Synthesis of oligo(2-ethynylpyridines): Novel building blocks for supramolecular systems

Article abstract of DOI:10.1016/S0040-4039(02)01542-3

New oligo(2-ethynylpyridines) 1 are synthesized as novel building blocks for the construction of supramolecular systems by the coupling reaction of the novel dibromopyridines 2 with ethynylpyridines 3.

Full text of DOI:10.1016/S0040-4039(02)01542-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6697–6700
Synthesis of oligo(2-ethynylpyridines): novel building blocks for
supramolecular systems
Tomikazu Kawano,* Takahiro Kato, Chong-Xu Du and Ikuo Ueda*
The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Received 1 July 2002; revised 25 July 2002; accepted 26 July 2002
Abstract—New oligo(2-ethynylpyridines) 1 are synthesized as novel building blocks for the construction of supramolecular
systems by the coupling reaction of the novel dibromopyridines 2 with ethynylpyridines 3. © 2002 Elsevier Science Ltd. All rights
reserved.
Oligopyridines have received considerable attention as
versatile building blocks for the construction of
supramolecular systems.1 We recently reported the syn-
theses and complexation studies of 2-ethynylpyridine
ligands.2–4 Continuing our investigations on 2-
ethynylpyridine ligands, we planned to prepare new
oligopyridine systems in which the pyridine rings are
separated from each other by ethynyl spacers. Metal
complexes derived from these new oligopyridines would
be expected to possess potential applications in mate-
rial, molecular and polymer science. Although there
have been many reports on the acetylenic-bridged
oligo(bi- or terpyridines)5 and the simple 2-
ethynylpyridines such as bis(2-pyridyl)acetylenes,6 no
oligo(2-ethynylpyridines) having more than four pyri-
dine rings have been documented in the literature.7 This
may be explained by the lack of a suitable synthetic
route to such higher oligopyridines. Herein, we report
a facile synthesis of new oligo(2-ethynylpyridines) 1
by using dibromopyridine derivatives 28 and
ethynylpyridine derivatives 3, both of which are novel
key intermediates (Fig. 1).
Scheme 1 shows the synthesis of dibromopyridine
derivative 2b. Treatment of 2-bromo-6-(hydroxy-
methyl)pyridine 4,9,10 which was prepared from com-
mercially available 2,6-dibromopyridine 2a, with
methanesulfonyl chloride (MsCl) in tetrahydrofuran
(THF) at −40°C, followed by displacement of the
resulting mesylate with iodide ion in acetone at 60°C
gave the corresponding primary iodide 5 in 93% yield
from 4. Arbuzov reaction of 5 with triethyl phosphite at
Figure 1.
* Corresponding authors. Fax: +81-6-6879-8474; e-mail: kawano@sanken.osaka-u.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01542-3

