Triazolopyridines. Part 24: New polynitrogenated potential helicating ligands

Article abstract of DOI:10.1016/j.tet.2004.05.002

The synthesis of novel 7-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3] triazolo[1,5-a]pyridines 7, 2-pyridyl-[1,2,3]triazolo[1,5-a]pyrid-7-ylmethanols 11, 3-(6-substituted-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridines 12, and 7,7′-disubstituted-3,3′-[1,2,3]triazolo[1,5-a]pyridine 20, interesting polynitrogenated ligands as potential helicating compounds or luminescent sensors, from [1,2,3]triazolo[1,5-a]pyridines is described.

Full text of DOI:10.1016/j.tet.2004.05.002

Tetrahedron 60 (2004) 5785–5792
Triazolopyridines. Part 24: New polynitrogenated potential
helicating ligandsq
*
Belen Abarca, Rafael Ballesteros and Mimoun Chadlaoui
´
´ ´ ´ ´
Departamento de Quımica Organica, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andres Estelles s/n,
46100 Burjassot (Valencia), Spain
Received 19 January 2004; revised 14 April 2004; accepted 3 May 2004
Abstract—The synthesis of novel 7-{[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3]triazolo[1,5-a]pyr0idines 7, 2-pyridyl-[1,2,3]triazolo[1,5-a]-
pyrid-7-ylmethanols 11, 3-(6-substituted-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridines 12, and 7,7 -disubstituted-3,30-[1,2,3]triazolo[1,5-a]-
pyridine 20, interesting polynitrogenated ligands as potential helicating compounds or luminescent sensors, from [1,2,3]triazolo[1,5-a]-
pyridines is described.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
potential helicating ligands 3c, 4, 5a-c, and 6a-c from
triazolopyridines 1a-c,5 (obtained by reaction of the
corresponding acylpyridine with N2H4 and then oxi-
dation with MnO2), by regioselective lithiation at 240 8C,
subsequent reaction with electrophiles and then triazolo ring
opening with loss of dinitrogen,6,7 (route a, Scheme 1) or
by lithiation at 270 8C, giving 7,70-bitriazolopyridines
and then opening of the triazolo ring to produce
2,20-bipyridines,8 (route b, Scheme 1). Following this
study we have designed new ligands 7-10, which can be
The synthetic chemical mimicry of the double-helix
structural motif is an interesting area of research with
intense activity in recent years.2 The formation of helicates,
term introduced by Lehn and co-workers in 1987 for the
description of a polymetallic helical double-stranded
complex,3 has become an important synthetic tool. Oligo-
pyridines and related compounds are very useful helicating
ligands.2,4 We have recently discovered a facile route to new
Scheme 1. (i) N2H4; (ii) MnO2, CL2CH2; (iii) LDA, THF, 240 8C; (iv) 2-PyCHO/air; (v) SeO2; (vi) LDA, THF, 270 8C; (vii) SeO2.
q See Ref. 1.
Keywords: Nitrogenated heterocycles; Helicating ligands; Lithiation; Luminescent sensors.
*
Corresponding author. Tel. þ34963544933; fax: þ34963544939; e-mail address: belen.abarca@uv.es
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.05.002

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B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
Scheme 2. (i) N2H4; (ii) MnO2,Cl2CH2; (iii) LDA, 240 8C; (iv) 2-Py-CHO/air; (v) SeO2.
easily accessible from compounds 3 if the methodology
summarised above in route a is applicable (see Scheme
2). The understanding that the availability of 3 is
important to success, led us to attempt to improve the
reported yield.9 We wish to report here our new results in
this project, that allow us to synthesize the novel
polynitrogenated ligands 7b,d, 7c0, 11b,d, 11c0, 12-14,
16, 18-20, liable to make helicates as versatile supra-
molecular complexes.10 These compounds have other
potential fields of applications based on its rich photo-
physical and photo-chemical properties,11 or as lumi-
nescent molecular sensors.12
Scheme 3.
Table 1. 1H NMR data for compounds 3a-d
H4
H5
H6
H7
H30
H40
H50
H60
Others
3a 7.84, dd,
7.29, dd,
J1¼8.85 Hz,
7.37, dd,
J1¼6.78 Hz,
—
—
8.15, ddd,
7.88, ddd,
J1¼J2¼7.71 Hz,
7.43, ddd,
8.44, ddd,
8.37, s, H3
J1¼8.85 Hz,
J1¼7.71 Hz,
J2¼1.10 Hz,
J3¼0.93 Hz
8.15, ddd,
J1¼7.71 Hz,
J2¼1.10 Hz,
J3¼0.93 Hz
8.01, ddd,
J1¼7.71 Hz,
J2¼4.71 Hz,
J3¼1.10 Hz
7.43, ddd,
J1¼7.71 Hz,
J2¼4.71 Hz,
J3¼1.10 Hz
7.47, ddd,
J1¼7.3 Hz,
J2¼4.8 Hz,
J3¼1.3 Hz
J1¼4.71 Hz,
J2¼1.68 Hz,
J3¼0.93 Hz
8.45, ddd,
J1¼4.71 Hz,
J2¼1.68 Hz,
J3¼0.93 Hz
8.73, ddd,
J1¼4.8 Hz,
J2¼1.6 Hz,
J3¼0.9 Hz
J2¼1.50 Hz
J2¼6.78 Hz
J2¼1.50 Hz
J3¼1.68 Hz
3b 7.73, dd,
7.23, dd,
J1¼8.85 Hz,
7.34, dd,
J1¼6.78 Hz,
7.88, ddd,
J1¼J2¼7.71 Hz,
2.57, s, CH3
J1¼8.85 Hz,
J2¼1.50 Hz
J2¼6.78 Hz
J2¼1.50 Hz
J3¼1.68 Hz
3c 8.01, ddd,
J1¼9.0 Hz,
J2¼1.1 Hz,
J3¼0.9 Hz
7.10, ddd,
J1¼6.0 Hz,
J2¼9.0 Hz,
J3¼0.9 Hz
6.95, ddd,
J1¼6.9 Hz,
J2¼6.0 Hz,
J3¼1.1 Hz
8.65, ddd,
J1¼6.9 Hz,
7.85, ddd,
J1¼7.3 Hz,
J2¼7.5 Hz,
J3¼1.6 Hz
8.40, dd,
J1¼7.6 Hz,
J1¼7.5 Hz,
J2¼J3¼0.9 Hz J2¼1.3 Hz,
J3¼0.9 Hz
J2¼1.3 Hz,
H300, 7.92, dd,
J1¼7.6 Hz,
J2¼7.7 Hz,
H400, 7.98, dd,
J1¼7.7 Hz,
J2¼1.3 Hz, H500
8.11–8.08, m,
1H, (Hp),
3d 7.90–7.87,
m, 3Hp
7.37–7.35,
m, 3Hp p
7.90–7.87,
m, 3Hp
—
8.17, ddd,
J¼7.92 Hz
7.90–7.87,
m, 3Hp
7.44–7.41,
m, 3Hp p
8.46, d,
J¼4.71 Hz
p
7.44–7.41, m,
3H, (2Hpo p p ),
7.37–7.35, m,
3H, (2Hpmp
)
p , p p , p p p Assigned by COSY experiments.

