Phloroglucinol based podands, versatile tripodal ligands

Article abstract of DOI:10.1016/S0040-4039(02)02213-X

The synthesis of four phloroglucinol based podands is described. Ligands 4 and 5 have three bipyridine arms and an induced octahedral cavity ideal for transition metal complexation. The iron(II) complex of 4 is described. Tripodes 6 and 7 possess three bipyridine-carboxylate arms, and are designed for the encapsulation of luminescent lanthanide salts. Some preliminary optical properties of the corresponding Eu³⁺ and Tb³⁺ are presented.

Full text of DOI:10.1016/S0040-4039(02)02213-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8835–8837
Phloroglucinol based podands, versatile tripodal ligands
Gilles Ulrich,* Se´bastien Bedel and Claude Picard
Laboratoire de Synthe`se et Physico-Chimie de Mole´cules d’Inte´reˆt Biologique, UMR 5068, Universite´ Paul Sabatier,
118 rte de Narbonne 31062 Cedex 4, Toulouse, France
Received 25 July 2002; accepted 7 October 2002
Abstract—The synthesis of four phloroglucinol based podands is described. Ligands 4 and 5 have three bipyridine arms and an
induced octahedral cavity ideal for transition metal complexation. The iron(II) complex of 4 is described. Tripodes 6 and 7 possess
three bipyridine-carboxylate arms, and are designed for the encapsulation of luminescent lanthanide salts. Some preliminary
optical properties of the corresponding Eu3+ and Tb3+ are presented. © 2002 Elsevier Science Ltd. All rights reserved.
A constant effort has been made, during the last 20
years, to synthesize polypyridine ligands1 in the hope of
complexing various metals from transition ones to lan-
thanides. One strategy used to build covalent assem-
blies, having bipyridine subunits, was to graft
bipyridine pendant arms on a molecular platform. The
choice of the central molecule allows the control of the
podand’s cavity geometry. Numerous molecular frame-
works were used to synthesize podands bearing three or
more bipyridine units, such as polyamines,2
polyamides,3 or calixarenes.4 Cage-type polypyridine
podands consisting of three covalently linked bipyridi-
nes provide an ideal octahedral environment for the
encapsulation of transition metal such as Ru(II).5 Sub-
stituted bipyridines possessing a carboxylate function at
the a position from one nitrogen atom were shown to
generate a cavity with nine coordination sites. Such a
configuration seems ideally appropriate for an efficient
encapsulation of luminescent lanthanide salts.6 We
present now the synthesis of podands with three
bipyridine arms derived from phloroglucinol (1), by
alkylation of the hydroxyl groups with two differently
substituted bipyridines bearing a benzylic bromide.
anhydrous degassed DMF, to obtain satisfactory
results. Two central structures were chosen for our
study; the free phloroglucinol (1), as a model com-
pound, and a functionalized phloroglucinol specially
designed to further link the resulting podand on a solid
support or on a biomolecule.
The phloroglucinol was mono functionalized using a
typical Friedel–Crafts reaction, with one equivalent of
p-nitrobenzoyl chloride in presence of AlCl3 as Lewis
acid, in nitrobenzene (Scheme 1).8 Compound 2 is
obtained after steam extraction of the nitrobenzene and
recrystallization in boiling water with 12% yield. The
nitro group is quantitatively reduced to the correspond-
ing aromatic amine 3, with hydrogen in ethanol, in the
presence of Pd/C as a catalyst.
The two central structures 1 and 3 (obtained by reduc-
tion of 2 and evaporation of the solvent, with no
The first step to be achieved is the trialkylation of
phloroglucinol with a good yield. The classical bases
such as sodium carbonate or triethylamine did not lead
to complete alkylation of the three hydroxyl groups.
Moreover, some degradation of the phloroglucinol is
observed, probably due to a partial oxidation. As previ-
ously described, Cs2CO3 is the appropriate base7 in
Keywords: bipyridine; podand; phloroglucinol; complexation.
