Microwave-assisted stille reactions as a powerful tool for building polyheteroaryl systems bearing a (1H)-1,2,4-triazole moiety

Article abstract of DOI:10.1055/s-0029-1218533

Stille couplings and the combination of Stille/Heck cross-coupling reactions provide useful access to tricyclic systems with valuable material properties from 3, 5-dibromo-1,2,4-triazoles. The reactions can all be dramatically improved under microwave irradiation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218533

LETTER
55
Microwave-Assisted Stille Reactions as a Powerful Tool for Building
Polyheteroaryl Systems Bearing a (1H)-1,2,4-Triazole Moiety
M
icrowave-Assis
.
te
d
Stille Re
C
actions ebrián,a A. de Cózar,a P. Prieto,*a A. Díaz-Ortiz,*a A. de la Hoz,a J. R. Carrillo,a A. M. Rodriguez,a F. Montillab
a
Facultad de Química, Universidad de Castilla-La Mancha, 13071, Ciudad Real, Spain
Fax +926-295318; E-mail: MariaPilar.Prieto@uclm.es
b
Facultad de Ciencias, Universidad de Alicante, Apdo. de Correos 99, 03080, Alicante, Spain
Received 29 September 2009
tion/deprotection strategies, which are a necessity with
most organometallic reactions. The process is often re-
giospecific with regards to the newly formed C–C s-bond
and is particularly effective for transformations of highly
functionalized molecules.14
Abstract: Stille couplings and the combination of Stille/Heck
cross-coupling reactions provide useful access to tricyclic systems
with valuable material properties from 3,5-dibromo-1,2,4-triazoles.
The reactions can all be dramatically improved under microwave ir-
radiation.
Key words: Stille reaction, microwave, (1H)-1,2,4-triazole, 1,2,3-
triazole, electropolymerization
However, to the best of our knowledge, reports related to
the Stille reaction of (1H)-1,2,4-triazoles have not been
published to date. Indeed, cross-coupling reactions on
azoles with three heteroatoms are very rare and are limited
to a few examples.15
Research on the electrochemistry of new monomers and
the electrosynthesis of electronically conducting poly-
mers (ECPs) has been of great interest in the last few de-
cades.1 Most of the classical conducting polymers are
based on polyaniline (PANI)2 or heterocycles such as
polypyrrole (PPy),3 or polythiophene (PTh).4
As a new synthetic approach for building polyheteroaryl
systems bearing a 1,2,4-triazole moiety, we report here
the first Stille cross-coupling reaction of 3,5-dibromo-1-
methyl-1H-1,2,4-triazole (1) with a range of stannyl de-
rivatives under microwave irradiation in solvent-free con-
ditions. Our aim was to develop a general procedure for
the preparation of compounds with potential applications
in different fields, such as electrochemistry, new materials
or medicinal chemistry. The different reactivity of posi-
tions 3 and 5 of compound 1 led to a wide range of mono-
and disubstituted, symmetric or asymmetric products.
On using either PdCl2(PPh3)2/LiCl16 or PdCl2(PPh3)2/
CuI17 as the catalytic system, dibromotriazole 1 reacted
with stannyl derivatives 2 (1.3 equiv) under microwave ir-
radiation at 110 °C for 15 minutes to afford the 5-mono-
substituted 1,2,4-triazoles 4 as the sole or main product
with good yields. The results are summarized in Table 1.18
A new synthetic approach to these materials involves the
insertion of a functional species between two polymeriz-
able moieties, for example, between two thiophene or pyr-
role rings.5 In this respect, the (1H)-1,2,4-triazole moiety
could be a convenient functional group for insertion. This
unit is of current interest owing to its widely reported
properties and applications, such as in new materials,6 in
medicinal chemistry7 and as a ligand.8
Many ECPs have been prepared through chemical meth-
ods – most involving organometallic coupling reactions,
which are a powerful tool in organic synthesis.9
Microwave-assisted organic synthesis (MAOS)10 is a rel-
atively new technique in synthetic chemistry. Homoge-
neous transition-metal catalyzed reactions, which
typically require long reaction times, represent one of the
most important and best studied reaction types in MAOS,
as evidenced by the numerous recent scientific publica-
tions, reviews and patents published in this field.11 In this
sense, Stille protocols are amongst the most versatile and
well-investigated microwave-assisted cross-coupling reac-
tions in modern organic synthesis and constitute a conve-
nient C–C bond-forming tool.12 The utility of the Stille
reaction is widely recognized by the synthetic community.
