Synthesis and solid state structural analysis exo-bisbidentate ligands based on [1.1.1.1]metacyclophane in 1,3-alternate conformation bearing 2,2'-bipyridine or bisquinoline chelates

Article abstract of DOI:10.1016/S0040-4039(00)01647-6

The synthesis and structural analysis of two new exoligands 1 and 2 based on a [1.1.1.1]-metacyclophane backbone bearing either 2,2'-bipyridine or bisquinoline chelating units have been achieved. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01647-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9043–9047
Synthesis and solid state structural analysis exo-bisbidentate
ligands based on [1.1.1.1]metacyclophane in 1,3-alternate
conformation bearing 2,2%-bipyridine or bisquinoline chelates
Ce´dric Klein, Ernest Graf, Mir Wais Hosseini,* Gilles Mislin and Andre´ De Cian
Laboratoire de Chimie de Coordination Organique, UMR-CNRS 7513, Universite´ Louis Pasteur, Institut Le Bel,
4, rue Blaise Pascal, F-67000 Strasbourg, France
Received 11 August 2000; accepted 20 September 2000
Abstract
The synthesis and structural analysis of two new exoligands 1 and 2 based on a [1.1.1.1]-metacy-
clophane backbone bearing either 2,2%-bipyridine or bisquinoline chelating units have been achieved.
© 2000 Elsevier Science Ltd. All rights reserved.
For a decade the design and preparation of coordination networks, hybrid metalloorganic
architectures based on the self-assembly of organic exoligands in which the coordination sites
are oriented in divergent manner and metal cations, has been under active investigation. The
majority of networks reported to date are based on combinations of bis-monodentate exoligands
and transition metal cations.1 However, examples of coordination polymers based on either
bis-bidentate2,3 or tetradentate exoligands4,5 in which the coordination sites are located by two
sets of two interaction sites, have also been reported. Finally, only a few examples of structurally
characterised coordination networks based on bis-tridentate ligands have been published.6,7 We
have previously reported the synthesis of exoligands of mercaptocalix[4]arene8 and
mercaptocyclophane9 types as well as macrocyclic ligands based on bipyridine units10 and
calix[4]arene derivatives bearing four catechol11 or pyridine12 moieties. In continuation of our
efforts13 to design new coordination networks, we report here the synthesis and structural
analysis of two new exoligands 1 and 2 based on a [1.1.1.1]cyclophane backbone bearing either
a 2,2%-bipyridine or bisquinoline chelating units.
The design of both ligands 1 and 2 is based on the use of a backbone allowing two chelating
sites to be positioned below and above a plane and with a 90° angle between them (Scheme 1).
For such a design the cyclophane 3, for which a synthetic procedure has been reported,14
appeared as an interesting candidate since 3 has been shown to adopt the 1,3-alternate
* Corresponding author. Fax: 33 388 41 62 66; e-mail: hosseini@chimie.u-strasbg.fr
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01647-6

9044
N
N
orN
=
=
N
Scheme 1.
conformation thus leading to divergent orientation of the four OH groups below and above the
main plane of the cyclophane; and on the other hand, the presence of the hydroxy groups may
be exploited to connect the chelating units (Scheme 2). An example of compound 3 bearing a
single bipyridine unit connected at the 6 and 6% positions has been previously reported.14 For the
ligand 1, as the chelating moiety, the 2,2%-bipyridine, the most used chelating unit,15 was
considered because of its ability to bind metal cations, whereas for the ligand 2, 2,2%-bisquinoline
was chosen because, in contrast to the 2,2%-bipyridine which would not select any coordination
geometry, it should lead to tetrahedral coordination around the metal cations. Dealing with the
connection of the chelating units to the cyclophane 3, the 4,4% positions on bipyridine and on
bisquinoline have been chosen since such linkages should orient the chelating units in a
divergent fashion.
6
5
7
8
HO
OH
5
2
10
X
X
X
X
9
6
4
4
2
N1
N1
6 X = CO2H
7 X = CO2Me
8 X = CH2OH
9 X = CH2Br
3
3
4 X = CH3
5 X = CH2Br
N
N
3
HO
OH
Scheme 2.
The synthesis of ligand 116 (Scheme 3) was based on the coupling of cyclophane 3, prepared
in two steps according to reported procedures,14 with dibromo 2,2%-bipyridine derivative 5 in dry
DMF and in the presence of Cs2CO3 as the base. Compound 5 was prepared by first coupling
g-picoline to generate compound 4 and then by bromination of the latter again according to
published procedures (Scheme 2).17
It is worth noting that the yield of compound 1 depends strongly on the addition rate of
reagents and a 9% yield could be obtained for a dropwise addition time of 74 hours.
