1-Chloro­acetyl-2,6-bis­(2-methoxy­phen­yl)-3,5-dimethyl­piperidin-4-one

G Aridoss; D Gayathri; D Velmurugan; M S Kim; Yeon Tae Jeong

doi:10.1107/S1600536809033674

. 2009 Aug 29;65(Pt 9):o2276–o2277. doi: 10.1107/S1600536809033674

1-Chloroacetyl-2,6-bis(2-methoxyphenyl)-3,5-dimethylpiperidin-4-one

G Aridoss ^a, D Gayathri ^b,^‡, D Velmurugan ^b, M S Kim ^a, Yeon Tae Jeong ^a,^*

PMCID: PMC2970045 PMID: 21577671

Abstract

The piperidone ring in the title compound, C₂₃H₂₆ClNO₄, adopts a boat conformation with its two out-of-plane C atoms deviating by 0.597 (2) and 0.630 (2) Å from the least-squares plane of the rest of atoms in the ring. The two aromatic rings are roughly perpendicular to each other, making a dihedral angle of 75.1 (1)°, and a C—H⋯π intramolecular interaction is observed. The crystal packing is stabilized by a C—H⋯O intermolecular interaction, generating a chain with a C(9) motif along the a axis.

Related literature

For the biological activity of the piperidine nucleus, see: Weintraub et al. (2003 ▶). For the biological activity of piperidones and their N-acyl derivatives, see: Perumal et al. (2001 ▶); Weintraub et al. (2003 ▶); Aridoss et al. (2008 ▶, 2009 ▶); Aridoss, Balasubramanian, Parthiban, Ramachandran & Kabilan (2007 ▶). For a related structure, see: Ramachandran et al. (2008 ▶). For the synthesis, see: Aridoss, Balasubramanian, Parthiban & Kabilan (2007 ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C₂₃H₂₆ClNO₄
M _r = 415.90
Triclinic,
a = 8.9921 (6) Å
b = 11.3725 (8) Å
c = 11.9373 (8) Å
α = 71.630 (1)°
β = 68.465 (1)°
γ = 72.903 (1)°
V = 1055.45 (12) Å³
Z = 2
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 293 K
0.27 × 0.22 × 0.20 mm

Data collection

Bruker SMART APEX CCD area-detector diffractometer
Absorption correction: none
11114 measured reflections
4603 independent reflections
4054 reflections with I > 2σ(I)
R _int = 0.026

Refinement

R[F ² > 2σ(F ²)] = 0.050
wR(F ²) = 0.145
S = 1.05
4603 reflections
266 parameters
H-atom parameters constrained
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.35 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: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97 and PARST (Nardelli, 1995 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809033674/is2452sup1.cif

e-65-o2276-sup1.cif^{(23.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809033674/is2452Isup2.hkl

e-65-o2276-Isup2.hkl^{(220.9KB, 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
C23—H23C⋯O1ⁱ	0.96	2.50	3.321 (3)	144
C9—H9⋯Cg	0.93	2.69	3.621 (2)	177

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Symmetry code: (i) Inline graphic . Cg is the centroid of the C17–C22 ring.

Acknowledgments

The authors thank Dr K. Ravikumar, Indian Institute of Chemical Technology, Hyderabad, India, for providing the X-ray data collection facility. GA and YTJ acknowledge the support provided by the second stage of the BK21 program, Republic of Korea. Financial support from the University Grants Commission (UGC–SAP) and the Department of Science & Technology (DST-FIST), Government of India, are acknowledged by DV for providing facilities to the department.

supplementary crystallographic information

Comment

Nitrogen containing heterocycles possess important biological profiles. For instance, the piperidine sub-structure is ubiquitous structural feature of many alkaloids, natural products and drug candidates (Weintraub et al., 2003). During the last decade, there were thousands of piperidine compounds mentioned in clinical and preclinical studies. As well owing to the relevance of piperidone-containing bioactive compounds, synthesis of piperidone derivatives have also attracted considerable attention among chemists and biologist (Perumal et al., 2001). It has been recognized well by our earlier studies that N-chloroacetyl and the further functionalized derivatives of 2,6-diarylpiperidin-4-one showed moderate to good antimicrobial, analgesic, antipyretic and antimycobacterial activities (Aridoss, Balasubramanian, Parthiban, Ramachandran & Kabilan, 2007; Aridoss et al., 2008,2009). As an extension to our studies on stereochemistry (Aridoss, Balasubramanian, Parthiban & Kabilan, 2007) and crystal studies (Ramachandran et al., 2008), we report here the X-ray crystallographic study of 1-chloroacetyl-2,6-bis (2-methoxyphenyl)-3,5-dimethylpiperidin-4-one.

The molecular structure of the title compound (I) is shown in Fig.1. The sum of the angles at N1 (358.9 (3)°) is in accordance with sp² hybridization. The two phenyl rings in the title compound (I) are nearly perpendicular with the dihedral angle being 75.1 (1)°. Methoxy group attached to the phenyl rings is planar as evident from the torsion angle [(C14—O2—C13—C12 (-3.7 (3)°) and C23—O4—C22—C21 (-1.4 (2)°)]. The torsion angle around O1—C6—C7—Cl1 [0.0 (2)°] indicates the planarity of chloroacetyl moiety. The piperidone ring in the title compound (I) adopts boat conformation with atoms C2 and C5 deviating by -0.597 (2) and -0.630 (2) Å, respectively, from the least-squares plane defined by rest of the atoms (N1/C1/C3/C4) in the ring. The puckering parameters (Cremer & Pople, 1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) for piperidone ring are q₂ = 0.709 (2) Å, q₃ = 0.022 (2) Å; Q_T = 0.710 (2) Å and θ = 88.3 (1)°.

The molecule of (I) is stabilized by weak C—H···O and C—H···π intramolecular interactions. In C—H···π intramolecular interaction, atom C9 acts as donor to the centroid (Cg) of the phenyl ring C17–C22 with H···Cg distance of 2.69 Å. The crystal packing is stabilized by C—H···O intermolecular interaction, wherein atom C23 acts as donor to O1 (1 + x, y, z) generating a chain C(9) along the a axis.

Experimental

The title compound was obtained by adopting our earlier method (Aridoss, Balasubramanian, Parthiban & Kabilan, 2007). To a solution of 2,6-bis(2- methoxyphenyl)-3,5-dimethylpiperidin-4-one (1 equiv.) and NEt₃ (1.5 equiv.) in freshly distilled benzene, chloroacetyl chloride (1 equiv.) in benzene was added in drop wise. Stirring was continued until the completion of reaction. Later, it was poured into water and extracted with ethyl acetate. The combined organic extracts was then washed well with 3% sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. This upon evaporation and subsequent recrystallization of title compound in distilled ethanol afforded fine white crystals suitable for X-ray diffraction study.