B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
5787
2. Results and discussion
dd, J1¼7.6 Hz, J2¼7.7 Hz, H400), 7.98 (1H, dd, J1¼7.7 Hz,
J2¼1.3 Hz, H500) for a 2,6-disubstituted pyridine are more in
agreement with structure 3c0. To account for this structure
we assume that, in solution, the first formed 3c is in
equilibrium with the diazo form A, this intermediate may
undergo a new ring-chain isomerization,13,14 giving 3c0
(Scheme 4). A X-ray study of this compound is in progress.
We had reported that reaction of triazolopyridine 1c in THF
solution at 240 8C with LDA gave the 7-lithio derivative 2c
which reacted with 2-pyridine carbaldehyde to form an
unstable diarylmethyl alkoxide intermediate, which pro-
vides rapid access to ketone 3c by spontaneous air oxidation
in work-up, with 35% yield.5 Since we had found later that
lithiation reactions of triazolopyridines 1 give better results
using toluene as solvent and n-BuLi as lithiating agent, we
thought that under these conditions, and with 2-cyano-
pyridine as co-reagent, we would be able to improve the
yield of 3c. However the new reaction gave, as only
characterised product, the compound 3c in almost the same
yield. This type of reaction was also performed with
compounds 1a,b. In the conditions above indicated, the
7-lithio derivatives 2a,b were formed. Subsequent reactions
with 2-cyanopyridine gave the corresponding 7-pyridyl-
carbonyl derivatives 3a,b in low yields.9 We have now
improved the results using as co-reagent ethyl picolinate,
and compounds 3a-d are obtained in 78, 75, 90 and 78%
yield, respectively (Scheme 3).
To obtain compounds 7 from 3 we tried the general
procedure for the synthesis of triazolopyridines, reaction of
an acylpyridine with N2H4·H2O, and without isolation of the
corresponding hydrazone, oxidation with MnO2.15 When 3b
was the starting material compound 7b (20%) was obtained
together with a surprising alcohol 11b (20%), and 3b (25%)
(Scheme 5). From 3c the only identified compound was an
alcohol, in the isomeric form 11c0, and compound 3d gave
also an alcohol in the form 11d (Fig. 1).
1
After a carefully study of the 300 MHz H NMR data of
these compounds, compiled in Table 1, we realized that the
d and J values for the compound obtained in the reaction
from 1c don’t fit properly with the structure 3c that we
proposed.5,9 If we look the d and J values for protons in
acylpyridine (H30, H40, H50, H60) and triazolopyridine (H4,
H5, H6) part of the compounds 3a,b,d, there are the
expected similarity in all of them, nevertheless for the
so-called 3c there are protons corresponding to an
acylpyridyl group, but there are interesting features in the
rest of data. Signals at d 8.65 (1H, ddd, J1¼6.9 Hz,
J2¼J3¼0.9 Hz, H7), 6.95 (1H, ddd, J1¼6.9 Hz, J2¼
6.0 Hz, J3¼1.1 Hz, H6), 7.10 (1H, ddd, J1¼9.0 Hz, J2¼
6.0 Hz, J3¼0.9 Hz, H5), 8.01 (1H, ddd, J1¼9.0 Hz, J2¼
0.9 Hz, J3¼1.1 Hz, H4) for a 3-substituted triazolopyridine
and 8.40 (1H, dd, J1¼7.6 Hz, J2¼1.3 Hz, H300), 7.92 (1H,
Figure 1.
The formation of alcohols 11 is not easy to explain on
treatment with an oxidizer. To check when they are formed
we analysed the crude of the reaction with hydrazine,
alcohols 11 are the only isolated compounds almost in
quantitative yield. To account for its formation we believe
that the hydrazones are formed and transformed to the diazo
compounds by oxidation due to molecular oxygen,16 that
before to lie the equilibrium to triazolopyridines, loose
nitrogen to form a carbene,17 that is trapped by water to
Scheme 4.
Scheme 5.