This is due to the growing availability of the organostan-
nane derivatives13 and their stability to air and moisture.
In addition, the process is compatible with virtually any
functional group, thereby eliminating the need for protec-
As one would expect, the higher reactivity of the 5-posi-
tion of 1,2,4-triazoles explains the formation of product 4.
Only in the case of the highly reactive thiophene deriva-
tive 2a was a small amount of the 3-substituted product 3a
obtained.
Experimental results showed that PdCl2(PPh3)2/LiCl was
the best catalytic system for five-membered heterocyclic
and aryl stannanes (Table 1, entries 1 and 2). In contrast,
PdCl2(PPh3)2/CuI gave higher yields of products with six-
membered heterocyclic stannanes (Table 1, entries 7 and
8).
In order to evaluate the influence of microwave irradia-
tion, we also performed the reaction between 1 and 2a in
an oil bath under similar reaction conditions (time and
temperature); in this case, compounds 3a and 4a were ob-
tained in 5% and 44% yield, respectively. When the reac-
tion time was extended to 60 minutes the yields only
improved to 7 and 57%, respectively. In the case of stan-
SYNLETT 2010, No. 1, pp 0055–0060
x
x.
x
x.
2
0
1
0
Advanced online publication: 02.12.2009
DOI: 10.1055/s-0029-1218533; Art ID: D27898ST
© Georg Thieme Verlag Stuttgart · New York

56
C. Cebrián et al.
LETTER
Table 1 Reactions between 3,5-Dibromo-1-methyl-(1H)-1,2,4-tri-
azole (1) and Organostannanes 2
Table 2 Reactions between 3,5-Dibromo-1-methyl-(1H)-1,2,4-tria-
zole (1) and Organostannanes 2
Br
R
Br
R
Br
catalyst
MW
Br
catalyst
MW
130 °C, 15 min
N
N
N
N
N
N
+
RSnBu3
+
RSnBu3
+
+
N
N
N
N
N
N
R
R
110 °C
15 min
Br
Br
N
R
N
N
N
N
Br
(1.3 equiv)
N
(2.6 equiv)
Me
Me
Me
Me
Me
Me
1
2
3
4
1
2
4
5
Entry
1
R
Catalytic system
Product [yield (%)]
Entry
1
R
Catalytic system
Product [yield (%)]
PdCl2(PPh3)2 + LiCl 3a (13) + 4a (84)
PdCl2(PPh3)2 + CuI 3a (8) + 4a (60)
PdCl2(PPh3)2 + LiCl 5a (98)
S
S
2a
2a
2
3
S
2
PdCl2(PPh3)2 + LiCl 4b (12) + 5b (85)
N
2a
Me
2b
PdCl2(PPh3)2 + LiCl 4b (88)
N
3
4
PdCl2(PPh3)2 + LiCl 5c (65)
PdCl2(PPh3)2 + CuI 4fa
Me
S
S
2b
2c
4
5
6
PdCl2(PPh3)2 + LiCl 4c (77)
PdCl2(PPh3)2 + LiCl 4d (82)
PdCl2(PPh3)2 + LiCl 4e (60)
S
S
N
2c
2d
2e
2f
N
5
6
PdCl2(PPh3)2 + CuI 4ga
PdCl2(PPh3)2 + LiCl 4ga
N
2g
N
N
7
8
PdCl2(PPh3)2 + LiCl 4f (41)
PdCl2(PPh3)2 + CuI 4f (79)
2g
N
a Only the 5-monosubstituted product 4 was obtained.
2f
probably due to the low reactivity of the 3-position, and
only the 5-monosubstituted product 4 was obtained.
