Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103026520/sq1138sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103026520/sq1138Isup2.hkl | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270103026520/sq1138IIsup3.hkl |
CCDC references: 231049; 231050
2E,4E-Dibenzylidenetropanone (Jung et al., 2001) was reduced stereoselectively to 2α,4α-dibenzyltropanone by catalytic hydrogenation (45psi H2) over Pd/C (10%) in absolute methanol. Using diisobutylaluminium hydride at 195 K in tetrahydrofuran, 2α,4α-dibenzyltropanone was then reduced stereoselectively to (I), which was purified by flash column chromatography on silica gel and then recrystallized from acetonitrile. M.p. 489 K. 1H NMR (300 MHz, CDCl3): δ 7.13–7.32 (m, 10H), 3.56 (m, 1H), 2.79 (m, 2H), 2.61–2.78 (m, 4H), 2.19 (s, 3H), 2.10–2.23 (m, 4H), 1.83 (m, 2H), 1.29 (d, J=5.4 Hz, 1H, OH); 13C NMR (75 MHz, CDCl3): δ 140.48, 129.17, 128.52, 126.03, 69.08, 64.03, 47.39, 40.89, 35.72, 22.00. Compound (II) was prepared stereoselectively by reduction of 2α,4α-dibenzyltropanone with Zn/Hg in 20% HCl/1, 4-dioxane (1:1) under reflux. Crude (II) was purified by the same method used for (I). M.p. 508 K. 1H NMR (300 MHz, CDCl3): δ 7.12–7.22 (m, 10H), 3.10–3.22 (m, 3H), 2.80 (m, 2H), 2.33 (dd, J=13.5, 10.2 Hz, 2H), 2.12 (s, 3H), 2.01 (m, 2H), 1.86 (m, 2H), 1.68 (m, 2H); 13C NMR (75 MHz, CDCl3): δ 140.45, 129.18, 128.59, 126.10, 74.39, 63.65, 50.97, 40.25, 36.56, 22.02. Crystals of (I) and (II) suitable for X-ray diffraction studies were obtained by slow evaporation of acetonitrile solutions at room temperature.
X-ray data were collected from flash-cooled crystals on a Nonius KappaCCD diffractometer. Crystals of (I) were observed to shatter upon cooling below about 200 K, so for this crystal, data were collected at 206 K.
For both structures, Friedel pairs were merged prior to the final refinement cycles because values of the Flack (1983) parameters (obtained in each case as a variable in the full-matrix least-squares scheme against unmerged data) refined to values with no physical interpretation. The quoted Flack parameters are thus from before the final refinement cycles.
For both compounds, 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: SHELX97-2 (Sheldrick, 1997) and local procedures.
C22H27NO | Dx = 1.175 Mg m−3 |
Mr = 321.45 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 11302 reflections |
a = 10.4244 (4) Å | θ = 1.0–27.5° |
b = 11.4988 (5) Å | µ = 0.07 mm−1 |
c = 15.1602 (5) Å | T = 206 K |
V = 1817.22 (12) Å3 | Block, colourless |
Z = 4 | 0.24 × 0.24 × 0.20 mm |
F(000) = 696 |
Nonius KappaCCD diffractometer | 1902 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.066 |
Graphite monochromator | θmax = 27.5°, θmin = 2.2° |
Detector resolution: 18 pixels mm-1 | h = −13→13 |
ω scans at fixed χ = 55° | k = −14→14 |
14506 measured reflections | l = −19→19 |
2371 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.043 | w = 1/[σ2(Fo2) + (0.0496P)2 + 0.0877P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.096 | (Δ/σ)max = 0.005 |
S = 1.44 | Δρmax = 0.18 e Å−3 |
2371 reflections | Δρmin = −0.17 e Å−3 |
219 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0126 (17) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. In the final refinement cycles, performed against Friedel-merged data, the Flack parameter was not refined because it had previously refined to a value with no physical interpretation. |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.7 (19) |
