Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803004501/dn6058sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536803004501/dn6058Isup2.hkl |
CCDC reference: 209912
The title compound was prepared by mixing 7,9-dibenzyl-2,5-methanobicyclo[4.3.0]-7,9-diazanon-3-en-8-one (0.88 g, 0.00267 mol) with LiAlH4 (1 g, 0.0267 mol) and anhydrous tetrahydofuran (35 ml) under argon. The mixture was refluxed for 21 h and cooled to 273 K before a 15% solution of sodium hydroxide (2 ml) was slowly added, with continuous stirring, over a period of 10 min at room temperature. The mixture was filtered through a Celite pad and washed with water (200 ml) before the filtrate was extracted with dichloromethane (300 ml). The organic phase was washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography on silica using dichloromethane/ethyl acetate (95/5) as eluant. Single crystals suitable for X-ray analysis were obtained by slow evaporation at room temperature from diethyl ether.
All H atoms were initially found in difference Fourier syntheses but were fixed in idealized positions in the final refinement. Riding isotropic displacement parameters, with Uiso(H) = 1.2Ueq(C), were used for all H atoms.
Data collection: COLLECT (Nonius, 1998); cell refinement: HKL SCALEPACK; data reduction: HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXTL (Sheldrick, 1995); program(s) used to refine structure: JANA2000 (Petricek & Dusek, 2000); molecular graphics: DIAMOND (Brandenburg & Berndt, 1999); software used to prepare material for publication: JANA2000.
Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids. H atoms have been omitted for clarity. |
C22H24N2 | F(000) = 680 |
Mr = 316.4 | Dx = 1.190 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71069 Å |
Hall symbol: -P 2ybc | Cell parameters from 17065 reflections |
a = 15.4338 (4) Å | θ = 2.9–32.0° |
b = 8.2487 (2) Å | µ = 0.07 mm−1 |
c = 13.8748 (3) Å | T = 150 K |
β = 92.7699 (8)° | Block, colourless |
V = 1764.32 (7) Å3 | 0.31 × 0.23 × 0.18 mm |
Z = 4 |
Nonius KappaCCD diffractometer | 4012 reflections with I > 2σ(I) |
Horizonally mounted graphite crystal monochromator | Rint = 0.056 |
Detector resolution: 9 pixels mm-1 | θmax = 32.0°, θmin = 2.9° |
ϕ–ω scans | h = −23→22 |
17647 measured reflections | k = −12→11 |
6050 independent reflections | l = −20→13 |
Refinement on F2 | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.059 | Weighting scheme based on measured s.u.'s w = 1/[σ2(I) + 0.0025I2] |
wR(F2) = 0.147 | (Δ/σ)max = 0.0004 |
S = 1.45 | Δρmax = 0.30 e Å−3 |
6050 reflections | Δρmin = −0.25 e Å−3 |
217 parameters |
C22H24N2 | V = 1764.32 (7) Å3 |
Mr = 316.4 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 15.4338 (4) Å | µ = 0.07 mm−1 |
b = 8.2487 (2) Å | T = 150 K |