N
2f
N
However, the different reactivities of the 3- and 5-posi-
tions of the dibromo derivative 1 allowed us to introduce
different substituents into the triazole moiety. Thus, start-
ing from 5-monosubstituted triazoles 4, Stille reactions
were performed with several organostannanes under mi-
crowave irradiation using different catalytic systems. The
availability and easy access to the organostannane deriva-
tives allowed the preparation of a wide range of polyhet-
eroaryl systems bearing a (1H)-1,2,4-triazole moiety in a
few minutes and in good yields. This approach represents
a general procedure for building this type of compound.
The main results are summarized in Table 3.20
9
PdCl2(PPh3)2 + CuI 4g (58)
N
2g
nyl derivative 2e, the product yield decreased to 21% with
classical heating. Microwave irradiation therefore repre-
sents the best heating source for performing these reac-
tions and allows the synthesis of the 5-monosubstituted-
1,2,4-triazoles 4 within 15 minutes in good yields.
As a new application of this approach, we carried out
these reactions under microwave irradiation with 2.6
equivalents of the organostannane derivative 2 in order to
obtain symmetrical disubstituted systems bearing a (1H)-
1,2,4-triazole moiety. The results are collected in
Table 2.19
However, as observed previously, the low reactivity of
six-membered heterocyclic organostannanes and the 3-
position of the 1,2,4-triazole unit, hampered our efforts to
introduce a six-membered heterocyclic system in this po-
sition of the triazole moiety (Table 3, entry 3).
These outcomes show that the five-membered, disubsti-
tuted heterocyclic systems can be synthesized in good to
excellent yields (65–98%). It is noteworthy that six-mem-
bered, disubstituted heterocyclic systems could not be ob-
tained under either of the proven reaction conditions,
Recently, we reported the first microwave-assisted Heck
reaction on a (1H)-1,2,4-triazole moiety as a new synthet-
ic methodology for the preparation of alkenyl-(1H)-1,2,4-
triazoles.15f As shown in Scheme 1, we carried out a com-
Synlett 2010, No. 1, 55–60 © Thieme Stuttgart · New York

LETTER
Microwave-Assisted Stille Reactions
57
Table 3 Reactions between Monosubtitued Triazole Derivatives 4
and Organostannanes 2
Table 4 Reactions between 1-Phenyl-4-(tributylstannyl)-1H-1,2,3-
triazole (11) and Halo Derivatives 12
R'
SnBu3
Br
R
catalyst
MW
N
N
N
N
PdCl2(PPh3)2/LiCl
R2SnBu3
(1.3 equiv)
+
RX
N
N
+
R1
N
MW, 150 °C, 15 min
N
R1
N
N
130 °C, 15 min
12
N
N
Me
Ph
Me
Ph
11
13
4
2
6
Entry
R1
R2
Product [yield (%)]
Entry RX
Product
Yield (%)
Me
1
6a (68)a
N
Me
S
Me
2b
4a
Me
1
54
N
N
N
I
Me
2
3
6b (72)a
S
S
12a
S
Ph
4a
2c
N
13a
Me
a,b
–
Me
Br
S
N
4a
N
2g
2
77
Me
N
N
N
Me
4
6c (83)b
Ph
12b
12c
S
N
13b
2a
4g
a Reaction conditions: PdCl2(PPh3)2, LiCl.
b Reaction conditions: PdCl2(PPh3)2, CuI.
Br
N
3
4
5
96
50
91
N
N
Br
Br
CF3
Ph
13c
Naph
I
Br
N
N
i)
N
N
+
N
N
N
N
S
N
Ph
Me
S
CF3
12d
Me
13d
4a
7
8 (61%)
N
N
SnBu3
N
Ph
N
Br
N
N
N
I
ii)
N
N
+
N
12e
N
Ph
N
N
Me
13e
Naph
Me
Naph
N
I
9
2e
N
(54%)
10
N
N
N
N
6
7
49
76
Scheme 1 Reagents and conditions: (i) Herrmann palladacycle, [(t-
Bu)3PH]BF4, Cy2NMe, bmimPF6, MW, 170 °C, 35 min; (ii)
PdCl2(PPh3)2, LiCl, MW, 130 °C,15 min.
