Microwave-controlled preparation of alkenyl-(1H)-1,2,4-triazoles: First heck reaction on a (1H)-1,2,4-triazole moiety

Article abstract of DOI:10.1071/CH09185

A new synthetic approach for the preparation of alkenyl-1,2,4-triazole derivatives based on microwave-induced CC cross-coupling Heck reactions is described. To the best of our knowledge, this is the first application of the Heck reaction to a dihalogenate

Full text of DOI:10.1071/CH09185

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2009, 62, 1600–1606
www.publish.csiro.au/journals/ajc
Microwave-Controlled Preparation of Alkenyl-
(1H)-1,2,4-triazoles: First Heck Reaction on a
(1H)-1,2,4-Triazole Moiety
Ángel Díaz-Ortiz,A,B Pilar Prieto,A Abel de Cózar,A Cristina Cebrián,A
Andrés Moreno,A and Antonio de la HozA
ADpto. Q. Orgánica, Facultad de Química, Universidad de Castilla-La Mancha,
13071-Ciudad Real, Spain.
BCorresponding author. Email: Angel.Diaz@uclm.es
A new synthetic approach for the preparation of alkenyl-1,2,4-triazole derivatives based on microwave-induced C–C
cross-coupling Heck reactions is described. To the best of our knowledge, this is the first application of the Heck reaction
to a dihalogenated 1,2,4-triazole. This approach allows the introduction of a wide range of equivalent or different alkenyl
substituents in the 5- and/or 3-positions, thus extending the possibilities for the preparation of these valuable derivatives.
A similar microwave-induced synthetic procedure has also been applied to the Heck reaction of 4-vinyl-1,2,3-triazoles.
Manuscript received: 2 April 2009.
Manuscript accepted: 12 June 2009.
Introduction
synthetic approaches for the C–C functionalization of valuable
and scarcely studied heterocyclic systems that would allow eas-
ier access to highly interesting derivatives. In this context, we
believe that the Heck reaction could provide an useful method
to prepare alkenyl-1,2,4-triazole derivatives.
Substituted 1,2,4-triazoles are of current interest owing to
their widely reported properties and applications. Some of
these derivatives have shown anti-inflammatory, insecticide,
antifungal, or antimicrobial activity.[1] Glycosylated triazole
derivatives (such as Virazole) belong to the highly potent
drugs that act against DNA- and RNA-viruses,[2] and also
show antitumour activity.[3] Some (1,2,4-triazol-3- and -5-yl)-
1,2,3,6-tetrahydropyridine derivatives have been evaluated on
M1, M2, and M3 muscarinic receptors.[4] It has also been
reported that 3,5-disubstituted 1,2,4-triazoles are a new class
of xanthine oxidase inhibitor[5] that can be used as antigout and
antihyperuricemia agents[6] or as hypnotic drugs.[7]
In most cases, the preparation of substituted 1,2,4-triazoles
involves cyclization processes.[4,5a,8] As an alternative approach,
halogenated (1H)-1,2,4-triazoles have been used in nucleophilic
substitution reactions to give 5-substituted triazoles.[9] Cross-
coupling reactions on halogenated (1H)-1,2,4-triazole nucleo-
sides under Suzuki conditions[10] and a direct Pd-catalyzed
arylation of 1-methyl-1,2,4-triazole have also been reported.[11]
The Heck reaction is the most powerful and widely
used method for the C–C coupling of alkenes with organic
moieties.[12] However, tothebestofourknowledge, reportsrelat-
ing to the Heck reaction of (1H)-1,2,4-triazoles have yet to be
published. Indeed, cross-coupling reactions on azoles with three
heteroatoms are very rare[13] and are almost exclusively limited
to the aforementioned examples.
Results and Discussion
The use of environmentally friendly organic reaction method-
ologies (e.g. microwave irradiation, solvent-free conditions,
recyclable catalysts) has been one of our longstanding aims.