c = 13.8748 (3) Å | 0.31 × 0.23 × 0.18 mm |
β = 92.7699 (8)° |
Nonius KappaCCD diffractometer | 4012 reflections with I > 2σ(I) |
17647 measured reflections | Rint = 0.056 |
6050 independent reflections |
R[F2 > 2σ(F2)] = 0.059 | 217 parameters |
wR(F2) = 0.147 | H-atom parameters constrained |
S = 1.45 | Δρmax = 0.30 e Å−3 |
6050 reflections | Δρmin = −0.25 e Å−3 |
x | y | z | Uiso*/Ueq | ||
C1 | 0.29800 (8) | 0.68691 (15) | 0.56942 (8) | 0.0302 (4) | |
C2 | 0.25773 (7) | 0.51423 (15) | 0.56402 (7) | 0.0277 (3) | |
C3 | 0.30753 (8) | 0.43162 (14) | 0.48335 (8) | 0.0287 (4) | |
C4 | 0.37042 (8) | 0.56670 (15) | 0.45149 (8) | 0.0308 (4) | |
C5 | 0.31535 (8) | 0.70000 (15) | 0.40606 (8) | 0.0311 (4) | |
C6 | 0.27266 (8) | 0.77125 (14) | 0.47567 (9) | 0.0307 (4) | |
C7 | 0.39271 (8) | 0.64171 (16) | 0.55105 (9) | 0.0353 (4) | |
N8 | 0.16599 (6) | 0.50104 (12) | 0.53085 (6) | 0.0263 (3) | |
C9 | 0.16293 (8) | 0.35733 (15) | 0.47011 (8) | 0.0300 (4) | |
N10 | 0.23897 (6) | 0.37750 (12) | 0.41297 (6) | 0.0279 (3) | |
C11 | 0.26002 (9) | 0.23275 (16) | 0.35880 (9) | 0.0370 (4) | |
C12 | 0.32950 (8) | 0.26487 (15) | 0.28897 (8) | 0.0318 (4) | |
C13 | 0.31562 (8) | 0.37723 (15) | 0.21476 (9) | 0.0343 (4) | |
C14 | 0.37901 (9) | 0.40565 (16) | 0.14919 (9) | 0.0376 (4) | |
C15 | 0.45710 (9) | 0.32241 (17) | 0.15740 (9) | 0.0397 (4) | |
C16 | 0.47172 (9) | 0.21215 (19) | 0.23084 (10) | 0.0437 (5) | |
C17 | 0.40807 (9) | 0.18315 (17) | 0.29610 (9) | 0.0401 (4) | |
C18 | 0.10522 (8) | 0.49820 (16) | 0.60808 (8) | 0.0317 (4) | |
C19 | 0.09539 (7) | 0.66495 (15) | 0.65063 (8) | 0.0289 (4) | |
C20 | 0.06706 (8) | 0.79258 (17) | 0.59187 (8) | 0.0338 (4) | |
C21 | 0.05771 (8) | 0.94699 (17) | 0.62898 (9) | 0.0384 (4) | |
C22 | 0.07794 (8) | 0.97644 (17) | 0.72603 (9) | 0.0370 (4) | |
C23 | 0.10671 (8) | 0.85089 (18) | 0.78528 (8) | 0.0358 (4) | |
C24 | 0.11531 (8) | 0.69628 (16) | 0.74764 (8) | 0.0324 (4) | |
H1 | 0.284 | 0.7519 | 0.6259 | 0.0364* | |
H2 | 0.2583 | 0.4685 | 0.6293 | 0.0334* | |
H3 | 0.3412 | 0.3323 | 0.4959 | 0.0345* | |
H4 | 0.4163 | 0.5313 | 0.4099 | 0.037* | |
H5 | 0.3082 | 0.7369 | 0.3389 | 0.0373* | |
H6 | 0.233 | 0.862 | 0.4614 | 0.0368* | |
H7a | 0.4312 | 0.736 | 0.5483 | 0.0426* | |
H7b | 0.4175 | 0.5633 | 0.5979 | 0.0426* | |
H9a | 0.1095 | 0.3545 | 0.4288 | 0.0361* | |
H9b | 0.1671 | 0.2582 | 0.5089 | 0.0361* | |
H11a | 0.207 | 0.1956 | 0.3237 | 0.0444* | |
H11b | 0.2798 | 0.149 | 0.4051 | 0.0444* | |
H13 | 0.261 | 0.4374 | 0.2086 | 0.0412* | |
H14 | 0.3683 | 0.4846 | 0.0974 | 0.0454* | |
H15 | 0.5021 | 0.3414 | 0.1112 | 0.048* | |
H16 | 0.5273 | 0.1546 | 0.2364 | 0.0524* | |
H17 | 0.4185 | 0.1037 | 0.3479 | 0.0482* | |
H18a | 0.1273 | 0.4229 | 0.6582 | 0.0382* | |
H18b | 0.049 | 0.4596 | 0.5815 | 0.0382* | |
H20 | 0.0533 | 0.7738 | 0.523 | 0.0407* | |