* Corresponding author. Tel.: 33 (0) 561556288; fax: 33 (0)
561556011; e-mail: ulrich@chimie.ups-tlse.fr
Scheme 1. Reagents and conditions: (a) AlCl3, CS2, PhNO2,
ClCOPhNO2, reflux, 12%; (b) H2, Pd/C, EtOH, quant.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02213-X

8836
G. Ulrich et al. / Tetrahedron Letters 43 (2002) 8835–8837
Scheme 2. Reagents and conditions: (a) Cs2CO3, 5-bromomethyl-R%-(2,2%-bipyridine) (3 equiv.), DMF, rt, 2–7 days, 30–83%; (b) i.
NaOH, MeOH/H2O, ii. HCl, 90%.
1
and by a clear H NMR spectrum (Fig. 1). This spec-
trum shows a nice C3 symmetry in the molecule and a
clear AB system centered at 5.09 ppm for the methylene
bridge, due to the rigid structure. A strong shielding
from 8.70 to 6.52 ppm of the H6 of the bipyridine can
be noted, the three H6 protons being blocked in the
shielding cone of the benzene ring. The model com-
pound 4 demonstrates that the phloroglucinol is indeed
a good candidate for the effective preparation of
podands with a three bipyridine coordination cavity.
These ligands (4, 5) are expected to be good candidates
additional purification), were alkylated with 3 equiv. of
5-bromomethyl-5%-methyl-2,2%-bipyridine,2 with cesium
carbonate (5 equiv.) as base, in anhydrous degassed
DMF, at room temperature during two days.7 After
chromatography on alumina, 4 and 5 were obtained
with a respective yields of 30 and 42% (Scheme 2).
The complexation abilities of these tripodal podands
were demonstrated by the synthesis of an iron(II) com-
plex using the highly symmetrical model podands 4.†
To a solution of 4 (1 equiv.) in CH2Cl2 was added a
2−
2+
methanolic solution of FeSO4. The counter ion SO4
for the preparation of long life luminescent Ru(bpy)3
was exchanged by using a saturated aqueous solution of
KPF6.2 Purification by chromatography over Al2O3,
with a standard eluent (CH2Cl2/MeOH, 95:5) led to
type complexes, in regard to the good results obtained
with the mesitylene based analogous products.5
‡
[Fe(4)](PF6)2 with a good yield (51%), despite the
The present study was continued with the synthesis of
phloroglucinol derivatives bearing three tritopic arms,
to form nonadentate cavity designed for lanthanide
complexation.6 For our purpose, we used the same
conditions for the nucleophilic substitution: Cs2CO3 as
base in DMF, at room temperature, 3 equiv. of ethyl
5%-methyl-6-(2,2%-bipyridine)-carboxylate,9 during two
days to obtain 6 with a 50% yield,10 and during 1 week
possibility of polymerization reactions. This complex is
clearly characterized by a well defined and intense
metal-to-ligand charge transfer UV–vis absorption
band at low energy umax=527 nm (m=6,400 M−1 cm−1),
† [1,3,5-Tri[(5%-methyl-2,2%-bipyridin-5-yl)methoxy] benzene. 1H NMR
(250 MHz, CDCl3): l=2.40 (s, 9H), 5.09 (s, 6H), 6.31 (s, 3H), 7.62
3
4
3
4
(dd, 3H, J = 8.1 Hz J=1.7 Hz), 7.87 (dd, 3H, J=8.2 Hz J=2.4
Hz), 8.29 (d, 3H, 3J=8.2 Hz), 8.38 (d, 3H, 3J=8.2 Hz), 8.50 (d, 3H,
4J=1.7 Hz), 8.70 (d, 3H, 4J=1.7 Hz). 13C{1H} JMOD NMR (62.5
MHz, CDCl3): l=18.4 (CH3), 67.7 (CH2), 95.2 (CH), 120.6 (CH),
120.7 (CH), 131.8 (Cq), 133.6 (Cq), 136.3 (CH), 137.5 (CH), 148.3
(CH), 149.6 (CH), 153.3 (Cq), 156.2 (Cq), 160.4 (Cq). IR (KBr):
1594 (s), 1470 (s), 1155 (s) cm−1. UV–vis (CH2Cl2, 23°C): umax (m,
M−1 cm−1)=291 (88000). MS (FAB+, mNBA): m/z (%)=673 (100)
[M+H+], 695 (9) [M+Na+].
