Synthesis of 6-phenyl-2,2′-bipyridine ligands bearing polyaromatic substituents

Article abstract of DOI:10.1016/j.tetlet.2007.09.011

A simple protocol for the efficient preparation of substituted 6-phenyl-2,2′-bipyridine derivatives is described. An inverse Diels-Alder reaction between a 3-phenyl-5-pyridyl-1,2,4-triazine and an electron-rich ethynyl species at high temperature provides a mixture of two products easily separable by column chromatography. The most encumbered isomer is favoured, likely due to favourable π-π stacking interactions in the transition state. A variety of those ligands suitable for the synthesis of cyclo-metallated complexes have been produced.

Full text of DOI:10.1016/j.tetlet.2007.09.011

Tetrahedron Letters 48 (2007) 8069–8073
Synthesis of 6-phenyl-2,20-bipyridine ligands bearing
polyaromatic substituents
a
b
a,
*
´
Stephane Diring, Pascal Retailleau and Raymond Ziessel
aLaboratoire de Chimie Mole´culaire, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France
bLaboratoire de Cristallochimie, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, Cedex, France
Received 20 June 2007; revised 6 August 2007; accepted 4 September 2007
Available online 6 September 2007
Abstract—A simple protocol for the efficient preparation of substituted 6-phenyl-2,20-bipyridine derivatives is described. An inverse
Diels–Alder reaction between a 3-phenyl-5-pyridyl-1,2,4-triazine and an electron-rich ethynyl species at high temperature provides a
mixture of two products easily separable by column chromatography. The most encumbered isomer is favoured, likely due to
favourable p–p stacking interactions in the transition state. A variety of those ligands suitable for the synthesis of cyclo-metallated
complexes have been produced.
Ó 2007 Elsevier Ltd. All rights reserved.
Versatile synthetic strategies leading to novel ligands
have been a major stimulus to recent developments in
the chemistry of transition and lanthanide metals.1,2
Intense interest in the particularly important family of
oligopyridine ligands has been driven largely by the
applications of their complexes in areas as diverse as
biological analysis, photocatalysis and molecular elec-
tronics.3–7 Current extensions of these applications in-
clude those in electroluminescent devices and in
information storage and processing.8,9
anionic ligand.11Such anions are known to strongly sta-
bilize d8 or d6 transition metals like Pt(II), Pd(II) and
Ir(III), particularly well-known being phenylpyridine
derivatives such as Ir(C^N)3 (C^N = 6-phenylpyri-
dine),12 although ortho-metallated Pt(II) and Pd(II)
complexes of 6-phenyl-2,20-bipyridine have also been
described.13,14
In this contribution, we present the synthesis and some
spectroscopic properties of 3 and 4-aryl 6-phenyl-2,20-
bipyridine ligands. Various aryl substituents have been
attached, some of them bearing N or O atoms in the
skeleton. To prepare these ligands, we developed a
[4+2] cyclo-addition reaction between a 2,6-disubsti-
tuted-1,3,4-triazine and ethynyaryl reagents (Scheme
1). This protocol was inspired by well-known reverse
Diels–Alder reactions of various electron-deficient
dienes such as 1,2,4,5-tetrazines and 1,2,4-triazines.15
Most prominent members of the oligopyridine group are
2,20:60,200-terpyridine and 2,20-bipyridine derivatives.
These are chelating ligands which show particularly high
affinities for transition metal ions and which frequently
stabilise unusually low oxidation state species because
of both dp–pp back-bonding by the cations and their
*
capacity to form ligated anion radicals. One deficiency
is that, as neutral ligands, they give cationic complexes
suited possibly to spin-coating techniques for film depo-
sition but usually unsuited to vapour deposition from
ultra-high vacuum. Neutral complexes derived from an-
ionic ligands are generally better suited to such a proce-
dure10 and thus it is of interest to explore the use
of oligopyridine analogues in which the replacement of
pyridine rings by phenyl leads to the possibility of
ortho-metallation and the generation thus of a formally
The target triazine was prepared in two steps from 2-
cyanopyridine and hydrazine followed by condensation
with phenylglyoxal (Scheme 1). Condensation of 1 with
hydrazine hydrate was carried out as described in the lit-
erature.16 Note that hydrazine should be handled with
care due to its high toxicity and powerful reducing prop-
erties. Interestingly, condensation with 4-ethynyltoluene
gave rise to two isomers, characterized by both NMR
spectroscopy and X-ray diffraction. The slightly more
polar species was the minor product (13% for the 4-
substituted or para isomer 5), whereas the 3-substituted
derivative (meta isomer 4) was the major one (42%).
*
Corresponding author. Tel.: +33 03 88 90 24 26 89; fax: +33 3 90 24
27 42; e-mail: ziessel@chimie.u-strasbg.fr
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.011