The synthesis of 218 (Scheme 3) was again based on a coupling reaction between the
cyclophane 3 and the dibromo derivative of bisquinoline 9 (Scheme 2). The latter was prepared
in three steps starting with the commercially available acid derivative 6, which was first esterified
(MeOH, H2SO4) yielding the diester 7 in 89% yield as a white powder. The latter was reduced
to the diol 8 in 86% yield using NaBH4 in EtOH. Finally, treatment of 8 by 33% HBr/AcOH

9045
O
O
O
O
N
N
N
N
N
N
O
O
N
N
O
O
1
2
Scheme 3.
afforded the dibromo compound 9 in 69% yield. As in the case of ligand 1 mentioned above, the
condensation of compounds 3 and 9 in dry DMF in the presence of Cs2CO3 (addition time 120
h) afforded the desired ligand 2 in 19% yield.
Whereas for compound 1 no suitable single crystals could be obtained so far, for ligand 2 its
solid state structure was investigated by X-ray crystallography on single crystals (Fig. 1).19
Although the obtained crystals show suitable quality, they diffract poorly and therefore an R
factor of only 0.11 was reached during the refinement. The study revealed the following relevant
features. As expected, the cyclophane backbone is indeed in 1,3-alternate conformation.
,
Probably due to the rigidity of the cyclophane and the ether junction (dCO=1.405 A, with an
average COC angle of ca. 114.6°) between the bisquinoline units and the macrocycle, the two
quinoline moieties are in syn conformation (average NCCN dihedral angle of ca. −1.1°). As it
can be seen in Fig. 1, due to the presence of the CH2 group between chelating units and oxygen
atoms of the cyclophane, the two bisquinoline units are tilted with CCOC dihedral angles of
86.4 and −82.9°.
Figure 1. Solid state structure of ligand 2. H atoms and solvent molecules are not represented for sake of clarity. For
bond distances and angles see text
In conclusion, using cyclophane 3 in 1,3-alternate conformation, two new exoligands 1 and 2
based either on 2,2%-bipyridine or on bisquinoline units have been prepared. Ligand 2 was
characterised in the solid state using the X-ray diffraction method. The use of both ligands in
the design of coordination networks, in particular of the helical type, is currently under
investigation.

9046
References
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2. Kaes, C.; Hosseini, M. W.; Rickard, C. E. F.; Skelton, B. W.; White, A. H. Angew. Chem., Int. Ed. 1998, 37,
920–922.
3. Velten, U.; Rehahn, M. J. Chem. Soc., Chem. Commun. 1996, 2639–2640; Decurtins, S.; Pellaux, R.; Hauser, A.;
von Arx, M. E. In Magnetism: A Supramolecular Function; Kahn, O., Ed.; Kluwer: Dordrecht, Netherlands,
1996; Vol. C484, pp. 487–508.
4. Mislin, G.; Graf, E.; Hosseini, M. W.; De Cian, A.; Kyritsakas, N.; Fischer, J. Chem. Commun. 1998, 2545–2546.
5. Klein, C.; Graf, E.; Hosseini, M. W.; De Cian, A.; Fischer, J. Chem. Commun. 2000, 239–240.
6. Constable, E. C.; Cargill Thompson, A. M. W. J. Chem. Soc., Dalton Trans. 1992, 3467–3475; Ferigo, M.;
Bonhoˆte, P.; Marty, W.; Stoeckli-Evans, H. J. Chem. Soc., Dalton Trans. 1994, 1549–1554; Constable, E. C.;
Edwards, A. J.; Phillips, D.; Raithby, P. R. Supramol. Chem. 1995, 5, 93–95.
7. Lo¨ı, M.; Graf, E.; Hosseini, M. W.; De Cian, A.; Fischer, J. Chem. Commun. 1999, 603–604.
8. Delaigue, X.; Harrowfield, J. McB.; Hosseini, M. W.; De Cian, A.; Fischer, J.; Kyritsakas, N. Chem. Commun.
1994, 1579–1580; Delaigue, X.; Hosseini, M. W.; Kyritsakas, N.; De Cian, A.; Fischer, J. Chem. Commun. 1995,
609–610.
9. Delaigue, X.; Hosseini, M. W. Tetrahedron Lett. 1993, 34, 8111–8112.
10. Kaes, C.; Hosseini, M. W.; Ruppert, R.; De Cian, A.; Fischer, J. Tetrahedron Lett. 1994, 35, 7233–7236; Kaes,
C.; Hosseini, M. W.; Ruppert, R.; De Cian, A.; Fischer, J. Chem. Commun. 1995, 1445–1446; Kaes, C.; Hosseini,
M. W.; De Cian, A.; Fischer, J. Tetrahedron Lett. 1997, 38, 3901–3904; Kaes, C.; Hosseini, M. W.; DeCian, A.;
Fischer, J. Tetrahedron Lett. 1997, 38, 4389–4392; Lagref, J. J.; Hosseini, M. W.; Planeix, J.-M.; DeCian, A.;
Fiischer, J. Chem. Commun. 1999, 2155–2156.