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T. Kawano et al. / Tetrahedron Letters 43 (2002) 6697–6700
Scheme 1. Preparation of key intermediate 2b. Reagents and conditions: (a) (1) n-BuLi, THF, −78°C, (2) DMF, THF, −78°C, (3)
NaBH4, THF, 0°C; (b) (1) MsCl, Et3N, DMAP, THF, −40°C, (2) NaI, acetone, 60°C; (c) P(OEt)3, 150°C; (d) (1) NaH, THF, rt,
(2) 2-bromo-6-formylpyridine, THF, rt; (e) Br2, CHCl3, rt; (f) tert-BuOK, THF, rt.
150°C gave the phosphonate 6 in quantitative yield.
Subjection of 2-bromo-6-formylpyridine, which was
prepared by oxidation of alcohol 4 with 1-iodoxybenz-
oic acid (IBX)11 in dimethylsulfoxide (DMSO) at room
temperature, to a Horner–Wadsworth–Emmons reac-
tion with the sodium salt of 6 in THF at room temper-
ature afforded exclusively trans-disubstituted ethylene
derivative 7 in 92% yield. Bromination of 7 with
bromine in chloroform at room temperature gave the
tetrabromide 8 in 92% yield. Dehydrobromination of 8
with potassium tert-butoxide at room temperature
yielded the desired product 2b in 90% yield.
The synthesis of oligo(2-ethynylpyridines) 1a–i were
achieved by the cross-coupling reaction of 2 with two
equivalents of 3 in the presence of a catalytic amount of
Pd(PPh3)4 in diethylamine at 90°C (Scheme 3 and Table
1). Isolated yields of compounds 1 decreased with an
increase in the molecular weight of 1, due to their poor
solubility. Especially, compounds 1h and 1i were only
dissolved in higher polar solvents such as DMSO and
DMF. The pure oligo(2-ethynylpyridines) 1a–i were
obtained as colorless crystals or white powders, and
characterized by spectroscopy (NMR, IR, and FAB
mass) and elemental analysis.12 All data were consistent
with the proposed structures. Slight bathochromic shift
with elongation of conjugated systems was observed in
absorption spectra of 1 (umax 321 nm for 1b (x=1), 323
nm for 1d (x=2), 325 nm for 1f (x=3), and 327 nm for
1h (x=4)). Furthermore, compounds 1 were found to
emit fluorescence around 341–346 nm. As a typical
example, excitation of 1a at 297 nm gave fluorescence
around 341 nm. Therefore, the p-conjugated framework
of compounds 1 should function as a novel fluorescent
probe. Furthermore, treatment of a colorless solution
Scheme 2 shows the synthesis of other key intermedi-
ates 3a–e. 2,6-Bis(ethynyl)pyridine, which was also pre-
pared from 2a, was converted into mono TMS–ethynyl
substituted pyridine 9 by treatment with ethylmagne-
sium bromide, followed by mono-silylation with
trimethylsilyl chloride (TMSCl) in THF at room tem-
perature in 64% yield. The cross-coupling reaction of
bromopyridine derivatives 10a,2 10b10 and 10c4 with
(trimethylsilyl)acetylene (TMSA) or compound 9 in the
presence of a catalytic amount of Pd(PPh3)4 in diethyl-
amine at 60°C gave the corresponding TMS-protected
derivatives 11a–e in 83–99% yields. Cleavage of the silyl
group with potassium hydroxide (KOH) in methanol at
0°C afforded the desired products 3a–e in 88, 92, 90,
97, and 95% yields, respectively.
of compound 1h, as
a
typical example, in
dichloromethane with a colorless solution of copper(I)
salts in dichloromethane at room temperature resulted
in the formation of a yellow solution of 1h–copper(I)
complex. The resulting yellow solution returned to a
colorless solution after addition of acetonitrile, indica-
Scheme 2. Preparation of ethynylpyridines 3a–e. Reagents and conditions: (a) (1) TMSA, PdCl2(PPh3)2, CuI, Et2NH, rt, (2) TBAF,
THF, rt; (b) (1) EtMgBr, THF, rt, (2) TMSCl, rt; (c) see Refs. 2, 4 and 10; (d) TMSA or compound 9, Pd(PPh3)4, Et2NH, 60°C;
(e) KOH, MeOH, 0°C.

T. Kawano et al. / Tetrahedron Letters 43 (2002) 6697–6700
6699
Scheme 3.
Table 1. Synthesis of oligo(2-ethynylpyridines) 1a–i
Entry
Cmpd 2a
Cmpd 3
R
Product 1
Yield (%)b
1
2
3
4
5
6
7
8
9
2a
2a
2a
2b
2b
2a
2a
2b
2b
3a (z=0)
3b (z=0)
3c (z=0)
3b
Me
TBDMS
1a (x=1)
1b (x=1)
1c (x=1)
1d (x=2)
1e (x=2)
1f (x=3)
1g (x=3)
1h (x=4)
1i (x=4)
93
95
92
96
86
80
75
71
68
(
L
)-Menthyl
TBDMS
)-Menthyl
TBDMS
)-Menthyl
TBDMS
)-Menthyl
3c
(L
3d (z=1)
3e (z=1)
3d
(
L
3e
(L
a Compound 2a (y=0); compound 2b (y=1).
b Isolated yield.
tive of the exchange of ligand. This finding indicates
that compounds 1 might also function as a copper(I)
scavenger.
References
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1996, 68, 253–260; (d) Constable, E. C. Prog. Inorg.
Chem. 1994, 42, 67–138.
In conclusion, we have synthesized new oligo(2-
ethynylpyridines) 1 from two key intermediates 2 and 3.
Several novel reaction intermediates in this study, such
as compounds 7 and 8, would also function as synthetic
blocks for the construction of oligo(pyridines) as well
as compounds 2 and 3, although the synthetic methods
reported in this study are conventional ones. Therefore,
further modification of the synthetic route by using
these synthetic blocks would lead to the generation of a
variety of functionalized oligo(2-ethynylpyridines). In
addition, our synthetic methods are also of particular
importance in that all compounds in this study were
derived from only one starting material, 2,6-dibromo-
pyridine. Further studies on the elongation of conju-
gated systems are now under investigation.
2. Kawano, T.; Kuwana, J.; Shinomaru, T.; Du, C.-X.;
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Acknowledgements
7. 2,6-Bis(2-pyridylethynyl)pyridine derivatives, which pos-
sess three pyridine rings, are still very rare. See: (a)
Inouye, M.; Chiba, J.; Nakazumi, H. J. Org. Chem. 1999,
We thank the Material Analysis Center of our institute
for assisting with elemental analysis.

