Download citation
Download citation
link to html
The title compound, 8,10-di­benzyl-1,4-methano­bi­cyclo­[4.3.0][8,10]­di­aza­non-5-ene, C22H24N2, was obtained through a [4 + 2]-cyclo­addition reaction. It crystallizes in the monoclinic space group P21/c (Z = 4). The 1,3-imidazole ring is endo with respect to the norbornyl­ene skeleton. The benzyl protecting groups are situated along the sides of the mol­ecule, towards the back.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803004501/dn6058sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536803004501/dn6058Isup2.hkl
Contains datablock I

CCDC reference: 209912

Key indicators

  • Single-crystal X-ray study
  • T = 150 K
  • Mean [sigma](C-C) = 0.002 Å
  • R factor = 0.059
  • wR factor = 0.147
  • Data-to-parameter ratio = 27.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry








Comment top

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].

Experimental top

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.

Refinement top

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.

Computing details top

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.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids. H atoms have been omitted for clarity.
(I) top
Crystal data top
C22H24N2F(000) = 680
Mr = 316.4Dx = 1.190 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybcCell parameters from 17065 reflections
a = 15.4338 (4) Åθ = 2.9–32.0°
b = 8.2487 (2) ŵ = 0.07 mm1
c = 13.8748 (3) ÅT = 150 K
β = 92.7699 (8)°Block, colourless
V = 1764.32 (7) Å30.31 × 0.23 × 0.18 mm
Z = 4
Data collection top
Nonius KappaCCD
diffractometer
4012 reflections with I > 2σ(I)
Horizonally mounted graphite crystal monochromatorRint = 0.056
Detector resolution: 9 pixels mm-1θmax = 32.0°, θmin = 2.9°
ϕω scansh = 2322
17647 measured reflectionsk = 1211
6050 independent reflectionsl = 2013
Refinement top
Refinement on F2H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.059Weighting scheme based on measured s.u.'s w = 1/[σ2(I) + 0.0025I2]
wR(F2) = 0.147(Δ/σ)max = 0.0004
S = 1.45Δρmax = 0.30 e Å3
6050 reflectionsΔρmin = 0.25 e Å3
217 parameters
Crystal data top
C22H24N2V = 1764.32 (7) Å3
Mr = 316.4Z = 4
Monoclinic, P21/cMo Kα radiation
a = 15.4338 (4) ŵ = 0.07 mm1
b = 8.2487 (2) ÅT = 150 K
c = 13.8748 (3) Å0.31 × 0.23 × 0.18 mm
β = 92.7699 (8)°
Data collection top
Nonius KappaCCD
diffractometer
4012 reflections with I > 2σ(I)
17647 measured reflectionsRint = 0.056
6050 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.059217 parameters
wR(F2) = 0.147H-atom parameters constrained
S = 1.45Δρmax = 0.30 e Å3
6050 reflectionsΔρmin = 0.25 e Å3
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.29800 (8)0.68691 (15)0.56942 (8)0.0302 (4)
C20.25773 (7)0.51423 (15)0.56402 (7)0.0277 (3)
C30.30753 (8)0.43162 (14)0.48335 (8)0.0287 (4)
C40.37042 (8)0.56670 (15)0.45149 (8)0.0308 (4)
C50.31535 (8)0.70000 (15)0.40606 (8)0.0311 (4)
C60.27266 (8)0.77125 (14)0.47567 (9)0.0307 (4)
C70.39271 (8)0.64171 (16)0.55105 (9)0.0353 (4)
N80.16599 (6)0.50104 (12)0.53085 (6)0.0263 (3)
C90.16293 (8)0.35733 (15)0.47011 (8)0.0300 (4)
