1-(2-Bromo­acet­yl)-3-methyl-2,6-diphenyl­piperidin-4-one

G Aridoss; S Sundaramoorthy; D Velmurugan; K S Park; Y T Jeong

doi:10.1107/S160053681001901X

. 2010 May 29;66(Pt 6):o1479. doi: 10.1107/S160053681001901X

1-(2-Bromoacetyl)-3-methyl-2,6-diphenylpiperidin-4-one

G Aridoss ^a, S Sundaramoorthy ^b, D Velmurugan ^b, K S Park ^a, Y T Jeong ^a,^*

PMCID: PMC2979607 PMID: 21579545

Abstract

In the title compound, C₂₀H₂₀BrNO₂, the piperidone ring adopts a boat conformation. The phenyl rings are oriented at dihedral angles of 97.8 (2) and 96.0 (1)° with respect to the best plane through the piperidine ring. The dihedral angle between the two phenyl rings is 49.7 (1)°. In the crystal, bifurcated C—H⋯O hydrogen bonds form a R ₂ ¹(7) ring motif, linking the molecules into centrosymmetric dimers.

Related literature

For the biological activity of functionalized piperidines, see: Richardo et al. (1979 ▶); Schneider (1996 ▶); Mukhtar & Wright (2005 ▶); Aridoss et al. (2007 ▶); Winkler & Holan (1989 ▶). For related structures see: Aridoss et al. (2009a ▶,b ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C₂₀H₂₀BrNO₂
M _r = 386.28
Monoclinic,
a = 21.4006 (8) Å
b = 14.5873 (6) Å
c = 13.8107 (5) Å
β = 125.368 (2)°
V = 3515.7 (2) Å³
Z = 8
Mo Kα radiation
μ = 2.35 mm⁻¹
T = 292 K
0.3 × 0.26 × 0.22 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.499, T _max = 0.596
17094 measured reflections
4398 independent reflections
2725 reflections with I > 2σ(I)
R _int = 0.035

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.213
S = 1.02
4398 reflections
218 parameters
H-atom parameters constrained
Δρ_max = 0.53 e Å⁻³
Δρ_min = −0.77 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 datablocks global, I. DOI: 10.1107/S160053681001901X/bt5275sup1.cif

e-66-o1479-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681001901X/bt5275Isup2.hkl

e-66-o1479-Isup2.hkl^{(211.2KB, 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
C2—H2A⋯O1ⁱ	0.97	2.56	3.458 (6)	154
C13—H13⋯O1ⁱ	0.93	2.51	3.404 (5)	161

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Symmetry code: (i) Inline graphic .

Acknowledgments

GA and YTJ are grateful for the support provided by the second stage of the BK21 program, Republic of Korea. SS and DV thank the TBI X-ray Facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection and the University Grants Commission (UGC&SAP) for financial support.

supplementary crystallographic information

Comment

Amides are prominent functional groups in chemistry due to their integral part in biologically important polymers such as peptides and proteins. Functionalized piperidines are among the most common building blocks in natural products and more interestingly, in many biologically active compounds such as anopterine, pergoline, scopolamine and morphine (Richardo et al., 1979, Schneider, 1996, Mukhtar & Wright, 2005). Piperidones also have high impact in medicinal field owing to their role as key chiral intermediates for the preparation of a variety of natural, synthetic and semi-synthetic pharmacophores with marked anticancer and anti-HIV activities (Winkler & Holan, 1989). It has been established by our earlier studies (Aridoss et al. 2009a, Aridoss et al. 2009b) that unlike the substitution of either alky or aryl system in the carbon skeleton of piperidone, incorporation of either chloroacetyl or bromoacetyl functionality at the nitrogen of piperidone remarkably changes the rigid chair confirmation of heterocyclic ring into non-chair conformation of its preference. Thus to find out the change in conformation of 2,6-diphenyl-3-methylpiperidin-4-one upon bromoacetylation, the title compound was synthesized and discussed here with its X-ray crystallographic data.

In the present structure, the piperidone ring adopts a boat conformation with atoms C1 and C4 deviating by 0.395 (1) and 0.334 (1) Å, respectively, from the least-sqaures plane defined by the remaining atoms (N1/C2/C3/C5) in the ring. When compared with the reported structures of piperidone derivatives (Aridoss et al., 2009b), it is clear that the conformation of the piperidone ring is highly influenced by the substitutions at various positions.The sum of the bond angles around the atom N1(357.6 (6)°) of the piperidone ring in the molecule is in accordance with sp² hybridization.

The puckering parameters (Cremer & Pople,1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) for piperidone ring are q₂ = 0.639 (4) Å, q₃ = 0.062 (1) Å; Q_T = 0.642 (4) Å and φ₂ = 84.4 (1) °, respectively. Atoms C2 and C13 act as donors to form bifurcated hydrogen bonds with atom O1' as an aceptor. In the crystal structure, the molecules at (x,y,z) and (-x,-y-1, -z ) are linked by C2—H2A···O1' hydrogen bonds into cyclic centrosymmetric R₂²(8) dimer.

Experimental

The title compound was obtained by adopting our earlier method (Aridoss et al. 2007). To a solution of 2,6-diphenyl-3-methylpiperidin -4-one (1 equiv.) and NEt3 (1.5 equiv.) in freshly distilled benzene, bromoacetyl chloride (1 equiv.) in benzene was added in drop wise. After the completion of reaction, the crude compound was obtained by evaporation of its ethyl acetate extract. This upon recrystallization in distilled ethanol afforded fine white crystals suitable for X-ray diffraction study.