8070
S. Diring et al. / Tetrahedron Letters 48 (2007) 8069–8073
of the tolyl aromatic ring. This difference is also system-
atically observed in all cases.
(i)
(ii)
3
N
2'
2
4
5
N
N
N
N
CN
N
NH2
N
NH2
1
2
The structures assigned spectroscopically (NMR) were
confirmed by X-ray diffraction on single crystals (Fig. 2).
6
(iii)
3
In both structures, the nitrogen atoms of the bipyridine
unit lie in a transoid array, as usually observed for var-
ious oligopyridines.17 However, while the two pyridine
rings of the para isomer (5) are only slightly distorted
with a small dihedral angle of 5.63° and 11.85° (two
molecules in the asymmetric unit), they are strongly
tilted by 67.06° and 60.86° in meta (4), as a direct result
of the proximity of the tolyl ring. The latter is also more
strongly tilted with respect to the central pyridine ring in
the meta isomer (dihedral 53.90°) than in the para iso-
mer (dihedral 30.92°).
b
6'
b'
a
b'
a'
a
5
5'
4'
N
6'
3'
3
5'
4'
N
b'
3'
a'
4
5
N
+
N
c
c'
d'
c
d
c'
d'
d
5, 13%
4, 42%
e
e
Scheme 1. Reagents and conditions: (i) N2H4 hydrate, EtOH; (ii) 2-
phenyl glyoxal, EtOH, reflux; (iii) 4-ethynyltoluene, o-dichlorobenz-
ene, 180 °C.
The proton NMR spectra (Fig. 1) provide ‘‘fingerprints’’
for these molecules.
N
N
N
N
The complete spectra of the two isomers could be unam-
biguously assigned. Protons 3 and 5 in the spectrum of
the para isomer (5, top) protons 3 and 5 appear as two
doublets (4J = 1.5 Hz) at 8.50 and 8.09 ppm, respec-
tively, indicating that they are weakly coupled, whereas
for the meta isomer (4, bottom) there is a stronger cou-
pling of protons 4 and 5 (JAB = 8.1 Hz, t0d = 12.7 Hz),
so that they appear as an obvious AB doublet pair (see
Scheme 1 for labelling). These proton signals allow clear
identification of the two isomers whatever be the substit-
uents on the central pyridine ring. An interesting obser-
vation is that the doublet at 8.61 ppm assigned to the
proton 30 on the outer pyridine ring of the para isomer
(5) is highly shifted (7.45 ppm) in the spectrum of the
meta isomer (4), probably influenced by the proximity
Pt
Pt
Cl
Cl
6
7
In order to test the coordination abilities of both iso-
mers towards Pt(II), we reacted them with K2PtCl4 in
refluxing acetonitrile/water mixture. Both being stable,
aa’
dd’, e, 5’
3
cc’
5
bb’
3’
4’
6’
8.8
8.6
8.4
8.2
5
8.0
7.8
7.6
7.4
aa’
4
bb’
cc’
dd’, e, 3’
5’
4’
6’
8.4
8.2
8.0
7.8
(ppm)
7.6
7.4
7.2
7.0
Figure 1. 1H NMR (300 MHz, CD3OD) of 5 (para isomer, top) and 4
(meta isomer, bottom).
Figure 2. ORTEP view of ligands 4 (top) and 5 (bottom) with atom
labeling. Probability displacement ellipsoids are shown at 50% level.