N
Ph
N
N
Ph
12f
Ph
13f
Br
bination of Stille/Heck cross-coupling reactions in order
to develop a new synthetic approach to highly conjugated
compounds with valuable properties as materials. In the
first case, we used Stille product 4a and performed a Heck
reaction with the styrene derivative 7 to obtain the disub-
stituted triazole 8 in 61% yield. Furthermore, Heck prod-
uct 9 was reacted with the stannyl derivative 2e to give
compound 10 in 54% yield. Both reactions were per-
formed under microwave irradiation in solvent-free con-
ditions. The properties of these systems are currently
under evaluation.
N
Br
N
N
N
N
N
N
Br
N
Me
N
Me
Ph
1
13g
Synlett 2010, No. 1, 55–60 © Thieme Stuttgart · New York

58
C. Cebrián et al.
LETTER
(4) Tourillon, G.; Garnier, F. J. Electroanal. Chem. 1982, 135,
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Finally, we applied the synthetic approach developed here
to the preparation of new biheteroaryl systems bearing a
1,2,3-triazole moiety. 1-Phenyl-4-(tributylstannyl)-1H-
1,2,3-triazole (11) was reacted with different aryl or het-
eroaryl halides using Stille conditions under microwave
irradiation to prepare new 1,2,3-triazole derivatives with-
in 15 minutes in good yields (49–96%). The wide avail-
ability of aryl and heteroaryl halides makes this synthetic
method widely applicable. Some of these compounds,
bearing two triazole rings, are currently being tested as
new ligands. The products synthesized are collected in
Table 4.21
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When the reaction was performed using the dihalogenated
compounds 12c or 1, only the monosubstitued derivative
was obtained (Table 4, Entries 3 and 7). In the case of 1,
the reactivity of the 5-position explains the formation of
product 13g.
In conclusion, we describe the first microwave-assisted
Stille reaction involving a (1H)-1,2,4-triazole moiety.
This methodology represents a general method for the
preparation of a wide range of symmetrical and non-sym-
metrical 3,5-disubstituted (1H)-1,2,4-triazole derivatives
in a few minutes and with good to excellent yields. The
combined Heck/Stille cross-coupling reaction expands
the applicability of this synthetic approach and allows the
preparation of highly conjugated systems bearing a (1H)-
1,2,4-triazole unit. Finally, we employed Stille conditions
in the reaction of 1-phenyl-4-(tributylstannyl)-1H-1,2,3-
triazole with halo derivatives in order to obtain new bihet-
eroaryl systems in good yields. The availability of the re-
agents, short reaction times and good yields of the
methods described here allow the easy preparation of a
wide range of products with potential properties as new
materials and in medicinal chemistry. The potential appli-
cations of these new compounds are currently under in-
vestigation in our laboratory.
(11) (a) Lahred, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res.
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
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Acknowledgment
Financial support from the DGCYT of Spain through project
CTQ2007-60037/BQU and from the Consejería de Educación y
Ciencia, JCCM through projects PBI08-0259-7224, PCI08-0040
and PII2I09-0100-9633 is gratefully acknowledged.
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Synlett 2010, No. 1, 55–60 © Thieme Stuttgart · New York

LETTER
Microwave-Assisted Stille Reactions
59
(18) General Procedure: A mixture of 3,5-dibromo-1-methyl-
1H-1,2,4-triazole (1; 200 mg, 0.83 mmol), stannyl derivative
(2; 1.08 mmol), PdCl2(PPh3)2 (12 mg, 0.017 mmol) and LiCl
(106 mg, 2.49 mmol) or CuI (15.8 mg, 0.083 mmol) was
irradiated under argon in a Discover™ (CEM) focused
microwave reactor at 110 °C for 15 min. The crude products
3a and 4a–g were purified by flash chromatography on silica
gel (hexane–EtOAc).
(CDCl3): d = 157.3, 150.0, 133.5, 128.9, 128.7, 128.6, 127.9,
127.6, 126.3, 126.2, 37.1 (CH3).
