2,4-Bis(3-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one.

In the crystal structure, the title compound, C(22)H(25)NO(3), exists in a twin-chair conformation with equatorial orientations of the meta-methoxy-phenyl groups on both sides of the secondary amino group. The title compound is a positional isomer of 2,4-bis-(2-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one and 2,4-bis-(4-methoxy-phen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one, which both also exhibit twin-chair conformations with equatorial dispositions of the anisyl rings on both sides of the secondary amino group. In the title compound, the meta-methoxy-phenyl rings are orientated at an angle of 25.02 (3)° with respect to each other, whereas in the ortho and para isomers, the anisyl rings are orientated at dihedral angles of 33.86 (3) and 37.43 (4)°, respectively. The crystal packing is dominated by van der Waals inter-actions and by an inter-molecular N-H⋯O hydrogen bond, whereas in the ortho isomer, an inter-molecular N-H⋯π inter-action (H⋯Cg = 2.75 Å) is found.

Related literature

For the synthesis and biological activity of 3-aza­bicyclo­[3.3.1]nonan-9-ones, see: Jeyaraman & Avila (1981 ▶). For the nicotinic acetyl­choline receptor antogonistic activity of diter­penoid/norditerpenoid alkaloids, see: Hardick et al. (1996 ▶); Barker et al. (2005 ▶). For the structures of the ortho and para OMe-substitued isomers, see: Parthiban et al. (2009a ▶); Cox et al. (1985 ▶). For related structures, see: Parthiban et al. (2008a ▶,b ▶,c ▶, 2009b ▶,c ▶), Smith-Verdier et al. (1983 ▶); Padegimas & Kovacic (1972 ▶). For ring puckering analysis, see: Cremer & Pople (1975 ▶); Nardelli (1983 ▶).

Experimental

Crystal data

C22H25NO3

M = 351.43

Monoclinic,

a = 22.3843 (9) Å

b = 6.5666 (3) Å

c = 13.0745 (4) Å

β = 106.382 (2)°

V = 1843.78 (13) Å3

Z = 4

Mo Kα radiation

μ = 0.08 mm−1

T = 298 K

0.40 × 0.28 × 0.15 mm

Data collection

Bruker APEXII CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 1999 ▶) T min = 0.967, T max = 0.988

12835 measured reflections

3971 independent reflections

2326 reflections with I > 2σ(I)

R int = 0.037

Refinement

R[F 2 > 2σ(F 2)] = 0.049

wR(F 2) = 0.136

S = 1.06

3971 reflections

241 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.30 e Å−3

Δρmin = −0.23 e Å−3

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: APEX2 and SAINT-Plus (Bruker, 2004 ▶); data reduction: SAINT-Plus and XPREP (Bruker, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809050697/zl2238sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050697/zl2238Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C22H25NO3	F(000) = 752
Mr = 351.43	Dx = 1.266 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 2453 reflections
a = 22.3843 (9) Å	θ = 2.9–22.7°
b = 6.5666 (3) Å	µ = 0.08 mm−1
c = 13.0745 (4) Å	T = 298 K
β = 106.382 (2)°	Block, colourless
V = 1843.78 (13) Å3	0.40 × 0.28 × 0.15 mm
Z = 4

Bruker APEXII CCD area-detector diffractometer	3971 independent reflections
Radiation source: fine-focus sealed tube	2326 reflections with I > 2σ(I)
graphite	Rint = 0.037
phi and ω scans	θmax = 28.3°, θmin = 2.9°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −27→28
Tmin = 0.967, Tmax = 0.988	k = −7→8
12835 measured reflections	l = −12→17

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.049	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.136	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0643P)2] where P = (Fo2 + 2Fc2)/3
3971 reflections	(Δ/σ)max < 0.001
241 parameters	Δρmax = 0.30 e Å−3
0 restraints	Δρmin = −0.23 e Å−3

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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.