11. Mislin, G.; Graf, E.; Hosseini, M. W. Tetrahedron Lett. 1996, 37, 4503–4506.
12. Jaunky, W.; Hosseini, M. W.; Planeix, J.-M.; De Cian, A.; Kyritsakas, N.; Fischer, J. Chem. Commun. 1999,
2313–2314.
13. Hosseini, M. W. In NATO ASI Series, Vol. 538, Serie c; Braga, D.; Grepiono, F.; Orpen, G., Eds.; Kluwer:
Dordrecht, Netherlands, 1999; pp. 181–208.
14. Pappalardo, S.; Ferguson, G.; Gallagher, J. F. J. Org. Chem. 1992, 57, 7102–7109.
15. Kaes, C.; Katz, A.; Hosseini, M. W. Chem. Rev. 2000, in press.
16. Compound 1: a dry DMF solution (100 ml) containing both compound 314 (216 mg, 0.365 mmol) and 517 (250
mg, 0.731 mmol) was added dropwise (74 h) to a dry DMF suspension (100 ml) of Cs2CO3 (2.85 g, 8.76 mmol)
at 55°C. The reaction mixture was further stirred at rt overnight before it was filtered and the solvent removed
under vacuum. The brownish residue thus obtained was washed with MeOH and the brown solid was dissolved
in CH2Cl2 (200 ml) and filtered. The filtrate was evaporated to dryness and the residue was purified by column
chromatography (Al2O3; CH2Cl2/MeOH: 97/3 then 95/5) affording the pure compound 1 (30 mg, 9% yield) as a
1
white powder. H NMR (CDCl3, 300 MHz, 25°C) l (ppm): 0.80 (s, 12H, CH3), 2.03 (s, 24H, CH3), 3.71 (s, 8H,
ArꢀCH2ꢀAr), 4.90 (s, 8H, ꢀCH2ꢀOꢀ), 7.17 (s, 4H, CH), 7.59 (d, J=4.9 Hz, 4H, CH), 8.77 (d, J=4.9 Hz, 4H,
CH); 13C NMR (CDCl3, 75 MHz, 25°C) l (ppm): 14.96, 17.13, 33.78, 74.90, 121.54, 125.88, 126.47, 131.14,
138.05, 145.80, 150.32, 152.27, 154.66; % calcd for C64H64N4O4.5H2O: C, 73.68; H, 7.14; found: C, 73.57; H, 7.04.
17. Sprintschnik, G.; Sprintschnik, H. W.; Kirsch, P. J. Am. Chem. Soc. 1977, 119, 4947–4954; Uenishi, J. I.; Tanaka,
T.; Nishiwaki, K. J. Org. Chem. 1993, 58, 4382–4388.
18. Compound 7: a solution of the commercially available compound 6 (500 mg, 1.4 mmol) in abs. MeOH (50 ml)
was refluxed in the presence of conc. H2SO4 (1 ml) for four days. The reaction mixture was then poured into H2O
(50 ml) and basified to pH 8–9 by addition of a solution of NaOH before it was extracted with CH2Cl2 (3×50
ml). The organic layer was isolated and dried (MgSO4) before the solvent was removed affording the compound
1
7 (478 mg, 89% yield) as a white powder. H NMR (CDCl3, 500 MHz, 25°C) l (ppm): 4.13 (s, 6H, CH3), 7.70
(dt, J=1.5 and 8.4 Hz, 2H, CHꢀAr), 7.82 (dt, J=1.5 and 8.4 Hz, 2H, CHꢀAr), 8.32 (d, J=8.4 Hz, 2H, CHꢀAr),
8.81 (d, J=8.4 Hz, 2H, CHꢀAr), 9.32 (s, 2H, CH); 13C NMR (CDCl3, 125 MHz, 25°C) l (ppm): 52.77, 120.45,
125.31, 125.62, 128.73, 129.97, 130.52, 135.87, 148.83, 154.93, 166.88. Compound 8: to a suspension of compound
7 (1.01 g, 2.73 mmol) in dry EtOH (65 ml), NaBH4 (2.45 g, 64.8 mmol) was added and the mixture refluxed for
5 h. After allowing the mixture to reach rt, the excess NaBH4 was neutralised with a saturated NH4Cl solution
(50 ml) before the solvents were removed under vacuum. The residue was further dried before the desired
compound 8 was extracted (soxhlet) into ethyl acetate, which was dried (MgSO4) and evaporated leaving the pure

9047
1