S. Diring et al. / Tetrahedron Letters 48 (2007) 8069–8073
8071
˚
neutral complexes 6 and 7 were isolated in good yields
(58 and 63%, respectively) and crystallized in a mixture
of CH2Cl2 and cyclohexane. Their molecular structures
determined by X-ray diffraction confirmed that the
Pt(II) centres are square planar and that the first coordi-
nation sphere is completed by a ligated Cl anion (Fig. 3).
ortho-metallated-phenyl group [Pt(1)-N(1) 2.096 A (6)
˚
and 2.109 A (7)] are noticeably longer than those trans
to the chlorine ligand [Pt(1)-N(2) 1.954 A (6) and
1.952 A (7)], which is consistent with the greater trans
˚
˚
influence exerted by the phenyl substituent.
To further characterise the behaviour of the 2,6-disub-
stituted-1,3,4-triazine 3 and the regioselectivity of its
reactions with monofunctionalised alkynes, 2-ethynyl-
9,9-dimethylfluorene18 and 3-ethynyl-9-methylcarbaz-
ole19 were reacted with 3 at high temperature in
o-dichlorobenzene. As found for 4-ethynyltoluene, the
major products were the meta isomers 8a and 9a
(isolated yields 33% and 43%), while the para isomers
8b and 9b were isolated in low yield (8% and 12%).
The tridentate cyclo-metallated ligand and the chlorine
are arranged in a distorted square-planar geometry
about the platinum atom. While in the para complex
(7), the ligand unit is close to planar, with very small
dihedral angles (3.06° with the pyridine; 2.00° with the
phenyl) between the outer rings and the central pyridine,
in the meta complex (6) there is a more significant distor-
tion, resulting in a dihedral angle of 9.20° between both
pairs. When compared to the respective uncomplexed li-
gands (4 and 5), the tilt between the tolyl substituent and
the central pyridine is greater for the meta complex (6),
with a dihedral angle of 64.28° and slightly lower for the
para complex (7), with a dihedral angle of only 28.16°.
The platinum–nitrogen bond lengths trans to the
1
For selected H NMR data see Table 1.
N
N
N
N
8a
8b
N
N
N
N
N
N
9a
9b
The use of even more electron-rich terminal alkynes,
such as 3-ethynylperylene or 1-ethynylpyrene, provided
almost exclusively the meta isomers 10 and 11, identified
by NMR spectroscopy (see Table 1).
N
N
N
N
10
11
Table 1. Selected NMR data for the new ligands
Compounds Protons 4,5 (ppm)
Protons 3,5 (ppm)
AB quartet (JAB, t0d, Hz)a Doublet (J4, Hz)a
For the meta isomer
For the para isomer
8a
8b
7.92 (8.1, 26.3)
—
—
8.71 (1.5), 8.05 (1.3)
9a
9b
7.93 (8.2, 33.0)
—
—
Figure 3. ORTEP view of complexes 6 (top) and 7 (bottom) with atom
labeling. Probability displacement ellipsoids are shown at 50% level.
8.57 (1.7), 8.12 (1.3)
—
—
—
8.60 (1.5), 8.09 (1.5)
8.67 (1.5), 8.15 (1.5)
10
11
7.92 (8.0, 6.8)
7.93 (7.7, 43.6)
7.85 (8.1, 16.4)
7.89 (8.2, 19.3)
—
˚
Selected distances (A) and angles (°) for 6: Pt(1)–N(1) 2.096, Pt(1)–
N(2) 1.954, Pt(1)–C(12) 1.983, Pt(1)–Cl(2) 2.309, N(1)–Pt(1)–N(2)
79.65, N(1)–Pt(1)–C(12) 162.42, N(2)–Pt(1)–Cl(2) 176.27; for 7: Pt(1)–
N(1) 2.109, Pt(1)–N(2) 1.952, Pt(1)–C(12) 1.988, Pt(1)–Cl(1) 2.305,
N(1)–Pt(1)–N(2) 79.38, N(1)–Pt(1)–C(12) 161.28, N(2)–Pt(1)–Cl(1)
177.81.
12a
12b
12c
a 1H NMR (300 MHz) spectra recorded in CDCl3.

