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

In the title compound, C28H37NO3, a crystallographic mirror plane bisects the molecule (one half-molecule in the asymmetric unit). The title compound exists in a twin-chair conformation with an equatorial orientation of the 4-butoxyphenyl groups. Both sides of the secondary amino group carry the 4-butoxyphenyl groups at an angle of 38.54 (3)° with respect to one another.

In the title compound, C 28 H 37 NO 3 , a crystallographic mirror plane bisects the molecule (one half-molecule in the asymmetric unit). The title compound exists in a twin-chair conformation with an equatorial orientation of the 4-butoxyphenyl groups. Both sides of the secondary amino group carry the 4-butoxyphenyl groups at an angle of 38.54 (3) with respect to one another.

Comment
Naturally abundant diterpenoid/norditerpenoid alkaloids contain the 3-azabicyclononane nucleus, which is an important class of pharmacophore due to its broad spectrum of biological activities such as antibacterial, antimycobacterial, antifungal, anticancer, antitussive, anti-inflammatory, sedative, antipyretic and calcium antagonistic activity (Jeyaraman & Avila, 1981; Barker et al., 2005;Parthiban et al., 2009aParthiban et al., , 2010bParthiban et al., , 2010c. Its biological significant prompted the medicinal chemists to synthesize some structural analogs. Since the stereochemistry plays an important role in biological actions, it is important to establish the stereochemistry of the synthesized bio-potent molecules. For the synthesized title compound, several stereomers are possible with conformations such as chair-chair (Parthiban et al., 2009b(Parthiban et al., , 2009c(Parthiban et al., , 2010aCox et al., 1985), chair-boat (Smith-Verdier et al., 1983) and boat-boat (Padegimas & Kovacic, 1972). Hence, the title crystal was undertaken for this study to explore its stereochemistry, unambiguously.
The analysis of torsion angles, asymmetry parameters and puckering parameters calculated for the title compound shows that the piperidine ring adopts a near ideal chair conformation. According to Cremer & Pople, the total puckering amplitude, Q T is -0.613 (2) Å and the phase angle θ is 178.67 (19)° (Cremer & Pople, 1975). The smallest displacement asymmetry parameters q 2 and q 3 are 0.005 (2) and -0.612 (2)°, respectively (Nardelli, 1983). However, the cyclohexane ring deviates from the ideal chair conformation according to Cremer and Pople by Q T = 0.573 (2) and θ = 16.1 (2)° (Cremer & Pople, 1975) as well as Nardelli by q 2 = 0.158 (2) and q 3 = 0.550 (2)° (Nardelli, 1983). Hence, the title compound C 28 H 37 NO 3 , exists in a twin-chair conformation with equatorial orientation of the 4-butoxyphenyl groups on both sides of the secondary amino group on the heterocycle. The aryl groups are orientated at an angle of 38.54 (3)° to each other. The torsion angle of C3-C2-C1-C6 and its mirror image is 176.03 (4)°. The crystal packing is stabilized by weak van der Waals interactions.

Experimental
The title compound was synthesized by a modified and an optimized Mannich condensation in one-pot, using 4-butoxybenzaldehyde (0.1 mol, 17.82 g/17.29 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. 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.

Refinement
The nitrogen H atom was located in a difference Fourier map and refined isotropically. Other hydrogen atoms were fixed geometrically and allowed to ride on the parent carbon atoms with aromatic C-H = 0.93 Å, aliphatic C-H = 0.98Å and methylene C-H = 0.97 Å. The displacement parameters were set for phenyl, methylene and aliphatic H atoms at U iso (H) = 1.2U eq (C).