compound 8 (0.74 g, 86% yield) as a white powder. H NMR (CD3OD, 300 MHz, 25°C) l (ppm): 5.31 (s, 4H,
CH2OH), 7.70 (dt, J=1.5 and 8.4 Hz, 2H, CHꢀAr), 7.86 (dt, J=1.5 and 8.4 Hz, 2H, CHꢀAr), 8.16 (d, J=8.4
Hz, 2H, CHꢀAr), 8.26 (d, J=8.4 Hz, 2H, CHꢀAr), 8.89 (s, 2H, CH); 13C NMR (d6-DMSO, 75 MHz, 25°C) l
(ppm): 60.09, 115.68, 123.36, 125.72, 126.88, 129.40, 129.85, 147.08, 148.58, 155.43; % calcd for C22H16N2O4: C,
75.93; H, 5.10; N, 8.85; found: C, 75.88; H, 5.21; N, 8.39. Compound 9: a suspension of compound 8 (739 mg,
2.33 mmol) in 33% HBr in acetic acid (75 ml) was heated to 60°C for 20 h. After the mixture was allowed to cool
to rt, the suspension was filtered, washed with acetic acid and ether affording a yellow solid which was suspended
in H2O (150 ml) and then CH2Cl2 (200 ml) was added and the mixture basified to pH 11–12 using a K2CO3
solution. The organic layer was isolated and evaporated to dryness affording the compound 9 (709 mg, 69% yield)
1
as a slightly yellowish powder. H NMR (CDCl3, 300 MHz, 25°C) l (ppm): 5.01 (s, 4H, CH2Br), 7.2 (dt, J=1.5
and 8.4 Hz, 2H, CHꢀAr), 7.3 (dt, J=1.5 and 8.4 Hz, 2H, CHꢀAr), 8.2 (d, J=8.4 Hz, 2H, CHꢀAr), 8.3 (d, J=8.4
Hz, 2H, CHꢀAr), 8.9 (s, 2H, CH); 13C NMR (d6-DMSO, 50 MHz, 25°C) l (ppm); 29.67, 119.19, 124.20, 125.81,
127.77, 129.91, 130.44, 144.46, 147.55, 154.62. Compound 2: a dry DMF solution (100 ml) containing both
compound 3 (135 mg, 0.228 mmol) and 9 (200 mg, 0.456 mmol) was added dropwise (120 h) to a dry DMF
suspension (100 ml) of Cs2CO3 (1.7 g, 5.22 mmol) at 55°C. The reaction mixture was further stirred at rt for three
days before it was filtered and the solvent removed under vacuum. The brownish residue thus obtained was
washed with MeOH and the brown solid was suspended in CH2Cl2 (200 ml) and filtered. The filtrate was
evaporated to dryness and the pure compound 2 (50 mg, 19% yield) was obtained as a white solid after
1
crystallisation from a CH2Cl2/MeOH mixture. H NMR (CDCl3, 300 MHz, 25°C) l (ppm); 0.97 (s, 12H, CH3),
1.60 (s, 24H, CH3), 3.49 (s, 8H, ArꢀCH2ꢀAr), 5.29 (s, 8H, CH2ꢀOꢀ), 7.50 (s, 4H, CH), 7.74 (dt, J=1.5 and 8.4
Hz, 4H, CH), 7.83 (dt, J=1.5 and 8.4 Hz, 4H, CH), 8.48 (d, J=8.4 Hz, 4H, CH), 8.52 (d, J=8.4 Hz, 4H, CH);
13C NMR (CDCl3, 75 MHz, 25°C) l (ppm): 14.34, 17.16, 33.47, 74.73, 119.18, 124.32, 127.82, 127.95, 129.93,
131.00, 131.70, 131.86, 138.12, 143.39, 148.89, 152.66, 153.66; % calcd for C80H72N4O4·5.5H20: C, 76.71; H, 6.68;
found: C, 76.43; H, 6.55.
19. X-Ray data for 2: C80H36N4O4·H2O·2CH2Cl2·4CH3OH (colourless), M=1433.25, monoclinic, a=31.118(1),
3
b=22.199(1), c=11.7830(5) A, i=99.349(5)°, U=8031(1) A , space group C12/c1, Z=4, Dc=1.19 g cm−3, v(Mo
Ka)=0.205 mm−1. Crystal dimensions 0.18×0.07×0.06 mm. Data were measured at 173 K on a kappa CCD
diffractometer and the structure was solved by direct methods using OpenMoleN 2.2 and refined anisotropically
using absorption corrected data. R=0.11, Rw=0.14 for 2765. Atomic coordinates, bond lengths and angles, and
thermal parameters have been deposited at the Cambridge Crystallographic Data Centre.
,
,
.