1-Methyl-3,5-bis(1-methyl-1H-pyrrol-2-yl)-1H-1,2,4-
triazole (5b): Mp 78–79 °C; 1H NMR (CDCl3): d = 6.74 (t,
J = 2.0 Hz, 1 H, H-5¢¢), 6.73 (dd, J = 2.0, 1.0 Hz, 1 H, H-5¢),
6.62 (t, J = 2.0 Hz, 1 H, H-3¢), 6.43 (dd, J = 4.4, 2.4 Hz, 1 H,
H-3¢¢), 6.17 (dd, J = 4.0, 2.4 Hz, 1 H, H-4¢¢), 6.10 (dd,
J = 3.4, 2.9 Hz, 1 H, H-4¢), 3.94 (s, 3 H, CH3), 3.91 (s, 3 H,
CH3), 3.85 (s, 3 H, CH3); 13C NMR (CDCl3): d = 155.9,
148.0, 126.1, 125.0, 124.8, 119.8, 112.3, 110.3, 108.0,
107.7, 36.7 (CH3), 36.6 (CH3), 36.1 (CH3).
3,5-Di(2,2¢-bithiophen-5-yl)-1-methyl-1H-1,2,4-triazole
(5c): Mp 146–148 °C; 1H NMR (CDCl3): d = 7.61 (d, J = 3.8
Hz, 1 H, H-3¢¢), 7.45 (d, J = 3.8 Hz, 1 H, H-3), 7.22–7.31 (m,
5 H, H-4, H-3¢, H-5¢, H-3¢¢¢, H-5¢¢¢), 7.17 (d, J = 3.8 Hz, 1 H,
H-4¢¢), 7.07 (dd, J = 4.9, 3.8 Hz, 1 H), 7.03 (t, J = 4.3 Hz,
1 H, H-4¢ and H-4¢¢¢); 13C NMR (CDCl3): d = 156.9, 149.7,
140.8, 138.2, 137.2, 136.1, 131.9, 129.0, 128.1, 127.9,
127.2, 126.9, 125.6, 124.8, 124.7, 124.2, 124.1, 124.0, 37.3
(CH3).
5-Bromo-1-methyl-3-(thiophen-2-yl)-1H-1,2,4-triazole
(3a): Mp 54–55 °C; 1H NMR (CDCl3): d = 7.58 (dd, J = 3.7,
1.2 Hz, 1 H, H-3¢), 7.28 (dd, J = 5.1, 1.2 Hz, 1 H, H-5¢), 7.02
(dd, J = 5.1, 3.7 Hz, 1 H, H-4¢), 3.84 (s, 3 H, CH3); 13C NMR
(CDCl3): d = 159.0, 132.8, 129.7, 127.7, 126.8, 126.5, 36.5
(CH3).
3-Bromo-1-methyl-5-(thiophen-2-yl)-1H-1,2,4-triazole
(4a): Mp 67–68 °C; 1H NMR (CDCl3): d = 7.54–7.62 (m,
2 H, H-3¢¢, H-5¢¢), 7.19 (dd, J = 5.1, 3.7 Hz, 1 H, H-4¢¢), 4.06
(s, 3 H, CH3); 13C NMR (CDCl3): d = 151.1, 138.7, 129.4,
129.0, 128.0, 127.9, 37.4 (CH3).
3-Bromo-1-methyl-5-(1-methyl-1H-pyrrol-2-yl)-1H-
1,2,4-triazole (4b): Mp 41–42 °C; 1H NMR (CDCl3): d =
6.74 (t, J = 1.8 Hz, 1 H, H-5¢¢), 6.41 (dd, J = 4.0, 1.5 Hz, 1 H,
H-3¢¢), 6.14 (dd, J = 3.7, 2.6 Hz, 1 H, H-4¢¢), 4.06 (s, 3 H,
CH3); 13C NMR (CDCl3): d = 149.9, 138.3, 126.8, 118.3,
113.1, 108.2, 37.1 (CH3), 36.0 (CH3).
5-(2,2¢-Bithiophen-5-yl)-3-bromo-1-methyl-1H-1,2,4-
triazole (4c): Mp 152–154 °C; 1H NMR (CDCl3): d = 7.61
(d, J = 3.9 Hz, 1 H, H-3), 7.31 (dd, J = 5.1, 1.1 Hz, 1 H, H-
3¢), 7.27 (dd, J = 3.8, 1.1 Hz, 1 H, H-5¢), 7.20 (d, J = 3.9 Hz,
1 H, H-4), 7.05 (dd, J = 5.1, 3.8 Hz, 1 H, H-4¢); 13C NMR
(CDCl3): d = 150.7, 141.7, 138.7, 135.7, 129.5, 128.1, 125.9,
125.9, 125.0, 124.1, 35.5 (CH3).