C22H27NO | V = 1817.22 (12) Å3 |
Mr = 321.45 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 10.4244 (4) Å | µ = 0.07 mm−1 |
b = 11.4988 (5) Å | T = 206 K |
c = 15.1602 (5) Å | 0.24 × 0.24 × 0.20 mm |
Nonius KappaCCD diffractometer | 1902 reflections with I > 2σ(I) |
14506 measured reflections | Rint = 0.066 |
2371 independent reflections |
R[F2 > 2σ(F2)] = 0.043 | H-atom parameters constrained |
wR(F2) = 0.096 | Δρmax = 0.18 e Å−3 |
S = 1.44 | Δρmin = −0.17 e Å−3 |
2371 reflections | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. In the final refinement cycles, performed against Friedel-merged data, the Flack parameter was not refined because it had previously refined to a value with no physical interpretation. |
219 parameters | Absolute structure parameter: 0.7 (19) |
0 restraints |
Experimental. The crystals underwent a destructive phase transition upon rapid cooling to 173 K. They survived cooling to 206 K. |
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. The absolute structure of the crystal cannot be determined from the X-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. Final refinement cycles were performed against Friedel-merged data because the Flack parameter refined to a value with no physical interpretation. |
x | y | z | Uiso*/Ueq | ||
N | 1.08785 (15) | 0.09661 (14) | −0.04257 (10) | 0.0277 (4) | |
O | 0.77051 (12) | 0.26049 (13) | −0.03745 (9) | 0.0319 (4) | |
H0 | 0.7232 | 0.3055 | −0.0096 | 0.048* | |
C1 | 1.01261 (19) | 0.14121 (17) | −0.11883 (13) | 0.0283 (5) | |
H1 | 1.0622 | 0.1331 | −0.1742 | 0.034* | |
C2 | 0.98372 (19) | 0.27026 (17) | −0.09993 (12) | 0.0251 (4) | |
H2 | 1.0673 | 0.3075 | −0.0870 | 0.030* | |
C3 | 0.90163 (17) | 0.28534 (18) | −0.01704 (12) | 0.0256 (4) | |
H3 | 0.9075 | 0.3675 | 0.0020 | 0.031* | |
C4 | 0.95351 (18) | 0.20822 (17) | 0.05783 (12) | 0.0258 (5) | |
H4 | 1.0357 | 0.2434 | 0.0768 | 0.031* | |
C5 | 0.98545 (18) | 0.08504 (17) | 0.02506 (13) | 0.0285 (5) | |
H5 | 1.0152 | 0.0358 | 0.0746 | 0.034* | |
C6 | 0.8735 (2) | 0.02548 (18) | −0.02408 (13) | 0.0345 (5) | |
H6A | 0.7906 | 0.0519 | −0.0012 | 0.041* | |
H6B | 0.8786 | −0.0593 | −0.0184 | 0.041* | |
C7 | 0.8920 (2) | 0.06369 (19) | −0.12132 (13) | 0.0342 (5) | |
H7A | 0.9052 | −0.0038 | −0.1597 | 0.041* | |
H7B | 0.8174 | 0.1075 | −0.1424 | 0.041* | |
C8 | 1.1487 (2) | −0.01515 (19) | −0.06362 (14) | 0.0398 (6) | |
H8A | 1.1966 | −0.0425 | −0.0128 | 0.060* | |
H8B | 1.2066 | −0.0052 | −0.1132 | 0.060* | |
H8C | 1.0832 | −0.0716 | −0.0788 | 0.060* | |
C9 | 0.9287 (2) | 0.33359 (17) | −0.18033 (14) | 0.0322 (5) | |
H9A | 0.9877 | 0.3239 | −0.2301 | 0.039* | |
H9B | 0.8469 | 0.2974 | −0.1965 | 0.039* | |
C10 | 0.9072 (2) | 0.46137 (18) | −0.16500 (12) | 0.0322 (5) | |
C11 | 0.7854 (2) | 0.5101 (2) | −0.17276 (14) | 0.0432 (6) | |
H11 | 0.7154 | 0.4632 | −0.1890 | 0.052* | |
C12 | 0.7670 (3) | 0.6283 (2) | −0.15647 (16) | 0.0562 (8) | |
H12 | 0.6843 | 0.6603 | −0.1613 | 0.067* | |
C13 | 0.8679 (3) | 0.6983 (2) | −0.13349 (16) | 0.0608 (9) | |
H13 | 0.8546 | 0.7779 | −0.1230 | 0.073* | |
C14 | 0.9881 (3) | 0.6518 (2) | −0.12591 (15) | 0.0518 (7) | |
H14 | 1.0575 | 0.6996 | −0.1102 | 0.062* | |
C15 | 1.0077 (3) | 0.53445 (19) | −0.14136 (14) | 0.0398 (6) | |
H15 | 1.0908 | 0.5035 | −0.1357 | 0.048* | |
C16 | 0.86604 (19) | 0.2089 (2) | 0.13859 (12) | 0.0318 (5) | |
H16A | 0.8296 | 0.2869 | 0.1453 | 0.038* | |