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B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
Scheme 6.
form the alcohols.18 We tried to avoid oxidation of the
hydrazone to the diazo compound carrying out the reaction
with 3b under a nitrogen atmosphere but, a new reaction
occurs giving two major products, triazolopyridine 1b and
an acylpyridine derivative.
NMR data suggest a very symmetric structure with two
3-substituted triazolopyridines and a 2,6-disubstituted
pyridine. We propose the structure 7c0 for it (Fig. 1). That
structure is resembling to terpyridines and the quelating
properties could be similar.4 Finally compound 3d gave a
mixture of 7d (2%), 11d (45%), 1d (15%) and 16 (38%)
(Scheme 6). Interesting the formation of 16, we have
verified that it is formed from 11d in basic medium. A
research is in progress to elucidate the mechanism and the
scope of this transformation.
When TsNHNH2 was used as co-reagent and the reaction
work-up with aqueous sodium hydroxide,19 compounds
7b-d were finally synthesized in low or excellent yields,
different secondary compounds were formed depending of
the starting material. From 3a in ethanol as solvent, an
intractable mixture was formed from which could only be
identified compound 12. From 3b in methanol as solvent,
compounds 7b (15%), 13 (15%), and 14 (15%) were
isolated and identified (Scheme 6).
The structures proposed for 3c0 and 7c0 make us to turn to the
structure of 5c,5 studying a more sensitive 1H NMR
spectrum we realised that the data fit better whit two
3-substituted triazolopyridines and one 6,60-disubstituted-
2,20-bipyridine as in structure 5c0 (Scheme 8).
The formation of 12, 13, and 14 from the corresponding 7a,
or 7b may be explained by the equilibrium between
bitriazolopyrines 7a,b and triazolopyridylpyridyl-diazo-
alkanes 15a,b that could loose nitrogen to form a carbene
trapped by solvents (ethanol, methanol, water) (Scheme 7).
From 1,2-di(2-pyridyl)-1,2-ethanodione 17 by reaction
Best result was found with 3c0, an unique product was
formed in very good yield (96%). This compound shows a
molecular ion of 313.1039 corresponding to a molecular
1
formula of C17H11N7. A carefully study of its H and 13C
Scheme 8.
Scheme 7.

B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
5789
Scheme 9.
with TsNHNH2 in basic medium we have synthesized
3,30-bitriazolopyridine 18. A secondary product was formed
in this reaction that was identified as 19. We have studied
the behaviour of 18 with lithiating agents. Compound 18 is
insoluble in toluene, we used THF as solve0nt and n-BuLi as
co-reagent, after quenching with D2O a 7,7 -dideuterio-3,30-
bitriazolopyridine was formed indicating the previous
formation of a dilithium derivative. This intermediate is
trapped by electrophiles. Reaction with two moles of ethyl
picolinate gave 20 in 66% yield (Scheme 9). We have tried
the0 lithiation of compound 7c0 in the same conditions, the
7,7 -dideuterio derivative have been identified after treat-
ment of the dilithium derivative with D2O, nevertheless
reaction of dilithium compound with ethyl picolinate gave
only polymeric compounds.
3.1. General procedure for lithiation of [1,2,3]triazolo-
[1,5-a]pyridines 1a-d and reaction with ethyl picolinate
To a solution of the corresponding [1,2,3]triazolo[1,5-a]-
pyridine 1 in anhydrous toluene at 240 8C, a solution of
n-butyllithium in hexane (2.5 M) (20% excess) was added
with stirring. A deep red colour developed. The mixture was
kept at 240 8C (4 h). Treatment with a dry toluene solution
(10 mL) of ethyl picolinate (20% excess) produced a colour
change to yellow. The mixture was left at 240 8C (2 h) and
allowed at room temperature overnight, then was treated
with a saturated solution of ammonium chloride. The
organic layer was separated and the aqueous layer extracted
with dichloromethane. After dried over anhydrous Na2SO4
and evaporation of the organic solvents, a residue was
obtained. Precipitation with ethyl acetate gave com-
pounds 3a-d as brown or yellow solids. In same cases
the filtrate was evaporated to dryness and the residue
purified by chromatotron with ethyl acetate/hexane as
eluent, to obtain additional amount of compound 3. The
yield and conditions of purification are given for each
compound.
All new synthesized compounds have interesting ligand
structures and should be able to form polynuclear
complexes with different metal ions. We have studied the
coordinating behaviour of 1b with Cu(II),20 and the spin
crossover behaviour of some complex formed with 1c
and Fe(II).21 We are at the present investigating the
luminescence properties of 5c0 and 7c0 and their use as
chemosensors.
3.1.1. 2-Pyridyl-[1,2,3]triazolo[1,5-a]pyrid-7-ylmetha-
none 3a. Compound 1a (1 g, 8.4 mmol), toluene (40 mL),
n-BuLi (4 mL), ethyl picolinate (1.5 mL), (78%). Purifi-
cation by recrystallization from ethyl acetate. Mp 158–
160 8C. Lit.9 158–160 8C.
3. Experimental
Melting points were determined on a Kofler heated stage
and are uncorrected. NMR spectra were recorded on a
Bruker AC 300 MHz in CDCl3 as solvent. COSY
experiments were done for all compounds. HRMS (EI)
determinations were made using a VG Autospec Trio 1000
(Fisons). Infrared spectra were recorded in KBr discs on a
Bio-Rad FTS-7. Ultraviolet spectra were recorded on a
Shimazu UV-2101 instrument. All the lithiation reactions
were done under inert atmosphere and dry solvents.22
3.1.2. 2-Pyridyl-3-methyl-[1,2,3]triazolo[1,5-a]pyrid-7-yl-
methanone 3b. Compound 1b (0.5 g, 3.75 mmol), toluene
(20 mL), n-BuLi (1.9 mL), ethyl picolinate (0.7 mL),
(75%). Purification by recrystallization from ethyl acetate.
