2,4-Bis(4-chloro­phen­yl)-1-methyl-3-aza­bicyclo­[3.3.1]nonan-9-one

P Parthiban; V Ramkumar; Yeon Tae Jeong

doi:10.1107/S1600536810004095

. 2010 Feb 6;66(Pt 3):o545. doi: 10.1107/S1600536810004095

2,4-Bis(4-chlorophenyl)-1-methyl-3-azabicyclo[3.3.1]nonan-9-one

P Parthiban ^a, V Ramkumar ^b, Yeon Tae Jeong ^a,^*

PMCID: PMC2983554 PMID: 21580316

Abstract

The title compound, C₂₁H₂₁Cl₂NO, exists in a twin-chair conformation with an equatorial orientation of the 4-chlorophenyl groups on both sides of the secondary amino group; the dihedral angle between the 4-chlorophenyl rings is 36.58 (2)°. The crystal packing is stabilized by an intermolecular N—H⋯O hydrogen bond and a weak Cl⋯Cl [3.4331 (9) Å] interaction.

Related literature

For the synthesis and biological activity of 3-azabicyclo[3.3.1] nonan-9-ones, see: Parthiban et al. (2009 ▶); Hardick et al. (1996 ▶); Jeyaraman & Avila (1981 ▶). For the structure of the non-methylated analog of the title compound, see: Parthiban et al. (2009a ▶). For related structures with similar conformations, see: Parthiban et al. (2009b ▶, 2010 ▶). For a related structure with chair–boat conformation, see: Smith-Verdier et al. (1983 ▶). For a related structure with boat–boat conformation, see: Padegimas & Kovacic (1972 ▶). For ring puckering and asymmetry parameters, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶). Scheme: resolution poor

Experimental

Crystal data

C₂₁H₂₁Cl₂NO
M _r = 374.29
Monoclinic,
a = 28.4515 (14) Å
b = 7.0380 (3) Å
c = 21.2771 (12) Å
β = 117.148 (4)°
V = 3791.2 (3) Å³
Z = 8
Mo Kα radiation
μ = 0.35 mm⁻¹
T = 298 K
0.58 × 0.42 × 0.18 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T _min = 0.822, T _max = 0.940
24985 measured reflections
4661 independent reflections
3149 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.045
wR(F ²) = 0.125
S = 1.02
4661 reflections
231 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.43 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT-Plus (Bruker, 2004 ▶); data reduction: SAINT-Plus and XPREP (Bruker, 2004 ▶); 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 Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810004095/hb5322sup1.cif

e-66-0o545-sup1.cif^{(21.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810004095/hb5322Isup2.hkl

e-66-0o545-Isup2.hkl^{(228.4KB, 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
N1—H1A⋯O1ⁱ	0.87 (2)	2.45 (2)	3.309 (2)	170.2 (18)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by the Corporate-affiliated Research Institute of Academic–Industrial–Institutional Cooperation Improvement Business No. S7080008110. The authors acknowledge the Department of Chemistry, IIT Madras, for the X-ray data collection.

supplementary crystallographic information

Comment

3-Azabicyclo[3.3.1]nonanes are an important class of heterocyclic compounds due to their broad spectrum of biological activities such as antibacterial, antifungal, analgesic, antogonistic, anti-inflammatory, local anesthetic and hypotensive activity, and their presence in a wide variety of naturally occurring diterpenoid/norditerpenoid alkaloids (Parthiban et al., 2009; Hardick et al., 1996; Jeyaraman & Avila, 1981). As stereochemistry plays a vital role in biological activities, it is essential to establish the stereochemistry of the synthesized bio-active molecules. Owing to the diverse possibilities in the conformation of the 3-azabicycle such as chair-chair (Parthiban et al., 2009b & 2010), chair-boat (Smith-Verdier et al., 1983) and boat-boat (Padegimas & Kovacic, 1972), the present crystal study was undertaken to examine the stereochemistry of the synthesized 2,4-bis(4-chlorophenyl)-1-methyl-3-azabicyclo[3.3.1]nonan-9-one.

The crystallographic analysis of the title compound shows that the piperidine ring adopts a near ideal chair conformation. The total puckering amplitude Q_T is 0.587 (2)Å and the phase angle θ is 1.8 (2)° (Cremer & Pople, 1975). The smallest displacement asymmetry parameters being q2 and q3 are 0.022 (2)Å and 0.587 (2) Å, respectively (Nardelli, 1983). The deviation of ring atoms C8 and N1 from the C1/C2/C6/C7 plane by 0.677 (3)Å and -0.642 (3) Å, respectively.

The crystallographic analysis of the title compound suggests that the cyclohexane ring deviates from the ideal chair conformation. The total puckering amplitude Q_T is 0.573 (2)Å and the phase angle θ is 13.8 (2)° (Cremer & Pople, 1975). The smallest displacement asymmetry parameters being q2 and q3 are 0.134 (2)Å and 0.556 (2) Å, respectively (Nardelli, 1983). The deviation of ring atoms C4 and C8 from the C2/C3/C5/C6 plane by -0.554 (4)Å and 0.723 (2) Å, respectively.

According to the crystallogrphic analysis, the title compound, C₂₁H₂₁Cl₂N O, exists in a twin-chair conformation with an equatorial orientation of the para-chlorophenyl groups on both sides of the secondary amino group.

In the title compound, the para-chlorophenyl rings are orientated at an angle of 36.58 (2)° with respect to one another, whereas in its non-methyl analog, 2,4-bis(4-chlorophenyl)-3- azabicyclo[3.3.1]nonan-9-one, the angle is 31.33 (3)°. The crystal structure of the title compound is stabilized by an intermolecular N—H···O interaction and a weak Cl—Cl interaction [Cl···Cl = 3.43 Å]. Though similar interactions observed in the non-methyl analog, the hydrogen bond geometries such as distance and angle of N1—H1···O1 [respectively, 3.1202Å and 160.2 (18)°] are comparatively lower than the title compound (Table 1).

In the title compound, the torsion angles of C1—C2—C8—C9 and C6—C7—C8—C16 are -178.85 (4)° and -179.35 (4)°, respectively (in the non-methyl analog of the title compound, they are -177.88 (4)° and -179.01 (4)°).

Experimental

The 1-methyl-2,4-bis(4-chlorophenyl)-3-azabicyclo[3.3.1]nonan-9-one was synthesized by a modified Mannich reaction in one-pot, using para-chlorobenzaldehyde (0.1 mol, 14.06 g), 2-methylcyclohexanone (0.05 mol, 5.61 g/6.07 ml) and ammonium acetate (0.075 mol, 5.78 g) in 50 ml of absolute ethanol. The mixture was gently warmed on a hot plate with stirring and continued at 303-308 K (30-35° C) till completion of the reaction. The progress was monitered by TLC. After all starting material was used up, the crude 3-azabicyclononan-9-one was separated by filtration and washed with a 1:5 ethanol-ether mixture, till the solid becomes colorless. Colourless blocks of (I) were obtained by slow evoporation from ethanol.