	x	y	z	Uiso*/Ueq
C1	0.32467 (7)	0.5186 (3)	0.49436 (13)	0.0356 (4)
H1	0.3471	0.6483	0.5098	0.043*
C2	0.30802 (8)	0.4800 (3)	0.37207 (13)	0.0388 (5)
H2	0.3464	0.4857	0.3502	0.047*
C3	0.27531 (9)	0.2775 (3)	0.33443 (15)	0.0479 (5)
H3A	0.2724	0.2589	0.2596	0.057*
H3B	0.3005	0.1674	0.3737	0.057*
C4	0.21054 (10)	0.2635 (3)	0.34870 (16)	0.0573 (6)
H4A	0.1892	0.1478	0.3085	0.069*
H4B	0.2141	0.2393	0.4234	0.069*
C5	0.17173 (9)	0.4527 (3)	0.31292 (15)	0.0484 (5)
H5A	0.1356	0.4469	0.3398	0.058*
H5B	0.1569	0.4529	0.2357	0.058*
C6	0.20648 (8)	0.6525 (3)	0.34984 (13)	0.0398 (4)
H6	0.1807	0.7660	0.3133	0.048*
C7	0.22453 (7)	0.6922 (3)	0.47199 (13)	0.0376 (4)
H7	0.2460	0.8237	0.4860	0.045*
C8	0.26600 (8)	0.6491 (3)	0.31776 (13)	0.0382 (4)
C9	0.36693 (7)	0.3516 (3)	0.55456 (12)	0.0351 (4)
C10	0.34445 (8)	0.1866 (3)	0.59844 (13)	0.0430 (5)
H10	0.3024	0.1796	0.5947	0.052*
C11	0.38393 (9)	0.0330 (3)	0.64743 (15)	0.0495 (5)
H11	0.3682	−0.0761	0.6771	0.059*
C12	0.44674 (9)	0.0379 (3)	0.65342 (14)	0.0489 (5)
H12	0.4732	−0.0664	0.6869	0.059*
C13	0.46919 (8)	0.2005 (3)	0.60884 (14)	0.0419 (5)
C14	0.42955 (8)	0.3570 (3)	0.56051 (13)	0.0386 (4)
H14	0.4453	0.4671	0.5317	0.046*
C15	0.16734 (8)	0.7034 (3)	0.51186 (13)	0.0371 (4)
C16	0.13403 (8)	0.8838 (3)	0.50128 (15)	0.0473 (5)
H16	0.1471	0.9958	0.4697	0.057*
C17	0.08192 (9)	0.8993 (3)	0.53688 (16)	0.0532 (5)
H17	0.0604	1.0220	0.5296	0.064*
C18	0.06116 (8)	0.7346 (3)	0.58332 (15)	0.0478 (5)
H18	0.0258	0.7451	0.6070	0.057*
C19	0.09401 (8)	0.5548 (3)	0.59381 (14)	0.0409 (5)
C20	0.14652 (8)	0.5399 (3)	0.55826 (14)	0.0403 (5)
H20	0.1681	0.4173	0.5658	0.048*
C21	0.57145 (9)	0.0580 (3)	0.65086 (19)	0.0692 (7)
H21A	0.5747	0.0431	0.7253	0.104*
H21B	0.6118	0.0868	0.6423	0.104*
H21C	0.5557	−0.0659	0.6141	0.104*
C22	0.03130 (10)	0.3935 (4)	0.69181 (18)	0.0737 (7)
H22A	0.0429	0.4937	0.7474	0.111*
H22B	0.0268	0.2633	0.7223	0.111*
H22C	−0.0075	0.4317	0.6421	0.111*
N1	0.26760 (6)	0.5346 (2)	0.52819 (12)	0.0370 (4)
O1	0.27803 (6)	0.7680 (2)	0.25553 (10)	0.0548 (4)
O2	0.53008 (6)	0.2212 (2)	0.60764 (11)	0.0612 (4)
O3	0.07815 (6)	0.3815 (2)	0.63810 (11)	0.0613 (4)
H1N	0.2775 (8)	0.558 (3)	0.5980 (15)	0.048 (6)*