Organometallic chemistry in general, and palladium-catalyzed
reactions in particular, have been performed with great suc-
cess under microwave irradiation. In the past 10 years a
plethora of new reactions have been described, including
Heck, Sonogashira, Suzuki, Stille, Negishi and aminocarbony-
lation reactions.[20–23] We therefore decided to use a recyclable
ionic liquid, N-butyl-Nꢀ-methylimidazolium hexafluorophos-
phate (bmimPF6), as the solvent and PdCl2 or Herrmann’s pal-
ladacycle as catalysts in the microwave-induced cross-coupling
reaction of 3,5-dibromo-1,2,4-triazole 1 with the vinylarenes
2 in order to develop a new approach for the preparation of
3-, 5- or 3,5-disubstituted alkenyl-1,2,4-triazoles (Scheme 1).
This involved an environmentally benign procedure that used
microwave irradiation as the energy source, an ionic liquid as
the solvent and microwave susceptor, a high concentration and
recyclable palladium catalysts.
Alkenyl-1,2,4-triazoles are very useful compounds with a
wide range of applications that include pest control agents,[14]
fungicides,[15] insecticides and miticides,[16] anti-inflammatory
agents,[17] antihypertensive agents,[18] or as metabotropic gluta-
mate receptor 5 (mGluR5) modulators.[19]
The main results obtained are summarized in Table 1. All of
the reactions were performed under microwave irradiation and
were completed in 35 min at 190 and 170◦C when PdCl2 and
Herrmann’s palladacycle were used, respectively.
Investigations on 3,5-dibromotriazole 1 showed that the halo-
gen in the 5-position is significantly more reactive than that in
the 3-position.[24] Thus, 5-substituted triazoles 3 were always the
The current synthesis of these materials necessitates the
development of new, sustainable and environmentally friendly
© CSIRO 2009
10.1071/CH09185
0004-9425/09/121600

Microwave-Controlled Preparation of Alkenyl-(1H)-1,2,4-triazoles
1601
Ar
Ar
Br
Br
N
N
N
N
(i)
N
N
N
N
ϩ
ϩ
ϩ
Ar
N
Br
Br
N
N
N
or (ii)
Ar
Ar
CH3
CH3
CH3
CH3
2
5
1
3
4
Scheme 1. Reagents and conditions: (i) PdCl2, P(o-tol)3, bmimPF6, Et3N, microwave, 190◦C, 35 min; (ii) palladacycle, Cy2NMe, [(t-Bu)3PH]BF4,
bmimPF6, microwave, 170◦C, 35 min.
Table 1. Heck reactions of dibromo-1,2,4-triazole 1 with vinylarenes 2a–e
Ar–CH=CH2
Product (yield [%])
Conditions AA
Conditions BB
3a (48) + 5a (18)
3a (34) + 4a (18) + 5a (22)
2a
3b (46) + 5b (17)
3c (31) + 5c (15)
3d (49)
3b (57) + 5b (26)
3c (23) + 5c (19)
3d (32)
2b
F3C
2c
Ph
2d
H3CO
3e (54)
3e (45)
2e
APdCl2, P(o-tol)3, bmimPF6, Et3N, microwave, 190◦C, 35 min.
BPalladacycle, Cy2NMe, [(t-Bu)3PH]BF4, bmimPF6, microwave, 170◦C, 35 min.
major products and 3-substituted products 4 were isolated only
using Herrmann’s palladacycle as the catalyst (see Table 1),
we employed these conditions in the preparation of the new
products. This synthetic approach allows the preparation of any
disubstituted alkenyltriazole (including electron-donating and
electron-withdrawing aryl groups) in two steps from dibromo-
triazole and gives acceptable yields (46–79%) in a few minutes
under microwave irradiation.
The 1,2,3-triazole derivatives are of interest owing to
their activity as anti-HIV[25] and antimicrobial[26] agents, as
human carbonic anhydrase isoenzymes[27] and purine nucleo-
side phosphorylase inhibitors,[28] and for their applications
in materials.[29] Substituted 4-vinyl-1,2,3-triazoles have also
shown antifungal activity.[30]
Substituted 5-vinyl-1,2,3-triazoles have been prepared using
Heck reactions from 5-iodo-1,2,3-triazoles.[31] In this work, as
a new application of the synthetic approach described above, we
propose the preparation of substituted alkenyl-1,2,3-triazoles 8
by Heck reaction of a vinyl-1,2,3-triazole with an aryl halide.
