°. In the crystal, the A and B molecules are connected by C—H⋯Cl and C—H⋯π interactions, forming a supramolecular chain along [101].

Related literature

For the biological activity of piperidine derivatives, see: Ramalingan et al. (2004 ▶); Ramachandran et al. (2011 ▶). For a related structure, see: Ramalingan et al. (2012 ▶). For additional conformational analysis, see: Spek (2009 ▶).

Experimental

Crystal data

C₂₆H₂₈ClN
M _r = 389.94
Monoclinic,
a = 13.4940 (6) Å
b = 17.3005 (6) Å
c = 18.5078 (6) Å
β = 100.892 (4)°
V = 4242.9 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 100 K
0.30 × 0.20 × 0.05 mm

Data collection

Agilent SuperNova Dual diffractometer with an Atlas detector
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.718, T _max = 1.000
28999 measured reflections
9798 independent reflections
7163 reflections with I > 2σ(I)
R _int = 0.044

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.125
S = 1.04
9798 reflections
505 parameters
H-atom parameters constrained
Δρ_max = 0.40 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); 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, 1997 ▶), DIAMOND (Brandenburg, 2006 ▶) and QMol (Gans & Shalloway, 2001 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812029212/hb6873sup1.cif

e-68-o2301-sup1.cif^{(34.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812029212/hb6873Isup2.hkl

e-68-o2301-Isup2.hkl^{(479.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812029212/hb6873Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

Cg1 is the centroid of the C35–C40 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C29—H29⋯Cl1	0.95	2.73	3.678 (2)	174
C24—H24⋯Cg1ⁱ	0.95	2.95	3.680 (2)	135

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors are grateful for facilities provided by the Chairman/Management of Kalasalingam University, and thank the Ministry of Higher Education (Malaysia) for funding structural studies through the High-Impact Research scheme (UM.C/HIR/MOHE/SC/3).

supplementary crystallographic information

Comment

The crystal structure determination of the title compound was undertaken in order to establish conformational details for a molecule designed and synthesized for the evaluation of its biological properties. The motivation for the biological trial arises as piperidine derivatives are an important class of heterocyclic compounds with potent pharmacological/biological activities (Ramalingan et al., 2004; Ramachandran et al., 2011).

Two independent molecules comprise the asymmetric unit of (I), Fig. 1. The inverted molecule of the N2-containing molecule is virtually super-imposable upon that of the N1-containing molecule, Fig. 2. The r.m.s. bond and angle fits are 0.0045 Å and 0.617°, respectively (Spek, 2009). Each piperidine ring has a chair conformation and the two aromatic rings, the benzyl residue and one methyl substituent occupy equatorial positions, as found in a related structure lacking one C-bound methyl group (Ramalingan et al., 2012), with the additional methyl substituent occupying an axial position. The dihedral angle formed between the C1–C6 chlorobenzene ring and the flanking C9–C14 and C21–C26 phenyl rings are 84.24 (9) and 24.85 (8)°, respectively; the dihedral angle between the phenyl rings is 62.03 (9)°. The comparable values found for the second independent molecule are 79.97 (9), 28.33 (9) and 54.39 (8)°, respectively. The chloro substituent is anti to the piperidine-N atom in each independent molecule.

In the crystal, the independent molecules are connected to each other by C—H···Cl and C—H···π interactions, Table 1, to form a supramolecular chain along [101], Fig. 3. These assemble into the three-dimensional architecture without specific intermolecular interactions between them, Fig. 4.

Experimental

A starting material, 3,5-dimethyl-2,6-diphenylpiperidine, was synthesized from benzaldehyde, 2-butanone and ammonium acetate through a Mannich-type reaction (for a typical synthesis, see Ramalingan et al. (2004)) followed by standard Wolff-Kishner reduction using hydrazine hydrate in diethylene glycol. The title compound was then synthesized as follows. To a DMF solution (15 ml) of 3,5-dimethyl-2,6-diphenylpiperidine (1.33 g, 0.005 mol) was added potassium tert-butoxide (0.67 g, 0.006 mol). The mixture was stirred for 30 minutes and 2-chlorobenzyl bromide (0.78 ml, 0.006 mol) was added drop-wise. Stirring was continued overnight before aqueous work-up. Extraction with diethyl ether followed by column chromatography separation using n-hexane/ethyl acetate (100:4) as an eluent eventually provided the pure title compound as a white solid. Re-crystallization was performed by slow evaporation of its ethanolic solution which afforded colourless prisms. M.pt: 357–358 K. Yield: 79%.