Segmented multitopic ligands constructed from bipyrimidine, phenanthroline, and terpyridine modules

Article abstract of DOI:10.1016/j.tetlet.2004.03.147

Starting from bromo-substituted 2,2′-bipyrimidine or 1,10-phenanthroline building blocks, the preparation in a first step of ethynyl grafted molecules allows the production in a second step of multitopic ligands by cross-coupling with difunctionalised chelating molecules. Various combinations allow the interconnection of bipyrimidine to terpyridine, pyrene, or phenanthroline fragments. When two alkyne functions are present, a simple protocol gives a large variety of linear or bent ligands with an increasing number of nitrogen atoms. It was also possible to construct a linear complex capped at the periphery by ruthenium(II) centers and retaining an uncomplexed phenanthroline fragment in its core.

Full text of DOI:10.1016/j.tetlet.2004.03.147

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4051–4055
Segmented multitopic ligands constructed from bipyrimidine,
phenanthroline, and terpyridine modules
Raymond Ziessel* and Christophe Stroh
Laboratoire de Chimie Molꢀeculaire, Ecole de Chimie, Polymꢁeres, Matꢀeriaux (ECPM), Universitꢀe Louis Pasteur (ULP),
25 rue Becquerel, 67087 Strasbourg Cedex 02, France
Received 5 February 2004; revised 24 March 2004; accepted 26 March 2004
Abstract—Starting from bromo-substituted 2,20-bipyrimidine or 1,10-phenanthroline building blocks, the preparation in a first step
of ethynyl grafted molecules allows the production in a second step of multitopic ligands by cross-coupling with difunctionalised
chelating molecules. Various combinations allow the interconnection of bipyrimidine to terpyridine, pyrene, or phenanthroline
fragments. When two alkyne functions are present, a simple protocol gives a large variety of linear or bent ligands with an increasing
number of nitrogen atoms. It was also possible to construct a linear complex capped at the periphery by ruthenium(II) centers and
retaining an uncomplexed phenanthroline fragment in its core.
Ó 2004 Elsevier Ltd. All rights reserved.
The engineering of new acetylene substituted molecules
has gained increasing attention due to their use in the
construction of carbon rich scaffolds,1 supramolecular
systems,2 molecular materials,3 nanoelectronic archi-
tectures,4 and liquid crystalline matter.5 One of the key
issue concerns how best to interconnect and interlock
the various modules into ordered arrays that allow
control of physical factors such as orientation of the
binding vectors and electrical dipoles, electric and elec-
tronic conductivity, and amphipatic character of the
molecules. Our own research into functionalised wave-
guides6;7 led us to consider whether functionalised
bipyrimidine and phenanthroline targets could be
adapted in the synthesis of such elaborated molecules.
The availability of families of molecules based on
bipyridine and terpyridine ligands allow to establish firm
structure/property relationship and to conclude that
ethynyl spacing units are among the most interesting
tools to introduce directionality and versatility in
sophisticated structures. Furthermore, such acetylenic
tethers offer an excellent control of the distance between
the chromophoric centers due to its linearity and rigid-
ity, and concomitantly provide a synthetic handle for
further elaboration of sophisticated molecular struc-
tures. One possible feature to induce electronic direc-
tionality is reducing the redox potential of the bridge.
Bipyrimidine is well known to be easier reducible than
its oligopyridinic partners but could also be doubly
reduced within a given potential windows.8 It was con-
sequently tempting to introduce such electron reservoir
as spacer between two chromophoric fragments.
Following the precedent of our recent work with ethy-
nylated polyaromatic and oligopyridinic derivatives,9 we
envisaged preparing a series of new ethynylated bipyr-
imidine and phenanthroline ligands with various sur-
rounding scaffolds such as pyrenes, terpyridines, and
bipyridines. The most prevalent method we found suit-
able for the alkynylation of oligopyridines involves
Sonogashira coupling reactions between a terminal
alkyne and an oligopyridinic bromide or triflate. In some
cases we found this protocol to be sensitive to the reac-
tion conditions but also to the stability of the ethynyl-
pyridinic frameworks. In our hands, one way to avoid
the formation of side-products was to apply a one-pot
deprotection/cross-coupling protocol under phase
transfer conditions.10
Access to bipyrimidine-based platforms first requires
producing the key starting materials 2 and 5 with good
yields (Scheme 1). Stimulated by our previous success in
the large scale preparation of 5- and 5,50-dibromo
substituted 2,2-bipyridine,11 we tested 2,20-bipyrimidine
under the same experimental conditions (pressurised
vessel containing derivative 1 as a solid with neat bro-
mine at 150–180 °C). Note that such sealed tubes must
Keywords: Multitopic ligands; Bipyrimidine; Phenanthroline; Pyrene;
Ruthenium; Palladium.