H21 | 0.0369 | 1.0352 | 0.5866 | 0.0463* | |
H22 | 0.0719 | 1.0856 | 0.7528 | 0.0446* | |
H23 | 0.1211 | 0.8716 | 0.8539 | 0.0432* | |
H24 | 0.1355 | 0.6078 | 0.7902 | 0.039* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0293 (6) | 0.0312 (7) | 0.0300 (6) | −0.0062 (5) | 0.0013 (5) | −0.0042 (5) |
C2 | 0.0292 (6) | 0.0291 (7) | 0.0245 (5) | −0.0022 (5) | −0.0016 (4) | 0.0033 (5) |
C3 | 0.0279 (6) | 0.0259 (6) | 0.0321 (6) | 0.0023 (5) | −0.0013 (4) | 0.0028 (5) |
C4 | 0.0244 (6) | 0.0335 (7) | 0.0347 (6) | −0.0024 (5) | 0.0028 (5) | −0.0005 (5) |
C5 | 0.0289 (6) | 0.0304 (7) | 0.0340 (6) | −0.0080 (5) | 0.0010 (5) | 0.0059 (5) |
C6 | 0.0297 (6) | 0.0215 (6) | 0.0409 (6) | −0.0049 (5) | 0.0016 (5) | 0.0034 (5) |
C7 | 0.0272 (6) | 0.0386 (8) | 0.0396 (7) | −0.0055 (5) | −0.0044 (5) | 0.0011 (6) |
N8 | 0.0272 (5) | 0.0271 (5) | 0.0247 (4) | −0.0050 (4) | 0.0024 (4) | −0.0007 (4) |
C9 | 0.0316 (6) | 0.0278 (7) | 0.0307 (6) | −0.0060 (5) | 0.0017 (4) | 0.0002 (5) |
N10 | 0.0299 (5) | 0.0244 (5) | 0.0294 (5) | −0.0029 (4) | 0.0026 (4) | −0.0033 (4) |
C11 | 0.0450 (8) | 0.0258 (7) | 0.0405 (7) | −0.0030 (6) | 0.0057 (6) | −0.0055 (6) |
C12 | 0.0367 (7) | 0.0253 (7) | 0.0336 (6) | 0.0003 (5) | 0.0013 (5) | −0.0099 (5) |
C13 | 0.0339 (7) | 0.0290 (7) | 0.0399 (6) | 0.0033 (5) | 0.0012 (5) | −0.0066 (6) |
C14 | 0.0454 (8) | 0.0293 (7) | 0.0384 (7) | 0.0021 (6) | 0.0050 (5) | −0.0047 (6) |
C15 | 0.0382 (7) | 0.0392 (8) | 0.0423 (7) | −0.0010 (6) | 0.0078 (5) | −0.0138 (6) |
C16 | 0.0375 (8) | 0.0481 (9) | 0.0451 (7) | 0.0128 (6) | −0.0002 (6) | −0.0113 (7) |
C17 | 0.0459 (8) | 0.0380 (8) | 0.0360 (6) | 0.0102 (6) | −0.0018 (6) | −0.0058 (6) |
C18 | 0.0326 (7) | 0.0334 (7) | 0.0294 (6) | −0.0069 (5) | 0.0050 (5) | 0.0017 (5) |
C19 | 0.0229 (6) | 0.0353 (7) | 0.0288 (6) | −0.0051 (5) | 0.0045 (4) | −0.0005 (5) |
C20 | 0.0305 (7) | 0.0418 (8) | 0.0289 (6) | 0.0004 (5) | −0.0013 (5) | −0.0002 (5) |
C21 | 0.0333 (7) | 0.0411 (8) | 0.0405 (7) | 0.0061 (6) | −0.0014 (5) | 0.0005 (6) |
C22 | 0.0280 (7) | 0.0412 (8) | 0.0419 (7) | 0.0036 (6) | 0.0026 (5) | −0.0090 (6) |
C23 | 0.0286 (6) | 0.0483 (8) | 0.0304 (6) | −0.0009 (6) | 0.0010 (5) | −0.0068 (6) |
C24 | 0.0284 (6) | 0.0401 (8) | 0.0288 (6) | −0.0032 (5) | 0.0020 (5) | 0.0022 (5) |
C1—C2 | 1.5544 (17) | C22—C23 | 1.3821 (19) |
C1—C6 | 1.5098 (16) | C23—C24 | 1.3869 (19) |
C1—C7 | 1.5416 (17) | C1—H1 | 0.9817 |
C2—C3 | 1.5462 (16) | C2—H2 | 0.9803 |
C2—N8 | 1.4715 (14) | C3—H3 | 0.9808 |
C3—C4 | 1.5558 (17) | C4—H4 | 0.9793 |
C3—N10 | 1.4740 (14) | C5—H5 | 0.9812 |
C4—C5 | 1.5090 (17) | C6—H6 | 0.9810 |
C4—C7 | 1.5373 (17) | C7—H7a | 0.9805 |
C5—C6 | 1.3318 (17) | C7—H7b | 0.9814 |
N8—C9 | 1.4539 (15) | C9—H9a | 0.9814 |
N8—C18 | 1.4580 (15) | C9—H9b | 0.9795 |
C9—N10 | 1.4572 (15) | C11—H11a | 0.9808 |
N10—C11 | 1.4559 (16) | C11—H11b | 0.9817 |