Mp 165–167 8C. Lit.9 165–167 8C.
3.1.3. 2-Pyridyl-6-[1,2,3]triazolo[1,5-a]pyrid-3-yl-2-pyri-
dylmethanone 3c0. Compound 1c (0.5 g, 2.5 mmol),
toluene (20 mL), n-BuLi (1.6 mL), ethyl picolinate
(0.4 mL), (90%). Purification by recrystallization from
ethyl acetate/hexane give two crystalline phases. At 194–
195 8C there is a phase transition forming needles that melt
at 220–221 8C.9 Lit.5 194–195 8C.
[1,2,3]Triazolo[1,5-a]pyridine 1a, 3-methyl-[1,2,3]tri-
azolo[1,5-a]pyridine 1b, 3-(2-pyridyl)-[1,2,3]triazolo[1,5-a]-
pyridine 1c, and 3-phenyl-[1,2,3]triazolo[1,5-a]pyridine 1d.
Prepared as described elsewhere.13,19,23

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B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
3.1.4. 2-Pyridyl-3-phenyl-[1,2,3]triazolo[1,5-a]pyrid-7-
ylmethanone 3d. Compound 1d (1 g, 5.13 mmol), toluene
(40 mL), n-BuLi (4 mL), ethyl picolinate (1.5 mL), (78%).
Purification by recrystallization from ethyl acetate/hexane.
Mp 169–171 8C. HRMS found for Mþ 300.0993;
C18H12N4O requires 300.1011. nmax (KBr) (cm21) 1689
(CO), 1584, 1313, 1293, 1063, 758, 693. lmax (nm) (log 1)
(EtOH) 293.5 (4.04), 381.5 (3.58). 13C NMR d 188.40 (CO),
153.08 (C), 149.25 (CH), 138.09 (C), 137.36 (CH), 135.12
(C), 131.15 (C), 130.74 (C), 129.03 (2CH), 128.10 (CH),
127.72 (CH), 126.90 (2CH), 125.00 (CH), 123.75 (CH),
121.10 (CH), 118.15 (CH). MS m/z (%) 300 (6), 272 (100),
271 (59), 243 (41), 194 (25), 166 (41), 78 (49).
procedure B from 3b (10 mg, 0.042 mmol), solvent
n-BuOH, refluxed 30 min, almost pure in quantitative yield.
3.2.3. 2-Pyridyl-6-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-2-
pyridylmethanol 11c0. The title compound was obtained
by procedure B from 3c0 (10 mg, 0.039 mmol), solvent
n-BuOH, refluxed 30 m, almost pure in quantitative yield.
Mp 124–126 8C (cyclohexane). HRMS found for Mþ
303.1122; C17H13N5O requires 303.1120. nmax (KBr)
(cm21) 3324, 3182, 1590, 1055, 745. lmax (nm) (log 1)
(EtOH) 207 (4.36), 268 (4.20), 326 (4.14). 1H NMR d 8.70
(d, J¼6.99 Hz, 1H, H7), 8.53 (m,0 2H, H4, H600), 8.19 (dd,
J1¼7.92 Hz, J2¼0.96 Hz, 1H, H5 ), 7.73 (dd, J1¼7.92 Hz,
J2¼7.71 Hz, 1H, H40), 7.63 (ddd, J1¼7.71 Hz, J2¼7.92 Hz,
J3¼1.5 Hz, 1H, H400), 7.49 (d, J¼7.92 Hz, 1H, H300), 7.41 (d,
J¼7.71 Hz, 1H, H30), 7.33 (ddd, J1¼6.78 Hz, J2¼9.06 Hz,
J3¼0.96 Hz, 1H, H5), 7.19 (ddd, J1¼7.71 Hz, J2¼5.1 Hz,
J3¼1.14 Hz, 1H, H500), 7.00 (ddd, J1¼6.99 Hz, J2¼6.78 Hz,
J3¼1.32 Hz, 1H, H6), 5.98 (s, 1H, CH–OH), 2.1 (brs, 1H,
OH). 13C NMR d 160.72 (C), 151.19 (C), 147.91 (CH),
138.18 (CH), 137.99 (CH), 137.50 (C), 132.36 (C), 126.96
(CH), 125.78 (CH), 123.31 (CH), 123.32 (C), 122.11 (CH),
121.36 (CH), 119.93 (CH), 119.89 (CH), 116.25 (CH),
75.63 (CH–OH).
3.2. General procedure for reaction of 2-pyridyl-
[1,2,3]triazolo[1,5-a]pyrid-7-yl methanones 3b-d with
hydrazine hydrate
Procedure A. A solution of the corresponding 2-pyridyl-
[1,2,3]triazolo[1,5-a]pyrid-7-ylmethanone in ethanol was
added to an excess of hydrazine hydrate, and was heated
under reflux. Then water (10 mL) was added and extracted
with dichroromethane (3£10 mL). The organic layer was
dried and evaporated, the residue was dissolved in chloro-
form (5 mL). Manganese oxide (50% excess) was added and
the mixture heated to reflux, then was filtered and the
solvent was evaporated. The residue was purified by
chromatotron using hexane/ethyl acetate as eluent.
3.2.4. 2-Pyridyl-3-phenyl-[1,2,3]triazolo[1,5-a]pyrid-7-
ylmethanol 11d. The title compound was obtained by
procedure B from 3d (50 mg, 0.19 mmol), solvent ethanol,
refluxed 2 h, in 53% yield. Mp 157–158 8C (hexane).
