2,4-Bis(2-ethoxyphenyl)-7-methyl-3-azabicyclo[3.3.1]nonan-9-one

The crystal structure of the title compound, C25H31NO3, exists in a twin-chair conformation with an equatorial orientation of the ortho-ethoxyphenyl groups. According to Cremer and Pople [Cremer & Pople (1975 ▶), J. Am. Chem. Soc. 97, 1354–1358], both the piperidone and cyclohexanone rings are significantly puckered with total puckering amplitutdes Q T of 0.5889 (18) and 0.554 (2) Å, respectively. The ortho-ethoxyphenyl groups are located on either side of the secondary amino group and make a dihedral angle of 12.41 (4)° with respect to each other. The methyl group on the cyclohexanone part occupies an exocyclic equatorial disposition. The crystal packing is stabilized by weak van der Waals interactions.

The crystal structure of the title compound, C 25 H 31 NO 3 , exists in a twin-chair conformation with an equatorial orientation of the ortho-ethoxyphenyl groups. According to Cremer and Pople [Cremer & Pople (1975), J. Am. Chem. Soc. 97, 1354-1358, both the piperidone and cyclohexanone rings are significantly puckered with total puckering amplitutdes Q T of 0.5889 (18) and 0.554 (2) Å , respectively. The ortho-ethoxyphenyl groups are located on either side of the secondary amino group and make a dihedral angle of 12.41 (4) with respect to each other. The methyl group on the cyclohexanone part occupies an exocyclic equatorial disposition. The crystal packing is stabilized by weak van der Waals interactions.

Comment
The 3-azabicycle nucleus is an important class of pharmacophore due to its broad spectrum of biological activities such as antibacterial, antimycobacterial, antifungal, anticancer, antitussive, antiinflammatory, sedative, antipyretic and calcium antagonistic activity (Jeyaraman & Avila, 1981;Barker et al., 2005;Parthiban et al., 2009aParthiban et al., , 2010bParthiban et al., , 2010cParthiban et al., , 2011. Its biological significane prompted the medicinal chemists to synthesize some structural analogs. Since the stereochemistry plays an important role in biological actions, it is of immense help to establish the stereochemistry of the synthesized bio-potent molecules. Since several stereomers are possible for the synthesized title compound along with different conformations such as chair-chair (Parthiban et al., 2009b(Parthiban et al., , 2009c(Parthiban et al., , 2010aCox et al., 1985), chair-boat (Parthiban et al., 2010c;Smith-Verdier et al., 1983) and boat-boat (Padegimas & Kovacic, 1972), the title compound was undertaken for the present single-crystal XRD study to establish the stereochemistry.
The analysis of torsion angles, asymmetry parameters and puckering parameters calculated for the title compound shows that the piperidine ring slightly deviates the ideal chair conformation. According to Cremer & Pople, the total puckering amplitude, Q T is 0.5889 (18) Å and the phase angle θ is 7.19 (18)° (Cremer & Pople, 1975) for the piperidine ring. Also according to Nardelli, the smallest displacement asymmetry parameters q 2 and q 3 are 0.0741 (18) and 0.5843 (18)°, respectively (Nardelli, 1983).
The above detailed analysis of the title compound C 25 H 31 NO 3 , clearly shows that the compound exists in a twin-chair conformation with an equatorial orientation of the ortho-ethoxyphenyl units on both sides of the secondary amino group.
The ortho-ethoxyphenyl groups are orientated at a dihedral angle of 12.41 (4)° with respect to each other. The methyl group attached to the cyclohexanone part occupies an exocyclic equatorial disposition. The crystal packing is stabilized by weak van der Waals interactions.

Experimental
The 7-methyl-2,4-bis(2-ethoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-one was synthesized by a modified and an optimized Mannich condensation in one-pot, using 2-ethoxybenzaldehyde (0.1 mol, 15.02 g/13.94 ml), 4-methylcyclohexanone (0.05 mol, 5.61 g/6.14 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 supplementary materials sup-2 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) and for methyl H atoms at U iso (H) = 1.5U eq (C).. Fig. 1. Anistropic displacement representation of the molecule with atoms represented with 30% probability ellipsoids.  (3)