Thus, reaction of 1-phenyl-4-vinyl-1,2,3-triazole (6) with aryl
halides 7a–d, promoted by microwave irradiation in the pres-
ence of PdCl2, P(o-tol)3, Et3N, and bmimPF6 at 150◦C in an
inert atmosphere for 15 min, afforded the corresponding coupled
with styrene (2a). In some reactions, mixtures of 5-substituted
and 3,5-disubstituted 1,2,4-triazoles, 3 and 5, respectively, were
obtainedandthesewereeasilyseparatedbychromatography.The
overall yields of these reactions were in the range 49–66% when
PdCl2 was used as the catalyst and 32–83% with Herrmann’s
palladacycle. The latter conditions afforded higher yields of 3,5-
disubstituted derivatives 5 than the former. An increase in the
reaction time and/or the triazole:vinylarene 1:2 ratio did not
afford higher yields of disubstituted products 5, but did lead
to a significant degree of decomposition with a decrease in the
overall yield.
Reactions catalyzed by Herrmann’s palladacycle failed with
classical heating in a pre-heated oil bath at 170◦C and cross-
coupling products could not be detected after 30 min. Reactions
catalyzed by PdCl2 in a pre-heated oil bath at 190◦C produced
less than 12% yield.
In order to increase the synthetic utility of this methodology
we reacted 5-monosubstituted triazoles 3b and 3e with several
vinylarenes 2 to prepare alkenyl-1,2,4-triazoles 5 bearing differ-
ent substituents in the 3- and 5-positions (Scheme 2). Since the
higher yields of disubstituted triazoles 5a–c had been obtained

1602
Á. Díaz-Ortiz et al.
OCH3
N
N
H3CO
N
N
3b
N
N
(i)
(i)
CH3
CH3
5f (60%)
5g (46%)
CF3
N
N
F3C
Ph
N
N
3e
N
N
(i)
(i)
CH3
CH3
H3CO
H3CO
5h (79%)
5i (61%)
Scheme 2. Reagents and conditions: (i) palladacycle, Cy2NMe, [(t-Bu)3PH]BF4, bmimPF6, microwave, 170◦C, 35 min.
Ar
N
N
N
(i)
Table 2. Heck reactions of vinyl-1,2,3-triazole 6 with aryl halides 7a–d
Ar
X
ϩ
N
N
N
7
Ar–X
Product
Yield [%]
Ph
Ph
6
8
Me
Scheme 3. Reagents and conditions: (i) PdCl2, P(o-tol)3, bmimPF6, Et3N,
inert atmosphere, microwave, 150◦C, 15 min.
Me
74
N
Me
N
N
products 8a–d in 54–88% yield (Scheme 3). The results are
summarized in Table 2.
Once again, the use of classical heating with a pre-heated oil
bath at 150◦C as the energy source did not provide products 8 in
a yield above 18%.
I
Me
8a
7a
Ph
Me
Me
Br
N
Conclusions
86
88
54
N
N
Me
In conclusion, we have performed for the first time a Heck reac-
tion on a 1,2,4-triazole moiety. This synthetic approach extends
the cross-coupling reactivity of these heterocyclic systems and
allows the preparation of a wide range of symmetrical or non-
symmetrical 3,5-substituted alkenyl-1,2,4-triazole derivatives
that are of potential pharmacological interest or can be applied in
materials chemistry.This approach can be applied to vinyl-1,2,3-
triazoles to obtain valuable substituted alkenyl-1,2,3-triazole
derivatives.Allofthereactionswereperformedundermicrowave
irradiation using a recyclable ionic liquid as a susceptor and
solvent.
Me
7b
8b
Ph
OCH3
OCH3
N
N
N
Br
8c
7c
Ph
N
I
Experimental
General
N
N
Monomode microwave irradiations were conducted using a Dis-
cover (CEM) focussed microwave reactor.All the reactions were
performed in the appropriate volume vessel with temperature
monitoring using an IR pyromether. Melting points were deter-
mined on a SPM apparatus and are uncorrected. NMR data
were obtained at 500 MHz for 1H and 125 MHz for 13C on
a Varian Inova spectrometer using CDCl3 as the solvent and
TMS as an internal standard. Chemical shifts were referenced
to internal TMS at 0 ppm. Coupling constants are given in Hz.
