supplementary materials


aa2083 scheme

Acta Cryst. (2013). E69, o768    [ doi:10.1107/S1600536813010180 ]

2,4-Bis(furan-2-yl)-1,5-dimethyl-3-azabicyclo[3.3.1]nonan-9-one

R. Venkateswaramoorthi, S. Rizwana Begum, R. Hema, K. Krishnasamy and A. G. Anitha

Abstract top

In the title compound, C18H21NO3, the bicyclic ring system adopts a twin-chair conformation. The two methyl groups attached to the bicycle are in an equatorial orientation for both rings. One of the furan rings is disordered over two orientations with an occupancy ratio of 0.686 (6):0.314 (6). In the crystal, very long N-H...O hydrogen bonds connect the molecules into a chain perpendicular to the ac plane.

Comment top

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 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 investigations 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.

In the crystal structure of the title compound, the bicycle system adopts twin-chair conformation with puckering parameters Q = 0.571 (2) Å, θ = 178.3 (2)° and φ = 360 (5)° for the piperidine ring N1/C2/C3/C8/C7/C9 and Q = 0.568 (2) Å, θ = 168.0 (2)° and φ = 121.4 (10)° for the cyclohexanone ring C3/C4/C5/C6/C7/C8 (Cremer & Pople, 1975).

The dihedral angle between the furyl ring C21/C22/C23/C24/O2 and the piperidine ring N1/C2/C3/C8/C7/C9 is 70.09 (8)° and the disordered furyl ring makes with the same piperidine ring two dihedral angles of 70.83 (23)° for major part C91/C92/C93/C94/O3 and 67.40 (36)° for minor part C91/C92'/C93'/C94'/O3'. The methyl groups attached at C7 and C3 are in equitorial orientation with torsion angles of 175.31 (19)° (N1–C9–C7–C11) and -174.72 (17)° (N1–C2–C3–C10).

Related literature top

For the synthesis and biological activity of 3-azabicyclo[3.3.1] nonan-9-ones, see: Parthiban et al. (2009); Hardick et al. (1996); Jeyaraman & Avila (1981). For puckering parameters, see: Cremer & Pople (1975).

Experimental top

The title compound was obtained by condensation of 2,6-dimethylcyclohexanone, furfuraldehyde and ammonium acetate in 1:2:1 ratio in ethanol. The reaction mixture was warmed and stirred until the completion of reaction. The crude product was washed with an ethanol - ethyl ether (1:5) mixture and recrystallized from ethanol - chloroform (1:1) to obtain the pure compound.