* Corresponding author. Tel./fax: +33-390-24-26-89; e-mail: ziessel@
chimie.u-strasbg.fr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.147

4052
R. Ziessel, C. Stroh / Tetrahedron Letters 45 (2004) 4051–4055
conditions.12 In the light of our previous findings,9
conversion of derivatives 2 and 5 into the corresponding
alkynylated species 3 and 6 is straightforward and does
not require special conditions (Scheme 1). Deprotection
is quantitative with KF in a protic solvent leading to the
key compounds 4 (FABþ/MS: m=z ¼ 207:1) and 7
(FABþ/MS: m=z ¼ 193:1).
R = TMS , 3
R = H , 4
N
N
N
N
(iv)
R
R
100 %
(iii)
62 %
N
N
N
N
N
N
N
Br
Br
Unfortunately, the preparation of similar phenanthro-
line targets by a conceptionally similar approach did not
proceed. As foreseen, the presence of the double bond
bridging both pyridines is detrimental for the bromina-
tion procedure. Indeed, 3-bromo-, and 3,8-dibromo-
1,10-phenanthroline were prepared according to the
literature procedure.13 Standard Sonogashira coupling
of 8 with trimethylsilyl acetylene or propargylic alcohol
yielded after standard deprotection the desired com-
pound 11 in fair yields (Scheme 2). Notice that the
propargylic route is less efficient but significantly
cheaper compared to the use of preformed trimethyl-
silylacetylene.
(ii)
(ii)
N
2 , 85 %
(i)
+
N
N
N
N
N
N
N
Br
N
n HBr
5 , 13 %
1
86 % (iii)
N
N
N
N
R = TMS , 6
R = H , 7
(iv)
R
100 %
In an attempt to test the reactivity of the monoethynyl
bipyrimidine we succeeded in producing, in fair yields,
the mono substituted derivative 12 to 14 in a single step
via a Sonogashira–Hagihara reaction promoted by low
valent palladium(0), as sketched in Scheme 3.14
Scheme 1. (i) HBr(g), EtOH; (ii) Br2, 150 °C; (iii) HCBCTMS,
[PdCl2(PPh3)2] 10 mol %, CuI 20 mol %, iPr2NH, THF; (iv) KF,
MeOH, rt.
Subjecting 5-ethynyl-2,20-bipyrimidine 6 (2 equiv) to
similar coupling conditions with disubstituted 3,8-dib-
romo-1,10-phenanthroline or 5,500-dibromo-2,20: 60,200-
terpyridine resulted in the formation of ligands 15 and
16 equipped with two bipyrimidine auxiliaries. Here the
yields are significantly lower due to the intermediate
formation of the mono-substituted derivatives, which
are less reactive towards ethynylation owing to the
withdrawing effect induced by the first ethynyl fragment.
be contained in a Bomben Rohr during the heating
process. As indeed expected, 5,50-dibromo-2,20-bipyr-
imidine was isolated as the main product (85% isolated
yield), whereas 5-bromo-2,20-bipyrimidine was obtained
as side product (13%), in the presence of 2 equiv of
bromine. Surprisingly, in this case the prior protonation
of the bipyrimidine is not mandatory to obtain a good
yield contrary to the bipyridine case where a mixture of
compounds was obtained in the absence of proton-
ation.11 Note that the use of 0.8 equiv of bromine and a
lower temperature (130 °C) gave rise to compound 5 in
44% yield along with unreacted starting material. De-
spite the fact that the reaction is difficult to monitor, the
harsh conditions do not induce any degradation or
formation of other brominated derivatives. This is
consistent with previous observations made with pro-
tonated bipyridine derivatives.11 Recently, 5-bromo and
5,50-dibromo bipyrimidine derivatives have been pro-
duced in low yield in solution under severe experimental
In the context of screening new potential ligands dis-
playing multiple complexation sites linked by unsatu-
rated spacers it can be easily imagined that other
peripheral entities can be introduced as their acetylene
derivatives in the same fashion from 5,50-diethynyl-2,20-
bipyrimidine. This is a convenient and versatile method
because the required ligands (Scheme 4) precipitate
during the reaction and could be recovered by centri-
fugation and adequate purification. During these reac-
(i)
63 %
Br
Br
N
N
N
N
9
HO
OH
8
58 %
(iii)
(ii)
90 %
(iv)
92 %
H
H
TMS
TMS
N
N
N
N
11
10
Scheme 2. (i) HCBCC(CH3)2OH, [Pd(PPh3)4] (6 mol %), benzene, nPrNH2, 60 °C; (ii) HCBCTMS, [Pd(PPh3)2Cl2] (6 mol %), CuI (12 mol %), THF,
iPr2NH, rt; (iii) KOH, toluene, 100 °C; (iv) KF, MeOH, rt.

