8,10 Di­benzyl­imidazonorbornyl­ene

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Acta Cryst.(2003). E59, o401±o402 DOI: 10.1107/S1600536803004501 Sebastien G. Gouinet al. C22H24N2

o401

organic papers

Acta Crystallographica Section E

Structure Reports

Online

ISSN 1600-5368

8,10-Dibenzylimidazonorbornylene

Sebastien G. Gouin,a

Jean-FrancËois Gestin,b

Jean Claude Meslin,aDavid

Deniaudaand Michel Evainc*

aLaboratoire de SyntheÁse Organique, UMR

CNRS 6513, Faculte des Sciences et des Techniques, 2 rue de la HoussinieÁre, BP 32229, 44322 Nantes Cedex 3, France,bINSERM U463,

Chimie des bioconjugueÂs, 9 quai Moncousu, 44093 Nantes Cedex, France, andcInstitut des

MateÂriaux Jean Rouxel, 2 rue de la HoussinieÁre, BP 92208, 44322 Nantes Cedex 3, France

Correspondence e-mail: evain@cnrs-imn.fr

Key indicators Single-crystal X-ray study T= 150 K

Mean(C±C) = 0.002 AÊ Rfactor = 0.059 wRfactor = 0.147

Data-to-parameter ratio = 27.9

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2003 International Union of Crystallography Printed in Great Britain ± all rights reserved

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 groupP21/c(Z= 4). The 1,3-imidazole ring isendowith

respect to the norbornylene skeleton. The benzyl protecting groups are situated along the sides of the molecule, towards the back.

Comment

Radioimmunotherapy is a new method for treating certain types of cancer, such as leukemia or lymphoma (Chatalet al., 1993). This approach, which is complementary to conventional treatments, led us to develop new radionuclide chelating agents (Gouin, Gestin, Joly et al., 2002; Gouin, Gestin, Reli-quetet al., 2002; Gouin, Gestin, Remaudet al., 2002; Ouadiet al., 2000). Moreover, numerous complexes of lanthanides and DTPA (diethylenetriaminepentaacetic acid) analogues have proved stable enough to be used in a physiological medium as radiopharmaceuticals (Liu & Edwards, 2001; Wuet al., 1997). The most promising results relate to studies aimed at increasing the rigidity of the chelating structure. The intro-duction of a semi-rigid preformed skeleton minimizes the freedom of donor atoms and thereby has a signi®cant effect on the stability of their metal complexes (Fossheimet al., 1991; McMurryet al., 1998). These considerations led us to synthe-size ligands with a rigid norbornane skeleton.

The synthetic strategy was based on obtaining the inter-mediate title compound, (I), where the two N atoms, useful for further metal chelation, are protected by the benzyl groups. The structure determination was a key element in showing that the two amines are indeed inendopositions of the ring. 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) AÊ above that plane and N8 and N10 ÿ1.199 (2) and

ÿ1.185 (2) AÊ, respectively, below it. The compound shows a staircase structure, with angles of 98.55 (9), 117.81 (9) and 104.20 (8) for C7ÐC4ÐC3, C4ÐC3ÐN10 and C3ÐN10Ð C9, respectively. The orientation of the benzyl protecting 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 con®rmed, insofar as the norbornylene double bond is conserved. The C5ÐC6 bond length is clearly in

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accordance with classical values for a Csp2ÐCsp2 bond

[1.3318 (17) AÊ].

Experimental

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 re¯uxed 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 tempera-ture. The mixture was ®ltered through a Celite pad and washed with water (200 ml) before the ®ltrate was extracted with dichloromethane (300 ml). The organic phase was washed with brine, dried (MgSO4),

®ltered and evaporated. The residue was puri®ed by ¯ash chroma-tography 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.

Crystal data C22H24N2

Mr= 316.4 Monoclinic,P21=c

a= 15.4338 (4) AÊ

b= 8.2487 (2) AÊ

c= 13.8748 (3) AÊ

= 92.7699 (8)

V= 1764.32 (7) AÊ3

Z= 4

Dx= 1.190 Mg mÿ3 Mo Kradiation

Cell parameters from 17065 re¯ections

= 2.9±32.0

= 0.07 mmÿ1

T= 150 K Block, colourless 0.310.230.18 mm Data collection

Nonius KappaCCD diffractometer

'and!scans

Absorption correction: none 17647 measured re¯ections 6050 independent re¯ections 4012 re¯ections withI> 2(I)

Rint= 0.056

max= 32.0

h=ÿ23!22

k=ÿ12!11

l=ÿ20!13

Re®nement Re®nement onF2

R[F2> 2(F2)] = 0.059

wR(F2) = 0.147

S= 1.45 6050 re¯ections 217 parameters

H-atom parameters constrained

w= 1/[2(I) + 0.0025I2] (/)max< 0.001

max= 0.30 e AÊÿ3

min=ÿ0.25 e AÊÿ3

All H atoms were initially found in a difference Fourier synthesis but were ®xed in idealized positions in the ®nal re®nement. Riding isotropic displacement parameters, with Uiso(H) = 1.2Ueq(C), were

used for all H atoms.

