Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Article abstract of DOI:10.1016/j.tetlet.2006.09.051

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl b

Full text of DOI:10.1016/j.tetlet.2006.09.051

Tetrahedron Letters 47 (2006) 8101–8103
Synthesis of novel fluorescent 3-aryl- and
-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki
cross-coupling reactions
3
a,
b
a
*
Bel e´ n Abarca, Ricardo Aucejo, Rafael Ballesteros,
a
b
Fernando Blanco and Enrique Garc ´ı a-Espa n˜ a
a
Departamento de Qu ı´ mica Org a´ nica, Facultad de Farmacia, Avd. Vicente Andr e´ s Estell e´ s s/n, 46100 Burjassot, Valencia, Spain
b
Instituto de Ciencia Molecular (ICMOL), Departamento de Qu ı´ mica Inorg a´ nica, Facultad de Qu ı´ mica, C. Dr. Moliner s/n,
4
6100 Burjassot, Valencia, Spain
Received 10 July 2006; revised 7 September 2006; accepted 12 September 2006
Available online 2 October 2006
Dedicated to Professor Joaquin Plumet on the occasion of his 60th birthday
Abstract—Two series of compounds, 3-aryl- (series A, compounds 2a–j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B,
compounds 3a–j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl
boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of com-
pounds 3f–j, are very high.
Ó 2006 Elsevier Ltd. All rights reserved.
+
2
1. Introduction
A Ni complex of 3-(2-pyridyl)-[1,2,3]triazolo[1,5-a]-
7
pyridine 2h has been used as a fluorescent indicator.
Biaromatic fluorophores have been exploited in several
analytical applications. Heterobiaryls have important
The structural feature of triazolopyridines with
conjugated aromatic substituents on 3- or 7-positions
should be associated with useful fluorescent properties.
This possibility encouraged us to investigate the syn-
thesis and fluorescent properties of two series
of compounds, 3-aryl- (series A, compounds 2) and
1
biological properties and the biaryl unit is represented
in several types of compounds of current interest includ-
ing natural products, polymers, advanced materials,
liquid crystals, luminescent molecular chemosensors,
2
,3
and molecules of medicinal interest. The architecture
of p-conjugated heteroaromatic compounds assumes
significance in view of the applications of these com-
pounds. Recently, we have obtained a sensor of cations
and anions based on the fluorogenic properties of a ter-
heteroaryl system in which the [1,2,3]triazolo[1,5-a]pyri-
R
Ar
CH3
N
N
N
4
N
N
N
dine nucleus is present. Nevertheless the fluorescence
N
N
N
properties of [1,2,3]triazolo[1,5-a]pyridines 1 have been
scarcely studied. A study of fluorescent spectra of some
Ar
3 a Ar = C H
1
a R = H
b R = CH3
2a Ar = C H
6 5
6
5
7
-substituted triazolopyridines showed that only methyl
b Ar =
c Ar =
d Ar =
e Ar =
f Ar =
p-MeOC H
6 4
b Ar =
c Ar =
d Ar =
e Ar =
f Ar =
p
p
m
-MeOC
-MeC
-MeC H4
6 4
H
H
6 4
3
-substituted-[1,2,3]triazolo[1,5-a]pyridine-7-propeno-
p
m
-MeC
-MeC
-MeC H
6
H
4
5
,6
6
H
4
6
ates showed relatively high fluorescence in methanol.
o
o-MeC H4
p-BrC H4
6
6
4
6
p
-BrC H
6
4
g Ar = 3-pyridyl
g Ar = 3-pyridyl
h Ar = 4-pyridyl
h Ar = 2-pyridyl
i Ar = 6-fluor-3-pyridyl
Keywords: Triazolopyridines; Suzuki cross-coupling reaction;
Fluorescence.
i Ar = 6-fluor-3-pyridyl
j Ar = 6-chloro-3-pyridyl j Ar = 6-chloro-3-pyridyl
*
Corresponding author. Tel.: +34 963544933; fax: +34 963544939;
e-mail: Belen.Abarca@uv.es
Figure 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.051