HRMS found for Mþ 302.1163; C18H14N4O requires
302.1167. nmax (KBr) (cm21) 3201, 1591, 1549, 1477,
1451, 1263, 1223, 1182, 1080, 995, 790, 705. lmax (nm) (log
Procedure B. A solution of the corresponding 2-pyridyl-
[1,2,3]triazolo[1,5-a]pyridin-7-ylmethanone in a organic
solvent was added to an excess of hydrazine hydrate,
and was heated under reflux. Then water (10 mL) was added
and extracted with dichroromethane (3£10 mL). The
organic layer was dried and evaporated. The residue was
purified by chromatotron using hexane/ethyl acetate as
eluent.
1
1) (EtOH) 301.5 (4.01), 322 (3.93). H NMR d 8.46 (0d,
J¼4.71 Hz, 1H, H60), 7.81–7.88 (m, 4H, 2Ho, H4, H30),
7.58 (ddd, J1¼7.92 Hz, J2¼7.53 Hz, J3¼1.71 Hz, 1H, H4 ),
7.38–7.44 (m, 2H, Hm), 7.31 (ddd, J1¼7.32 Hz, J2¼J3¼
1.32 Hz, 1H, Hp), 7.24 (dd, J1¼J2¼8.85 Hz, 1H, H5),
7.15 (ddd, J1¼7.53 Hz, J2¼4.71 Hz, J3¼0.93 Hz, 1H, H5),
7.10 (d, J¼6.78 Hz, 1H, H6), 6.68 (brs, 1H, CH), 5.75
(brs, 1H, OH). 13C NMR d 157.31 (C), 148.42 (CH), 140.15
(C), 138.12 (C), 137.18 (CH), 131.31 (C), 130.93 (C),
128.95 (2CH), 127.88 (CH), 126.63 (2CH), 126.10 (CH),
123.46 (CH), 122.16 (CH), 117.08 (CH), 112.84 (CH),
70.01 (CH). MS m/z (%) 302 (8), 274 (48), 257 (100), 168
(37), 78 (19).
3.2.1. 3-Methyl-7-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-
[1,2,3]triazolo[1,5-a]pyridine 7b. The title compound
was obtained by procedure
A from 3b (100 mg,
0.42 mmol), refluxed 24 h and after addition of the oxidant
an additional time (1 h 30 m) was refluxed, 7b was the first
eluted product (20%). Mp 218–220 8C (AcOEt). HRMS
found Mþ 250.0971; C13H10N6 requires 250.0966. nmax
(KBr) (cm21) 3110, 1643, 1627, 1536, 1407, 1218, 1162,
780, 740. lmax (nm) (log 1) (Cl2CH2) 229 (4.08), 2830(4.08),
349.5 (3.96). 1H NMR d 8.74 (d, J¼6.96 Hz, 1H, H7 ), 8.41
(d, J¼9.24 Hz, 1H, H4), 7.68 (dd, J1¼6.75 Hz, J2¼1.14 Hz,
1H, H6), 7.62 (dd, J1¼8.67 Hz, J2¼1.14 Hz, 1H, H40), 7.31
(m, 2H, H5, H50), 7.04 (ddd, J1¼6.96 Hz, J2¼6.78 Hz,
J¼1.14 Hz, 1H, H60), 2.63 (s, 3H, CH3). 13C NMR d 134.87
(C), 132.49 (C), 130.39 (C), 130.34 (C), 130.24 (C), 126.10
(CH), 125.35 (CH), 124.29 (CH), 122.49 (CH), 116.26
(CH), 115.92 (CH), 115.67 (CH), 10.51 (CH3). MS m/z (%)
250 (29), 222 (12), 194 (33), 193 (100), 192 (31), 179 (16),
166 (12). Then starting material 3b (25%) was eluted,
further elution gave 2-pyridyl-3-methyl-[1,2,3]-triazolo-
[1,5-a]pyrid-7-ylmethanol 11b (20%). Mp 113–115 8C.
Lit.24 113–115 8C (CH2Cl2/hexane).
3.3. General procedure for reaction of 2-pyridyl-[1,2,3]-
triazolo[1,5-a]pyrid-7-yl methanones 3a-d with
tosylhydrazine
A solution of the corresponding 2-pyridyl-[1,2,3]triazolo-
[1,5-a]pyrid-7-ylmethanone in suitable alcohol was added
to an equimolar solution of tosylhydrazine in ethanol, the
mixture was boiled under reflux for 5 h, and then was treated
with aqueous sodium hydroxide and refluxed for an
additional time (1 h). The mixture was concentrated under
reduced pressure to 10–15 mL and, in some cases, after
cooling a precipitate was formed that was filtered and
identified. The filtrate was extracted with an organic solvent
(3£10 mL). The organic layer was dried (Na2SO4),
evaporated, and the crude purified by chromatotron eluting
with ethyl acetate/hexane. The yield and conditions of
purification are given for each compound.
3.2.2. 2-Pyridyl-3-methyl-[1,2,3]triazolo[1,5-a]pyrid-7-
ylmethanol 11b. The title compound was obtained by

B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
5791
3.3.1. 3-[6-(1-Ethoxyethyl)-2-pyridyl]-[1,2,3]triazolo-
[1,5-a]pyridine 12. Compound 3a (0.1 g, 0.45 mmol),
tosylhydrazine (0.11 g, 0.6 mmol), ethanol (50 mL),
NaOH (3 mL, 2 N). No precipitate was formed, and the
solution was extracted with dichloromethane. The only
isolated compound as an oil was identified as 3-[6-(1-
filtrate was extracting with dichloromethane (50 mL).