Refinement top

The methyl H atoms were constrained to an ideal geometry (C—H = 0.96 Å) with Uiso(H) = 1.5Ueq(C), but were allowed to rotate freely about the C—C bonds. All remaining H atoms were placed in geometrically idealized positions (C—H = 0.93–0.98 Å) and constrained to ride on their parent atoms with Uiso(H) = 1.2Ueq(C). In order to bring the Uij parameters of the disordered atoms to the tolerant levels the restraints SADI, SIMU and ISOR were used.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. View of the molecule of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary radii.
2,4-Bis(furan-2-yl)-1,5-dimethyl-3-azabicyclo[3.3.1]nonan-9-one top
Crystal data top
C18H21NO3F(000) = 1280
Mr = 299.36Dx = 1.252 Mg m3
Monoclinic, C2/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -C 2ycCell parameters from 11487 reflections
a = 21.268 (2) Åθ = 1.8–28.4°
b = 6.7031 (9) ŵ = 0.09 mm1
c = 22.303 (2) ÅT = 293 K
β = 92.776 (6)°Block, brown
V = 3175.7 (6) Å30.30 × 0.25 × 0.20 mm
Z = 8
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2127 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.031
Graphite monochromatorθmax = 25.0°, θmin = 1.9°
ω scanh = 2325
11487 measured reflectionsk = 57
2784 independent reflectionsl = 2226
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.130 w = 1/[σ2(Fo2) + (0.0637P)2 + 1.7182P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
2784 reflectionsΔρmax = 0.19 e Å3
252 parametersΔρmin = 0.20 e Å3
220 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0024 (5)
Crystal data top
C18H21NO3V = 3175.7 (6) Å3
Mr = 299.36Z = 8
Monoclinic, C2/cMo Kα radiation
a = 21.268 (2) ŵ = 0.09 mm1
b = 6.7031 (9) ÅT = 293 K
c = 22.303 (2) Å0.30 × 0.25 × 0.20 mm
β = 92.776 (6)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
2127 reflections with I > 2σ(I)
11487 measured reflectionsRint = 0.031
2784 independent reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.044H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.130Δρmax = 0.19 e Å3
S = 1.05Δρmin = 0.20 e Å3
2784 reflectionsAbsolute structure: ?
252 parametersFlack parameter: ?
220 restraintsRogers parameter: ?
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 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 (Å2) top
xyzUiso*/UeqOcc. (<1)
N10.17290 (7)0.0845 (3)0.13064 (7)0.0446 (4)
H10.1765 (10)0.215 (4)0.1368 (9)0.058 (6)*
C20.23315 (8)0.0076 (3)0.15048 (8)0.0391 (4)
H20.23980.01980.19350.047*
C30.23109 (8)0.2391 (3)0.14260 (8)0.0403 (4)
C40.21984 (10)0.3083 (3)0.07672 (8)0.0506 (5)
H4A0.25300.25390.05320.061*
H4B0.22330.45260.07550.061*
C50.15671 (10)0.2485 (3)0.04728 (9)0.0562 (6)
H5A0.15010.32090.00980.067*
H5B0.15730.10720.03800.067*
C60.10205 (10)0.2917 (3)0.08770 (9)0.0544 (5)
H6A0.09420.43420.08730.065*
H6B0.06460.22670.07060.065*
C70.11233 (9)0.2234 (3)0.15358 (8)0.0455 (5)