8102
B. Abarca et al. / Tetrahedron Letters 47 (2006) 8101–8103
N
N
N
I
Ar
N
i
ii
+
N
N
N
N
N
N
N
N
N
N
N
1
4
2a-j
6
Scheme 1. Reagents and conditions: (i) I
2
, DMF, KOH; (ii) ArB(OH)
2
, dioxane, Na
2
3 3 4
CO , Pd(PPh ) .
0
27–81%). A secondary compound, 3,3 -bitri-azolopyri-
(
CH3
N
CH
3
CH3
N
1
0,14
dine 6,
was also formed as the consequence of a
i
iii
15
homocoupling Ullman reaction (Scheme 1).
N
N
ii
N
N
N
N
N
The cross-coupling reactions between 3-methyl-7-bro-
mo-[1,2,3]triazolo[1,5-a]pyridine 5 with aryl boronic
acids gave clean reactions in average to very good yields
Br
Ar
1b
5
3a-j
à
Scheme 2. Reagents and conditions: (i) n-BuLi/toulene, ꢀ40 °C; (ii)
DBTCE; (iii) ArB(OH) , dioxane, Na CO , Pd(PPh
(52–96%) to give compounds 3a–g (Scheme 2). The
2
2
3
3 4
) .
analytical and spectroscopic data for all new com-
pounds are in agreement with the proposed structures
(see Supplementary data).
3
-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B,
compounds 3) (Fig. 1).
All compounds studied are highly fluorescent. The fluo-
rescence excitation, emission maxima, and quantum
yields of both series, are recorded in Table 1. As we
can see the conjugation of triazolopyridine with an aryl
or heteroaryl group gives highly fluorescent compounds.
It does not matter if the conjugation is through 3-posi-
tion or through 7-position because no significant differ-
ence in the emission band is noted. In both series, the
presence of one halogen in the 6-position of a 3-pyridyl
group does not have significant effect in the fluorescence
emission band, but these halo derivatives have the great-
est relative fluorescence intensity. The quantum yields
have been calculated taking anthracene dissolved in
2
. Results and discussion
The preparation of heterobiaryls using the Suzuki cou-
pling reaction, in which the aryl moieties are one hetero-
cyclic and one carbocyclic ring or both heterocycles, has
attracted considerable attention, and there are many
2
examples of this type of synthesis. We have used Suzuki
8
methodology, with a triazolopyridine halide and an
aryl or heteroaryl boronic acid in dioxane, sodium
carbonate as base, and tetrakistriphenylphosphine
palladium as catalyst, for the synthesis of all new
compounds in the two series. We obtained compounds
2
b–g,i,j and 3a–g in very good yields (60–90%). 3-Phen-
yl-[1,2,3]triazolo[1,5-a]pyridine 2a and 3-(2-pyridyl)-
1,2,3]triazolo[1,5-a]pyridine 2h had been obtained
General procedure for the preparation of 3-aryl-[1,2,3]triazolo[1,5-a
]
pyridines 2. To a mixture of 3-iodo[1,2,3]triazolo[1,5-a]pyridine 4
[
(1 mmol), the corresponding arylboronic acid (1.2 mmol), and
Pd(PPh3)4 (4–5%) in dioxane (15 mL), was added a solution of
sodium carbonate (2.4 mmol) in water (3 mL). The reaction mixture
was heated at 85 °C with vigorous stirring and the rate of reaction
was followed by TLC. Water was added at room temperature and the
mixture was extracted with dichloromethane. The organic layer was
previously from the corresponding 2-pyridylarylketone
by reaction with hydrazine hydrate and further
9
,10
oxidation with manganese dioxide in chloroform.
-Pyridyltriazolopyridines 3h–j were also previously
7
synthesized, in low yield, also by Suzuki type reactions,
but in this case with pinacol ester of 7-boronictriazolo-
pyridine acid and the corresponding aryl halide.
2 4
dried (Na SO ), filtered, and concentrated under reduced pressure.
The reaction crude was purified by chromatotron using ethyl acetate/
1
1
hexane in increasing amounts as eluent. Triphenylphosphine oxide,
0
3
,3 -bi[1,2,3]triazolo[1,5-a]pyridine 6, and starting material were
As starting triazolopyridines halides we used the new 3-
isolated in some reactions in low proportions.
à
iodo-[1,2,3]triazolo[1,5-a]pyridine 4, synthesized by
General procedure for the preparation of 7-aryl-3-methyl-[1,2,3]tri-
azolo[1,5-a]pyridines 3. To a mixture of 7-bromo-3-methyl-
[1,2,3]triazolo[1,5-a]pyridine 5 (1 mmol), the corresponding aryl-
1
2
Bocchi procedure, with iodine in dimethylformamide
and potassium hydroxide, and 3-methyl-7-bromo-
boronic acid (1.2 mmol), and Pd(PPh
was added a solution of sodium carbonate (2.4 mmol) in water
3 mL). The reaction mixture was heated at 85 °C with vigorous
3 4
) (4–5%) in dioxane (15 mL),
[
1,2,3]triazolo[1,5-a]pyridine 5 that was prepared, as
1
3
described,
from 3-methyltriazolopyridine 1b by
(
regioselective lithiation at position 7 followed by
reaction with dibromotetrachloroethane (DBTCE).
stirring, the rate of reaction was followed by TLC. Water was added
at room temperature and the mixture was extracted with dichloro-
2 4
methane. The organic layer was dried (Na SO ), filtered, and
3
-Iodo-[1,2,3]triazolo[1,5-a]triazolopyridine 4 reacted,
concentrated under reduced pressure. The reaction crude was purified
by chromatotron using ethyl acetate/hexane in increasing amounts as
eluent. Triphenylphosphine oxide was isolated together with
3-methyltriazolopyridine as secondary products in some reactions.
8
under the conditions of the Suzuki reaction, with the
corresponding commercial aryl boronic acid to give
3
-aryltriazolopyridines 2b–g,i,j in medium to good yields

B. Abarca et al. / Tetrahedron Letters 47 (2006) 8101–8103
8103
Table 1. Relative fluorescence intensities and quantum yields of
triazolopyridines
Valenciana, and R.A. thanks Ministerio de Educaci o´ n,
Cultura y Deporte for pre-doctoral fellowships.
Compound
kmax (nm)
Relative fluorescence
U
intensity (2j = 100)
Excitation Emission
Supplementary data
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
360
370
364
361
348
363
357
361
364
365
365
363
372
368
351
377
374
378
351
359
431
448
440
432
431
431
424
412
432
431
436
428
428
437
430
442
438
448
439
439
9.61
43.55
18.53
12.24
7.34
11.89
5.64
6.09
93.88
100
9.35
8.31
13.59
4.01
4.40
3.75
1.21
22.15
22.64
36.09
0.12
0.44
0.29
0.54
0.40
0.38
—
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.09.051.
g
h
i
—
—
References and notes
j
0.10
0.13
0.12
0.25
0.12
0.08
0.62
0.69
0.89
—
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Acknowledgements
Financial support from DGICYT (Projets BQU2003-
1
0
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