H16B | 0.7948 | 0.1550 | 0.1281 | 0.038* | |
C17 | 0.93121 (19) | 0.17546 (18) | 0.22361 (13) | 0.0308 (5) | |
C18 | 1.0323 (2) | 0.2401 (2) | 0.25647 (16) | 0.0487 (6) | |
H18 | 1.0651 | 0.3026 | 0.2235 | 0.058* | |
C19 | 1.0862 (3) | 0.2129 (3) | 0.33874 (17) | 0.0638 (8) | |
H19 | 1.1549 | 0.2571 | 0.3609 | 0.077* | |
C20 | 1.0379 (3) | 0.1209 (3) | 0.38687 (16) | 0.0634 (9) | |
H20 | 1.0731 | 0.1030 | 0.4423 | 0.076* | |
C21 | 0.9400 (3) | 0.0562 (3) | 0.35463 (17) | 0.0602 (8) | |
H21 | 0.9080 | −0.0069 | 0.3873 | 0.072* | |
C22 | 0.8875 (2) | 0.0830 (2) | 0.27393 (14) | 0.0443 (6) | |
H22 | 0.8198 | 0.0372 | 0.2522 | 0.053* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N | 0.0273 (8) | 0.0264 (9) | 0.0293 (8) | 0.0055 (8) | 0.0016 (8) | −0.0004 (7) |
O | 0.0204 (7) | 0.0408 (9) | 0.0344 (8) | 0.0022 (6) | −0.0017 (6) | −0.0048 (7) |
C1 | 0.0298 (11) | 0.0298 (11) | 0.0254 (10) | 0.0029 (10) | −0.0010 (9) | −0.0002 (8) |
C2 | 0.0249 (10) | 0.0253 (10) | 0.0251 (10) | 0.0004 (9) | −0.0004 (8) | −0.0011 (8) |
C3 | 0.0212 (9) | 0.0297 (11) | 0.0259 (9) | −0.0019 (9) | −0.0015 (8) | −0.0036 (8) |
C4 | 0.0217 (9) | 0.0297 (11) | 0.0261 (10) | −0.0003 (9) | 0.0011 (8) | −0.0015 (9) |
C5 | 0.0286 (10) | 0.0298 (11) | 0.0270 (9) | −0.0025 (9) | −0.0006 (9) | 0.0017 (8) |
C6 | 0.0373 (12) | 0.0287 (12) | 0.0375 (12) | −0.0080 (10) | 0.0019 (10) | −0.0004 (9) |
C7 | 0.0393 (12) | 0.0305 (12) | 0.0329 (11) | −0.0053 (11) | −0.0041 (10) | −0.0050 (9) |
C8 | 0.0450 (13) | 0.0332 (12) | 0.0413 (12) | 0.0129 (11) | 0.0030 (11) | −0.0001 (10) |
C9 | 0.0370 (12) | 0.0324 (12) | 0.0273 (10) | 0.0013 (10) | 0.0000 (10) | 0.0010 (9) |
C10 | 0.0413 (13) | 0.0329 (12) | 0.0222 (10) | 0.0052 (11) | 0.0045 (10) | 0.0062 (8) |
C11 | 0.0451 (14) | 0.0456 (15) | 0.0388 (12) | 0.0085 (13) | 0.0085 (11) | 0.0158 (11) |
C12 | 0.0705 (19) | 0.0515 (18) | 0.0468 (15) | 0.0313 (16) | 0.0202 (14) | 0.0242 (13) |
C13 | 0.110 (3) | 0.0305 (14) | 0.0416 (14) | 0.0195 (17) | 0.0187 (16) | 0.0108 (11) |
C14 | 0.087 (2) | 0.0331 (13) | 0.0352 (13) | −0.0033 (15) | −0.0038 (14) | 0.0029 (10) |
C15 | 0.0526 (15) | 0.0336 (12) | 0.0331 (11) | 0.0021 (12) | −0.0001 (11) | 0.0038 (9) |
C16 | 0.0255 (10) | 0.0406 (12) | 0.0294 (10) | 0.0013 (10) | −0.0001 (9) | 0.0002 (9) |
C17 | 0.0281 (10) | 0.0376 (12) | 0.0266 (10) | 0.0059 (10) | 0.0041 (9) | −0.0005 (9) |
C18 | 0.0458 (15) | 0.0657 (17) | 0.0346 (12) | −0.0059 (13) | −0.0060 (12) | −0.0013 (12) |
C19 | 0.0445 (15) | 0.100 (2) | 0.0472 (15) | 0.0012 (17) | −0.0123 (13) | −0.0168 (16) |
C20 | 0.0530 (17) | 0.109 (3) | 0.0285 (12) | 0.0328 (18) | 0.0036 (13) | 0.0103 (15) |
C21 | 0.0540 (16) | 0.085 (2) | 0.0419 (14) | 0.0183 (17) | 0.0063 (13) | 0.0213 (14) |
C22 | 0.0435 (13) | 0.0525 (15) | 0.0369 (12) | 0.0051 (12) | 0.0055 (11) | 0.0093 (11) |
N—C8 | 1.468 (3) | C9—H9A | 0.9800 |
N—C5 | 1.486 (2) | C9—H9B | 0.9800 |
N—C1 | 1.488 (2) | C10—C15 | 1.390 (3) |
O—C3 | 1.430 (2) | C10—C11 | 1.393 (3) |
O—H0 | 0.8300 | C11—C12 | 1.394 (4) |
C1—C2 | 1.541 (3) | C11—H11 | 0.9400 |
C1—C7 | 1.542 (3) | C12—C13 | 1.370 (4) |
C1—H1 | 0.9900 | C12—H12 | 0.9400 |
C2—C3 | 1.530 (3) | C13—C14 | 1.366 (4) |
C2—C9 | 1.531 (3) | C13—H13 | 0.9400 |
C2—H2 | 0.9900 | C14—C15 | 1.385 (3) |
C3—C4 | 1.539 (3) | C14—H14 | 0.9400 |
C3—H3 | 0.9900 | C15—H15 | 0.9400 |
C4—C16 | 1.527 (3) | C16—C17 | 1.507 (3) |
C4—C5 | 1.537 (3) | C16—H16A | 0.9800 |
C4—H4 | 0.9900 | C16—H16B | 0.9800 |
C5—C6 | 1.544 (3) | C17—C18 | 1.382 (3) |