C80.17479 (9)0.3139 (3)0.17506 (8)0.0444 (5)
C90.11855 (8)0.0068 (3)0.16110 (9)0.0461 (5)
H90.12590.03370.20410.055*
C100.29224 (10)0.3283 (3)0.16918 (10)0.0595 (6)
H10A0.30070.27610.20880.089*
H10B0.32620.29410.14430.089*
H10C0.28830.47080.17110.089*
C110.05852 (10)0.2986 (4)0.19039 (11)0.0701 (7)
H11A0.05910.44170.19140.105*
H11B0.01910.25370.17240.105*
H11C0.06350.24760.23060.105*
C210.28552 (8)0.0899 (3)0.11924 (8)0.0418 (4)
C220.34330 (9)0.1509 (3)0.13830 (10)0.0559 (5)
H220.36110.14050.17710.067*
C230.37202 (10)0.2347 (3)0.08755 (11)0.0627 (6)
H230.41220.28930.08690.075*
C240.33033 (10)0.2198 (3)0.04147 (11)0.0616 (6)
H240.33680.26370.00270.074*
O10.17859 (7)0.4444 (3)0.21255 (7)0.0744 (5)
O20.27645 (6)0.1308 (2)0.05925 (6)0.0564 (4)
C910.0595 (4)0.114 (2)0.1410 (2)0.0532 (11)0.686 (6)
C920.0368 (2)0.1727 (7)0.0867 (2)0.0656 (11)0.686 (6)
H920.05610.16160.05030.079*0.686 (6)
C930.0247 (4)0.2576 (19)0.0973 (3)0.0883 (17)0.686 (6)
H930.05350.30890.06860.106*0.686 (6)
C940.03169 (18)0.2467 (7)0.1581 (3)0.0947 (15)0.686 (6)
H940.06670.29340.17720.114*0.686 (6)
O30.02057 (15)0.1562 (6)0.18791 (19)0.0811 (11)0.686 (6)
C91'0.0638 (9)0.116 (5)0.1303 (6)0.064 (2)0.314 (6)
C92'0.0621 (4)0.1568 (14)0.0708 (4)0.0480 (18)0.314 (6)
H92'0.09290.13180.04360.058*0.314 (6)
C93'0.0022 (4)0.2467 (14)0.0597 (5)0.082 (2)0.314 (6)
H93'0.01370.28750.02210.098*0.314 (6)
C94'0.0289 (9)0.265 (4)0.1116 (7)0.082 (2)0.314 (6)
H94'0.06800.32450.11580.099*0.314 (6)
O3'0.0093 (4)0.1787 (15)0.1571 (5)0.094 (2)0.314 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0369 (8)0.0346 (9)0.0622 (10)0.0025 (7)0.0027 (7)0.0001 (7)
C20.0388 (9)0.0386 (10)0.0398 (9)0.0028 (8)0.0001 (7)0.0037 (8)
C30.0432 (10)0.0366 (10)0.0414 (10)0.0047 (8)0.0041 (8)0.0007 (8)
C40.0621 (12)0.0438 (11)0.0471 (11)0.0023 (9)0.0137 (9)0.0073 (9)
C50.0743 (14)0.0538 (13)0.0401 (10)0.0032 (11)0.0026 (10)0.0072 (9)
C60.0555 (12)0.0462 (12)0.0607 (13)0.0067 (9)0.0071 (10)0.0054 (9)
C70.0431 (10)0.0451 (11)0.0486 (11)0.0034 (8)0.0069 (8)0.0035 (8)
C80.0551 (11)0.0418 (11)0.0365 (9)0.0000 (8)0.0039 (8)0.0026 (8)
C90.0386 (10)0.0501 (12)0.0499 (11)0.0001 (9)0.0054 (8)0.0064 (9)
C100.0556 (12)0.0497 (12)0.0733 (14)0.0126 (10)0.0026 (10)0.0093 (11)
C110.0558 (13)0.0720 (16)0.0838 (16)0.0081 (11)0.0176 (12)0.0169 (13)
C210.0400 (10)0.0379 (10)0.0473 (10)0.0038 (8)0.0005 (8)0.0019 (8)
C220.0410 (11)0.0607 (14)0.0654 (13)0.0006 (9)0.0031 (9)0.0045 (11)
C230.0416 (11)0.0576 (14)0.0899 (17)0.0072 (10)0.0141 (11)0.0002 (12)
C240.0550 (13)0.0567 (14)0.0746 (15)0.0069 (10)0.0171 (11)0.0122 (11)
O10.0700 (10)0.0808 (12)0.0729 (10)0.0022 (8)0.0074 (8)0.0381 (9)
O20.0516 (8)0.0614 (10)0.0559 (9)0.0083 (7)0.0004 (6)0.0124 (7)
C910.029 (2)0.045 (2)0.086 (3)0.0037 (18)0.0108 (19)0.010 (3)
C920.038 (2)0.058 (2)0.098 (3)0.010 (2)0.018 (2)0.007 (2)
