Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103022339/sx1126sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103022339/sx1126Isup2.hkl |
CCDC reference: 226138
A mixture of 3-hydroxy-4-methoxybezaldehyde (0.456 g, 3 mmol) and 1-azabicyclo[2.2.2]octan-3-one hydrochloride (0.483 g, 3 mmol) was dissolved in 10% methanolic KOH (10 ml) and the solution refluxed for 5 h. The cooled reaction mixture was poured onto crushed ice (100 g) and the solution was carefully neutralized by dropwise addition of dilute hydrochloric acid. The yellow crystalline solid that separated was collected by filtration and dried. Recrystallization from methanol afforded a yellow crystalline product, (I), which was suitable for X-ray analysis. Spectroscopic analysis: 1H NMR (CDCl3, δ, p.p.m.): 2.01 (td, J = 7.8 and 3 Hz, 4H), 2.61 (p, J = 3 Hz, 1H), 2.95–3.02 (m, 2H), 3.09–3.19 (m, 2H), 3.92 (s, 3H), 5.62 (s, 1H), 6.84(d, J = 8.1 Hz, 1H), 6.93 (s, 1H), 7.37 (dd, J = 8.25 and 1.8 Hz, 1H), 8.03 (d, J = 1.8 Hz, 1H); 13C NMR (CDCl3, δ, p.p.m.): 26.3, 40.6, 47.8, 56.1, 110.2, 117.6, 125.1, 126.0, 127.8, 143.4, 145.3, 148.0, 206.5; high-resolution MS, calculated: 259.1208; found: 259.1204.
Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL (Sheldrick, 1994); software used to prepare material for publication: SHELXL97 and local procedures.
C15H17NO3 | F(000) = 552 |
Mr = 259.30 | Dx = 1.338 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 10.7480 (4) Å | Cell parameters from 9554 reflections |
b = 5.8950 (2) Å | θ = 1.0–25.4° |
c = 20.4650 (8) Å | µ = 0.09 mm−1 |
β = 97.030 (2)° | T = 173 K |
V = 1286.90 (8) Å3 | Hemi-wedge slab, pale yellow |
Z = 4 | 0.17 × 0.15 × 0.04 mm |
Nonius KappaCCD area-detector diffractometer | 2251 independent reflections |
Radiation source: fine-focus sealed tube | 1493 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.083 |
Detector resolution: 18 pixels mm-1 | θmax = 25.0°, θmin = 1.9° |
ω scans at fixed χ = 55° | h = −12→12 |
Absorption correction: multi-scan SCALEPACK (Otwinowski & Minor, 1997) | k = −7→7 |
Tmin = 0.984, Tmax = 0.996 | l = −24→24 |
8509 measured reflections |
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)] = 0.054 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 1.03 | w = 1/[σ2(Fo2) + (0.0543P)2 |
2251 reflections | (Δ/σ)max = 0.003 |
174 parameters | Δρmax = 0.20 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
C15H17NO3 | V = 1286.90 (8) Å3 |
Mr = 259.30 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 10.7480 (4) Å | µ = 0.09 mm−1 |
b = 5.8950 (2) Å | T = 173 K |
c = 20.4650 (8) Å | 0.17 × 0.15 × 0.04 mm |
β = 97.030 (2)° |
Nonius KappaCCD area-detector diffractometer | 2251 independent reflections |
Absorption correction: multi-scan SCALEPACK (Otwinowski & Minor, 1997) | 1493 reflections with I > 2σ(I) |
