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

In the title compound, C25H30NO3, a crystallographic mirror plane bisects the molecule. Although it is a positional isomer of 2,4-bis(4-ethoxyphenyl)-7-methyl-3-azabicyclo[3.3.1]nonan-9-one [C25H31NO3, M r = 393.51; Park et al. (2012c ▶). Acta Cryst. E68, o779–780], its molecular weight is 392.50 due to the 50:50 ratio of the methyl group at bridgehead C atoms. However, the title compound exists in the same twin-chair conformation as its 7-methyl isomer. Also, the 4-ethoxyphenyl groups are equatorially oriented on the bicycle as in its isomer. In the title compound, the cyclohexanone ring deviates from an ideal chair (total puckering amplitude Q T = 0.5390 Å) and the piperidone ring is closer to an ideal chair (Q T = 0.6064 Å). These Q T values are very similar to those of its isomer. Even though a center of symmetry passes through the 7-methyl analog, the benzene rings are oriented 26.11 (3)° with respect to each other, whereas the orientation is 53.10 (3)° for the title compound. The title compound exhibits intermolecular N—H⋯O interactions [H⋯A = 2.25 (2) Å, versus 2.26 (2) Å for the analog].

In the title compound, C 25 H 30 NO 3 , a crystallographic mirror plane bisects the molecule. Although it is a positional isomer of 2,4-bis(4-ethoxyphenyl)-7-methyl-3-azabicyclo[3.3.1]nonan-9-one [C 25 H 31 NO 3 , M r = 393.51; Park et al. (2012c). Acta Cryst. E68, o779-780], its molecular weight is 392.50 due to the 50:50 ratio of the methyl group at bridgehead C atoms. However, the title compound exists in the same twin-chair conformation as its 7-methyl isomer. Also, the 4-ethoxyphenyl groups are equatorially oriented on the bicycle as in its isomer. In the title compound, the cyclohexanone ring deviates from an ideal chair (total puckering amplitude Q T = 0.5390 Å ) and the piperidone ring is closer to an ideal chair (Q T = 0.6064 Å ). These Q T values are very similar to those of its isomer. Even though a center of symmetry passes through the 7-methyl analog, the benzene rings are oriented 26.11 (3) with respect to each other, whereas the orientation is 53.10 (3) for the title compound. The title compound exhibits intermolecular N-HÁ Á ÁO interactions [HÁ Á ÁA = 2.25 (2) Å , versus 2.26 (2) Å for the analog].

Comment
Synthesis and stereochemical analysis of the 3-azabicyclononanes are interesting due to their biological actions (Park et al., 2012a). Stereochemical analysis of the biologically active molecules are crucial in drug-design and drug-development programs. Hence, we synthesized the title compound by a modified and an optimized successive double Mannich condensation in one-pot in order to explore its stereochemistry in solid-state.
The detailed analysis and comparison of the torsion angles clearly indicates that the title molecule, C 25 H 30 NO 3 , exists in a twin-chair conformation with an equatorial orientation of the 4-ethoxyphenyl groups on both sides of the secondary amino group.

Experimental
The title compound 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), 2-methylcyclohexanone (0.05 mol, 5.61 g/6.07 ml) and ammonium acetate (0.075 mol, 5.78 g) in a 50 ml of absolute ethanol (Park et al., 2011a). 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 = 0.98 Å 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).

Figure 1
Anisotropic displacement representation of the molecule with atoms represented with 30% probability ellipsoids.  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ.  (2)