C930.049 (3)0.076 (3)0.138 (4)0.009 (2)0.016 (3)0.005 (4)
C940.0333 (18)0.089 (3)0.162 (4)0.0174 (18)0.000 (2)0.018 (3)
O30.0495 (16)0.090 (2)0.105 (3)0.0131 (13)0.0101 (16)0.013 (2)
C91'0.042 (4)0.058 (4)0.092 (4)0.003 (4)0.017 (4)0.014 (4)
C92'0.025 (3)0.054 (3)0.064 (4)0.016 (3)0.003 (3)0.004 (3)
C93'0.057 (4)0.073 (4)0.114 (5)0.004 (4)0.021 (4)0.000 (4)
C94'0.043 (4)0.072 (4)0.130 (5)0.014 (4)0.009 (4)0.002 (5)
O3'0.066 (4)0.084 (3)0.133 (4)0.008 (3)0.009 (4)0.007 (4)
Geometric parameters (Å, º) top
N1—C91.464 (2)C11—H11A0.9600
N1—C21.471 (2)C11—H11B0.9600
N1—H10.89 (2)C11—H11C0.9600
C2—C211.493 (2)C21—C221.344 (3)
C2—C31.562 (3)C21—O21.370 (2)
C2—H20.9800C22—C231.427 (3)
C3—C81.514 (3)C22—H220.9300
C3—C101.525 (3)C23—C241.328 (3)
C3—C41.548 (3)C23—H230.9300
C4—C51.520 (3)C24—O21.368 (2)
C4—H4A0.9700C24—H240.9300
C4—H4B0.9700C91—C921.342 (5)
C5—C61.533 (3)C91—O31.393 (4)
C5—H5A0.9700C92—C931.455 (7)
C5—H5B0.9700C92—H920.9300
C6—C71.544 (3)C93—C941.373 (7)
C6—H6A0.9700C93—H930.9300
C6—H6B0.9700C94—O31.405 (5)
C7—C81.517 (3)C94—H940.9300
C7—C111.526 (3)C91'—C92'1.353 (8)
C7—C91.557 (3)C91'—O3'1.395 (8)
C8—O11.210 (2)C92'—C93'1.421 (7)
C9—C911.497 (4)C92'—H92'0.9300
C9—C91'1.512 (8)C93'—C94'1.366 (10)
C9—H90.9800C93'—H93'0.9300
C10—H10A0.9600C94'—O3'1.396 (9)
C10—H10B0.9600C94'—H94'0.9300
C10—H10C0.9600
C9—N1—C2114.00 (15)C3—C10—H10A109.5
C9—N1—H1110.0 (13)C3—C10—H10B109.5
C2—N1—H1107.4 (14)H10A—C10—H10B109.5
N1—C2—C21109.54 (15)C3—C10—H10C109.5
N1—C2—C3111.35 (14)H10A—C10—H10C109.5
C21—C2—C3113.59 (14)H10B—C10—H10C109.5
N1—C2—H2107.4C7—C11—H11A109.5
C21—C2—H2107.4C7—C11—H11B109.5
C3—C2—H2107.4H11A—C11—H11B109.5
C8—C3—C10111.32 (16)C7—C11—H11C109.5
C8—C3—C4105.37 (15)H11A—C11—H11C109.5
C10—C3—C4109.95 (16)H11B—C11—H11C109.5
C8—C3—C2107.08 (14)C22—C21—O2109.35 (17)
C10—C3—C2109.08 (15)C22—C21—C2132.61 (18)
C4—C3—C2113.99 (15)O2—C21—C2118.04 (15)
C5—C4—C3115.06 (16)C21—C22—C23106.79 (19)
C5—C4—H4A108.5C21—C22—H22126.6
C3—C4—H4A108.5C23—C22—H22126.6
C5—C4—H4B108.5C24—C23—C22106.79 (18)
C3—C4—H4B108.5C24—C23—H23126.6
H4A—C4—H4B107.5C22—C23—H23126.6
C4—C5—C6112.07 (17)C23—C24—O2110.22 (19)
C4—C5—H5A109.2C23—C24—H24124.9
C6—C5—H5A109.2O2—C24—H24124.9
C4—C5—H5B109.2C24—O2—C21106.86 (16)
C6—C5—H5B109.2C92—C91—O3114.7 (3)
H5A—C5—H5B107.9C92—C91—C9132.1 (4)
C5—C6—C7115.29 (16)O3—C91—C9113.2 (3)
C5—C6—H6A108.5C91—C92—C93104.8 (4)
C7—C6—H6A108.5C91—C92—H92127.6
C5—C6—H6B108.5C93—C92—H92127.6
C7—C6—H6B108.5C94—C93—C92106.3 (5)
H6A—C6—H6B107.5C94—C93—H93126.9
C8—C7—C11111.48 (16)C92—C93—H93126.9
C8—C7—C6105.26 (15)C93—C94—O3111.7 (5)
C11—C7—C6109.79 (17)C93—C94—H94124.2
C8—C7—C9107.09 (15)O3—C94—H94124.2
C11—C7—C9109.36 (17)C91—O3—C94102.6 (4)
C6—C7—C9113.80 (16)C92'—C91'—O3'112.1 (7)
O1—C8—C3122.80 (18)C92'—C91'—C9121.8 (8)
O1—C8—C7122.38 (17)O3'—C91'—C9126.1 (8)
C3—C8—C7114.66 (15)C91'—C92'—C93'103.8 (7)