The organic layer was dried (Na2SO4) and evaporated
giving a crude, that was treated with ethanol (10 mL) and
compound 7c0 was precipitated (10 mg) (total yield 96%).
Mp 279–281 8C (EtOH/H2O). HRMS found for Mþ
313.1039; C17H11N7 requires 313.1075. nmax (KBr)
(cm21) 3087, 1631, 1595, 1570, 1529, 1448, 1402, 1162,
821, 740. lmax (nm) (log 1) (EtOH) 294 (5.56), 336.5 (5.53).
1H NMR d 8.74 (ddd, J1¼6.99 Hz, J2¼J3¼0.93 Hz, 2H, H7,
H70), 8.54 (ddd, J1¼8.85 Hz, J2¼J3¼1.32 Hz, 2H, H4, H40),
8.1090 (d, J¼7.71 Hz, 1H, H400), 7.88 (t, J¼7.71 Hz, 2H, H300,
H5 ), 7.30 (ddd, J1¼8.85 Hz, J2¼6.78 Hz, J3¼0.93 Hz, 2H,
H5, H50), 7.01 (ddd, J1¼6.99 Hz, J2¼6.78 Hz, J3¼1.32 Hz,
2H, H6, H60). 13C NMR d 151.39 (2C), 137.90 (2C), 137.58
(CH), 131.89 (2C), 126.34 (2CH), 125.59 (2CH), 120.49
(2CH), 119.62 (2CH), 115.77 (2CH). MS m/z (%), 313 (32),
285 (10), 257 (95), 256 (100), 229 (23), 179 (78), 78(13).
ethoxiethyl)-2-pyridyl]-[1,2,3]triazolo[1,5-a]pyridine
12
(26 mg, 23%). HRMS found for Mþ 254.1127;
C14H14N4O requires 254.1167. 1H NMR d 8.67 (d, J¼
6.59 Hz, 1H, H7), 80.65 (d, J¼8.29 Hz, 1H, H4), 8.16 (d,
J1¼7.91 Hz, 1H, H5 ), 7.73 (dd, J1¼7.91 Hz, J2¼7.70 Hz,
1H, 4H0), 7.32–7.27 (m, 2H, H5, H30), 6.96 (ddd,
J1¼6.97 Hz, J2¼6.59 Hz, J3¼1.32 Hz, 1H, H6), 4.65(s,
2H, CH2), 3.60 (c, J¼6.97 Hz, 2H, CH2), 1.35 (t,
J¼6.97 Hz, 3H, CH3). 13C NMR d 158.42 (C), 151.25
(C), 137.28(CH),136.57(C),132.00(C),126.23(CH),125.20
(CH), 120.53 (CH), 119.44 (CH), 118.92 (CH), 115.83 (CH),
73.82 (CH2), 66.44 (CH3), 15.32 (CH3). MS m/z (%) 254 (22),
226 (39), 181 (100), 169 (16), 142 (10), 78 (11).
3.3.4. 3-Phenyl-7-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-
[1,2,3]triazolo[1,5-a]pyridine 7d. Compound 3d (0.2 g,
0.66 mmol), tosylhydrazine (0.36 g, 1.98 mmol), ethanol
(110 mL), NaOH (6 mL, 2 N). A yellow solid was filtrated,
identified as compound 7d (4 mg, 2%) almost pure. Mp
218–220 8C (EtOH/H2O). HRMS found for Mþ 312.1077;
3.3.2. 3-Methyl-7-{[1,2,3]triazolo[1,5-a]pyrid-3-yl}-
[1,2,3]triazolo[1,5-a]pyridine 7b. Compound 3b (0.1 g,
0.44 mmol), tosylhydrazine (0.08 g, 0.42 mmol), methanol
(10 mL), NaOH (7 mL, 2 N). The precipitate was 3-methyl-
{7-[1,2,3]triazolo[1,5-a]pyridin-3-yl}-[1,2,3]triazolo[1,5-a]-
pyridine 7b almost pure (15 mg, 14%). The filtrate was
extracting with ether (3£10 mL). The organic layer was
dried (Na2SO4), evaporated, and the crude (66 mg) purified
by chromatotron eluting with ethyl acetate/hexane. First
was eluted 3-[6-(1-methoxyethyl)-2-pyridyl]-[1,2,3]tri-
azolo[1,5-a]pyridine 13 (15 mg, 15%) as an oil. HRMS
found for Mþ 254.1130; C14H14N4O requires 254.1167. 1H
NMR d 8.68 (m, 2H, H4, H7), 8.17 (dd, J1¼7.92 Hz,
J2¼0.96 Hz, 1H, H50), 7.74 (dd, J1¼7.92 Hz, J2¼7.74 Hz,
1H, H40), 7.30 (ddd, J1¼8.85 Hz, J2¼6.88 Hz, J3¼1.14 Hz,
1H, H5), 7.26 (dd, J1¼7.74 Hz, J2¼0.96 Hz, 1H, H30), 6.97
(ddd, J1¼6.96 Hz, J2¼6.88 Hz, J3¼1.14 Hz, 1H, H6), 4.46
(c, J¼6.57 Hz, 1H, CH), 3.31 (s, OCH3) 2.50 (d, J¼6.57 Hz,
3H, CH3). 13C NMR d 162.44 (C), 151.28 (C), 137.40 (CH),
136.56 (C), 132.08 (C), 126.28 (CH), 125.20 (CH), 121.51
(CH), 118.94 (CH), 118.18 (CH), 115.83 (CH), 80.85 (CH),
56.96 (OCH2), 22.18 (CH3). MS m/z (%) 254 (24), 226 (50),
211 (45), 195 (100), 181 (37), 169 (14), 168 (37), 78 (19).