C11—C12 | 1.5030 (18) | C13—H13 | 0.9782 |
C12—C13 | 1.3942 (17) | C14—H14 | 0.9782 |
C12—C17 | 1.3868 (19) | C15—H15 | 0.9806 |
C13—C14 | 1.3879 (19) | C16—H16 | 0.9801 |
C14—C15 | 1.3869 (19) | C17—H17 | 0.9804 |
C15—C16 | 1.376 (2) | C18—H18a | 0.9811 |
C16—C17 | 1.389 (2) | C18—H18b | 0.9798 |
C18—C19 | 1.5074 (18) | C20—H20 | 0.9804 |
C19—C20 | 1.3892 (17) | C21—H21 | 0.9802 |
C19—C24 | 1.3904 (15) | C22—H22 | 0.9803 |
C20—C21 | 1.3839 (19) | C23—H23 | 0.9814 |
C21—C22 | 1.3889 (17) | C24—H24 | 0.9805 |
C2—C1—C6 | 107.12 (9) | N10—C3—H3 | 102.79 |
C2—C1—C7 | 98.66 (10) | C3—C4—H4 | 115.62 |
C6—C1—C7 | 100.21 (9) | C5—C4—H4 | 112.36 |
C1—C2—C3 | 103.13 (9) | C7—C4—H4 | 120.82 |
C1—C2—N8 | 117.34 (10) | C4—C5—H5 | 131.12 |
C3—C2—N8 | 104.20 (8) | C6—C5—H5 | 121.00 |
C2—C3—C4 | 103.22 (9) | C1—C6—H6 | 131.21 |
C2—C3—N10 | 104.30 (9) | C5—C6—H6 | 121.05 |
C4—C3—N10 | 117.81 (9) | C1—C7—H7a | 113.30 |
C3—C4—C5 | 107.09 (9) | C1—C7—H7b | 113.06 |
C3—C4—C7 | 98.55 (9) | C4—C7—H7a | 113.23 |
C5—C4—C7 | 100.32 (10) | C4—C7—H7b | 113.17 |
C4—C5—C6 | 107.88 (10) | H7a—C7—H7b | 109.31 |
C1—C6—C5 | 107.75 (10) | N8—C9—H9a | 111.13 |
C1—C7—C4 | 94.19 (9) | N8—C9—H9b | 111.26 |
C2—N8—C9 | 104.21 (9) | N10—C9—H9a | 111.14 |
C2—N8—C18 | 114.51 (8) | N10—C9—H9b | 111.20 |
C9—N8—C18 | 114.13 (9) | H9a—C9—H9b | 109.40 |
N8—C9—N10 | 102.58 (9) | N10—C11—H11a | 108.09 |
C3—N10—C9 | 104.20 (8) | N10—C11—H11b | 108.01 |
C3—N10—C11 | 114.79 (9) | C12—C11—H11a | 109.84 |
C9—N10—C11 | 113.14 (10) | C12—C11—H11b | 109.72 |
N10—C11—C12 | 111.85 (10) | H11a—C11—H11b | 109.27 |
C11—C12—C13 | 120.29 (11) | C12—C13—H13 | 120.14 |
C11—C12—C17 | 121.13 (11) | C14—C13—H13 | 119.30 |
C13—C12—C17 | 118.58 (12) | C13—C14—H14 | 119.63 |
C12—C13—C14 | 120.56 (12) | C15—C14—H14 | 120.38 |
C13—C14—C15 | 119.99 (12) | C14—C15—H15 | 120.48 |
C14—C15—C16 | 119.91 (13) | C16—C15—H15 | 119.61 |
C15—C16—C17 | 120.05 (13) | C15—C16—H16 | 119.36 |
C12—C17—C16 | 120.90 (12) | C17—C16—H16 | 120.59 |
N8—C18—C19 | 110.71 (10) | C12—C17—H17 | 119.26 |
C18—C19—C20 | 119.77 (10) | C16—C17—H17 | 119.83 |
C18—C19—C24 | 121.81 (11) | N8—C18—H18a | 108.48 |
C20—C19—C24 | 118.42 (11) | N8—C18—H18b | 108.56 |
C19—C20—C21 | 120.97 (11) | C19—C18—H18a | 109.79 |
C20—C21—C22 | 119.95 (12) | C19—C18—H18b | 109.88 |
C21—C22—C23 | 119.75 (12) | H18a—C18—H18b | 109.39 |
C22—C23—C24 | 119.93 (11) | C19—C20—H20 | 119.95 |
C19—C24—C23 | 120.98 (11) | C21—C20—H20 | 119.09 |
C2—C1—H1 | 115.84 | C20—C21—H21 | 119.78 |
C6—C1—H1 | 112.25 | C22—C21—H21 | 120.27 |
C7—C1—H1 | 120.68 | C21—C22—H22 | 120.46 |
C1—C2—H2 | 108.81 | C23—C22—H22 | 119.79 |
C3—C2—H2 | 121.11 | C22—C23—H23 | 119.82 |
N8—C2—H2 | 103.02 | C24—C23—H23 | 120.25 |
C2—C3—H3 | 121.12 | C19—C24—H24 | 119.59 |
C4—C3—H3 | 108.45 | C23—C24—H24 | 119.43 |
