2,4-Bis(4-eth­oxy­phen­yl)-3-aza­bicyclo­[3.3.1]nonan-9-one

Dong Ho Park; V Ramkumar; P Parthiban

doi:10.1107/S1600536812037385

. 2012 Sep 5;68(Pt 10):o2841. doi: 10.1107/S1600536812037385

2,4-Bis(4-ethoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-one

Dong Ho Park ^a, V Ramkumar ^b, P Parthiban ^a,^*

PMCID: PMC3470201 PMID: 23125645

Abstract

The title compound, C₂₄H₂₉NO₃, exists in a twin-chair conformation with an equatorial orientation of the 4-ethoxyphenyl groups. The benzene rings are inclined to each other at an angle of 28.0 (1)°. In the crystal, weak C—H⋯O interactions link molecules related by translation into chains along the b axis. The crystal packing exhibits π–π interactions between the benzene rings of neighbouring molecules [centroid–centroid distance = 3.692 (3) Å].

Related literature

For the synthesis and stereochemistry of 3-azabicyclo[3.3.1]nonan-9-ones, see: Park et al. (2011a ▶). For the biological activity of 3-azabicyclo[3.3.1]nonan-9-ones, see: Barker et al. (2005 ▶); Parthiban et al. (2009 ▶, 2010a ▶,b ▶, 2011a ▶). For related structures, see: Parthiban et al. (2011b ▶); Park et al. (2012 ▶).

Experimental

Crystal data

C₂₄H₂₉NO₃
M _r = 379.48
Monoclinic,
a = 14.0319 (11) Å
b = 7.3143 (6) Å
c = 20.5820 (17) Å
β = 106.841 (3)°
V = 2021.8 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 293 K
0.35 × 0.28 × 0.25 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.972, T _max = 0.980
15180 measured reflections
5415 independent reflections
3042 reflections with I > 2σ(I)
R _int = 0.034

Refinement

R[F ² > 2σ(F ²)] = 0.072
wR(F ²) = 0.232
S = 1.05
5415 reflections
255 parameters
H-atom parameters constrained
Δρ_max = 0.49 e Å⁻³
Δρ_min = −0.51 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); 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.

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536812037385/cv5330sup1.cif

e-68-o2841-sup1.cif^{(22.3KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812037385/cv5330Isup2.hkl

e-68-o2841-Isup2.hkl^{(265.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812037385/cv5330Isup3.cml

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
C18—H18⋯O1ⁱ	0.93	2.57	3.428 (3)	154
C14—H14⋯O1ⁱ	0.92	2.61	3.501 (3)	159

Open in a new tab

Symmetry code: (i) Inline graphic .

Acknowledgments

This research was supported by the Inje University research grant 2011. The authors acknowledge the Department of Chemistry, IIT Madras, for the data collection.

supplementary crystallographic information

Comment

Alkaloids with 3-azabicyclononane nucleus display broad-spectrum of biological activities ranging from antibacterial to anticancer (Barker et al., 2005; Parthiban et al., 2009, 2010a, 2010b, 2011a). Hence, the synthesis of new molecules that contain 3-azabicyclononane pharmacophore as well as their isolaton from the natural products are important in the field of medicinal chemistry. Accordingly, we synthesized the title compound by a non-laborious method to explore its stereochemistry in the solid-state.

Examination of the asymmery parameters and torsion angles of the title compound reveal that the values are similar to those observed in the analogs viz., 2,4-bis(4-ethoxyphenyl)-7-methyl-3-azabicyclo[3.3.1]nonan-9-one (Park et al., 2012) and 2,4-bis(2-ethoxyphenyl)-7-methyl -3-azabicyclo[3.3.1]nonan-9-one (Parthiban et al., 2011b). The torsion angles of the title compound C2—C8—C6—C7, C1—C2—C8—C6, C2—C8—C6—C5 and C3—C2—C8—C6 are -62.5 (2), 62.3 (2), 62.6 (2) and -62.6 (2)°, respectively, that clearly assign the chair-chair conformation to the bicycle as in the analogs. The orientations of the ethoxyphenyl groups on both sides of the secondary amino group are identified by their torsion angles. The torsion angles C8—C2—C1—C9 and C8—C6—C7—C17 are 179.34 (18) and -178.52 (18)°, respectively. This clearly conform their equatorial orientations and it is very similar to those in 7-methylated 4-ehtoxyphenyl [C3—C2—C1—C7 and its mirror image is 176.7 (5)%, center of symmetry bisects the molecule] and 2-ethoxyphenyl analogs [C8—C6—C7—C15 and C8—C2—C1—C9 are 176.83 (14) and -179.07 (14)°, respectively]. In the title compound, two benzene rings are inclined to each other with an angle of 28.0 (1)° as in 7-methylated analog (26.11 (3)°), while in 7-methylated ortho analog this angle is 12.41 (4)°.

The crystal packing is stabilized by the weak intermolecular C—H···O hydrogen bonds (Table 1) and π–π interactions.

Experimental

The 2,4-bis(4-ethoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-one was synthesized by a modified and an optimized Mannich condensation in one-pot, using 4-ethoxybenzaldehyde (0.1 mol, 15.018 g/13.91 ml), cyclohexanone (0.05 mol, 4.90 g/5.18 ml) and ammonium acetate (0.075 mol, 5.78 g) in a 50 ml of absolute ethanol (Park et al., 2011). The mixture was gently warmed on a hot plate at 303–308 K (30–35° C) with moderate stirring till the complete consumption of the starting materials, which was monitored by TLC. At the end, the crude azabicyclic ketone was separated by filtration and gently washed with 1:5 cold ethanol-ether mixture. X-ray diffraction quality crystals of the title compound were obtained by slow evaporation from ethanol.