(20) General Procedure: A mixture of 5-monosubstituted
triazole 4 (1 equiv), stannyl derivative (2; 1.3 equiv),
PdCl2 (PPh3)2 (0.02 equiv) and LiCl (3 equiv) or CuI (0.1
equiv) was irradiated at the appropriate temperature and for
the appropriate time under argon in a Discover™ (CEM)
focused microwave reactor. The crude products 6a–c were
purified by flash chromatography on silica gel (hexane–
EtOAc).
1-Methyl-3-(1-methyl-1H-pyrrol-2-yl)-5-(thiophen-2-
yl)-1H-1,2,4-triazole (6a): Mp 88–89 °C; 1H NMR
(CDCl3): d = 7.53 (dd, J = 3.7, 1.5 Hz, 1 H, H-3¢¢), 7.52 (dd,
J = 5.1, 1.1 Hz, 1 H, H-5¢¢), 7.18 (dd, J = 5.1, 3.7 Hz, 1 H, H-
4¢¢), 6.81 (dd, J = 3.7, 1.8 Hz, 1 H, H-5¢), 6.70 (t, J = 2.2 Hz,
1 H, H-3¢), 6.17 (dd, J = 3.7, 2.6 Hz, 1 H, H-4¢), 4.08 (s, 3 H,
CH3), 4.00 (s, 3 H, CH3); 13C NMR (CDCl3): d = 156.3,
149.1, 129.5, 128.5, 128.2, 127.8, 125.2, 124.4, 110.8,
107.8, 37.0 (CH3), 36.5 (CH3).
3-Bromo-1-methyl-5-phenyl-1H-1,2,4-triazole (4d): Mp
120–121 °C; 1H NMR (CDCl3): d = 7.59–7.61 (m, 2 H, o-
PhH), 7.44–7.46 (m, 3 H, m-PhH, p-PhH), 3.91 (s, 3 H,
CH3); 13C NMR (CDCl3): d = 156.6, 139.1, 130.7, 129.0,
128.7, 126.7, 37.3 (CH3).
3-Bromo-1-methyl-5-(phenylethynyl)-1H-1,2,4-triazole
(4e): Mp 119–120 °C; 1H NMR (CDCl3): d = 7.52–7.55 (m,
2 H, o-PhH), 7.28–7.94 (m, 3 H, m-PhH, p-PhH), 3.97 (s,
3 H, CH3); 13C NMR (CDCl3): d = 147.7, 140.3, 132.1,
132.0, 129.2, 128.7, 128.4, 121.7, 97.4, 89.5, 36.5 (CH3).
2-(3-Bromo-1-methyl-1H-1,2,4-triazol-5-yl)pyridine(4f):
Mp 78–80 °C; 1H NMR (CDCl3): d = 8.68 (dd, J = 4.8, 1.8
Hz, 1 H, H-6), 8.20 (dd, J = 7.7, 1.1 Hz, 1 H, H-3), 7.85 (td,
J = 7.7, 1.8 Hz, 1 H, H-4), 7.37 (ddd, J = 7.7, 4.8, 1.1 Hz,
1 H, H-5), 4.36 (s, 3 H, CH3); 13C NMR (CDCl3): d = 153.4,
148.9, 146.8, 138.3, 137.1, 124.5, 124.0, 39.3 (CH3).
2-(3-Bromo-1-methyl-1H-1,2,4-triazol-5-yl)pyrazine
(4g): Mp 131–133 °C; 1H NMR (CDCl3): d = 9.45 (s, 1 H,
H-3), 8.67, 8.64 (2 × s, 2 H, H-5 and H-6), 4.34 (s, 3 H,
CH3); 13C NMR (CDCl3): d = 151.1, 145.2, 154.1, 143.1,
142.5, 138.8, 39.3 (CH3).