N100.23897 (6)0.37750 (12)0.41297 (6)0.0279 (3)
C110.26002 (9)0.23275 (16)0.35880 (9)0.0370 (4)
C120.32950 (8)0.26487 (15)0.28897 (8)0.0318 (4)
C130.31562 (8)0.37723 (15)0.21476 (9)0.0343 (4)
C140.37901 (9)0.40565 (16)0.14919 (9)0.0376 (4)
C150.45710 (9)0.32241 (17)0.15740 (9)0.0397 (4)
C160.47172 (9)0.21215 (19)0.23084 (10)0.0437 (5)
C170.40807 (9)0.18315 (17)0.29610 (9)0.0401 (4)
C180.10522 (8)0.49820 (16)0.60808 (8)0.0317 (4)
C190.09539 (7)0.66495 (15)0.65063 (8)0.0289 (4)
C200.06706 (8)0.79258 (17)0.59187 (8)0.0338 (4)
C210.05771 (8)0.94699 (17)0.62898 (9)0.0384 (4)
C220.07794 (8)0.97644 (17)0.72603 (9)0.0370 (4)
C230.10671 (8)0.85089 (18)0.78528 (8)0.0358 (4)
C240.11531 (8)0.69628 (16)0.74764 (8)0.0324 (4)
H10.2840.75190.62590.0364*
H20.25830.46850.62930.0334*
H30.34120.33230.49590.0345*
H40.41630.53130.40990.037*
H50.30820.73690.33890.0373*
H60.2330.8620.46140.0368*
H7a0.43120.7360.54830.0426*
H7b0.41750.56330.59790.0426*
H9a0.10950.35450.42880.0361*
H9b0.16710.25820.50890.0361*
H11a0.2070.19560.32370.0444*
H11b0.27980.1490.40510.0444*
H130.2610.43740.20860.0412*
H140.36830.48460.09740.0454*
H150.50210.34140.11120.048*
H160.52730.15460.23640.0524*
H170.41850.10370.34790.0482*
H18a0.12730.42290.65820.0382*
H18b0.0490.45960.58150.0382*
H200.05330.77380.5230.0407*
H210.03691.03520.58660.0463*
H220.07191.08560.75280.0446*
H230.12110.87160.85390.0432*
H240.13550.60780.79020.039*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0293 (6)0.0312 (7)0.0300 (6)0.0062 (5)0.0013 (5)0.0042 (5)
C20.0292 (6)0.0291 (7)0.0245 (5)0.0022 (5)0.0016 (4)0.0033 (5)
C30.0279 (6)0.0259 (6)0.0321 (6)0.0023 (5)0.0013 (4)0.0028 (5)
C40.0244 (6)0.0335 (7)0.0347 (6)0.0024 (5)0.0028 (5)0.0005 (5)
C50.0289 (6)0.0304 (7)0.0340 (6)0.0080 (5)0.0010 (5)0.0059 (5)
C60.0297 (6)0.0215 (6)0.0409 (6)0.0049 (5)0.0016 (5)0.0034 (5)
C70.0272 (6)0.0386 (8)0.0396 (7)0.0055 (5)0.0044 (5)0.0011 (6)
N80.0272 (5)0.0271 (5)0.0247 (4)0.0050 (4)0.0024 (4)0.0007 (4)
C90.0316 (6)0.0278 (7)0.0307 (6)0.0060 (5)0.0017 (4)0.0002 (5)
N100.0299 (5)0.0244 (5)0.0294 (5)0.0029 (4)0.0026 (4)0.0033 (4)
C110.0450 (8)0.0258 (7)0.0405 (7)0.0030 (6)0.0057 (6)0.0055 (6)
C120.0367 (7)0.0253 (7)0.0336 (6)0.0003 (5)0.0013 (5)0.0099 (5)
C130.0339 (7)0.0290 (7)0.0399 (6)0.0033 (5)0.0012 (5)0.0066 (6)
C140.0454 (8)0.0293 (7)0.0384 (7)0.0021 (6)0.0050 (5)0.0047 (6)
C150.0382 (7)0.0392 (8)0.0423 (7)0.0010 (6)0.0078 (5)0.0138 (6)
C160.0375 (8)0.0481 (9)0.0451 (7)0.0128 (6)0.0002 (6)0.0113 (7)
C170.0459 (8)0.0380 (8)0.0360 (6)0.0102 (6)0.0018 (6)0.0058 (6)
C180.0326 (7)0.0334 (7)0.0294 (6)0.0069 (5)0.0050 (5)0.0017 (5)
C190.0229 (6)0.0353 (7)0.0288 (6)0.0051 (5)0.0045 (4)0.0005 (5)
C200.0305 (7)0.0418 (8)0.0289 (6)0.0004 (5)0.0013 (5)0.0002 (5)
C210.0333 (7)0.0411 (8)0.0405 (7)0.0061 (6)0.0014 (5)0.0005 (6)
C220.0280 (7)0.0412 (8)0.0419 (7)0.0036 (6)0.0026 (5)0.0090 (6)
C230.0286 (6)0.0483 (8)0.0304 (6)0.0009 (6)0.0010 (5)0.0068 (6)
C240.0284 (6)0.0401 (8)0.0288 (6)0.0032 (5)0.0020 (5)0.0022 (5)
Geometric parameters (Å, º) top
C1—C21.5544 (17)C22—C231.3821 (19)
C1—C61.5098 (16)C23—C241.3869 (19)
C1—C71.5416 (17)C1—H10.9817
C2—C31.5462 (16)C2—H20.9803