Assignment of spectra was carried out using nuclear Overhauser
Ph
7d
8d
effect correlation spectroscopy-1D (NOESY-1D), g-correlation
spectroscopy (g-COSY) and g-hetero nuclear single quantum
coherence (g-HSQC) experiments. High-resolution mass spec-
tra were recorded on an Agilent-Micromass LCT Time of Flight

Microwave-Controlled Preparation of Alkenyl-(1H)-1,2,4-triazoles
1603
mass spectrometer with electrospray ionisation and a Lockmass
device for mass calibration. Column chromatography was per-
formed using 230–400 mesh Merck type 60 silica gel. Reagents
were purchased from commercial suppliers or were prepared
according to literature procedures.
Reaction of 3,5-Dibromo-1-methyl-1H-1,2,4-triazole (1)
with Styrene (2a)
MethodA. From styrene (2a) (172 mg) and using hexane/AcOEt
4:1 as the eluent, 3-bromo-1-methyl-5-styryl-1H-1,2,4-triazole
(3a) (106 mg, 48%) and 1-methyl-3,5-distyryl-1H-1,2,4-triazole
(5a) (42 mg, 18%) were obtained.
Method B. From styrene (2a) (172 mg) and using hexane/
AcOEt 9:1 as the eluent, 3-bromo-1-methyl-5-styryl-1H-1,2,4-
triazole (3a) (74 mg, 34%), 5-bromo-1-methyl-3-styryl-1H-
1,2,4-triazole (4a) (40 mg, 18%) and 1-methyl-3,5-distyryl-1H-
1,2,4-triazole (5a) (52 mg, 22%) were obtained.
Data for 3-bromo-1-methyl-5-styryl-1,2,4-triazole ( 3a): pale
yellow solid, mp 86–87◦C. δH 7.68 (1H, d, J 16.1, H-2 vinyl),
7.47 (2H, dd, J 8.0 and 1.4, o-H Ph), 7.29–7.34 (3H, m, m-
and p-H Ph), 6.74 (1H, d, J 16.1, H-1 vinyl), 3.84 (3H, s,
CH3). δC 154.8 (C), 139.4 (C), 139.2 (C), 135.3 (CH), 130.0
(CH), 129.2 (CH), 127.7 (CH), 109.6 (CH), 35.7 (CH3). HRMS:
C11H10BrN3 requires[M + H]+ 263.0058;found263.0052. Ele-
mental analysis requires C 50.02, H 3.82, Br 30.25, N 15.91;
found C 50.19, H 3.80, Br 30.05, N 15.96%.
Data for 5-bromo-1-methyl-3-styryl-1H-1,2,4-triazole ( 4a):
paleyellowsolid, mp69–70◦C. δH 7.62(1H, d, J16.1, H-2vinyl),
7.56 (2H, d, J 7.7, o-H Ph), 7.39 (2H, t, J 7.3, m-H Ph), 7.33
(1H, t, J 7.3, p-H Ph), 7.08 (1H, d, J 16.1, H-1 vinyl), 3.88 (1H,
s, CH3). δC 160.6 (C), 136.0 (C), 142.5 (C), 134.5 (CH), 128.7
(CH), 128.6 (CH), 126.9 (CH), 116.8 (CH), 36.8 (CH3). HRMS:
C11H10BrN3 requires[M + H]+ 263.0058;found263.0061. Ele-
mental analysis requires C 50.02, H 3.82, Br 30.25, N 15.91;
found C 50.19, H 3.77, Br 30.36, N 15.98%.
Data for 1-methyl-3,5-distyryl-1H-1,2,4-triazole ( 5a): pale
yellow solid, mp 110–111◦C. δH 7.79 (1H, d, J 16.1, H-2 5-
vinyl), 7.64 (1H, d, J 16.1, H-2 3-vinyl), 7.55–7.61 (4H, m, o-
H Ar and o-H Arꢀ), 7.35–7.43 (4H, m, m-H Ar and m-H Arꢀ),
7.28–7.30 (2H, m, p-H Ar and p-H Arꢀ), 7.07 (1H, d, J 16.1,
H-1 3-vinyl), 6.90 (1H, d, J 16.1, H-1 5-vinyl), 3.96 (3H, s,
CH3). δC 160.9 (C), 153.4 (C), 137.9 (CH), 136.8 (C), 135.8
(C), 134.0 (CH), 129.6 (CH), 129.2 (CH), 129.0 (CH), 128.5
(CH), 127.6 (CH), 127.2 (CH), 117.8 (CH), 110.9 (CH), 35.5
(CH3). HRMS: C19H17N3 requires [M + H]+ 287.1422; found
287.1420. Elemental analysis requires C 79.41, H 5.96, N 14.62;
found C 79.40, H 5.90, N 14.57%.