N1—C9—C91111.1 (4)C91'—C92'—H92'128.1
N1—C9—C91'103.0 (10)C93'—C92'—H92'128.1
N1—C9—C7111.54 (15)C94'—C93'—C92'111.0 (10)
C91—C9—C7112.2 (6)C94'—C93'—H93'124.5
C91'—C9—C7111.8 (15)C92'—C93'—H93'124.5
N1—C9—H9107.2C93'—C94'—O3'106.8 (11)
C91—C9—H9107.2C93'—C94'—H94'126.6
C91'—C9—H9116.0O3'—C94'—H94'126.6
C7—C9—H9107.2C91'—O3'—C94'106.3 (9)
C9—N1—C2—C21176.84 (14)C6—C7—C9—C91'53.2 (5)
C9—N1—C2—C356.7 (2)N1—C2—C21—C22137.4 (2)
N1—C2—C3—C854.15 (19)C3—C2—C21—C2297.4 (2)
C21—C2—C3—C8178.38 (14)N1—C2—C21—O242.4 (2)
N1—C2—C3—C10174.73 (15)C3—C2—C21—O282.80 (19)
C21—C2—C3—C1061.0 (2)O2—C21—C22—C230.1 (2)
N1—C2—C3—C462.0 (2)C2—C21—C22—C23179.75 (19)
C21—C2—C3—C462.3 (2)C21—C22—C23—C240.1 (3)
C8—C3—C4—C553.4 (2)C22—C23—C24—O20.2 (3)
C10—C3—C4—C5173.44 (17)C23—C24—O2—C210.3 (2)
C2—C3—C4—C563.7 (2)C22—C21—O2—C240.2 (2)
C3—C4—C5—C646.9 (2)C2—C21—O2—C24179.64 (16)
C4—C5—C6—C746.7 (2)N1—C9—C91—C9242.8 (16)
C5—C6—C7—C852.7 (2)C91'—C9—C91—C927 (11)
C5—C6—C7—C11172.77 (18)C7—C9—C91—C9282.9 (14)
C5—C6—C7—C964.3 (2)N1—C9—C91—O3138.8 (8)
C10—C3—C8—O17.6 (3)C91'—C9—C91—O3175 (13)
C4—C3—C8—O1111.5 (2)C7—C9—C91—O395.6 (10)
C2—C3—C8—O1126.8 (2)O3—C91—C92—C932.0 (13)
C10—C3—C8—C7176.76 (16)C9—C91—C92—C93176.5 (14)
C4—C3—C8—C764.1 (2)C91—C92—C93—C941.9 (11)
C2—C3—C8—C757.6 (2)C92—C93—C94—O31.3 (10)
C11—C7—C8—O17.1 (3)C92—C91—O3—C941.2 (12)
C6—C7—C8—O1111.9 (2)C9—C91—O3—C94177.5 (8)
C9—C7—C8—O1126.7 (2)C93—C94—O3—C910.2 (10)
C11—C7—C8—C3177.27 (17)N1—C9—C91'—C92'37 (3)
C6—C7—C8—C363.8 (2)C91—C9—C91'—C92'177 (15)
C9—C7—C8—C357.7 (2)C7—C9—C91'—C92'83 (3)
C2—N1—C9—C91177.1 (5)N1—C9—C91'—O3'146 (3)
C2—N1—C9—C91'176.8 (13)C91—C9—C91'—O3'0 (9)
C2—N1—C9—C756.8 (2)C7—C9—C91'—O3'95 (3)
C8—C7—C9—N154.4 (2)O3'—C91'—C92'—C93'1 (3)
C11—C7—C9—N1175.29 (16)C9—C91'—C92'—C93'176 (3)
C6—C7—C9—N161.5 (2)C91'—C92'—C93'—C94'3 (2)
C8—C7—C9—C91179.8 (2)C92'—C93'—C94'—O3'3 (3)
C11—C7—C9—C9159.3 (3)C92'—C91'—O3'—C94'0 (3)
C6—C7—C9—C9163.9 (3)C9—C91'—O3'—C94'178 (3)
C8—C7—C9—C91'169.1 (5)C93'—C94'—O3'—C91'2 (3)
C11—C7—C9—C91'70.0 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.89 (2)2.84 (2)3.647 (2)152.0 (13)
Symmetry code: (i) x, y+1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.89 (2)2.84 (2)3.647 (2)152.0 (13)
Symmetry code: (i) x, y+1, z.
references
References top

Bruker (2008). APEX2 and SAINT . Bruker AXS Inc., Madison, Wisconsin, USA.

Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.

Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.

Hardick, D. J., Blagbrough, I. S., Cooper, G., Potter, B. V. L., Critchley, T. & Wonnacott, S. (1996). J. Med. Chem. 39, 4860–4866.

Jeyaraman, R. & Avila, S. (1981). Chem. Rev. 81, 149–174.

Parthiban, P., Aridoss, G., Rathika, P., Ramkumar, V. & Kabilan, S. (2009). Bioorg. Med. Chem. Lett. 19, 6981–6985.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.