C5—H5 | 0.9900 | C17—C22 | 1.386 (3) |
C6—C7 | 1.550 (3) | C18—C19 | 1.403 (3) |
C6—H6A | 0.9800 | C18—H18 | 0.9400 |
C6—H6B | 0.9800 | C19—C20 | 1.381 (4) |
C7—H7A | 0.9800 | C19—H19 | 0.9400 |
C7—H7B | 0.9800 | C20—C21 | 1.354 (4) |
C8—H8A | 0.9700 | C20—H20 | 0.9400 |
C8—H8B | 0.9700 | C21—C22 | 1.375 (3) |
C8—H8C | 0.9700 | C21—H21 | 0.9400 |
C9—C10 | 1.504 (3) | C22—H22 | 0.9400 |
C8—N—C5 | 112.46 (15) | H8A—C8—H8C | 109.5 |
C8—N—C1 | 111.14 (15) | H8B—C8—H8C | 109.5 |
C5—N—C1 | 100.85 (14) | C10—C9—C2 | 113.41 (17) |
C3—O—H0 | 109.5 | C10—C9—H9A | 108.9 |
N—C1—C2 | 106.88 (15) | C2—C9—H9A | 108.9 |
N—C1—C7 | 104.45 (15) | C10—C9—H9B | 108.9 |
C2—C1—C7 | 113.70 (17) | C2—C9—H9B | 108.9 |
N—C1—H1 | 110.5 | H9A—C9—H9B | 107.7 |
C2—C1—H1 | 110.5 | C15—C10—C11 | 117.7 (2) |
C7—C1—H1 | 110.5 | C15—C10—C9 | 121.2 (2) |
C3—C2—C9 | 112.98 (15) | C11—C10—C9 | 121.0 (2) |
C3—C2—C1 | 111.78 (16) | C10—C11—C12 | 120.2 (3) |
C9—C2—C1 | 112.53 (16) | C10—C11—H11 | 119.9 |
C3—C2—H2 | 106.3 | C12—C11—H11 | 119.9 |
C9—C2—H2 | 106.3 | C13—C12—C11 | 120.8 (3) |
C1—C2—H2 | 106.3 | C13—C12—H12 | 119.6 |
O—C3—C2 | 109.51 (15) | C11—C12—H12 | 119.6 |
O—C3—C4 | 112.36 (16) | C14—C13—C12 | 119.7 (2) |
C2—C3—C4 | 110.12 (15) | C14—C13—H13 | 120.1 |
O—C3—H3 | 108.2 | C12—C13—H13 | 120.1 |
C2—C3—H3 | 108.2 | C13—C14—C15 | 120.1 (3) |
C4—C3—H3 | 108.2 | C13—C14—H14 | 119.9 |
C16—C4—C5 | 113.14 (16) | C15—C14—H14 | 119.9 |
C16—C4—C3 | 112.27 (15) | C14—C15—C10 | 121.4 (3) |
C5—C4—C3 | 111.64 (16) | C14—C15—H15 | 119.3 |
C16—C4—H4 | 106.4 | C10—C15—H15 | 119.3 |
C5—C4—H4 | 106.4 | C17—C16—C4 | 114.56 (15) |
C3—C4—H4 | 106.4 | C17—C16—H16A | 108.6 |
N—C5—C4 | 107.22 (15) | C4—C16—H16A | 108.6 |
N—C5—C6 | 104.45 (15) | C17—C16—H16B | 108.6 |
C4—C5—C6 | 113.63 (17) | C4—C16—H16B | 108.6 |
N—C5—H5 | 110.4 | H16A—C16—H16B | 107.6 |
C4—C5—H5 | 110.4 | C18—C17—C22 | 117.7 (2) |
C6—C5—H5 | 110.4 | C18—C17—C16 | 121.0 (2) |
C5—C6—C7 | 103.85 (16) | C22—C17—C16 | 121.20 (19) |
C5—C6—H6A | 111.0 | C17—C18—C19 | 120.4 (3) |
C7—C6—H6A | 111.0 | C17—C18—H18 | 119.8 |
C5—C6—H6B | 111.0 | C19—C18—H18 | 119.8 |
C7—C6—H6B | 111.0 | C20—C19—C18 | 119.6 (3) |
H6A—C6—H6B | 109.0 | C20—C19—H19 | 120.2 |
C1—C7—C6 | 103.99 (16) | C18—C19—H19 | 120.2 |
C1—C7—H7A | 111.0 | C21—C20—C19 | 120.3 (3) |
C6—C7—H7A | 111.0 | C21—C20—H20 | 119.8 |
C1—C7—H7B | 111.0 | C19—C20—H20 | 119.8 |
C6—C7—H7B | 111.0 | C20—C21—C22 | 119.9 (3) |
H7A—C7—H7B | 109.0 | C20—C21—H21 | 120.0 |
N—C8—H8A | 109.5 | C22—C21—H21 | 120.0 |
N—C8—H8B | 109.5 | C21—C22—C17 | 122.0 (2) |
H8A—C8—H8B | 109.5 | C21—C22—H22 | 119.0 |
N—C8—H8C | 109.5 | C17—C22—H22 | 119.0 |
C8—N—C1—C2 | −165.20 (16) | C2—C1—C7—C6 | −88.4 (2) |
C5—N—C1—C2 | 75.39 (18) | C5—C6—C7—C1 | 0.1 (2) |
C8—N—C1—C7 | 74.00 (19) | C3—C2—C9—C10 | 55.7 (2) |
C5—N—C1—C7 | −45.41 (18) | C1—C2—C9—C10 | −176.53 (18) |
N—C1—C2—C3 | −62.4 (2) | C2—C9—C10—C15 | 58.9 (3) |
C7—C1—C2—C3 | 52.3 (2) | C2—C9—C10—C11 | −120.2 (2) |
N—C1—C2—C9 | 169.24 (16) | C15—C10—C11—C12 | −0.4 (3) |
C7—C1—C2—C9 | −76.0 (2) | C9—C10—C11—C12 | 178.65 (19) |
C9—C2—C3—O | 49.3 (2) | C10—C11—C12—C13 | 0.6 (3) |
C1—C2—C3—O | −78.81 (19) | C11—C12—C13—C14 | −0.4 (4) |
C9—C2—C3—C4 | 173.36 (16) | C12—C13—C14—C15 | 0.0 (4) |
C1—C2—C3—C4 | 45.2 (2) | C13—C14—C15—C10 | 0.2 (3) |
O—C3—C4—C16 | −50.8 (2) | C11—C10—C15—C14 | 0.0 (3) |
C2—C3—C4—C16 | −173.21 (16) | C9—C10—C15—C14 | −179.0 (2) |
O—C3—C4—C5 | 77.42 (19) | C5—C4—C16—C17 | 74.8 (2) |