R. Ziessel, C. Stroh / Tetrahedron Letters 45 (2004) 4051–4055
4053
N
N
N
N
N
a
85 %
N
12
N
N
N
b
78 %
N
N
13
c
85 %
N
N
N
N
N
N
N
N
N
N
(i)
H
14
6
N
N
N
N
N
N
d
56 %
N
N
N
N
15
N
N
N
e
57 %
16
N
N
N
N
N
N
N
N
i
Scheme 3. Reagents and conditions: (i) [Pd(PPh3)4] (3 mol %), benzene, Pr2NH, 80 °C; (a) 40-{[(trifluoromethyl)sulfonyl]oxy}-2,20: 60,200-terpyridine
(1 equiv), (b) 1-bromopyrene (1 equiv), (c) 3-bromo-1,10-phenanthroline (1 equiv), (d) 3,8-dibromo-1,10-phenanthroline (0.5 equiv), (e) 5,500-dibromo-
2,20:60,200-terpyridine (0.5 equiv).
a
N
N
N
N
17
72%
N
N
H
N
N
N
N
b
63%
N
N
18
N
N
N
N
N
N
(i)
c
N
N
N
N
52%
N
N
N
N
19
H
N
N
N
N
N
N
N
N
N
N
N
N
d
50%
4
20
e
80%
N
N
N
N
21
N
N
N
N
N
N
N
N
i
Scheme 4. Reagents and conditions: (i) [Pd(PPh3)4] (3 mol %), benzene, Pr2NH, 80 °C; (a) 1-bromopyrene (2 equiv), (b) 40-{[(trifluoromethyl) sul-
fonyl]oxy}-2,20:60,200-terpyridine (2 equiv), (c) 3-bromo-1,10-phenanthroline (2 equiv), (d) 3-bromo-2,20-bipyrimidine (2 equiv), (e) 5-bromo-50-(5-
ethynyl-2,20-bipyridine-yl)-2,20-bipyridine (2 equiv).
tions it was soon established by thin layer chromato-
graphy that the mono-substituted derivatives are pref-
erentially formed at the early stage of the reaction. The
use of lower temperature (ca. 50 °C) favors the precipi-
tation of the mono-substituted compound and inhibits
partly the second substitution process, a situation, which
is not targeted in this context but auspicious for the
potential engineering of molecules bearing different
coordination sites. Interestingly, around 80 °C the
mono-derivative is soluble and reactive towards further

4054
R. Ziessel, C. Stroh / Tetrahedron Letters 45 (2004) 4051–4055
substitution leading to compounds 17, 18,15 19, and 2016
in acceptable yields. We also noticed that under these
conditions the chemical stability of the diethynyl deriv-
ative 4 is poor affording side products. Cross linking of
synthesis of derivative 23 were the isolated yields could
be improved to 50% (Scheme 5).
Finally, an elegant way to smoothly prepare molecules
bearing at the periphery metal complexes with an
additional recognition center able to trap specific ana-
lytes was realized by cross-coupling reaction 3,8-di-
ethynyl-1,10-phenanthroline 11 with an adequate
metallo-synthon grafted with a reactive bromine func-
tion. Complex 2420 could be isolated pure in 51%, when
all attempts to prepare the same species by a more
classical pathway, using metal free ligand 23 and cis-
[Ru(terpy)(DMSO)Cl2]21 as metal precursor, failed
(Scheme 5).
5-bromo-50-(5-ethynyl-2,20-bipyridine-yl)-2,
20-bipy-
ridine17 with 4, very efficiently provides the hexatopic
ligand 21.