‡ {1,3,5-Tri[(5%-methyl-2,2%-bipyridin-5-yl)methoxy]benzene} iron(II)
hexafluorophosphate. 1H NMR (250 MHz, (CD3)2CO): l=2.21 (s,
9H), 5.10 (AB sys, 6H, Dw=38.4 Hz, JAB=12.7 Hz), 6.39 (s, 3H),
6.53 (d, 3H, 4J=1.5 Hz), 7.65 (s, 3H), 8.05 (d, 3H, 3J=8.5 Hz), 8.36
(d, 3H, 3J=8.2 Hz, 4J=1.5 Hz), 8.66 (d, 3H, 3J=8.2 Hz), 8.77 (d,
3H, 3J=8.2 Hz). 13C{1H} JMOD NMR (62.5 MHz, (CD3)2CO):
l=18.6 (CH3), 71.3 (CH2), 111.0 (CH), 124.6 (CH), 124.9 (CH),
135.5 (Cq), 139.6 (Cq), 140.3 (CH), 141.4 (CH), 154.0 (CH), 155.3
(CH), 157.0 (Cq), 159.5 (Cq), 160.5 (Cq). IR (KBr): 1649 (s), 1443
(m) cm−1. UV–vis (CH2Cl2, 23°C): umax (m, M−1 cm−1)=304 (6800),
527 (6400). MS (ES+, CH3CN): m/z (%)=873.2 [{L+Fe}PF6]+,
Figure 1. 1H NMR spectra of 4 (in CDCl3) and [Fe(4)](PF6)2
(in CD3COCD3).
364.2 [L+Fe]2+
.

G. Ulrich et al. / Tetrahedron Letters 43 (2002) 8835–8837
Table 1. Selected photophysical data for the lanthanide complexes
8837
ma
M
−1cm−1
~
~
nH2Oc
ƒ
a
b
H2O
b
D2O
d
Comp.
umax (nm)
[Eu(8)]
[Tb(8)]
309
309
37000
38000
1.95
1.27
2.80
1.69
0.2
0.8
0.10
0.12
a Measured in water at 300 K.
b At 300 K.
c Calculated from Horrock’s equation.11
d Calculated with Ru(bpy)3Cl2 as reference for Eu3+ complex and quinine sulfate for Tb3+ complex.
to give 7§ with a yield of 83% (Scheme 2). The substitu-
tion process is slow, and the yields can be increased by
lengthening the reaction time. Compound 6 was
saponified with NaOH in a MeOH/H2O mixture, and
the corresponding triacid 8 was recovered by precipita-
tion at pH 4.6 Preliminary photophysical measurements
were performed on the in situ generated complexes of 8
with Eu3+ and Tb3+. Upon formation, the complexes
induce a small bathochromic shift of the p–p* band of
the bipyridine core in the UV spectra, from 291 to 309
nm, in water. The [Eu(8)] model complex exhibits a
very long-lived emission of 1.8 ms, a quantum yield in
water of 10%, and no water molecule is present in the
first coordination sphere (Table 1). In the case of the
Tb3+ complex, the emission lifetime is shortened, proba-
bly by the presence of a water molecule. These results
confirm the ability of the phloroglucinol based podands
to encapsulate efficiently lanthanide salts.
Acknowledgements
The authors are grateful to the CNRS for its financial
supports and G.U. thanks Professor A. Vigroux for
helpful and fruitful discussions.
References
1. Kaes, C.; Katz, A.; Hosseini, M. W. Chem. Rev. 2000,
100, 3553–3590.