General Procedures
Method A
A mixture of 1.5 equiv. (328 mg) of bmimPF6, 0.04 equiv.
(6 mg) of PdCl2, and 0.08 equiv. (20 mg) of P(o-tol)3 were placed
in an open microwave vessel equipped with a magnetic stirrer
and heated to 80◦C for 5 min in an oil bath to form the ionic liq-
uid solution of the catalyst.The corresponding vinylarene (2a–e)
(2 equiv.), triethylamine (126 mg, 1.5 equiv.), and 3,5-dibromo-
1-methyl-1H-1,2,4-triazole (1) (200 mg, 1 equiv.) were added,
and the reaction mixture was irradiated at 170◦C for 35 min.
The crude reaction mixture was extracted with ethyl acetate
(3 × 30 mL), the solvent was evaporated under reduced pressure
and the crude product was purified by silica gel flash column
chromatography using hexane/ethyl acetate as the eluent.
Method B
A mixture of 1 equiv. (220 mg) of bmimPF6, 0.015 equiv.
(12 mg) of Herrmann’s palladacycle, 0.03 equiv. (8 mg) of [(t-
Bu)3PH]BF4, 1 equiv. (200 mg) of 3,5-dibromo-1-methyl-1H-
1,2,4-triazole (1), 2 equiv. of the corresponding vinylarene (2a–
e), and 1.5 equiv. (244 mg) of N-methyldicyclohexylamine were
placed in an open microwave vessel and irradiated at 170◦C
for 35 min. The crude reaction mixture was extracted with ethyl
acetate (3 × 30 mL), the solvent was evaporated under reduced
pressure and the crude product was purified by silica gel flash
columnchromatographyusinghexane/ethylacetateastheeluent.
Method C
A mixture of 1 equiv. (80 mg) of bmimPF6, 0.015 equiv.
(4 mg) of Herrmann’s palladacycle, 0.03 equiv. (2 mg) of [(t-
Bu)3PH]BF4, 1 equiv. of monohalogenated 1,2,4-triazole (3b
or 3e), 2 equiv. of the corresponding vinylarene (2a–e), and
1.5 equiv. (90 mg) of N-methyldicyclohexylamine were placed
in an open microwave vessel and irradiated at 170◦C for 35 min.
The crude reaction mixture was extracted with ethyl acetate
(3 × 30 mL), the solvent was evaporated under reduced pressure
and the crude product was purified by silica gel flash column
chromatography using hexane/ethyl acetate 9:1 as the eluent.
Reaction of 3,5-Dibromo-1-methyl-1H-1,2,4-triazole (1)
with 2-Vinylnaphthalene (2b)
Method B. From 2-vinylnaphthalene (256 mg) (2b) and
using hexane/AcOEt 9:1 as the eluent, 3-bromo-1-methyl-
5-[2-(naphthalen-2-yl)vinyl]-1H-1,2,4-triazole (3b) (148 mg,
57%)and1-methyl-3,5-bis[2-(naphthalen-2-yl)vinyl]-1H-1,2,4-
triazole (5b) (84 mg, 26%) were obtained.
Method D
A mixture of 1.5 equiv. (540 mg) of bmimPF6, 0.04 equiv.
(8 mg) of PdCl2, and 0.08 equiv. (28 mg) of P(o-tol)3 were placed
in an microwave vessel equipped with a magnetic stirrer and
heated to 80◦C for 5 min in an oil bath to form the ionic liquid
solution of the catalyst. The 1-phenyl-4-vinyl-1,2,3-triazole (6)
(200 mg, 2equiv.), triethylamine(176 mg, 1.5 equiv.)andthecor-
responding aryl halide (7a–d) (1 equiv.) were added, the vessel
closed and the reaction mixture irradiated at 150◦C for 15 min
in an inert atmosphere (Ar). The crude reaction mixture was
extracted with ethyl acetate (3 × 30 mL), the solvent was evapo-
rated under reduced pressure and the crude product was purified
by silica gel flash column chromatography using hexane/ethyl
acetate 8:1 as the eluent.