	U11	U22	U33	U12	U13	U23
C1	0.0318 (9)	0.0366 (11)	0.0398 (10)	0.0004 (8)	0.0123 (8)	−0.0011 (8)
C2	0.0399 (10)	0.0469 (12)	0.0347 (10)	0.0054 (9)	0.0190 (8)	0.0037 (8)
C3	0.0630 (13)	0.0441 (12)	0.0381 (10)	0.0039 (10)	0.0168 (9)	−0.0040 (9)
C4	0.0650 (14)	0.0463 (13)	0.0560 (13)	−0.0119 (11)	0.0097 (11)	−0.0059 (10)
C5	0.0440 (11)	0.0584 (14)	0.0405 (11)	−0.0084 (10)	0.0083 (9)	−0.0056 (10)
C6	0.0372 (10)	0.0426 (11)	0.0390 (10)	0.0050 (8)	0.0096 (8)	0.0064 (9)
C7	0.0341 (9)	0.0372 (11)	0.0428 (10)	0.0001 (8)	0.0128 (8)	−0.0016 (8)
C8	0.0431 (10)	0.0402 (11)	0.0314 (9)	−0.0028 (9)	0.0107 (8)	0.0010 (9)
C9	0.0369 (10)	0.0408 (11)	0.0293 (9)	0.0022 (8)	0.0120 (7)	−0.0016 (8)
C10	0.0375 (10)	0.0547 (13)	0.0401 (10)	0.0012 (9)	0.0165 (8)	0.0066 (9)
C11	0.0554 (12)	0.0529 (13)	0.0456 (12)	0.0049 (10)	0.0229 (10)	0.0154 (10)
C12	0.0512 (12)	0.0535 (13)	0.0420 (11)	0.0125 (10)	0.0133 (9)	0.0123 (10)
C13	0.0333 (10)	0.0524 (13)	0.0400 (10)	0.0034 (9)	0.0101 (8)	−0.0009 (9)
C14	0.0362 (10)	0.0417 (11)	0.0392 (10)	0.0000 (8)	0.0128 (8)	0.0021 (9)
C15	0.0339 (9)	0.0407 (11)	0.0357 (9)	0.0034 (8)	0.0081 (8)	−0.0037 (8)
C16	0.0430 (11)	0.0400 (12)	0.0612 (13)	0.0041 (9)	0.0184 (9)	0.0037 (10)
C17	0.0451 (12)	0.0464 (13)	0.0692 (14)	0.0152 (10)	0.0177 (10)	0.0001 (11)
C18	0.0355 (10)	0.0562 (14)	0.0537 (12)	0.0086 (10)	0.0162 (9)	−0.0021 (10)
C19	0.0383 (10)	0.0435 (12)	0.0414 (11)	0.0041 (9)	0.0121 (8)	0.0005 (9)
C20	0.0382 (10)	0.0389 (11)	0.0452 (11)	0.0104 (8)	0.0140 (8)	0.0008 (9)
C21	0.0418 (12)	0.0740 (17)	0.0868 (17)	0.0182 (11)	0.0098 (11)	0.0064 (13)
C22	0.0694 (15)	0.0840 (19)	0.0840 (17)	0.0043 (13)	0.0481 (14)	0.0144 (14)
N1	0.0325 (8)	0.0488 (10)	0.0313 (9)	0.0070 (7)	0.0114 (7)	−0.0019 (7)
O1	0.0582 (9)	0.0581 (10)	0.0507 (8)	−0.0021 (7)	0.0194 (7)	0.0200 (7)
O2	0.0350 (8)	0.0656 (10)	0.0832 (11)	0.0114 (7)	0.0167 (7)	0.0151 (8)
O3	0.0600 (9)	0.0554 (10)	0.0812 (10)	0.0095 (7)	0.0406 (8)	0.0162 (8)