The second fraction was an oil identified as 3-[6-(1-
hydroxyethyl)-2-pyridyl]-[1,2,3]triazolo[1,5-a]pyridine 14
(16 mg, 15%). HRMS found Mþ 240.1022; C13H12N4O
requires 240.1011. 1H NMR d 8.71 (d, J¼7.17 Hz, 1H, H7),
8.52 (d, J¼9.03 Hz, 1H, H4), 8.21 (d, J¼7.74 Hz, 1H, H50),
7.76 (dd, J1¼J2¼7.74 Hz, 1H, H40), 7.34 (ddd, J1¼9.03 Hz,
J2¼6.96 Hz, J3¼0.96 Hz, 1H, H5), 7.17 (d, J¼7.74 Hz, 1H,
H30), 7.01 (ddd, J1¼6.96 Hz, J2¼7.17 Hz, J3¼1.14 Hz, 1H,
H6), 4.94 (c, J¼6.42 Hz, 1H, CH), 3.60 (brs, 1OH), 1.54 (d,
J¼6.42 Hz, 3H, CH3). 13C NMR d 162.58 (C), 150.59 (C),
137.68 (CH), 137.07 (C), 131.87 (C), 126.66 (CH), 125.43
(CH), 120.74 (CH), 119.23 (CH), 118.17 (CH), 115.89
(CH), 69.22 (CH), 24.34 (CH3). MS m/z (%) 240 (46), 212
(73), 197 (100), 169 (89), 78 (20).
1
C18H12N6 requires 312.1123. H NMR d 8.77 (ddd, J1¼
6.96 Hz, J2¼1.14 Hz, J3¼0.93 Hz, 1H, H70), 8.48 (ddd,
J1¼9.21 Hz, J2¼1.14 Hz, J3¼0.93 Hz, 1H, H40), 8.02 (dd,
J1¼8.85 Hz, J2¼1.14 Hz, 1H, H4), 7.97–794 (m, 2H, Ho),
7.78 (dd, J1¼6.96 Hz, J2¼1.14 Hz, 1H, H6), 7.54–7.41 (m,
3H, H5, 2Hm), 7.39–7.33 (m, 2H, H50, Hp) 7.07 (ddd,
J1¼6.96 Hz, J2¼6.78 Hz, J3¼1.14 Hz, 1H, H60). MS
m/z(%) 312 (8), 284 (9), 256 (58), 255 (100), 230 (8), 152
(5), 78 (6). First fraction eluted from chromatotron was
3-phenyl-[1,2,3]triazolo[1,5-a]pyridine 1d (19 mg, 15%).
The second fraction was a yellow solid identified as
3-phenyl-6,7-dihydro[1,2,3]triazolo[1,5-a]pyridine 16 (50
mg, 38%). Mp 100–102 8C (hexane). HRMS found for Mþ
1
197.0870; C12H11N3 requires 197.0953. H NMR d 7.75
(dd, J1¼7.14 Hz, J2¼1.5 Hz, 2H, Ho), 7.45 (dd,
J1¼J2¼7.14 Hz, 2H, Hm), 7.36 (dd, J1¼7.14 Hz, J2¼
1.5 Hz, 1H, Hp), 6.78 (ddd, J1¼9.99 Hz, J2¼J3¼1.89 Hz,
1H, H4), 6.19 (ddd, J1¼9.99 Hz, J2¼J3¼4.35 Hz, 1H, H5),
4.45 (t, J¼7.74 Hz, 2H, H7, H70), 2.67 (m, 2H, H6, H60). 13
C
NMR d 142.06 (C), 131.23 (C), 128.85 (2CH), 127.97 (CH),
127.58 (CH), 126.93 (2CH), 126.17 (C), 116.25 (CH), 44.09
(CH2), 23.92 (CH2). MS m/z (%) 197 (58), 169 (100), 168
(93), 154 (50), 141 (46), 115 (36), 104 (20), 77 (12), 66 (44).
The last fraction was 2-pyridy-3-phenyl-[1,2,3]triazolo-
[1,5-a]pyridin-7-ylmethanol 11d (89 mg, 45%).