3-(2,2¢-Bithiophen-5-yl)-1-methyl-5-(thiophen-2-yl)-1H-
1,2,4-triazole (6b): Mp 124–126 °C; 1H NMR (CDCl3): d =
7.62 (d, J = 3.8 Hz, 1 H, H-4¢¢), 7.57 (dd, J = 3.7, 1.1 Hz,
1 H, H-3¢¢¢), 7.55 (dd, J = 5.1, 1.1 Hz, 1 H, H-5¢¢¢), 7.24–7.23
(m, 2 H, H-3¢, H-5¢), 7.20 (dd, J = 5.1, 3.7 Hz, 1 H, H-4¢¢¢),
7.07 (dd, J = 3.8 Hz, 1 H, H-3¢¢), 7.03 (dd, J = 3.8, 4.9 Hz,
1 H, H-4¢), 4.09 (s, 3 H, CH3); 13C NMR (CDCl3): d = 156.9,
150.1, 138.2, 137.2, 131.9, 128.9, 128.8, 128.7, 127.9,
126.9, 124.7, 124.4, 124.0, 37.2 (CH3).
2-[1-Methyl-3-(thiophen-2-yl)-1H-1,2,4-triazol-5-
yl]pyrazine (6c): Mp 139–140 °C; 1H NMR (CDCl3): d =
9.55 (d, J = 1.7 Hz, 1 H, H-3 Py), 8.64–8.67 (m, 2 H, H-5,
H-6 Py), 7.75 (dd, J = 3.7, 1.1 Hz, H-3 thioph), 7.37 (dd,
J = 5.1, 1.1 Hz, 1 H, H-5 thioph), 7.13 (dd, J = 5.1, 3.7 Hz,
1 H, H-4 thioph), 4.37 (s, 3 H, CH3); 13C NMR (CDCl3): d =
157.5, 150.1, 145.4, 144.7, 143.5, 143.0, 133.5, 127.7,
126.5, 126.3.
(19) General Procedure: A mixture of 3,5-dibromo-1-methyl-
1H-1,2,4-triazole (1; 200 mg, 0.83 mmol), stannyl derivative
(2; 2.16 mmol, 2.6 equiv), PdCl2 (PPh3)2 (24 mg, 0.033
mmol) and LiCl (106 mg, 2.49 mmol) was irradiated under
argon in a Discover™ (CEM) focused microwave reactor at
130 °C for the appropriate time. The crude products 5a–c
were purified by flash chromatography on silica gel
(hexane–EtOAc).
(21) General Procedure: A mixture of 1-phenyl-4-(tributyl-
stannyl)-1H-1,2,3-triazole (11; 100 mg, 0.23 mmol),
halogenated derivative 12 (0.25 mmol), PdCl2(PPh3)2 (3 mg,
0.004 mmol) and LiCl (29.3 mg, 0.69 mmol) was irradiated
at the appropriate temperature and for the appropriate time
under argon in a Discover™ (CEM) focused microwave
reactor. The crude products 13a–g were purified by flash
chromatography (hexane–EtOAc).
1-Methyl-3,5-di(thiophen-2-yl)-1H-1,2,4-triazole (5a):
Mp 107–108 °C; 1H NMR (CDCl3): d = 7.71 (dd, J = 3.7, 1.1
Hz, 1 H, H-3¢), 7,54 (dd, J = 3.7, 1.1 Hz, 1 H, H-3¢¢), 7.53
(dd, J = 5.1, 1.1 Hz, 1 H, H-5¢¢), 7.34 (dd, J = 4.8, 1.1 Hz,
1 H, H-5¢), 7.18 (dd, J = 5.1, 3.7 Hz, 1 H, H-4¢¢), 7.10 (dd,
J = 5.1, 3.7 Hz, 1 H, H-4¢), 4.07 (s, 3 H, CH3); 13C NMR
4-(3,5-Dimethylphenyl)-1-phenyl-1H-1,2,3-triazole
(13a): Mp 115–116 °C; 1H NMR (CDCl3): d = 8.1 (s, 1 H,
H-5), 7.8 (d, J = 7.3 Hz, 2 H, o-PhH), 7.5 (m, 4 H, Ph¢H), 7.4
(t, J = 7.3 Hz, 1 H, p-Ph¢H), 7.0 (s, 1 H, p-PhH), 2.2 (s, 6 H,
2 × CH3); 13C NMR (CDCl3): d = 148.6, 138.5, 137.1, 130.1,
Synlett 2010, No. 1, 55–60 © Thieme Stuttgart · New York

60
C. Cebrián et al.
LETTER
129.9, 128.7, 123.6, 120.5, 117.5, 21.3 (CH3).