8072
S. Diring et al. / Tetrahedron Letters 48 (2007) 8069–8073
To broaden the synthetic scope of these reactions, we
also tested a double condensation with a diethynyl
derivative. 1,4-Diethynyl-3,6-dibutoxyphenyl was cho-
sen due to its availability, good thermal stability, and
relative solubility in o-dichlorobenzene. As anticipated,
three products were separated by flash column chroma-
tography. The meta/meta derivative 12a was isolated in
21% yield, and the meta/para 12b in 11%. The less
favoured para/para isomer 12c was formed in very low
yield (3%).
stituents. In compounds 10 and 11, the increase of
extinction coefficient is due to the strong and structured
absorption of spin-allowed transitions involving the per-
ylene and pyrene fragments, respectively. All the com-
pounds exhibit a relatively intense emission (Table 2)
in solution at room temperature. For 10 and 11 the in-
tense fluorescence is due to the peripheral perylene and
pyrene subunits. The emission spectrum is similar in
shape and the emission is significantly red-shifted com-
pared to the absorption spectrum, indicating a strong
N
N
O
O
N
N
N
O
N
O
N
N
12b
N
12a
O
O
N
N
N
12c
Considering the possible mechanisms, we hypothesized
that the meta isomer is favoured owing to favourable
(i)
+
3
p–p interaction in the transition state between the ethyn-
*
N
ylaryl and the pyridine ring. In the absence of such a
stabilizing interaction, the para isomer should be fa-
voured for steric reasons. In keeping with such a
hypothesis is the fact that when tert-butylacetylene was
used only the para isomer could be isolated. Here, the
steric course of the reaction can be understood assuming
that the reaction partners adopt an orientation in the
transition state that minimizes unfavourable steric inter-
action between the bulky tert-butyl group and the pyri-
dine substituent. Such regio-selectivity has previously
been observed with stannane derivatives.20
N
O
N O
COOH
NH2
+
13
Scheme 2. (i) Anthranilic acid, o-dichlorobenzene, isoamyl nitrite in
o-dichlorobenzene at 180 °C, 3 h.
Stokes shift, which suggests a reorganization occurring
in the excited state. Surprisingly, for the para derivatives
a hypsochromic shift of about 30 nm is observed. Note
that for complexes 6 and 7 the low energy absorption
band corresponds to a metal-to-ligand charge transfer
absorption band and the emission probably involves
the same state.22
Finally, in order to avoid isomer mixtures, we used benz-
yne as a synthetic equivalent of symmetrical acetylenic
derivatives. This highly reactive reagent, prepared from
anthranilic acid and isoamyl nitrite21 was condensed
in situ to provide the fused isoquinoline molecule 13 in
low yield (Scheme 2).
In summary, a series of tridentate (C^N^N) ligands have
been prepared and characterized by NMR spectroscopy
and X-diffraction on single crystals in some key cases.
The regioselectivity of the syntheses can be controlled
by steric influences. The coordination potential of the li-
gands, as anionic species formed through ortho-metalla-
tion, has been tested by complexation with Pt(II). High
solubility in apolar solvents can be ensured by the use of
butoxy substituents. The synthetic strategy tolerates the
Selected spectroscopic data are gathered for all com-
pounds in Table 2. The absorption spectra of most com-
pounds exhibit an intense band between 240 and 320 nm
(e in the range 16,000–44,000 Mꢀ1 cmꢀ1), which can be
assigned to the spin-allowed p–p transitions involving
*
the pyridyl/phenyl/ancillary aryl rings. Such a band is
slightly red-shifted for the fluorene and carbazole cases
8 and 9 because of the presence of additional aryl sub-

S. Diring et al. / Tetrahedron Letters 48 (2007) 8069–8073
8073
Table 2. Selected data for the new ligands
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)
(nm)b
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4
42
13
58
63
33
8
43
12
9
20
21
11
3
323.1 (100)
323.1 (100)
516.1 (80)
289 (22,900)
264 (43,300) 362
433 (2,700) 575
—
5
6
7
552.1 (95)
436 (5,200) 567
8a
8b
9a
9b
10
11
12a
12b
12c
13
425.1 (100)
425.1 (100)
412.1 (100)
412.2 (100)
483.1 (100)
433.1 (100)
683.3 (100)
682.3 (100)c
682.3 (100)c
282.1 (100)
318 (33,000) 412
318 (41,000) 380
319 (20,500) 438
320 (19,000) 405
450 (34,500) 470
349 (40,100) 425
338 (sh, 17,600) 424
328 (sh, 18,500) 424
318 (23,000) 424
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20
a FAB mass spectroscopy, the molecular peak corresponds to [M+H]+
except for 6 and 7 where m/z accounts for [MꢀCl]+.
b Averaged value determined from at least two different solutions of
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`
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Acknowledgements
`
The Ministere de la Recherche et des Nouvelles Tech-
nologies is gratefully acknowledged for financial support
of this work in the form of an Allocation de Recherche
for S.D. We are also indebted to Professor J. Harrow-
field for his critical reading and commenting of the
manuscript.
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