Experimental details
Crystal data | |
Chemical formula | C22H24N2 |
Mr | 316.4 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 150 |
a, b, c (Å) | 15.4338 (4), 8.2487 (2), 13.8748 (3) |
β (°) | 92.7699 (8) |
V (Å3) | 1764.32 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.31 × 0.23 × 0.18 |
Data collection | |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 17647, 6050, 4012 |
Rint | 0.056 |
(sin θ/λ)max (Å−1) | 0.746 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.059, 0.147, 1.45 |
No. of reflections | 6050 |
No. of parameters | 217 |
No. of restraints | ? |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.30, −0.25 |
Computer programs: COLLECT (Nonius, 1998), HKL SCALEPACK, HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997), SHELXTL (Sheldrick, 1995), JANA2000 (Petricek & Dusek, 2000), DIAMOND (Brandenburg & Berndt, 1999), JANA2000.
Radioimmunotherapy is a new method for treating certain types of cancer, such as leukemia or lymphoma (Chatal et al., 1993). This approach, which is complementary to conventional treatments, led us to develop new radionuclide chelating agents (Gouin et al., 2002; Ouadi et al., 2000). Moreover, numerous complexes of lanthanides and DTPA analogues have proved stable enough to be used in physiological medium as radiopharmaceuticals (Liu et al., 2001; Wu et al., 1997). The most promising results relate to studies aimed at increasing the rigidity of the chelating structure. The introduction of a semi-rigid preformed skeleton minimizes the freedom of donor atoms and thereby has a significant effect on the stability of the metal complexes formed (Fosshein et al., 1991; McMurry et al., 1998). These considerations led us to synthesize ligands with a rigid norbornane skeleton.
The synthesis strategy was based on obtaining the intermediary title compound, (I), by allowing the positioning of two N atoms axially on the same plane. The structure determination was a key element to show that the two amines are indeed in endo positions of the cycle. Atom C7 is clearly on the opposite side from atoms N8 and N10 relative to the C1/C2/C3/C4 plane, with C7 0.921 (2) Å above that plane and N8 and N10 − 1.199 (2)and −1.185 (2) Å, respectively, below that plane. The compound shows a staircase structure, with angles of 98.55 (9), 117.81 (9) and 104.20 (8)° for C7—C4—C3, C4—C3—N10 and C3—N10—C9, respectively. The orientation of the protective benzyl groups minimizes the interactions. The compound was obtained after selective reduction of a carbonyl group in the C9 position by the action of lithium aluminium hydride. This selectivity is confirmed, insofar as the double norbornylene bond is conserved. The C5—C6 bond length is clearly in accordance with classical values for a Csp2—Csp2 bond [1.3318 (17) Å].