Tmin = 0.984, Tmax = 0.996 | Rint = 0.083 |
8509 measured reflections |
R[F2 > 2σ(F2)] = 0.054 | 0 restraints |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.20 e Å−3 |
2251 reflections | Δρmin = −0.21 e Å−3 |
174 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.21481 (18) | 0.3178 (4) | 0.35399 (10) | 0.0266 (6) | |
O1 | 0.26177 (14) | 0.1631 (2) | 0.40028 (7) | 0.0388 (5) | |
H1 | 0.2357 | 0.1932 | 0.4363 | 0.058* | |
C2 | 0.23686 (18) | 0.2850 (3) | 0.28987 (9) | 0.0264 (5) | |
H2 | 0.2835 | 0.1565 | 0.2789 | 0.032* | |
C3 | 0.19115 (17) | 0.4397 (3) | 0.24054 (10) | 0.0244 (5) | |
C4 | 0.12091 (19) | 0.6229 (4) | 0.25767 (10) | 0.0309 (6) | |
H4 | 0.0863 | 0.7255 | 0.2245 | 0.037* | |
C5 | 0.10033 (18) | 0.6585 (4) | 0.32275 (10) | 0.0310 (6) | |
H5 | 0.0539 | 0.7868 | 0.3340 | 0.037* | |
C6 | 0.14761 (19) | 0.5068 (4) | 0.37074 (10) | 0.0280 (6) | |
O6 | 0.13528 (13) | 0.5236 (2) | 0.43653 (7) | 0.0368 (4) | |
C7 | 0.0677 (2) | 0.7131 (4) | 0.45709 (10) | 0.0413 (6) | |
H7A | 0.1069 | 0.8537 | 0.4443 | 0.062* | |
H7B | 0.0690 | 0.7093 | 0.5050 | 0.062* | |
H7C | −0.0192 | 0.7066 | 0.4361 | 0.062* | |
C8 | 0.21365 (19) | 0.4120 (3) | 0.17184 (10) | 0.0257 (6) | |
H8 | 0.1560 | 0.4893 | 0.1406 | 0.031* | |
C9 | 0.30265 (19) | 0.2948 (3) | 0.14611 (10) | 0.0240 (5) | |
N10 | 0.40498 (15) | 0.1774 (3) | 0.18391 (8) | 0.0292 (5) | |
C11 | 0.3971 (2) | −0.0666 (3) | 0.16643 (10) | 0.0348 (6) | |
H11A | 0.3197 | −0.1314 | 0.1805 | 0.042* | |
H11B | 0.4695 | −0.1475 | 0.1904 | 0.042* | |
C12 | 0.3964 (2) | −0.1041 (3) | 0.09149 (10) | 0.0343 (6) | |
H12A | 0.4665 | −0.2049 | 0.0833 | 0.041* | |
H12B | 0.3168 | −0.1767 | 0.0729 | 0.041* | |
C13 | 0.41041 (19) | 0.1281 (3) | 0.05868 (10) | 0.0269 (5) | |
H13 | 0.4103 | 0.1112 | 0.0101 | 0.032* | |
C14 | 0.53194 (19) | 0.2391 (4) | 0.09005 (10) | 0.0341 (6) | |
H14A | 0.5430 | 0.3885 | 0.0694 | 0.041* | |
H14B | 0.6046 | 0.1423 | 0.0834 | 0.041* | |
C15 | 0.52378 (19) | 0.2692 (4) | 0.16483 (9) | 0.0318 (6) | |
H15A | 0.5954 | 0.1904 | 0.1902 | 0.038* | |
H15B | 0.5300 | 0.4325 | 0.1761 | 0.038* | |
C16 | 0.30473 (19) | 0.2767 (4) | 0.07394 (10) | 0.0256 (5) | |
O16 | 0.22933 (13) | 0.3689 (2) | 0.03237 (7) | 0.0335 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0276 (13) | 0.0326 (14) | 0.0191 (13) | 0.0025 (11) | 0.0008 (10) | 0.0030 (11) |
O1 | 0.0529 (11) | 0.0449 (10) | 0.0197 (9) | 0.0144 (8) | 0.0095 (8) | 0.0054 (8) |
C2 | 0.0278 (13) | 0.0305 (13) | 0.0213 (13) | 0.0016 (10) | 0.0051 (10) | −0.0018 (11) |
C3 | 0.0236 (12) | 0.0319 (13) | 0.0177 (13) | 0.0009 (10) | 0.0028 (10) | −0.0019 (10) |
C4 | 0.0342 (14) | 0.0356 (14) | 0.0229 (14) | 0.0041 (11) | 0.0031 (11) | 0.0020 (11) |
C5 | 0.0300 (13) | 0.0369 (14) | 0.0270 (14) | 0.0085 (11) | 0.0067 (11) | −0.0026 (12) |