2-(1-Phenyl-1H-1,2,3-triazol-4-yl)pyrazine (13e):
4-(2,6-Dimethylphenyl)-1-phenyl-1H-1,2,3-triazole
(13b): Colorless oil; 1H NMR (CDCl3): d = 7.9 (s, 1 H, H-5),
7.8 (d, J = 7.1 Hz, 2 H, o-PhH), 7.5 (t, J = 6.9 Hz, 2 H,
m-PhH), 7.4 (t, J = 7.3 Hz, 1 H, p-PhH), 7.2–7.1 (m, 3 H,
PhH¢), 2.3 (s, 6 H, 2 × CH3); 13C NMR (CDCl3): d = 146.2,
137.9, 137.1, 129.8, 129.6, 123.6, 120.3, 117.5, 20.8 (CH3).
4-(3-Bromophenyl)-1-phenyl-1H-1,2,3-triazole (13c):
Yellow oil; 1H NMR (CDCl3): d = 8.2 (s, 1 H), 8.0 (m, 1 H),
7.8–7.7 (m, 3 H), 7.6–7.5 (m, 4 H), 7.3 (t, J = 7.3 Hz, 1 H,
p-PhH); 13C NMR (CDCl3): d = 147.0, 136.9, 132.3, 131.3,
130.5, 129.8, 128.9, 128.8, 124.4, 123.0, 120.6, 117.9.
4-(Naphthalen-1-yl)-1-phenyl-1H-1,2,3-triazole (13d):
Mp 106–107 °C; 1H NMR (CDCl3): d = 8.5–8.4 (m, 1 H, H-
Naph), 8.2 (s, 1 H, H-5), 7.9–7.8 (m, 5 H), 7.6–7.4 (m, 6 H);
13C NMR (CDCl3): d = 147.6, 137.1, 133.9, 131.2, 129.9,
129.8, 129.2, 128.8, 128.5, 127.7, 127.4, 126.7, 126.1,
125.4, 120.6.
Colorless oil; 1H NMR (CDCl3): d = 9.5 (s, 1 H, H-Py), 8.6
(s, 1 H, H-5), 8.6–8.5 (m, 2 H, H-Py), 7.8 (d, J = 7.3 Hz, 2 H,
o-PhH), 7.5 (t, J = 7.3 Hz, 2 H, m-PhH), 7.4 (t, J = 7.3 Hz,
1 H, p-PhH); 13C NMR (CDCl3): d = 146.6, 145.7, 144.1,
143.9, 142.3, 136.7, 129.9, 129.2, 120.9, 120.6.
1,1¢-Diphenyl-1H,1¢H-4,4¢-bi(1,2,3-triazole) (13f): Mp
118–119 °C; 1H NMR (CDCl3): d = 8.6 (s, 1 H), 8.0 (s, 1 H),
7.7 (d, J = 7.3 Hz, 4 H, o-PhH), 7.5 (t, J = 7.3 Hz, 4 H,
m-PhH), 7.4 (d, J = 7.3 Hz, 2 H, p-PhH). 13C NMR (CDCl3):
d = 137.0, 134.4, 129.7, 128.7, 121.6, 120.6.
4-(3-Bromo-1-methyl-1H-1,2,4-triazol-5-yl)-1-phenyl-
1H-1,2,3-triazole (13g): Mp 104–105 °C; 1H NMR
(CDCl3): d = 8.5 (s, 1 H, H-5), 7.7 (d, J = 7.3 Hz, 2 H,
o-PhH), 7.5 (t, J = 8 Hz, 2 H, m-PhH), 7.4 (d, J = 7.1 Hz,
1 H, p-PhH), 4.3 (s, 3 H, CH3); 13C NMR (CDCl3): d =
147.5, 138.9, 137.7, 136.3, 130.1, 129.6, 122.6, 120.6, 38.3
(CH3).
Synlett 2010, No. 1, 55–60 © Thieme Stuttgart · New York

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