Data for 3-bromo-1-methyl-5-[2-(naphthalen-2-yl)vinyl]-
1H-1,2,4-triazole ( 3b): pale yellow solid, mp 160–161◦C. δH
7.91 (1H, d, J 15.7, H-2 vinyl), 7.82–7.92 (4H, m, H-1, -4, -5,
-8 naph), 7.70 (1H, dd, J 8.8 and 1.8, H-3 naph), 7.53–7.49
(2H, m, H-6 and -7 naph), 6.91 (1H, d, J 16.1, H-1 vinyl),
3.95 (3H, s, CH3). δC 154.6 (C), 139.2 (C), 139.0 (CH), 133.9
(C), 133.4 (C), 132.5 (C), 129.0 (CH), 128.7 (CH), 128.5 (CH),
127.6 (CH), 127.1 (CH), 126.8 (CH), 123.0 (CH), 109.5 (CH),
35.7 (CH3). HRMS: C15H12BrN3 requires [M + H]+ 313.0215;
found 313.0212. Elemental analysis requires C 57.34, H 3.85,
Br 25.43, N 13.37; found C 57.45, H 3.89, Br 25.33, N 13.48%.
Data for 1-methyl-3,5-bis[2-(naphthalen-2-yl)vinyl]-1H-1,2,
4-triazole( 5b):paleyellowsolid, mp210–211◦C. δH 7.98(1H, d,

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Á. Díaz-Ortiz et al.
J 16.1, H-2 vinyl-5), 7.83 (1H, d, J 16.1, H-2 vinyl-3), 7.75–7.99
(8H, m, H-1, -4, -5, -8, -1ꢀ, -4ꢀ, -5ꢀ, -8ꢀ naph), 7.44–7.54
(6H, m, H-3, -6, -7, -3ꢀ, -6ꢀ, -7ꢀ naph), 7.20 (1H, d, J 16.1,
H-1 vinyl-3), 7.03 (1H, d, J 15.7, H-1 vinyl-5), 4.01 (3H, s, CH3).
δC 160.7 (C), 153.3 (C), 137.7 (CH), 134.1 (C), 133.8 (CH),
133.6 (C), 133.5 (C), 133.4 (CH), 133.0 (C), 128.7 (CH), 128.4
(CH), 128.3 (CH), 128.2 (CH), 127.8 (CH), 127.7 (CH), 127.6
(CH), 126.8 (CH), 126.7 (CH), 126.4 (CH), 126.2 (CH), 124.4
(C), 124.0 (C), 123.5 (CH), 123.2 (CH), 117.9 (CH), 110.8 (CH),
35.3 (CH3). HRMS: C27H21N3 requires [M + H]+ 387.1735;
found 387.1740. Elemental analysis requires C 83.69, H 5.46,
N 10.84; found C 83.88, H 5.47, N 10.72%.
7.50 (2H, d, J 8.8, o-H Ph), 6.92 (2H, d, J 8.8, m-H Ph), 6.67 (1H,
d, J 15.7, H-1 vinyl), 3.90 (3H, s, OCH3), 3.85 (3H, s, CH3). δC
160.9 (C), 154.9 (C), 139.1 (C), 138.6 (CH), 129.0 (CH), 127.8
(C), 114.4 (CH), 107.0 (CH), 55.4 (OCH3), 35.3 (CH3). HRMS:
C12H12BrN3O requires [M + H]+ 293.0164; found 293.0168.
Elemental analysis requires C 49.00, H 4.11, Br 27.16, N 14.29;
found C 48.78, H 4.02, Br 27.36, N 14.09%.
1-Methyl-5-[2-(naphthalen-2-yl)vinyl]-3-styryl-1H-
1,2,4-triazole (5f)
Method C. From 3-bromo-1-methyl-5-[2-(naphthalen-2-yl)
vinyl]-1H-1,2,4-triazole (100 mg) (3b) and styrene (66 mg)
(2a), 1-methyl-5-[2-(naphthalen-2-yl)vinyl]-3-styryl-1H-1,2,4-
triazole (5f) (64 mg, 60%) was obtained as a pale yellow solid.
