1-[2,4,6-Trimethyl-3,5-bis­(4-oxopiperidin-1-ylmeth­yl)benz­yl]piperidin-4-one

K Rajesh; V Vijayakumar; S Sarveswari; T Narasimhamurthy; Edward R T Tiekink

doi:10.1107/S1600536810016570

. 2010 May 12;66(Pt 6):o1306–o1307. doi: 10.1107/S1600536810016570

1-[2,4,6-Trimethyl-3,5-bis(4-oxopiperidin-1-ylmethyl)benzyl]piperidin-4-one

K Rajesh ^a, V Vijayakumar ^a,^‡, S Sarveswari ^a, T Narasimhamurthy ^b, Edward R T Tiekink ^c,^*

PMCID: PMC2979355 PMID: 21579402

Abstract

In the structure of the title compound, C₂₇H₃₉N₃O₃, each of the (4-oxopiperidin-1-yl)methyl residues adopts a flattened chair conformation (with the N and carbonyl groups being oriented to either side of the central C₄ plane) and they occupy positions approximately orthogonal to the central benzene ring [C_benzene—C—C_methylene—N torsion angles 103.4 (2), −104.4 (3) and 71.9 (3)°]; further, two of these residues are oriented to one side of the central benzene ring with the third to the other side. In the crystal packing, supramolecular layers in the ab plane are sustained by C—H⋯O interactions.

Related literature

For background to the biological significance of piperidin-4-one and analogous pyran and thiopyran species, see: El-Subbagh et al. (2000 ▶); Ganellin et al. (1965 ▶); Hagenbach & Gysin (1952 ▶); Ileana et al. (1985 ▶); Mokio et al. (1989 ▶); Pathak et al. (2007 ▶). For a related structure, see: Vijayakumar et al. (2010 ▶).

Experimental

Crystal data

C₂₇H₃₉N₃O₃
M _r = 453.61
Triclinic,
a = 7.9315 (16) Å
b = 12.449 (3) Å
c = 14.618 (3) Å
α = 67.641 (3)°
β = 87.749 (4)°
γ = 73.630 (3)°
V = 1277.0 (5) Å³
Z = 2
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.28 × 0.21 × 0.17 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1998 ▶) T _min = 0.981, T _max = 0.987
12284 measured reflections
4490 independent reflections
3008 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.062
wR(F ²) = 0.183
S = 1.02
4490 reflections
301 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); 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 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810016570/hg2682sup1.cif

e-66-o1306-sup1.cif^{(25.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810016570/hg2682Isup2.hkl

e-66-o1306-Isup2.hkl^{(215.5KB, 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
C20—H20a⋯N3	0.96	2.46	3.184 (4)	132
C9—H9a⋯O2ⁱ	0.97	2.60	3.412 (5)	142
C21—H21b⋯O3ⁱⁱ	0.97	2.48	3.252 (4)	136

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

Acknowledgments

VV is grateful to DST India for funding through the Young Scientist Scheme (Fast Track Proposal). TN acknowledges the establishment of the CCD facility under the IRHPA-DST programme at the Indian Institute of Science, Bangalore.

supplementary crystallographic information

Comment

Piperidin-4-one and their analogous pyran and thiopyran species attract interest owing to their biological properties, viz. anti-viral, anti-tumour (El-Subbagh et al., 2000), central nervous system (Ganellin et al., 1965), local anesthetic (Hagenbach et al., 1952), anti-cancer (Ileana et al., 1985), and anti-microbial (Mokio et al., 1989; Pathak et al., 2007) activities. As a continuation of structural studies of piperidine-4-ones (Vijayakumar et al., 2010), the title compound, (I), was synthesised and characterised by X-ray crystallography.

In compound (I), Fig. 1, the (4-oxopiperidin-1-yl)methyl residues containing the N1 and N2 atoms lie to one side of the central benzene ring and that with the N3 atom to the other. Owing to the presence of methyl substituents on either side of each 4-oxopiperidin-1-yl)methyl residue, the piperidin-4-one rings adopt side-on conformations to minimise steric interactions so that the N atoms occupy positions approximately normal to the plane through the benzene rings. This is quantified by the C2–C1–C7–N1 [103.4 (2) °], C2–C3–C14–N2 [-104.4 (3) °], and C4–C5–C21–N3 [71.9 (3) °] torsion angles. Each of the six-membered piperidin-4-one rings adopts a slightly flattened chair conformation with the N and carbonyl groups lying to either side of the central C₄ plane in each case. Only the amine-N3 atom forms a significant intra- or inter-molecular interaction, i.e. an intramolecular C–H···N contact, Table 1. In the crystal packing, molecules are sustained into layers by C–H···O interactions; Table 1. Layers are formed in the ab plane and stack along the c axis, Fig. 2.

Experimental

To a suspension of 1.5 equiv. of 4-piperidone hydrochloride monohydrate in benzene (20 ml), 3.0 equiv of K₂CO₃ was added. After stirring well for 30 min, 2,4,6-tris(bromomethyl)mesitylene (0.5 equiv) in benzene (10 ml) was added, followed by refluxing for 10 h. The completion of reaction was monitored by TLC. The reaction mixture was then allowed to cool to room temperature, filtered to remove the insoluble solids and then the filter cake was washed with dichloromethane. Excess solvents were removed under reduced pressure and the obtained crude product was purified by crystallization using 1:1 ratio of chloroform and methanol; m.pt. 483 K.