C2—C3—C4—C5 | −45.0 (2) | C3—C4—C16—C17 | −157.74 (18) |
C8—N—C5—C4 | 166.13 (16) | C4—C16—C17—C18 | 61.0 (3) |
C1—N—C5—C4 | −75.41 (17) | C4—C16—C17—C22 | −122.6 (2) |
C8—N—C5—C6 | −73.0 (2) | C22—C17—C18—C19 | −1.0 (3) |
C1—N—C5—C6 | 45.47 (18) | C16—C17—C18—C19 | 175.5 (2) |
C16—C4—C5—N | −170.24 (15) | C17—C18—C19—C20 | 0.1 (4) |
C3—C4—C5—N | 62.0 (2) | C18—C19—C20—C21 | 0.8 (4) |
C16—C4—C5—C6 | 74.9 (2) | C19—C20—C21—C22 | −0.7 (4) |
C3—C4—C5—C6 | −52.9 (2) | C20—C21—C22—C17 | −0.3 (4) |
N—C5—C6—C7 | −28.0 (2) | C18—C17—C22—C21 | 1.1 (3) |
C4—C5—C6—C7 | 88.53 (19) | C16—C17—C22—C21 | −175.4 (2) |
N—C1—C7—C6 | 27.8 (2) |
C22H27NO | Dx = 1.227 Mg m−3 |
Mr = 321.45 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Cmc21 | Cell parameters from 4871 reflections |
a = 17.8580 (8) Å | θ = 1.0–27.5° |
b = 10.5480 (9) Å | µ = 0.07 mm−1 |
c = 9.2364 (8) Å | T = 173 K |
V = 1739.8 (2) Å3 | Needle, colourless |
Z = 4 | 0.50 × 0.10 × 0.08 mm |
F(000) = 696 |
Nonius KappaCCD diffractometer | 861 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.075 |
Graphite monochromator | θmax = 27.4°, θmin = 2.2° |
Detector resolution: 18 pixels mm-1 | h = −23→22 |
ω scans at fixed χ = 55° | k = −13→13 |
5089 measured reflections | l = −11→8 |
1085 independent reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.050 | w = 1/[σ2(Fo2) + (0.0372P)2P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.085 | (Δ/σ)max < 0.001 |
S = 1.49 | Δρmax = 0.20 e Å−3 |
1085 reflections | Δρmin = −0.21 e Å−3 |
117 parameters | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
5 restraints | Extinction coefficient: 0.0042 (10) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. Final refinement cycles were performed against Friedel-merged data because the Flack parameter refined to a value with no physical interpretation. |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −1 (2) |
C22H27NO | V = 1739.8 (2) Å3 |
Mr = 321.45 | Z = 4 |
Orthorhombic, Cmc21 | Mo Kα radiation |
a = 17.8580 (8) Å | µ = 0.07 mm−1 |
b = 10.5480 (9) Å | T = 173 K |
c = 9.2364 (8) Å | 0.50 × 0.10 × 0.08 mm |
Nonius KappaCCD diffractometer | 861 reflections with I > 2σ(I) |
5089 measured reflections | Rint = 0.075 |
1085 independent reflections |
R[F2 > 2σ(F2)] = 0.050 | H-atom parameters constrained |
wR(F2) = 0.085 | Δρmax = 0.20 e Å−3 |
S = 1.49 | Δρmin = −0.21 e Å−3 |
1085 reflections | Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. Final refinement cycles were performed against Friedel-merged data because the Flack parameter refined to a value with no physical interpretation. |
117 parameters | Absolute structure parameter: −1 (2) |
5 restraints |
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. The absolute structure of the crystal cannot be determined from the X-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. In the final refinement cycles, performed against Friedel-merged data, the Flack parameter was not refined because it had previously refined to a value with no physical interpretation. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
N | 0.0000 | 0.2661 (2) | 0.3866 (3) | 0.0220 (7) | |
O | 0.0000 | 0.58540 (19) | 0.1440 (2) | 0.0313 (6) | |
H0 | 0.0068 | 0.6083 | 0.0579 | 0.047* | 0.50 |
C1 | 0.06407 (11) | 0.2693 (2) | 0.2841 (2) | 0.0249 (6) | |
H1 | 0.1112 | 0.2424 | 0.3341 | 0.030* | |
C2 | 0.07162 (11) | 0.4056 (2) | 0.2277 (2) | 0.0233 (6) | |
H2 | 0.0796 | 0.4621 | 0.3133 | 0.028* | |