C2—N81.4715 (14)C3—H30.9808
C3—C41.5558 (17)C4—H40.9793
C3—N101.4740 (14)C5—H50.9812
C4—C51.5090 (17)C6—H60.9810
C4—C71.5373 (17)C7—H7a0.9805
C5—C61.3318 (17)C7—H7b0.9814
N8—C91.4539 (15)C9—H9a0.9814
N8—C181.4580 (15)C9—H9b0.9795
C9—N101.4572 (15)C11—H11a0.9808
N10—C111.4559 (16)C11—H11b0.9817
C11—C121.5030 (18)C13—H130.9782
C12—C131.3942 (17)C14—H140.9782
C12—C171.3868 (19)C15—H150.9806
C13—C141.3879 (19)C16—H160.9801
C14—C151.3869 (19)C17—H170.9804
C15—C161.376 (2)C18—H18a0.9811
C16—C171.389 (2)C18—H18b0.9798
C18—C191.5074 (18)C20—H200.9804
C19—C201.3892 (17)C21—H210.9802
C19—C241.3904 (15)C22—H220.9803
C20—C211.3839 (19)C23—H230.9814
C21—C221.3889 (17)C24—H240.9805
C2—C1—C6107.12 (9)N10—C3—H3102.79
C2—C1—C798.66 (10)C3—C4—H4115.62
C6—C1—C7100.21 (9)C5—C4—H4112.36
C1—C2—C3103.13 (9)C7—C4—H4120.82
C1—C2—N8117.34 (10)C4—C5—H5131.12
C3—C2—N8104.20 (8)C6—C5—H5121.00
C2—C3—C4103.22 (9)C1—C6—H6131.21
C2—C3—N10104.30 (9)C5—C6—H6121.05
C4—C3—N10117.81 (9)C1—C7—H7a113.30
C3—C4—C5107.09 (9)C1—C7—H7b113.06
C3—C4—C798.55 (9)C4—C7—H7a113.23
C5—C4—C7100.32 (10)C4—C7—H7b113.17
C4—C5—C6107.88 (10)H7a—C7—H7b109.31
C1—C6—C5107.75 (10)N8—C9—H9a111.13
C1—C7—C494.19 (9)N8—C9—H9b111.26
C2—N8—C9104.21 (9)N10—C9—H9a111.14
C2—N8—C18114.51 (8)N10—C9—H9b111.20
C9—N8—C18114.13 (9)H9a—C9—H9b109.40
N8—C9—N10102.58 (9)N10—C11—H11a108.09
C3—N10—C9104.20 (8)N10—C11—H11b108.01
C3—N10—C11114.79 (9)C12—C11—H11a109.84
C9—N10—C11113.14 (10)C12—C11—H11b109.72
N10—C11—C12111.85 (10)H11a—C11—H11b109.27
C11—C12—C13120.29 (11)C12—C13—H13120.14
C11—C12—C17121.13 (11)C14—C13—H13119.30
C13—C12—C17118.58 (12)C13—C14—H14119.63
C12—C13—C14120.56 (12)C15—C14—H14120.38
C13—C14—C15119.99 (12)C14—C15—H15120.48
C14—C15—C16119.91 (13)C16—C15—H15119.61
C15—C16—C17120.05 (13)C15—C16—H16119.36
C12—C17—C16120.90 (12)C17—C16—H16120.59
N8—C18—C19110.71 (10)C12—C17—H17119.26
C18—C19—C20119.77 (10)C16—C17—H17119.83
C18—C19—C24121.81 (11)N8—C18—H18a108.48
C20—C19—C24118.42 (11)N8—C18—H18b108.56
C19—C20—C21120.97 (11)C19—C18—H18a109.79
C20—C21—C22119.95 (12)C19—C18—H18b109.88
C21—C22—C23119.75 (12)H18a—C18—H18b109.39
C22—C23—C24119.93 (11)C19—C20—H20119.95
C19—C24—C23120.98 (11)C21—C20—H20119.09
C2—C1—H1115.84C20—C21—H21119.78
C6—C1—H1112.25C22—C21—H21120.27
C7—C1—H1120.68C21—C22—H22120.46
C1—C2—H2108.81C23—C22—H22119.79
C3—C2—H2121.11C22—C23—H23119.82
N8—C2—H2103.02C24—C23—H23120.25
C2—C3—H3121.12C19—C24—H24119.59
C4—C3—H3108.45C23—C24—H24119.43

Experimental details

Crystal data
Chemical formulaC22H24N2
Mr316.4
Crystal system, space groupMonoclinic, P21/c
Temperature (K)150
a, b, c (Å)15.4338 (4), 8.2487 (2), 13.8748 (3)
β (°) 92.7699 (8)
V3)1764.32 (7)
Z4
Radiation typeMo Kα
µ (mm1)0.07
Crystal size (mm)0.31 × 0.23 × 0.18
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
17647, 6050, 4012
Rint0.056
(sin θ/λ)max1)0.746
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.059, 0.147, 1.45
No. of reflections6050
No. of parameters217
No. of restraints?
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)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.

 

Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds