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

The crystal structure of the title compound, C21H21F2NO, shows that the compound exists in a twin-chair conformation with an equatorial orientation of the ortho-fluorophenyl groups on either side of the secondary amino group. The title compound is a 1-methylated analog of 2,4-bis(2-fluorophenyl)-3-azabicyclo[3.3.1]nonan-9-one; the two compound both exhibit the same stereochemistry but the orientation of the ortho-fluorophenyl rings differs slightly. In the title compound, the rings are orientated at a dihedral angle of 36.70 (3)° with respect to one another, whereas in the non-methyl analog, the angle is 25.68 (4)°. The crystal structure of the title compound is stabilized by an intermolecular N—H⋯π interaction and a weak C—H⋯F interaction.

The crystal structure of the title compound, C 21 H 21 F 2 NO, shows that the compound exists in a twin-chair conformation with an equatorial orientation of the ortho-fluorophenyl groups on either side of the secondary amino group. The title compound is a 1-methylated analog of 2,4-bis(2-fluorophenyl)-3-azabicyclo[3.3.1]nonan-9-one; the two compound both exhibit the same stereochemistry but the orientation of the ortho-fluorophenyl rings differs slightly. In the title compound, the rings are orientated at a dihedral angle of 36.70 (3) with respect to one another, whereas in the non-methyl analog, the angle is 25.68 (4) . The crystal structure of the title compound is stabilized by an intermolecular N-HÁ Á Á interaction and a weak C-HÁ Á ÁF interaction.

Comment
Molecules with the 3-azabicyclo[3.3.1]nonane nucleus are of great interest due to their presence in a wide variety of naturally occurring diterpenoid/norditerpenoid alkaloids and their broad-spectrum biological activities such as antimicrobial, analgesic, antogonistic, anti-inflammatory, local anesthetic hypotensive activity and so on (Parthiban, Aridoss et al. 2009;Hardick et al. 1996;Jeyaraman & Avila, 1981). Hence, the synthesis of new molecules with the 3-azabicyclo[3.3.1]nonane nucleus and their stereochemical investigation are of interest in the field of medicinal chemistry. Also, the stereochemistry of the synthesized molecules is a major criterium for their biological response. Hence, it is important to establish the stereochemistry of the bio-active molecules. As a consequence, the present study was undertaken to examine the configuration and conformation of the synthesized title compound.
The study of asymmetry parameters, ring puckering parameters, torsion angles and least-square planes calculated for the title compound shows that the bicycle exist in a twin-chair conformation. Of the chairs, the piperidine ring exists in a near ideal chair conformation with a total puckering amplitude Q T of 0.605 (2) Å and a phase angle θ of 179.46 (19)° (Cremer & Pople, 1975). The smallest displacement asymmetry parameters are q 2 = 0.015 (2) and q 3 = -0.605 (2) Å (Nardelli, 1983).
Hence the title compound, C 21 H 21 F 2 NO, exists in a twin-chair conformation with equatorial orientation of the orthofluorophenyl groups on both sides of the secondary amino group on the heterocycle. The stereochemistry of the title compound resembles that of its non-methyl analog 2,4-bis(2-fluorophenyl) -3-azabicyclo[3.3.1]nonan-9-one. However, the orientation of the ortho-fluorophenyl rings differ slightly. In the title compound, the ortho-fluorophenyl rings are orientated at an angle of 36.70 (3)° with respect to one another whereas in the non-methyl analog, they are orientated at an angle of 25.68 (4)°.

Experimental
The title compound was synthesized by a modified Mannich reaction in one-pot using 0.1 mol (12.41 g/10.52 ml) orthofluorobenzaldehyde, 0.05 mol (5.61 g/6.07 ml) 2-methlycyclohexanone and 0.075 mol (5.78 g) ammonium acetate in 50 ml of absolute ethanol. The mixture was gently warmed on a hot plate at 303-308 K (30-35° C) with moderate stirring overnight.
The reaction was monitored by TLC. After all starting material was used up, the crude compound was separated by filtration and washed with a 1:5 ethanol-ether mixture. X-ray diffraction quality crystals of 1-methyl-2,4-bis(2-fluorophenyl)-3azabicyclo[3.3.1]nonan-9-one were obtained by slow evoporation 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, methylene C-H = 0.97 Å, methine C-H = 0.98 Å and methyl C-H = 0.96 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 atU iso (H) = 1.5U eq (C) Figures   Fig. 1. Anistropic displacement representation of the molecule with atoms represented with 30% probability ellipsoids.