C3 | 0.0000 | 0.4493 (3) | 0.1515 (4) | 0.0249 (8) | |
H3 | 0.0000 | 0.4148 | 0.0506 | 0.030* | |
C7 | 0.04318 (12) | 0.1735 (2) | 0.1653 (3) | 0.0309 (6) | |
H7A | 0.0630 | 0.0882 | 0.1882 | 0.037* | |
H7B | 0.0630 | 0.2007 | 0.0701 | 0.037* | |
C8 | 0.0000 | 0.1481 (3) | 0.4720 (4) | 0.0266 (8) | |
H8A | 0.0000 | 0.0698 | 0.4106 | 0.040* | |
H8B | 0.0463 | 0.1423 | 0.5347 | 0.040* | |
C9 | 0.13890 (11) | 0.4226 (2) | 0.1261 (3) | 0.0273 (6) | |
H9A | 0.1320 | 0.3657 | 0.0419 | 0.033* | |
H9B | 0.1383 | 0.5107 | 0.0892 | 0.033* | |
C10 | 0.21525 (11) | 0.3970 (2) | 0.1904 (2) | 0.0245 (6) | |
C11 | 0.24339 (12) | 0.4722 (2) | 0.3020 (3) | 0.0295 (7) | |
H11 | 0.2131 | 0.5379 | 0.3408 | 0.035* | |
C12 | 0.31448 (13) | 0.4532 (2) | 0.3574 (3) | 0.0357 (7) | |
H12 | 0.3325 | 0.5051 | 0.4340 | 0.043* | |
C13 | 0.35933 (12) | 0.3582 (2) | 0.3005 (3) | 0.0350 (7) | |
H13 | 0.4087 | 0.3459 | 0.3362 | 0.042* | |
C14 | 0.33182 (13) | 0.2820 (2) | 0.1922 (3) | 0.0367 (7) | |
H14 | 0.3622 | 0.2161 | 0.1541 | 0.044* | |
C15 | 0.26049 (13) | 0.3002 (2) | 0.1381 (3) | 0.0318 (6) | |
H15 | 0.2422 | 0.2457 | 0.0642 | 0.038* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N | 0.0236 (15) | 0.0224 (16) | 0.0202 (16) | 0.000 | 0.000 | 0.0046 (12) |
O | 0.0420 (14) | 0.0226 (12) | 0.0293 (14) | 0.000 | 0.000 | 0.0043 (12) |
C1 | 0.0216 (12) | 0.0276 (14) | 0.0255 (14) | 0.0037 (11) | −0.0007 (11) | 0.0005 (13) |
C2 | 0.0248 (12) | 0.0221 (13) | 0.0230 (14) | −0.0013 (10) | 0.0017 (10) | −0.0016 (11) |
C3 | 0.0318 (17) | 0.0201 (18) | 0.0228 (19) | 0.000 | 0.000 | 0.0025 (16) |
C7 | 0.0405 (13) | 0.0235 (13) | 0.0288 (14) | 0.0011 (10) | 0.0027 (12) | −0.0019 (12) |
C8 | 0.0277 (18) | 0.028 (2) | 0.024 (2) | 0.000 | 0.000 | 0.0042 (16) |
C9 | 0.0284 (13) | 0.0275 (13) | 0.0259 (14) | −0.0057 (10) | 0.0030 (11) | 0.0009 (12) |
C10 | 0.0260 (12) | 0.0231 (13) | 0.0244 (15) | −0.0045 (10) | 0.0038 (11) | 0.0052 (11) |
C11 | 0.0292 (13) | 0.0300 (16) | 0.0291 (16) | −0.0001 (11) | 0.0078 (12) | −0.0002 (13) |
C12 | 0.0335 (14) | 0.0431 (18) | 0.0306 (15) | −0.0096 (13) | 0.0025 (12) | 0.0026 (13) |
C13 | 0.0278 (13) | 0.0415 (16) | 0.0356 (17) | 0.0001 (13) | 0.0026 (13) | 0.0140 (15) |
C14 | 0.0326 (14) | 0.0247 (13) | 0.0528 (18) | 0.0035 (11) | 0.0125 (14) | 0.0056 (14) |
C15 | 0.0321 (13) | 0.0254 (13) | 0.0379 (16) | −0.0050 (11) | 0.0082 (13) | −0.0041 (14) |
N—C8 | 1.474 (4) | C8—H8A | 1.0016 |
N—C1 | 1.485 (3) | C8—H8B | 1.0106 |
N—C1i | 1.486 (3) | C9—C10 | 1.512 (3) |
O—C3 | 1.437 (3) | C9—H9A | 0.9900 |
O—H0 | 0.8400 | C9—H9B | 0.9900 |
C1—C2 | 1.536 (3) | C10—C15 | 1.389 (3) |
C1—C7 | 1.537 (3) | C10—C11 | 1.395 (3) |
C1—H1 | 1.0000 | C11—C12 | 1.383 (3) |
C2—C3 | 1.531 (3) | C11—H11 | 0.9500 |
C2—C9 | 1.535 (3) | C12—C13 | 1.386 (3) |
C2—H2 | 1.0000 | C12—H12 | 0.9500 |
C3—C2i | 1.531 (3) | C13—C14 | 1.374 (3) |
C3—H3 | 1.0000 | C13—H13 | 0.9500 |
C7—C7i | 1.542 (4) | C14—C15 | 1.382 (3) |
C7—H7A | 0.9900 | C14—H14 | 0.9500 |
C7—H7B | 0.9900 | C15—H15 | 0.9500 |
C8—N—C1 | 111.08 (17) | N—C8—H8A | 113.1 |
C8—N—C1i | 111.08 (17) | N—C8—H8B | 110.9 |
C1—N—C1i | 100.8 (2) | H8A—C8—H8B | 106.0 |
C3—O—H0 | 109.5 | C10—C9—C2 | 116.4 (2) |
N—C1—C2 | 107.73 (18) | C10—C9—H9A | 108.2 |
N—C1—C7 | 104.69 (17) | C2—C9—H9A | 108.2 |
C2—C1—C7 | 113.22 (19) | C10—C9—H9B | 108.2 |
N—C1—H1 | 110.3 | C2—C9—H9B | 108.2 |
C2—C1—H1 | 110.3 | H9A—C9—H9B | 107.3 |
C7—C1—H1 | 110.3 | C15—C10—C11 | 117.8 (2) |
C3—C2—C9 | 109.72 (18) | C15—C10—C9 | 121.3 (2) |