Similarly, reaction of 3,8-diethynyl-1,10-phenanthroline
11 provides some additional ligands (Scheme 5). The
low yields found for derivatives 22 and 23 are probably
due to the high reactivity and detrimental decomposi-
tion of the starting material 11. After some experimen-
tation we were pleased to find that in situ deprotection
of 3,8-di(trimethylsilylacetylene)-1,10-phenanthroline 10
could be performed in a biphasic mixture using benzene
and aqueous sodium hydroxide and 10 mol % of a
quaternary ammonium salt favoring the phase transfer
(Scheme 5). The cross-coupling reaction between the
resulting 3,8-diethynyl-1,10-phenanthroline 11 and
40-{[(trifluoromethyl)sulfonyl]oxy}-2,20:60,200-terpyridine
occurs in the organic phase and is promoted by Pd(0).
The nascent acid is quenched in the aqueous basic
solution by phase transfer. According to previous
studies18;19 and because the reaction requires mild heat-
ing it is believed that the deprotection step is relatively
slow while the cross coupling reaction would be much
faster under the phase transfer conditions. This proce-
dure, not yet optimised seems to be well adapted for the
In summary, we have prepared new-segmented ligands
bearing a controlled number of chelating fragments by a
rational approach, using transition metal-catalyzed
coupling reactions. The next phase of this work is to
complex the empty coordination sites in a controlled
manner with specific transition metal salts and to study
their optical and redox properties. It is foreseen that the
triple bond will serve as an efficient conduit for shuttling
the electron. The development of these photosensitisers
would expand the opportunities for applications in
the field of sensors and bipolar electroluminescent
materials. The study of these scaffoldings is currently
underway and the results will be disclosed in the near
future.
X
(i)
20%
N
N
N
N
22
X = H
11
N
N
N
N
N
(ii)
15%
N
23
X
N
N
10 X = TMS (iii) 50%
(v)
N
(iv)
N
N
11
N
Ru
Br
N
X = H
N
51%
4+
N
N
N
N
N
N
-
N
4 PF6
N
N
N
Ru
N
Ru
N
N
24
N
Scheme 5. Reagents and conditions: (i) [Pd(PPh3)4] (3 mol %), benzene, iPr2NH, 80 °C, 1-bromopyrene (2 equiv); (ii) [Pd(PPh3)4] (3 mol %), benzene,
iPr2NH, 80 °C, 40-{[(trifluoromethyl)sulfonyl]oxy}-2,20:60,200-terpyridine (2 equiv); (iii) phase transfer conditions; [Pd(PPh3)2Cl2] 6 mol %, CuI
10 mol %, benzene, water, NaOH, Et3BzNCl, 40-{[(trifluoromethyl)sulfonyl]oxy}-2,20:60,200-terpyridine (2 equiv), 60 °C; (iv) [PdCl2(PPh3)2] 6 mol %,
i
CuI 10 mol %, Pr2NH, THF, rt; (v) cis-[Ru(terpy)(DMSO)Cl2] (2 equiv), AgBF4 (2.2 equiv), MeOH, CH2Cl2 (1/1, v/v), 50 °C.

R. Ziessel, C. Stroh / Tetrahedron Letters 45 (2004) 4051–4055
4055
10. De Nicola, A.; Liu, Y. L.; Schanze, K. S.; Ziessel, R.
Chem. Commun. 2003, 288, and references cited therein.
11. Romero, F. M.; Ziessel, R. Tetrahedron Lett. 1995, 36,
6471.
12. Schwab, P. F. H.; Fleischer, F.; Michl, J. J. Org. Chem.
2002, 67, 443.
Acknowledgements
This work was supported by the Centre National de la
ꢀ
Recherche Scientifique, the Universite Louis Pasteur
ꢁ
Nouvelles Technologies.
and the Ministere de la Recherche Franßcaise et des
13. Tzalis, D.; Tor, Y.; Faila, S.; Siegel, J. S. Tetrahedron Lett.
1995, 36, 3489.