3.3.5. 3,30-Bi[1,2,3]triazolo[1,5-a]pyridine 18. A mixture
of 1,2-di(2-pyridil)-1,2-ethanodione (1 g, 4.7 mmol) and
tosylhydrazine (1.85 g, 9.9 mmol) in ethanol (50 mL) was
boiled under reflux (8 h). After treating with aqueous
sodium hydroxide (7 mL, 2 N) the reaction was refluxed
for 2 h. Then the solvent was concentrated in vacuo to
10–15 mL and a precipitate was obtained. By filtration,
compound 18 was separated (0.45 g) almost pure. Mp 262–
264 8C (EtOH). Lit.19 254–255 8C (EtOH). No spectro-
scopical data is in the literature. HRMS found for Mþ
3.3.3. 3-{6-([1,2,3]Triazolo[1,5-a]pyrid-3-yl)-2-pyridyl}-
[1,2,3]triazolo[1,5-a]pyridine 7c0. Compound 3c0 (0.1 g,
0.33 mmol), ethanol (50 mL), tosylhydrazine (0.08 g,
0.42 mmol), ethanol (50 mL), NaOH (3 mL, 2 N). The
precipitate was compound 7c0 almost pure (90 mg). The
236.0806; C12H8N6 requires 236.0810. nmax (KBr) (cm21
)
3113, 1630, 1530, 1504, 1152, 1015, 755. lmax (nm) (log 1)
1
(EtOH) 294.5 (5.36), 349.5 (5.29). H NMR d 8.71 (ddd,

5792
B. Abarca et al. / Tetrahedron 60 (2004) 5785–5792
J1¼6.99 Hz, J2¼J3¼0.96 Hz, 2H, H7, H70), 8.62 (ddd,
J1¼9.03 Hz, J2¼J3¼1.11 Hz, 2H, H4, H40), 7.32 (ddd,
J1¼9.03 Hz, J2¼6.99 Hz, J3¼0.96 Hz, 2H, H5, H50), 7.01
(ddd, J1¼J2¼6.99 Hz, J3¼1.11 Hz, 2H, H6, H60). 13C NMR
d 134.22 (C3, C30), 131.02 (C3a, 0C3a0), 125.65 (C70, C70),
125.01 (C4, C40), 120.50 (C5, C5 ), 116.11 (C6, C6 ). MS
m/z (%) 236 (17), 180 (100). The filtrate was extracted with
ether (3£25 mL). The organic layer was dried (Na2SO4),
evaporated, and the crude purified by chromatotron, eluting
with ethyl acetate hexane bitriazoplopyridine 18 was first
eluted (0.08 g, total yield 48%), the second fraction was
2-pyridyl-[1,2,3]triazolo[1,5-a]pyridin-3-ylmethanone 19
(0.081 g, 8%). Mp 150–152 8C (MeOH/H2O). Lit.22
151 8C (acetone). No spectroscopical data are in the
literature. HRMS found for Mþ 224.0695; C12H8N4O
requires 224.0698. nmax (KBr) (cm21) 3077, 3030, 1655
(CO), 1626, 1514, 1418, 1229, 943, 770. lmax (nm) (log 1)
(EtOH) 327 (4.18). 1H NMR d 8.81 (m, 2H, H60, H7), 8.48
(ddd, J1¼8.85 Hz, J2¼J3¼1.11 Hz, 1H, H4), 8.33 (ddd,
J1¼7.71 Hz, J2¼J3¼0.93 Hz, 1H, H30), 7.85 (ddd, J1¼
J2¼7.71 Hz, J3¼1.68 Hz, 1H, H40), 7.57 (ddd, J1¼8.85 Hz,
J2¼6.78 Hz, J3¼0.93 Hz, 1H, H5), 7.44 (ddd, J1¼7.71 Hz,
J2¼4.68 Hz, J3¼1.11 Hz, 1H, H50), 7.15 (ddd, J1¼J2¼
6.78 Hz, J3¼1.11 Hz, 1H, H6). 13C NMR d 185.40 (CO),
154.41 (C), 149.73 (CH), 136.77 (CH), 136.47 (C), 136.16
(C), 130.40 (CH), 126.36 (CH), 125.86 (CH), 125.42 (CH),
120.48 (CH), 117.04 (CH). MS m/z (%) 224 (10), 196 (9),
168 (100), 140 (12), 78 (12).
Acknowledgements
Our thanks are due to the Ministerio de Ciencia y
´
Tecnologıa (Project ref. BQU2003-09215-C03-03) for its
financial support, and to the SCSIE for the realization of the
HRMS spectra.
References and notes
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azolo[1,5-a]pyridine 20. To a solution of 3,30-bi[1,2,3]tri-
azolo[1,5-a]pyridine 18 (0.1 g, 0.42 mmol) in anhydrous
THF (100 mL) at 240 8C, a solution of n-butyllithium in
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(2 h). Further, a deep orange-yellow colour was developed
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The mixture was kept at 240 8C (2 h). Then was treated
with a dry THF solution (5 mL) of ethyl picolinate (0.2 g,
1.32 mmol, 3 equiv.). The mixture was left at 240 8C (2 h),
and treated with a saturated solution of ammonium chloride.
The organic layer was separated and the aqueous layer
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drous Na2SO4 and evaporation of the organic solvents, a
residue was obtained (0.2 g). Precipitation with ethyl acetate
gave the compound 20 as a yellow solid (0.1 g) almost pure.
Mp 190–192 8C (AcOEt). HRMS found for Mþ22N2
390.1137; C24H14N4O2 requires 390.1116. nmax (KBr)
(cm21) 3095, 3060, 2924, 2859, 1684 (CO), 1581, 1313,
1063, 743. lmax (nm) (log 1) (EtOH) 291 (3.93), 402 (3.61).
1H NMR d 8.75 (dd, J1¼8.46 Hz, J2¼1.5 Hz, 1H, H4), 8.43
(ddd, J1¼4.71 Hz, J2¼1.68 Hz, J3¼0.75 Hz, 1H, H60), 8.18
(d, J¼7.71 Hz, 1H, H30), 7.91 (ddd, J1¼ J2¼7.71 Hz,
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20. Ballesteros, R.; Abarca, B.; Samadi, A.; Server-Carrion, J.;
J3¼1.68 Hz, 1H, H40), 7.48–7.39 (m, 3H, H50, H5, H6). 13
C
´
Escriva, E. Polyhedron 1999, 18, 3129–3133.
NMR 186.46 (CO), 152.18 (C), 149.57 (CH), 138.11 (CH),
134.34 (C), 130.39 (C), 130.26 (C), 128.60 (CH), 126.91
(CH), 123.37(CH), 121.45 (CH), 118.71 (CH). MS m/z (%),
300 (6), 272 (100), 271 (59), 243 (41), 194 (25), 166 (41), 78
(49). The filtrate was evaporated and purified by chromato-
tron with ethyl acetate/hexane as eluent. An additional
amount of compound 20 (0.017 g) was obtained (total yield
66%), ethyl picolinate (0.078 g, 38%) and starting material
(0.005 g, 5%).
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24. Abarca, B.; Ballesteros, R.; Elmasnaouy, M.; D’Ocon, P.;
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