C1—N1	1.469 (2)	C11—C12	1.386 (3)
C1—C9	1.516 (2)	C11—H11	0.9300
C1—C2	1.557 (2)	C12—C13	1.378 (3)
C1—H1	0.9800	C12—H12	0.9300
C2—C8	1.498 (2)	C13—O2	1.374 (2)
C2—C3	1.531 (2)	C13—C14	1.388 (2)
C2—H2	0.9800	C14—H14	0.9300
C3—C4	1.516 (3)	C15—C20	1.378 (2)
C3—H3A	0.9700	C15—C16	1.385 (2)
C3—H3B	0.9700	C16—C17	1.376 (2)
C4—C5	1.512 (3)	C16—H16	0.9300
C4—H4A	0.9700	C17—C18	1.383 (3)
C4—H4B	0.9700	C17—H17	0.9300
C5—C6	1.532 (2)	C18—C19	1.378 (2)
C5—H5A	0.9700	C18—H18	0.9300
C5—H5B	0.9700	C19—O3	1.368 (2)
C6—C8	1.506 (2)	C19—C20	1.384 (2)
C6—C7	1.555 (2)	C20—H20	0.9300
C6—H6	0.9800	C21—O2	1.425 (2)
C7—N1	1.463 (2)	C21—H21A	0.9600
C7—C15	1.514 (2)	C21—H21B	0.9600
C7—H7	0.9800	C21—H21C	0.9600
C8—O1	1.2119 (19)	C22—O3	1.419 (2)
C9—C14	1.382 (2)	C22—H22A	0.9600
C9—C10	1.386 (2)	C22—H22B	0.9600
C10—C11	1.374 (2)	C22—H22C	0.9600
C10—H10	0.9300	N1—H1N	0.890 (18)
N1—C1—C9	111.34 (13)	C11—C10—H10	119.8
N1—C1—C2	110.15 (13)	C9—C10—H10	119.8
C9—C1—C2	110.43 (13)	C10—C11—C12	121.21 (18)
N1—C1—H1	108.3	C10—C11—H11	119.4
C9—C1—H1	108.3	C12—C11—H11	119.4
C2—C1—H1	108.3	C13—C12—C11	118.63 (18)
C8—C2—C3	108.17 (15)	C13—C12—H12	120.7
C8—C2—C1	107.60 (13)	C11—C12—H12	120.7
C3—C2—C1	115.21 (14)	O2—C13—C12	124.24 (17)
C8—C2—H2	108.6	O2—C13—C14	115.51 (16)
C3—C2—H2	108.6	C12—C13—C14	120.25 (16)
C1—C2—H2	108.6	C9—C14—C13	120.99 (17)
C4—C3—C2	113.59 (15)	C9—C14—H14	119.5
C4—C3—H3A	108.8	C13—C14—H14	119.5
C2—C3—H3A	108.8	C20—C15—C16	118.10 (16)
C4—C3—H3B	108.8	C20—C15—C7	122.51 (16)
C2—C3—H3B	108.8	C16—C15—C7	119.40 (16)
H3A—C3—H3B	107.7	C17—C16—C15	120.87 (18)
C5—C4—C3	113.46 (16)	C17—C16—H16	119.6
C5—C4—H4A	108.9	C15—C16—H16	119.6
C3—C4—H4A	108.9	C16—C17—C18	120.83 (18)
C5—C4—H4B	108.9	C16—C17—H17	119.6
C3—C4—H4B	108.9	C18—C17—H17	119.6
H4A—C4—H4B	107.7	C19—C18—C17	118.55 (17)
C4—C5—C6	114.18 (15)	C19—C18—H18	120.7
C4—C5—H5A	108.7	C17—C18—H18	120.7
C6—C5—H5A	108.7	O3—C19—C18	124.06 (16)
C4—C5—H5B	108.7	O3—C19—C20	115.45 (16)
C6—C5—H5B	108.7	C18—C19—C20	120.48 (17)
H5A—C5—H5B	107.6	C15—C20—C19	121.17 (16)
C8—C6—C5	108.04 (15)	C15—C20—H20	119.4
C8—C6—C7	107.14 (13)	C19—C20—H20	119.4
C5—C6—C7	115.39 (14)	O2—C21—H21A	109.5
C8—C6—H6	108.7	O2—C21—H21B	109.5
C5—C6—H6	108.7	H21A—C21—H21B	109.5