1
14. Tritopic ligand 12: Isolated yield 85%. H NMR (CDCl3)
d ¼ 9:09 (s, 2H), 9.01 (d, 3J ¼ 4:8 Hz, 2H), 8.72 (d,
References and notes
3
3J ¼ 4:8 Hz, 2H), 8.64 (d, J ¼ 8:0 Hz, 2H), 8.55 (s, 2H),
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7.92 (td, 3J ¼ 7:9 Hz, 4J ¼ 1:8 Hz, 2H), 7.42 (ddd,
3J ¼ 5:0 Hz, 3J ¼ 4:8 Hz, 4J ¼ 1:2 Hz, 2H), 7.53 (t,
3J ¼ 4:8 Hz, 1H). FABþ (m-NBA) m=z (relative intensity
in %) 414.2 ([M þ H]þ, 100), 232.2 (20). IR (KBr, cmꢀ1
)
3425, 2147 (w), 1585, 1456, 1392, 1264, 1093, 1037, 878.
Anal. Calcd for C25H15N7 (Mr ¼ 413:43): C, 72.63;
H, 3.66; N, 23.72. Found: C, 72.37; H, 3.29; N,
23.34.
2. Romero, F. M.; Ziessel, R.; Dupont-Gervais, A.; Van
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J.; Lee, S. H.; Son, K. H.; Kim, Y. H.; Doo, J.-Y.; Lee, G.
J.; Kang, T. I.; Lee, Y. K.; Cho, M.; Jeon, S.-J. Chem.
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Chem. Soc. 2003, 125, 13279.
15. Tetratopic ligand 18: Isolated yield: 63%. Ligand too
insoluble to run NMR spectrosocpies. FABþ (m-NBA)
m=z (relative intensity in %) 669.2 ([M]þ, 100), 478.2 (20).
IR (KBr, cmꢀ1) 3404, 1584, 1566, 1467, 1446, 1425, 1392,
1156, 1090, 1046, 799. Anal. Calcd for C42H24N10
(Mr ¼ 668:73): C, 75.44; H, 3.62; N, 20.95. Found: C,
75.29; H, 3.39; N, 20.75.
16. Hexatopic ligand 20: Isolated yield: 50%. 1H NMR (d7-
3
DMF) d ¼ 9:06 (s, 4H), 9.08 (s, 4H), 8.99 (d, J ¼ 5:0 Hz,
4H), 7.47 (t, 2H, 3J ¼ 5:0 Hz). FABþ (m-NBA) m=z
(relative intensity in %) 519.2 ([M þ H]þ, 100), 338.2
(20). IR (KBr, cmꢀ1) 3418, 2976, 2163, 1578, 1523, 1507,
1423, 1236, 876. Anal. Calcd for C28H14N12 (Mr ¼ 518:49):
C, 64.86; H, 2.72; N, 32.42. Found: C, 64.45; H, 2.56; N,
32.05.
17. Khatyr, A.; Ziessel, R. Org. Lett. 2001, 3, 1857.
18. Carpita, A.; Lessi, A.; Rossi, R. Synthesis 1984, 571;
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19. De Nicola, A.; Liu, Y. L.; Schanze, K. S.; Ziessel, R.
Chem. Commun. 2003, 288.
20. Dinuclear Complex 24: Isolated yield: 51%. 1H NMR
(CD3CN) d ¼ 9:49 (d, 2H, 3J ¼ 2; 0 Hz), 8.99 (s, 4H), 8.84
(d, 2H, 3J ¼ 2:0), 8.78 (d, 4H, 3J ¼ 8:4), 8.41–8.59 (m,
10 H), 8.19 (s, 2H), 7.90–8.02 (m, 8H), 7.38–7.43 (m, 8H),
7.15–7.25 (m, 8H). ESI-MS m=z (nature of the peak,
relative intensity in %) 1795.2 ([M ꢀ PF6]þ, 100), 825.2
([M ꢀ 2PF6]2þ, 40), 501.8 ([M ꢀ 3PF6]3þ, 10). IR (KBr,
cmꢀ1) 3420, 1604, 1449, 1424, 840, 788, 768, 557. UV–vis
(CH3CN) kmax, nm (e, Mꢀ1 cmꢀ1) 495.0 (94,500), 307.0
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€
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€
Chem. Soc. 2004, 126, 177.
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(16,900),
272.0
(14,900).
Anal.
Calcd
for
C76H48N14P4F24Ru2 (Mr ¼ 1939:32): C, 47.07; H, 2.49;
N, 10.11. Found: C, 47.09; H, 2.43; N, 10.49.
21. Grosshenny, V.; Ziessel, R. J. Organomet. Chem. 1993,
453, C19.