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T. Kawano et al. / Tetrahedron Letters 43 (2002) 6697–6700
64, 8170–8176; (b) Inouye, M.; Takahashi, K.;
71.60; H, 6.91; N, 8.35%. Found: C, 71.46; H, 6.72; N,
8.15%. FABMS (NBA) m/z 671 [M+H]+. UV umax (log
m): 323 (4.65), 302 (4.49), 294 (4.53), 275 (4.47) nm.
Fluorescence (ex. 324 nm) 346 nm. Compound 1f: white
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1
powder, mp 258°C (dec.), H NMR (400 MHz, CDCl3) l
8. No synthetic methods for compound 2b have been
reported in the literature to date, although complexation
studies by using 2b have been reported. See: (a)
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7.76–7.70 (m, 5H), 7.63 (d, 3H, J=7.8 Hz), 7.62 (d, 3H,
J=7.8 Hz), 7.55 (d, 2H, J=7.8 Hz), 7.52 (d, 2H, J=7.6
Hz), 4.87 (s, 4H), 0.97 (s, 18H), 0.13 (s, 12H) ppm. IR
(KBr) w 3061, 2931, 2857, 2327, 1578, 1455, 1255, 1114,
850 cm−1. Anal. calcd for C47H49N5O2Si2: C, 73.11; H,
6.40; N, 9.07%. Found: C, 73.38; H, 6.30; N, 9.18%.
FABMS (NBA) m/z 772 [M+H]+. UV umax (log m): 325
(4.66), 300 (4.48), 294 (4.51), 285 (4.49) nm. Fluorescence
(ex. 325 nm) 344 nm. Compound 1h: white powder, mp
335°C (dec.), 1H NMR (400 MHz, DMSO-d6) l 7.77–
7.71 (m, 6H), 7.63 (d, 4H, J=7.6 Hz), 7.62 (d, 4H, J=7.6
Hz), 7.55 (d, 2H, J=7.8 Hz), 7.52 (d, 2H, J=7.8 Hz),
4.87 (s, 4H), 0.97 (s, 18H), 0.13 (s, 12H) ppm. IR (KBr)
w 3062, 2929, 2856, 2322, 1555, 1454, 1254, 1112, 839
cm−1. Anal. calcd for C54H52N6O2Si2: C, 74.28; H, 6.00;
N, 9.62%. Found: C, 74.01; H, 5.81; N, 9.53%. FABMS
(NBA) m/z 873 [M+H]+. UV umax (log m): 327 (4.90), 300
(4.70), 294 (4.71), 290 (4.70) nm. Fluorescence (ex. 326
nm) 344 nm.
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12. Selected physical data are as follows. Compound 1d:
white powder, mp 216°C (dec.), 1H NMR (600 MHz,
CDCl3) l 7.74 (t, 2H, J=7.7 Hz), 7.73 (t, 2H, J=7.3 Hz),
7.62 (d, 4H, J=7.7 Hz), 7.55 (d, 2H, J=8.0 Hz), 7.52 (d,
2H, J=7.7 Hz), 4.87 (s, 4H), 0.97 (s, 18H), 0.13 (s, 12H)
ppm. IR (KBr) w 3054, 2930, 2857, 2327, 1577, 1461,
1254, 1112, 852 cm−1. Anal. calcd for C40H46N4O2Si2: C,