C6 | 0.0270 (13) | 0.0389 (14) | 0.0189 (14) | −0.0006 (11) | 0.0058 (10) | −0.0031 (11) |
O6 | 0.0449 (10) | 0.0464 (10) | 0.0203 (10) | 0.0112 (8) | 0.0089 (8) | −0.0023 (8) |
C7 | 0.0556 (16) | 0.0445 (15) | 0.0266 (15) | 0.0034 (13) | 0.0164 (12) | −0.0065 (12) |
C8 | 0.0255 (13) | 0.0289 (13) | 0.0220 (13) | −0.0022 (10) | 0.0002 (10) | 0.0023 (10) |
C9 | 0.0262 (13) | 0.0270 (13) | 0.0185 (12) | −0.0001 (10) | 0.0022 (10) | 0.0011 (10) |
N10 | 0.0312 (11) | 0.0357 (12) | 0.0207 (11) | 0.0048 (9) | 0.0033 (9) | −0.0004 (9) |
C11 | 0.0433 (15) | 0.0308 (14) | 0.0311 (15) | 0.0042 (11) | 0.0080 (12) | 0.0048 (11) |
C12 | 0.0434 (15) | 0.0313 (14) | 0.0282 (14) | 0.0009 (11) | 0.0040 (11) | −0.0033 (11) |
C13 | 0.0339 (13) | 0.0338 (13) | 0.0139 (12) | −0.0002 (11) | 0.0062 (10) | −0.0038 (10) |
C14 | 0.0306 (14) | 0.0415 (14) | 0.0311 (14) | 0.0003 (11) | 0.0071 (11) | −0.0008 (12) |
C15 | 0.0285 (14) | 0.0388 (14) | 0.0269 (14) | 0.0034 (11) | −0.0008 (10) | −0.0080 (11) |
C16 | 0.0283 (13) | 0.0288 (13) | 0.0204 (13) | −0.0057 (10) | 0.0049 (11) | −0.0008 (10) |
O16 | 0.0389 (10) | 0.0428 (10) | 0.0185 (9) | 0.0038 (8) | 0.0019 (8) | 0.0016 (7) |
C1—O1 | 1.366 (2) | C9—N10 | 1.442 (2) |
C1—C2 | 1.375 (3) | C9—C16 | 1.484 (3) |
C1—C6 | 1.393 (3) | N10—C11 | 1.482 (2) |
O1—H1 | 0.8400 | N10—C15 | 1.482 (2) |
C2—C3 | 1.404 (3) | C11—C12 | 1.549 (3) |
C2—H2 | 0.9500 | C11—H11A | 0.9900 |
C3—C4 | 1.387 (3) | C11—H11B | 0.9900 |
C3—C8 | 1.465 (3) | C12—C13 | 1.540 (3) |
C4—C5 | 1.393 (3) | C12—H12A | 0.9900 |
C4—H4 | 0.9500 | C12—H12B | 0.9900 |
C5—C6 | 1.379 (3) | C13—C16 | 1.497 (3) |
C5—H5 | 0.9500 | C13—C14 | 1.530 (3) |
C6—O6 | 1.372 (2) | C13—H13 | 1.0000 |
O6—C7 | 1.424 (2) | C14—C15 | 1.554 (3) |
C7—H7A | 0.9800 | C14—H14A | 0.9900 |
C7—H7B | 0.9800 | C14—H14B | 0.9900 |
C7—H7C | 0.9800 | C15—H15A | 0.9900 |
C8—C9 | 1.339 (3) | C15—H15B | 0.9900 |
C8—H8 | 0.9500 | C16—O16 | 1.228 (2) |
O1—C1—C2 | 118.40 (19) | C11—N10—C15 | 108.43 (16) |
O1—C1—C6 | 121.45 (18) | N10—C11—C12 | 111.78 (16) |
C2—C1—C6 | 120.15 (19) | N10—C11—H11A | 109.3 |
C1—O1—H1 | 109.5 | C12—C11—H11A | 109.3 |
C1—C2—C3 | 120.59 (19) | N10—C11—H11B | 109.3 |
C1—C2—H2 | 119.7 | C12—C11—H11B | 109.3 |
C3—C2—H2 | 119.7 | H11A—C11—H11B | 107.9 |
C4—C3—C2 | 118.51 (19) | C13—C12—C11 | 108.40 (16) |
C4—C3—C8 | 119.23 (19) | C13—C12—H12A | 110.0 |
C2—C3—C8 | 122.25 (18) | C11—C12—H12A | 110.0 |
C3—C4—C5 | 120.9 (2) | C13—C12—H12B | 110.0 |
C3—C4—H4 | 119.5 | C11—C12—H12B | 110.0 |
C5—C4—H4 | 119.5 | H12A—C12—H12B | 108.4 |
C6—C5—C4 | 119.7 (2) | C16—C13—C14 | 107.01 (16) |
C6—C5—H5 | 120.1 | C16—C13—C12 | 108.17 (17) |
C4—C5—H5 | 120.1 | C14—C13—C12 | 108.74 (17) |
O6—C6—C5 | 125.48 (19) | C16—C13—H13 | 110.9 |
O6—C6—C1 | 114.48 (18) | C14—C13—H13 | 110.9 |
C5—C6—C1 | 120.03 (19) | C12—C13—H13 | 110.9 |
C6—O6—C7 | 117.43 (16) | C13—C14—C15 | 108.29 (17) |
O6—C7—H7A | 109.5 | C13—C14—H14A | 110.0 |
O6—C7—H7B | 109.5 | C15—C14—H14A | 110.0 |
H7A—C7—H7B | 109.5 | C13—C14—H14B | 110.0 |
O6—C7—H7C | 109.5 | C15—C14—H14B | 110.0 |
H7A—C7—H7C | 109.5 | H14A—C14—H14B | 108.4 |
H7B—C7—H7C | 109.5 | N10—C15—C14 | 111.84 (16) |
C9—C8—C3 | 130.2 (2) | N10—C15—H15A | 109.2 |
C9—C8—H8 | 114.9 | C14—C15—H15A | 109.2 |
C3—C8—H8 | 114.9 | N10—C15—H15B | 109.2 |
C8—C9—N10 | 124.84 (19) | C14—C15—H15B | 109.2 |
C8—C9—C16 | 121.82 (19) | H15A—C15—H15B | 107.9 |
N10—C9—C16 | 113.33 (17) | O16—C16—C9 | 124.66 (19) |
C9—N10—C11 | 108.61 (16) | O16—C16—C13 | 124.60 (19) |
C9—N10—C15 | 107.98 (16) | C9—C16—C13 | 110.74 (18) |
O1—C1—C2—C3 | −179.69 (17) | C8—C9—N10—C15 | −122.5 (2) |
C6—C1—C2—C3 | −0.6 (3) | C16—C9—N10—C15 | 56.9 (2) |
C1—C2—C3—C4 | −1.5 (3) | C9—N10—C11—C12 | 56.0 (2) |
C1—C2—C3—C8 | 179.40 (18) | C15—N10—C11—C12 | −61.1 (2) |
C2—C3—C4—C5 | 2.6 (3) | N10—C11—C12—C13 | 2.6 (2) |
C8—C3—C4—C5 | −178.23 (18) | C11—C12—C13—C16 | −58.1 (2) |
C3—C4—C5—C6 | −1.7 (3) | C11—C12—C13—C14 | 57.8 (2) |
C4—C5—C6—O6 | 179.21 (19) | C16—C13—C14—C15 | 56.6 (2) |
C4—C5—C6—C1 | −0.5 (3) | C12—C13—C14—C15 | −60.0 (2) |
O1—C1—C6—O6 | 0.9 (3) | C9—N10—C15—C14 | −58.8 (2) |
C2—C1—C6—O6 | −178.11 (17) | C11—N10—C15—C14 | 58.7 (2) |
O1—C1—C6—C5 | −179.33 (18) | C13—C14—C15—N10 | 1.7 (2) |
C2—C1—C6—C5 | 1.6 (3) | C8—C9—C16—O16 | 1.8 (3) |
C5—C6—O6—C7 | 0.2 (3) | N10—C9—C16—O16 | −177.58 (18) |
C1—C6—O6—C7 | 179.93 (17) | C8—C9—C16—C13 | −177.45 (17) |
C4—C3—C8—C9 | 159.1 (2) | N10—C9—C16—C13 | 3.1 (2) |
C2—C3—C8—C9 | −21.8 (3) | C14—C13—C16—O16 | 119.9 (2) |
C3—C8—C9—N10 | −4.5 (3) | C12—C13—C16—O16 | −123.1 (2) |
C3—C8—C9—C16 | 176.18 (18) | C14—C13—C16—C9 | −60.8 (2) |
C8—C9—N10—C11 | 120.2 (2) | C12—C13—C16—C9 | 56.2 (2) |
C16—C9—N10—C11 | −60.4 (2) |
Experimental details
Crystal data | |
Chemical formula | C15H17NO3 |
Mr | 259.30 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 173 |
a, b, c (Å) | 10.7480 (4), 5.8950 (2), 20.4650 (8) |
β (°) | 97.030 (2) |
V (Å3) | 1286.90 (8) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.17 × 0.15 × 0.04 |
Data collection | |
Diffractometer | Nonius KappaCCD area-detector diffractometer |
Absorption correction | Multi-scan SCALEPACK (Otwinowski & Minor, 1997) |
Tmin, Tmax | 0.984, 0.996 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8509, 2251, 1493 |
Rint | 0.083 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.054, 0.119, 1.03 |
No. of reflections | 2251 |
No. of parameters | 174 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.20, −0.21 |
Computer programs: COLLECT (Nonius, 1998), SCALEPACK (Otwinowski & Minor, 1997), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), XP in SHELXTL (Sheldrick, 1994), SHELXL97 and local procedures.
C1—O1 | 1.366 (2) | C8—C9 | 1.339 (3) |
C1—C6 | 1.393 (3) | C9—N10 | 1.442 (2) |
O1—H1 | 0.8400 | C9—C16 | 1.484 (3) |
C2—C3 | 1.404 (3) | N10—C11 | 1.482 (2) |
C3—C8 | 1.465 (3) | N10—C15 | 1.482 (2) |
C6—O6 | 1.372 (2) | C13—C16 | 1.497 (3) |
O6—C7 | 1.424 (2) | C16—O16 | 1.228 (2) |
O1—C1—C2 | 118.40 (19) | C8—C9—C16 | 121.82 (19) |
O1—C1—C6 | 121.45 (18) | N10—C9—C16 | 113.33 (17) |
C2—C3—C8 | 122.25 (18) | C9—N10—C11 | 108.61 (16) |
O6—C6—C1 | 114.48 (18) | C9—N10—C15 | 107.98 (16) |
C6—O6—C7 | 117.43 (16) | C11—N10—C15 | 108.43 (16) |
C9—C8—C3 | 130.2 (2) | O16—C16—C9 | 124.66 (19) |
C8—C9—N10 | 124.84 (19) | O16—C16—C13 | 124.60 (19) |
O1—C1—C2—C3 | −179.69 (17) | C1—C6—O6—C7 | 179.93 (17) |
O1—C1—C6—O6 | 0.9 (3) | C4—C3—C8—C9 | 159.1 (2) |
C2—C1—C6—O6 | −178.11 (17) | C2—C3—C8—C9 | −21.8 (3) |
O1—C1—C6—C5 | −179.33 (18) | C3—C8—C9—N10 | −4.5 (3) |
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Dopamine is a biogenic amine biosynthesized in the hypothalamus, the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and dopamine analogues play an important role in cardiovascular, renal, hormonal and central nervous system regulation through stimulation of α and β adrenergic and dopaminergic receptors.
Dopamine receptor agonists and antagonists have been evaluated and extensively reviewed as medications for cocaine abuse (Witkin, 1994; Mello & Negus, 1996). Although the behavioural effects of cocaine are not consistently altered by selective dopamine receptor antagonists (Spealman et al., 1990; Witkin et al., 1991), many studies have reported their mediation of the reinforcing effects of cocaine (Corrigal & Coen, 1991; Britton et al., 1991).
The dopamine D3 receptor has been of particular interest, because of its relatively restricted localization within the limbic system compared with the dopamine D2 receptor, and due to its role as a possible target for the treatment of schizophrenia and drug abuse (Shafer & Levant, 1998). A recent report of selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist suggested that this receptor is an important target for the development of medications for cocaine abuse (Pilla et al., 1999).
The nicotinic modulation of [3H]-dopamine release from striatal preparations has been exploited as a model system for examining native nicotine acetylcholine receptor (nAChR) responses (Soliakov & Wonnacott, 1996; Grady et al., 1997) and evaluating novel ligands (Holladay et al., 1997; Bencherif et al., 1998; Xu et al., 2002). 1-Azabicyclo[2.2.2]octane is a very important biological moiety, and its analogues are agonists at the α7 nAChR subtype, with selective affinity for the α7 versus α4β2 nAChR subtype (Mullen et al., 2000).
In view of these findings, we planned to synthesize rigid analogues of dopamine. The title compound, (I), is a synthetic precursor of a drug candidate designed as a conformationally restrained dopamine analogue with defined double-bond geometry, and was prepared by condensation of 3-hydroxy-4-methoxybenzaldehyde with 1-azabicyclo[2.2.2]octan-3-one under base catalysis to afford a single geometrical isomer. The product, (Z)-2-(3-hydroxy-4-methoxybenzylidene)-1-azabicyclo[2.2.2]octan-3-one, (I), was identified by NMR spectroscopy. In order to confirm the geometry of this compound, and to obtain more detailed information on the structural conformation of the molecule and on synthetic products derived from this intermediate that may be of value in subsequent structure-activity studies, an X-ray structure determination was carried out and the results are presented here. \sch
The present X-ray data confirm the Z geometry of the molecule and show that in the crystal structure of (I), the H atom attached to atom O1 is involved in an intermolecular hydrogen bond [2.774 (2) Å] between atom O1 and atom O16(x, 1/2 − y, z + 1/2) of a c-glide related molecule. An ellipsoid plot of (I) is shown in Fig. 1 and selected geometric parameters are presented in Table 1.
The molecule of (I) contains a double bond that connects a 1-azabicyclo[2.2.2] ring system to a 3-hydroxy-4-methoxybenzylidene group between atoms C8 and C9; geometric isomerism about this double bond affords the possibility of E and Z isomers. In the Z isomer, the C9—C16 bond is in a trans position with respect to the C3—C8 bond. The double bond has a nearly planar atomic arrangement, since the root-mean-square deviation from the best plane passing through atoms N10, C9, C16, C8 and C3 is 0.018 (1) Å. Deviations from ideal geometry are observed in the bond angles around atoms C3 and C9. While the C8—C9—C16 angle of 121.82 (19)° is close to the ideal value of 120°, the N10—C9—C16, C8—C9—N10 and C9—C8—C3 angles are more distorted, at 113.33 (17), 124.84 (19) and 130.2 (2)°, respectively, as a consequence of the strain induced by the double-bond linkage at C8—C9.
The azabicyclic system of (I) presents small distortions in its geometry with respect to literature data on the 1-azabicyclo[2.2.2]octane moiety, which is caused by the effect of the double bonds connecting C8—C9 and C16—O16 on the bicyclic system. In both cases, Csp2 atoms replace Csp3 atoms, and as a result, atoms N10, C9, C16 and C13 assume a planar arrangement [N10—C9—C16—C13 torsion angle 3.1 (2)°], with partial conjugation between the double bond and the carbonyl bond, as indicated by the significant shortening of the C9—C16 single bond [1.484 (3) Å]. The bond angles for atoms C12, C13, C14 and N10 are, on average, smaller than the ideal tetrahedral value of 109.5°, while those for atoms C11 and C15 are, on average, slightly larger than the tetrahedral value. The bond angles about the sp2 atoms C9 and C16 show values larger than the ideal.
The value of the C2—C3—C8—C9 torsion angle [−21.8 (3)°] indicates a deviation of the phenyl ring from the plane of the double bond connected to the azabicyclic ring. However, the C3—C8 bond length [1.465 (3) Å], when compared with the standard value for a single bond connecting a Carm to a Csp2 [1.470 ± 0.015 Å],suggests extensive conjugation, beginning at the O16 carbonyl and extending through to the aromatic ring. The observed C6—O6 [1.372 (2) Å], O6—C7 [1.424 (2) Å] and C1—O1[1.366 (2) Å] bond lengths are comparable with values found for aromatic methoxy and hydroxy groups in the literature, and there is an intramolecular O1—H1···O6 hydrogen bond [2.676 Å], because of the close proximity of these atoms on the phenyl ring.
The mode of packing of compound (I) along the b direction is illustrated in Fig. 2. It is important to note that in the structurally related compound 2-(1-benzyl-1H-indol-3-ylmethylene)-1-azabicyclo[2.2.2]octane-3-one (Sonar et al., 2003), the C2—C3—C10—C11 torsion angle, which corresponds to the C2—C3—C8—C9 torsion angle in (I), is −4.4 (3)°, suggesting that in addition to van der Waal's forces, and in the absence of steric factors, intermolecular hydrogen bonding contributes significantly to the stabilization of the crystal structure conformation of (I).