C3—C2—C1 | 111.38 (17) | C11—C10—C9 | 120.9 (2) |
C9—C2—C1 | 112.67 (17) | C12—C11—C10 | 121.4 (2) |
C3—C2—H2 | 107.6 | C12—C11—H11 | 119.3 |
C9—C2—H2 | 107.6 | C10—C11—H11 | 119.3 |
C1—C2—H2 | 107.6 | C11—C12—C13 | 119.7 (2) |
O—C3—C2 | 108.83 (16) | C11—C12—H12 | 120.2 |
O—C3—C2i | 108.83 (16) | C13—C12—H12 | 120.2 |
C2—C3—C2i | 113.3 (2) | C14—C13—C12 | 119.5 (2) |
O—C3—H3 | 108.6 | C14—C13—H13 | 120.3 |
C2—C3—H3 | 108.6 | C12—C13—H13 | 120.3 |
C2i—C3—H3 | 108.6 | C13—C14—C15 | 120.8 (2) |
C1—C7—C7i | 104.05 (11) | C13—C14—H14 | 119.6 |
C1—C7—H7A | 110.9 | C15—C14—H14 | 119.6 |
C7i—C7—H7A | 110.9 | C14—C15—C10 | 120.8 (2) |
C1—C7—H7B | 110.9 | C14—C15—H15 | 119.6 |
C7i—C7—H7B | 110.9 | C10—C15—H15 | 119.6 |
H7A—C7—H7B | 109.0 | ||
C8—N—C1—C2 | −166.2 (2) | C2—C1—C7—C7i | −89.49 (15) |
C1i—N—C1—C2 | 76.0 (2) | C3—C2—C9—C10 | 173.7 (2) |
C8—N—C1—C7 | 73.0 (2) | C1—C2—C9—C10 | −61.6 (3) |
C1i—N—C1—C7 | −44.8 (3) | C2—C9—C10—C15 | 117.3 (2) |
N—C1—C2—C3 | −59.2 (2) | C2—C9—C10—C11 | −64.4 (3) |
C7—C1—C2—C3 | 56.1 (2) | C15—C10—C11—C12 | 1.2 (3) |
N—C1—C2—C9 | 177.05 (17) | C9—C10—C11—C12 | −177.1 (2) |
C7—C1—C2—C9 | −67.7 (2) | C10—C11—C12—C13 | 0.5 (4) |
C9—C2—C3—O | −73.4 (3) | C11—C12—C13—C14 | −1.6 (3) |
C1—C2—C3—O | 161.2 (2) | C12—C13—C14—C15 | 0.9 (3) |
C9—C2—C3—C2i | 165.40 (17) | C13—C14—C15—C10 | 0.9 (4) |
C1—C2—C3—C2i | 39.9 (3) | C11—C10—C15—C14 | −2.0 (3) |
N—C1—C7—C7i | 27.57 (16) | C9—C10—C15—C14 | 176.4 (2) |
Symmetry code: (i) −x, y, z. |
Experimental details
(I) | (II) | |
Crystal data | ||
Chemical formula | C22H27NO | C22H27NO |
Mr | 321.45 | 321.45 |
Crystal system, space group | Orthorhombic, P212121 | Orthorhombic, Cmc21 |
Temperature (K) | 206 | 173 |
a, b, c (Å) | 10.4244 (4), 11.4988 (5), 15.1602 (5) | 17.8580 (8), 10.5480 (9), 9.2364 (8) |
V (Å3) | 1817.22 (12) | 1739.8 (2) |
Z | 4 | 4 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.07 | 0.07 |
Crystal size (mm) | 0.24 × 0.24 × 0.20 | 0.50 × 0.10 × 0.08 |
Data collection | ||
Diffractometer | Nonius KappaCCD diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 14506, 2371, 1902 | 5089, 1085, 861 |
Rint | 0.066 | 0.075 |
(sin θ/λ)max (Å−1) | 0.649 | 0.648 |
Refinement | ||
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.096, 1.44 | 0.050, 0.085, 1.49 |
No. of reflections | 2371 | 1085 |
No. of parameters | 219 | 117 |
No. of restraints | 0 | 5 |
H-atom treatment | H-atom parameters constrained | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.18, −0.17 | 0.20, −0.21 |
Absolute structure | Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. In the final refinement cycles, performed against Friedel-merged data, the Flack parameter was not refined because it had previously refined to a value with no physical interpretation. | Flack H D (1983), Acta Cryst. A39, 876-881 The absolute structure of the crystal cannot be determined from the x-ray data because it is an all light atom structure determined with Mo Kα data. The quoted value of the Flack parameter was obtained in the conventional way, as a variable in a full-matrix least-squares refinement against data with unmerged Friedel opposites. Final refinement cycles were performed against Friedel-merged data because the Flack parameter refined to a value with no physical interpretation. |
Absolute structure parameter | 0.7 (19) | −1 (2) |
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), SHELX97-2 (Sheldrick, 1997) and local procedures.
