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

R Ramachandran; G Aridoss; D Velmurugan; S Kabilan; Y T Jeong

doi:10.1107/S1600536808030213

. 2008 Sep 27;64(Pt 10):o2009–o2010. doi: 10.1107/S1600536808030213

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

R Ramachandran ^a, G Aridoss ^b, D Velmurugan ^c, S Kabilan ^a, Y T Jeong ^b,^*

PMCID: PMC2959452 PMID: 21201207

Abstract

In the title compound, C₂₃H₂₆BrNO₄, the piperidinone ring adopts a boat conformation. The dihedral angle between the two benzene rings is 70.9 (1)°. The two methoxy groups are close to coplanar with the attached benzene rings [C—C—O—C torsion angles of 6.3 (5) and 16.4 (4)°]. A weak C—H⋯Br intramolecular interaction is observed. In the crystal structure, molecules are linked into a chain along [101] by intermolecular C—H⋯O hydrogen bonds. A short intermolecular Br⋯O contact [3.063 (2) Å] is observed.

Related literature

For background on the piperidine ring system, see: O’Hagan (2000 ▶); Pinder (1992 ▶). For information on the arylpiperidine scaffold, see: Horton et al. (2003 ▶). For piperidone derivatives, see: Baluja et al. (1964 ▶); Mutus et al. (1989 ▶). For the biological activities of compounds possessing an amide bond linkage, see: Priya et al. (2007 ▶); Bylov et al. (1999 ▶); Dollery (1999 ▶). For the activivities of chloroacetyl and heterocyclicacetyl derivatives of variously functionalized 2,6-diarylpiperidin-4-ones, see: Aridoss et al. (2007a ▶,b ▶; 2008a ▶). For a related structure, see: Aridoss et al. (2008b ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C₂₃H₂₆BrNO₄
M _r = 460.36
Monoclinic,
a = 12.9487 (9) Å
b = 25.2882 (18) Å
c = 8.9701 (6) Å
β = 132.930 (1)°
V = 2150.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 1.94 mm⁻¹
T = 293 (2) K
0.30 × 0.20 × 0.16 mm

Data collection

Bruker Kappa APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.594, T _max = 0.747
13660 measured reflections
5139 independent reflections
3748 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.098
S = 1.02
5139 reflections
266 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.22 e Å⁻³
Absolute structure: Flack (1983 ▶), 1651 Friedel pairs
Flack parameter: 0.004 (7)

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2003 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808030213/ci2672sup1.cif

e-64-o2009-sup1.cif^{(22.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808030213/ci2672Isup2.hkl

e-64-o2009-Isup2.hkl^{(246.6KB, 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
C1—H1⋯Br1	0.98	2.82	3.523 (3)	129
C20—H20C⋯O1ⁱ	0.96	2.60	3.357 (7)	136

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Symmetry code: (i) Inline graphic .

Acknowledgments

GA and YTJ acknowledge 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

The piperidine ring system is ubiquitous structural component of naturally occurring alkaloid and pharmaceuticals (O'Hagan, 2000; Pinder, 1992). Its biological properties are highly dependent on the type and location of substituents on the heterocyclic ring. The arylpiperidine scaffold is a key element involved in binding to a variety of receptors and therefore can be described as a privileged structure (Horton et al., 2003). Similarly, piperidone derivatives have also received wide interest among chemists and biologists due to their envisaged mode of interaction with cellular thiols, with modest or no affinity for the hydroxy and amine groups found in nucleic acids (Baluja et al., 1964; Mutus et al., 1989). Generally, compounds possessing an amide bond linkage have a wide range of biological activities such as antimicrobial (Priya et al., 2007), anti-inflammatory (Bylov et al., 1999), antiviral, antimalarial and general anesthetics (Dollery, 1999). Recently, we have explored the antimicrobial, analgesic and antipyretic activities associated with chloroacetyl and heterocyclicacetyl derivatives of variously functionalized 2,6-diarylpiperidin-4-ones besides the change in piperidone ring conformation (Aridoss et al., 2007a,b, 2008a). Thus, it has spurred our interest to synthesize diversely substituted 2,6-diarylpiperidin-4-ones and their derivatives. In order to establish the change in molecular conformation of piperidone ring upon bromoacetylation, the present investigation was made and confirmed by X-ray diffraction study.

The bond lengths and angles in the title molecule (Fig.1) are comparable to those observed in a related structure (Aridoss et al., 2008b). The sum of the angles at N1 (359.0 (6)°) is in accordance with sp² hybridization. The decrease in the N1—C22 bond length (1.368 (3) Å) when compared to C1—N1 (1.481 (3) Å) and C5—N1 (1.481 (3) Å) lengths indicates the effective conjugation between lone pair of nitrogen with carbonyl group. The N-COCH₂ group is coplanar as confirmed by the torsion angles C1—N1—C22—C23 of -4.0 (4)° and C5—N1—C22—O1 of -172.4 (2)°. The dihedral angle between the two benzene rings is 70.9 (1)°. The C10—C9—O3—C20 (6.3 (5)°) and C16—C15—O4—C21 (16.4 (4)°) torsion angles indicate that the methoxy groups almost lie in the plane of the phenyl rings C6—C11 and C12—C17, respectively, to which they are attached.

The piperidinone ring adopts a boat conformation with the puckering parameters (Cremer & Pople, 1975) and the smallest displacement asymmetry parameters (Nardelli, 1983) being q₂ = 0.673 (4) Å, q₃ = -0.051 (4) Å, Q_T = 0.675 (4)Å, θ = 94.3 (3)° and ΔC_s(C2) = 10.0 (3)°. A weak C—H···Br intramolecular interaction is observed in the molecular structure. In the crystal packing, the molecules are linked into a chain along [101] by intermolecular C—H···O hydrogen bonds (Fig. 2). A short intermolecular Br1···O4 (1+x, y, 1+z) contact of 3.063 (2) Å has been observed.

Experimental

The title compound was obtained by adopting our earlier method (Aridoss et al., 2007a). To a well stirred solution of 3,5-dimethyl-2,6-bis(p-methoxyphenyl)piperidin-4-one (1 equiv.) and triethylamine (1 equiv.) in freshly distilled benzene, bromoacetyl chloride (1 equiv.) in benzene was added in drop wise through the addition funnel for about half an hour. Stirring was continued until the completion of reaction. Later, it was poured into water and extracted with DCM. The combined DCM extracts was then washed well with 3% sodium bicarbonate solution and dried over anhydrous sodium sulfate. This upon evaporation and subsequent recrystallization in distilled ethanol furnished the diffraction-quality crystals of the title compound.