C7—C6—H6	108.7	O2—C21—H21C	109.5
N1—C7—C15	111.28 (14)	H21A—C21—H21C	109.5
N1—C7—C6	109.93 (14)	H21B—C21—H21C	109.5
C15—C7—C6	111.21 (13)	O3—C22—H22A	109.5
N1—C7—H7	108.1	O3—C22—H22B	109.5
C15—C7—H7	108.1	H22A—C22—H22B	109.5
C6—C7—H7	108.1	O3—C22—H22C	109.5
O1—C8—C2	124.55 (16)	H22A—C22—H22C	109.5
O1—C8—C6	123.99 (16)	H22B—C22—H22C	109.5
C2—C8—C6	111.46 (14)	C7—N1—C1	113.91 (13)
C14—C9—C10	118.53 (17)	C7—N1—H1N	109.3 (12)
C14—C9—C1	119.04 (16)	C1—N1—H1N	109.6 (11)
C10—C9—C1	122.31 (15)	C13—O2—C21	117.20 (16)
C11—C10—C9	120.39 (17)	C19—O3—C22	118.64 (15)
N1—C1—C2—C8	56.22 (18)	C10—C11—C12—C13	−0.1 (3)
C9—C1—C2—C8	179.60 (13)	C11—C12—C13—O2	−178.66 (17)
N1—C1—C2—C3	−64.51 (19)	C11—C12—C13—C14	1.0 (3)
C9—C1—C2—C3	58.88 (19)	C10—C9—C14—C13	0.3 (3)
C8—C2—C3—C4	−53.64 (19)	C1—C9—C14—C13	−175.81 (15)
C1—C2—C3—C4	66.8 (2)	O2—C13—C14—C9	178.61 (16)
C2—C3—C4—C5	45.2 (2)	C12—C13—C14—C9	−1.0 (3)
C3—C4—C5—C6	−44.8 (2)	N1—C7—C15—C20	−25.2 (2)
C4—C5—C6—C8	52.4 (2)	C6—C7—C15—C20	97.7 (2)
C4—C5—C6—C7	−67.4 (2)	N1—C7—C15—C16	155.10 (16)
C8—C6—C7—N1	−57.64 (18)	C6—C7—C15—C16	−82.0 (2)
C5—C6—C7—N1	62.69 (18)	C20—C15—C16—C17	0.5 (3)
C8—C6—C7—C15	178.66 (15)	C7—C15—C16—C17	−179.85 (16)
C5—C6—C7—C15	−61.0 (2)	C15—C16—C17—C18	−0.6 (3)
C3—C2—C8—O1	−116.08 (19)	C16—C17—C18—C19	0.4 (3)
C1—C2—C8—O1	118.86 (18)	C17—C18—C19—O3	−179.87 (18)
C3—C2—C8—C6	63.68 (17)	C17—C18—C19—C20	−0.2 (3)
C1—C2—C8—C6	−61.37 (18)	C16—C15—C20—C19	−0.3 (3)
C5—C6—C8—O1	116.90 (19)	C7—C15—C20—C19	−179.91 (15)
C7—C6—C8—O1	−118.19 (18)	O3—C19—C20—C15	179.84 (16)
C5—C6—C8—C2	−62.87 (18)	C18—C19—C20—C15	0.1 (3)
C7—C6—C8—C2	62.04 (19)	C15—C7—N1—C1	−178.96 (13)
N1—C1—C9—C14	−158.74 (15)	C6—C7—N1—C1	57.38 (18)
C2—C1—C9—C14	78.57 (19)	C9—C1—N1—C7	−179.40 (14)
N1—C1—C9—C10	25.3 (2)	C2—C1—N1—C7	−56.55 (19)
C2—C1—C9—C10	−97.36 (18)	C12—C13—O2—C21	3.2 (3)
C14—C9—C10—C11	0.5 (3)	C14—C13—O2—C21	−176.39 (17)
C1—C9—C10—C11	176.49 (16)	C18—C19—O3—C22	−10.4 (3)
C9—C10—C11—C12	−0.6 (3)	C20—C19—O3—C22	169.87 (17)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1i	0.890 (18)	2.352 (18)	3.1901 (19)	157.0 (16)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N⋯O1i	0.890 (18)	2.352 (18)	3.1901 (19)	157.0 (16)

Symmetry code: (i) .