2. Ziessel, R.; Hissler, M.; Ulrich, G. Synthesis 1998, 1339–
1346.
3. Grammenudi, S.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl.
1986, 25, 1122–1125.
4. Ulrich, G.; Ziessel, R.; Manet, I.; Guardigli, M.; Sabba-
tini, N.; Fraternali, F.; Wipff, G. Chem. Eur. J. 1997, 3,
1815–1822.
5. Beeston, R. F.; Larson, S. L.; Fitzgerald, M. C. Inorg.
Chem. 1989, 28, 4187–4189.
6. Charbonnie`re, L. J.; Ziessel, R.; Guardigli, M.; Roda, A.;
Sabbatini, N.; Cesario, M. J. Am. Chem. Soc. 2001, 123,
2436–2437.
7. Groth, A. M.; Lindoy, L. F.; Meehan, G. V. J. Chem.
Soc., Perkin Trans. 1 1996, 1553–1558.
8. Crombie, L.; Jones, R. C. F.; Palmer, C. J. J. Chem. Soc.,
Perkin Trans. 1 1987, 317–331.
The complexation studies of 7 with Eu(III) and Tb(III)
and the optical properties of the corresponding com-
plexes are in progress. Investigations for an optimal
method to link these new podands on a biomolecule,
using the residual amino function, are also under way.
In conclusion, we have shown that phloroglucinol is a
good candidate for the efficient preparation of podands
bearing three coordinating arms capable of inducing a
coordination cavity. Moreover, the easy functionaliza-
tion of the aromatic ring opens up new horizons for
further functionalizations of the podands or their metal
complexes.
9. Ulrich, G.; Bedel, S.; Picard, C.; Tisne`s, P. Tetrahedron
Lett. 2001, 42, 6113–6115.
10. Bedel, S.; Ulrich, G.; Picard, C.; Tisne`s, P. Synthesis
2002, 1564–1570.
11. Horrocks, W. D. J.; Sudnick, D. R. Acc. Chem. Res.
1981, 14, 384–392.
§ (4-Aminophenyl)(2,4,6-tri[(6%-ethoxycarbonyl-2,2%-bipyridin-5-yl)
methoxy] phenyl) methanone. 1H NMR (250 MHz, CDCl3): l=
1.44–1.50 (m, 9H), 4.44–4.54 (m, 6H), 5.10 (s, 4H), 5.13 (s, 2H), 6.34
(s, 2H), 6.61 (d, 2H, 3J=8.5 Hz), 7.57 (dd, 2H, 3J=8.2 Hz 4J=2.4
Hz), 7.66 (d, 2H, 3J=8.5 Hz), 7.89–8.00 (m, 4H), 8.10 (dd, 2H,
3J=7.7 Hz, 4J=0.8 Hz), 8.40 (d, 2H, 3J=8.2 Hz), 8.51–8.62 (m,
7H), 8.73 (d, 1H, 4J=1.8 Hz).13C{1H} JMOD NMR (62.5 MHz,
CDCl3): l=14.3 (CH3), 61.9 (CH2), 67.7 (CH2), 68.0 (CH2),
94.0(CH), 97.5 (CH), 113.7 (CH), 121.4 (CH), 121.5 (CH), 124.1
(CH), 124.8 (CH), 125.0 (CH), 128.3 (Cq), 131.9 (CH), 132.5 (Cq),
132.6 (Cq), 135.8 (CH), 136.3 (CH), 137.8 (CH), 137.9 (CH), 147.6
(CH), 147.65 (Cq), 147.7 (Cq), 148.2 (CH), 152.1 (Cq), 154.6 (Cq),
155.0 (Cq), 155.9 (Cq), 156.0 (Cq), 156.9 (Cq), 160.5 (Cq), 165.2
(CꢀO), 192.3 (CꢀO).IR (KBr): 3440 (m), 1740 (m), 1715 (m), 1644
(sh), 1595 (s) cm−1. MS (FAB+, mNBA): m/z (%)=966 (100)
[M+H+], 988 (25) [M+Na+].