Data collection:COLLECT(Nonius, 1998); cell re®nement:HKL SCALEPACK(Otwinowski & Minor, 1997); data reduction: HKL DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXTL (Sheldrick, 1995); program(s) used to re®ne structure:JANA2000 (Petricek & Dusek, 2000); molecular graphics: DIAMOND (Brandenburg & Berndt, 1999); software used to prepare material for publication:JANA2000.

The authors are grateful to the French Ministry of Educa-tion, the CNRS, and the `Ligue Nationale Contre le Cancer' for ®nancial support.

References

Brandenburg, K & Berndt, M. (1999). DIAMOND. Crystal Impact GbR, Bonn, Germany.

Chatal, J.-F., Peltier, P., Bardies, M., Chetanneau, A., Resche, I., Mahe, M. & Charbonnel, B. (1993).Med. Nucl. Imag. Met.17, 81±94.

Fossheim, R., Dugstad, H. & Dahl, S. G. (1991).J. Med. Chem.34, 819±826. Gouin, S. G., Gestin, J.-F., Joly, K., Loussouarn, A., Reliquet, A., Meslin, J.-C.

& Deniaud, D. (2002).Tetrahedron,58, 1131±1136.

Gouin, S. G., Gestin, J.-F., Reliquet, A., Meslin, J.-C. & Deniaud, D. (2002).

Tetrahedron Lett.43, 3003±3005.

Gouin, S. G., Gestin, J.-F., Remaud, P., Faivre-Chauvet, A., Meslin, J.-C. & Deniaud, D. (2002).Synlett,12, 2080±2082.

Liu, S. & Edwards, S. (2001).Bioconjugate Chem.12, 7±34.

McMurry, T. J., Pippin, C. G., Wu, C., Deal, K. A., Brechbiel, M. W., Mirzadeh, S. & Gansow, O. A. (1998).J. Med. Chem.41, 3546±3549.

Nonius (1998).COLLECT. Nonius BV, Delft, The Netherlands.

Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,

Macromolecular Crystallography, Part A, edited by C. W. Carter Jr and R. M. Sweet, pp. 307±326. New York: Academic Press.

Ouadi, A., Loussouarn, A., Remaud, P., Morandeau, L., Apostolidis, C., Musikas, C., Faivre-Chauvet, A. & Gestin, J.-F. (2000).Tetrahedron Lett.41, 7207±7209.

Petricek, V. & Dusek, M. (2000).JANA2000. Institute of Physics, Prague, Czech Republic.

Sheldrick, G. M. (1995). SHELXTL.Version 5.0. Analytical X-ray Instru-ments Inc., Madison, Wisconsin, USA.

Wu, C., Kobayashi, H., Sun, B., Yoo, T. M., Paik, C. H., Gansow, O. A., Carrasquillo, J. A., Pastan, I. & Brechbiel, M. W. (1997). Bioorg. Med. Chem.5, 1925±1934.

Figure 1

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Acta Cryst. (2003). E59, o401–o402

supporting information

Acta Cryst. (2003). E59, o401–o402 [doi:10.1107/S1600536803004501]

8,10-Dibenzylimidazonorbornylene

Sebastien G. Gouin, Jean-Fran

ç

ois Gestin, Jean Claude Meslin, David Deniaud and Michel Evain

S1. Comment

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].

S2. Experimental

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.

S3. Refinement

All H atoms were initially found in difference Fourier syntheses but were fixed in idealized positions in the final

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Figure 1

The molecular structure of (I), showing 50% probability displacement ellipsoids. H atoms have been omitted for clarity.

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Crystal data C22H24N2

Mr = 316.4

Monoclinic, P21/c

Hall symbol: -P 2ybc a = 15.4338 (4) Å b = 8.2487 (2) Å c = 13.8748 (3) Å β = 92.7699 (8)° V = 1764.32 (7) Å3

Z = 4

F(000) = 680 Dx = 1.190 Mg m−3

Mo radiation, λ = 0.71069 Å Cell parameters from 17065 reflections θ = 2.9–32.0°

µ = 0.07 mm−1

T = 150 K Block, colourless 0.31 × 0.23 × 0.18 mm

Data collection Nonius KappaCCD

diffractometer

Horizonally mounted graphite crystal monochromator

Detector resolution: 9 pixels mm-1

φω scans

17647 measured reflections

6050 independent reflections 4012 reflections with I > 2σ(I) Rint = 0.056

θmax = 32.0°, θmin = 2.9°

h = −23→22 k = −12→11 l = −20→13

Refinement Refinement on F2

R[F2 > 2σ(F2)] = 0.059

wR(F2) = 0.147

S = 1.45 6050 reflections 217 parameters

H-atom parameters constrained

Weighting scheme based on measured s.u.'s w = 1/[σ2(I) + 0.0025I2]

(Δ/σ)max = 0.0004

Δρmax = 0.30 e Å−3

Δρmin = −0.25 e Å−3

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq

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Acta Cryst. (2003). E59, o401–o402

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*

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Atomic displacement parameters (Å2)

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)

Geometric parameters (Å, º)

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

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Acta Cryst. (2003). E59, o401–o402

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

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References

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