N—C5 | 1.486 (2) | C2—C9 | 1.531 (3) |
N—C1 | 1.488 (2) | C3—C4 | 1.539 (3) |
C2—C3 | 1.530 (3) | C4—C16 | 1.527 (3) |
N—C1—C2 | 106.88 (15) | O—C3—C4 | 112.36 (16) |
C3—C2—C9 | 112.98 (15) | C16—C4—C3 | 112.27 (15) |
O—C3—C2 | 109.51 (15) | N—C5—C4 | 107.22 (15) |
C3—C2—C9—C10 | 55.7 (2) | C3—C4—C16—C17 | −157.74 (18) |
C1—C2—C9—C10 | −176.53 (18) | C4—C16—C17—C18 | 61.0 (3) |
C2—C9—C10—C15 | 58.9 (3) |
N—C1 | 1.485 (3) | C2—C3 | 1.531 (3) |
N—C1i | 1.486 (3) | C3—C2i | 1.531 (3) |
O—C3—C2 | 108.83 (16) | O—C3—C2i | 108.83 (16) |
C9—C2—C3—O | −73.4 (3) | C1—C2—C9—C10 | −61.6 (3) |
C3—C2—C9—C10 | 173.7 (2) |
Symmetry code: (i) −x, y, z. |
The tropane ring system is present in the natural product cocaine and in a number of other compounds that display interesting pharmacological properties. Numerous novel tropane analogs have been synthesized and evaluated as inhibitors of dopamine, serotonin and norepinephrine transporters in an effort to probe the topology of the cocaine binding site on these biogenic amine transporters (Carrol et al., 1999; Newman, 2000; Cappelli et al., 2002; Newman & Kulkarni, 2002). In efforts to develop novel therapeutic agents for treating central nervous system disorders, we have designed and synthesized a number of tropane derivatives. Compounds (I) and (II) are two isomeric tropane derivatives that we prepared recently. Both (I) and (II) were synthesized stereospecifically and identified initially by MS and NMR spectroscopy. In order to unequivocally confirm the stereochemistry of these compounds, and to gather more detailed information on the structural conformation of the molecules for our molecular recognition studies, their crystal structures have been determined.
The molecular structures of (I) and (II) are shown in Fig. 1, while selected geometric parameters are presented in Tables 1 and 2. As expected, the structures of (I) and (II) are similar, with the piperidine ring in a chair conformation and the pyrrolidine ring in an envelope conformation with atom N as the flap, and the benzyl groups and the bridgehead N-methyl group are bonded equatorially to the piperidine ring. However, in (I), the hydroxy group is attached axially to the piperidine ring on atom C3, whereas in (II), the hydroxy group is attached equatorially to the piperidine ring on atom C3. In (I), because of the steric interactions between the hydroxy group and the benzyl groups, the C2 and C4 benzyl groups are not mirror symmetric, as indicated by the unequal torsion angles around the C2—C9 and C9—C10 bonds and around the C4—C16 and C16—C17 bonds (Table 1). This conformation probably results from a repulsive interaction between the H atoms on atom C16 and the hydroxy group on atom C3, which causes the exocyclic O—C3—C4 angle [112.36 (16)°] to be slightly larger than the O—C3—C2 angle [109.51 (15)°]. In addition to the asymmetric phenyl rings in (I), the tropane ring system itself is also slightly contorted, as evidenced by the endocyclic bond lengths and angles (Table 1). The C1—C2 and C9—C10 bonds in (I) are approximately coplanar [C1—C2—C9—C10 = −176.53 (18)°]. In (II), where there is less intramolecular crowding, the whole molecule is mirror symmetric, with atoms N, O, C3 and C8 lying on the mirror plane (Table 2). In contrast to (I), the C2—C3 and C9—C10 bonds in (II) are approximately coplanar, as evidenced by the C3—C2—C9—C10 torsion angle [173.7 (2)°].
The molecules of (I) form infinite chains along the a axis (Fig. 2), and the molecules in these chains are connected by a zigzag pattern of intermolecular O—H···N hydrogen bonds [symmetry code: x − 1/2, −y + 1/2, −z; H···N=1.962 Å, O.·N=2.793 Å and O—H···N=170.01°]. In the crystal of (II), the parallel intermolecular O—H···N hydrogen bonds (symmetry code: −x, −y + 1, z − 1/2; H···N=2.067 Å, O···N=2.846 Å and O—H.·N=154.19°) link the molecules into an infinite one-dimensional linear array, which is parallel to the b axis (Fig. 3).