Ethyl 3-methyl-2,6-diphenyl­piperidine-1-carboxyl­ate

Sampath Natarajan; Rita Mathews

doi:10.1107/S1600536811019155

. 2011 May 25;67(Pt 6):o1530. doi: 10.1107/S1600536811019155

Ethyl 3-methyl-2,6-diphenylpiperidine-1-carboxylate

Sampath Natarajan ^a,^*, Rita Mathews ^a

PMCID: PMC3120568 PMID: 21754890

Abstract

In the title compound, C₂₁H₂₅NO₂, the piperidine ring adopts a twisted boat conformation characterized by puckering parameters θ = 89.5 (1) and ϕ = 257.5 (2)°. The phenyl groups are located in equatorial and axial positions on the central piperidine ring, while the methyl group is in an equatorial position. The dihedral angle between the phenyl rings is 49.8 (1)°. An intramolecular C—H⋯O interaction occurs. The crystal structure features weak intermolecular C—H⋯O interactions and a stabilizing intermolecular C—H⋯π contact involving the axial phenyl ring.

Related literature

For the biological activity of related piperidines, see: Parthiban et al. (2009 ▶); Aridoss et al. (2007 ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1995 ▶). For the conformation of piperidine derivatives, see: Ravindran et al. (1991 ▶); Krishna Kumar & Krishna Pillay (1996 ▶). For the synthesis of the title compound, see: Sampath et al. (2003 ▶); Noller & Baliah (1948 ▶).

Experimental

Crystal data

C₂₁H₂₅NO₂
M _r = 323.42
Monoclinic,
a = 10.4113 (3) Å
b = 10.6073 (6) Å
c = 16.2782 (6) Å
β = 95.960 (2)°
V = 1787.98 (13) Å³
Z = 4
Cu Kα radiation
μ = 0.60 mm⁻¹
T = 293 K
0.26 × 0.22 × 0.18 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
3698 measured reflections
3502 independent reflections
2428 reflections with I > 2σ(I)
R _int = 0.012
Standard reflections: 3; every 60 minutes intensity decay: none

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.136
S = 1.03
3502 reflections
218 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 ▶); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms, 1996 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97 and PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811019155/bh2353sup1.cif

e-67-o1530-sup1.cif^{(19.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811019155/bh2353Isup2.hkl

e-67-o1530-Isup2.hkl^{(168.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811019155/bh2353Isup3.cml

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

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

Cg1 is the centroid of the C13–C18 phenyl ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C18—H18⋯O1	0.93	2.91	3.519 (2)	125
C14—H14⋯O2ⁱ	0.93	2.82	3.406 (2)	122
C10—H10⋯O1ⁱⁱ	0.93	2.67	3.460 (3)	144
C3—H3B⋯Cg1ⁱⁱⁱ	0.97	2.70	3.666 (2)	172

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

supplementary crystallographic information

Comment

Piperidines and its N-substituted derivatives show significant pharmacological properties (Parthiban et al., 2009; Aridoss et al., 2007). Substitution by electron withdrawing groups (CHO, COCH₂CH₃, COPh, NO, etc.) at N-th position of piperidine ring causes major changes in the ring conformation (Ravindran et al., 1991; Krishna Kumar & Krishna Pillay, 1996). In the title compound (Fig. 1), the ethylacetate group substituting the piperidine ring shows extended conformation and the hetero π electron delocalization through the atoms N1, C20, O1 and O2 causes twisted boat conformation for the piperidine core, with puckering amplitude, Q_T = 0.718 (1) Å and phase angle = 89.5 (2)° (Nardelli, 1995; Cremer & Pople, 1975).

The phenyl rings at C2 and C6 atoms are oriented in the axial and equatorial positions, respectively, and the dihedral angle between them is 49.8 (1)°. Similarly, the methyl group at C5 is also oriented in equatorial position. All these substitutions are confirmed by the respective torsion angles. In addition, the substitution of ethylacetate group on N1 atom showed extended conformation with respect to the piperidine ring, which is also confirmed by the torsion angles.

The packing diagram of the title compound viewed down a-axis is shown in Fig. 2. The molecules did not present any classical H-bonds. However, the molecules are involved in weak intra- and intermolecular C—H···O interactions (Table 1), which stabilize the molecules in the crystal packing. Interestingly, a C—H···π interaction (C3—H3B···Cg1; Cg1 is the centroid of the ring C13···C18) also helps for the crystal packing.

Experimental

The compound, 3-methyl-2,6-diphenylpiperidin-4-one was obtained by adopting an earlier method (Sampath et al., 2003; Noller & Baliah, 1948) and it was reduced using amalgamated zinc in aqueous methanol solution in the presence of HCl, giving 3-methyl-2,6-diphenylpiperidine as a product. To a well stirred solution of 3,5-dimethyl-2,6-diphenylpiperidin-4-one (2 mM) and triethylamine (4 mM) in freshly distilled benzene (50 ml), a little excess amount of ethylchloroacetate (2.2 mM) in benzene (10 ml) was added drop-wise over about half an hour and stirring was continued until the completion of reaction. The reaction mixture was then poured into water and extracted with dichloromethane. Recrystallization of the title compound using pure ethanol resulted in suitable colorless crystals.