Mp 146–147◦C. δH 7.89 (1H, s, H-1 naph), 7.88 (1H, d, J 16.1,
H-2 vinyl-5), 7.75–7.81 (3H, m, H-4, -5, -8 naph), 7.67 (1H, dd,
J 8.4 and 1.5, H-3 naph), 7.59 (1H, d, J 16.1, H-2 vinyl-3), 7.50
(2H, d, J 7.3, o-H Ph), 7.42–7.44 (2H, m, H-6, -7 naph), 7.30
(2H, t, J 7.3, m-H Ph), 7.22 (1H, t, J 7.3, p-H Ph), 7.01 (1H, d, J
16.1, H-1 vinyl-5), 6.93 (1H, d, J 15.7, H-1 vinyl-3), 3.90 (3H,
s, CH3). δC 160.7 (C), 153.3 (C), 137.7 (CH), 136.5 (C), 133.8
(C), 133.7 (CH), 133.5 (C), 133.0 (C), 128.7 (CH), 128.6 (CH),
128.5 (CH), 128.4 (CH), 128.3 (CH), 127.8 (CH), 126.9 (CH),
126.8 (CH), 126.7 (CH), 123.2 (CH), 117.6 (CH), 100.7 (CH),
35.3 (CH3). HRMS: C23H19N3 requires [M + H]+ 337.1579;
found 337.1585. Elemental analysis requires C 81.87, H 5.68, N
12.45; found C 82.06, H 5.55, N 12.31%.
Reaction of 3,5-Dibromo-1-methyl-1H-1,2,4-triazole (1)
with 4-(Trifluoromethyl)styrene (2c)
Method A. From 4-(trifluoromethyl)styrene (286 mg) (2c) and
using hexane/AcOEt 4:1 as the eluent, 3-bromo-1-methyl-5-
[4-(trifluoromethyl)styryl]-1H-1,2,4-triazole (3c) (86 mg, 31%)
and
1-methyl-3,5-bis[4-(trifluoromethyl)styryl]-1H-1,2,4-
triazole (5c) (52 mg, 15%) were obtained.
Data for 3-bromo-1-methyl-5-[4-(trifluoromethyl)styryl]-
1H-1,2,4-triazole ( 3c): white solid, mp 156–157◦C. δH 7.78 (1H,
d, J 15.7, H-2 vinyl), 7.65 (4H, m, o,m-H Ph), 6.90 (1H, d, J 15.7,
H-1 vinyl), 3.95 (3H, s, CH3). δC 154.0 (C), 139.4 (C), 138.4
(CF3), 137.2 (CH), 127.6 (2 × CH), 126.0 (C), 125.9 (C), 111.7
(CH), 35.6 (CH3). HRMS: C12H9BrF3N3 requires [M + H]+
330.9932; found 330.9934. Elemental analysis requires C 43.40,
H 2.73, F 17.16, N 12.65; found C 43.33, H 2.76, F 17.10, N
12.55%.
3-(4-Methoxystyryl)-1-methyl-5-[2-(naphthalen-2-yl)vinyl]-
Data for 1-methyl-3,5-bis[4-(trifluoromethyl)styryl]-1H-1,2,
4-triazole ( 5c): pale yellow oil. δH 7.75 (1H, d, J 15.7, H-2
vinyl-5), 7.56–7.61 (9H, m, H-2 vinyl-3, o,m-H Ar and Arꢀ),
7.07 (1H, d, J 16.1, H-1 vinyl-3), 6.92 (1H, d, J 15.7, H-1 vinyl-
5), 3.93 (3H, s, CH3). δC 160.3 (C), 152.9 (C), 140.0 (CF3),
138.9 (CF3), 136.2 (CH), 132.3 (CH), 129.3 (C), 127.5 (CH),
127.1 (CH), 126.1 (C), 126.0 (CH), 125.9 (CH), 125.8 (C), 125.7
(C), 120.0 (CH), 112.9 (CH), 35.5 (CH3). HRMS: C21H15F6N3
requires [M + H]+ 423.1170; found 423.1166. Elemental anal-
ysis requires C 59.58, H 3.57, F 26.93, N 9.93; found C 59.78,
H 3.66, F 27.01, N 9.81%.
1H-1,2,4-triazole (5g)
Method C. From 3-bromo-1-methyl-5-[2-(naphthalen-2-yl)
vinyl]-1H-1,2,4-triazole (100 mg) (3b) and 4-methoxystyrene
(86 mg) (2e), 3-(4-methoxystyryl)-1-methyl-5-[2-(naphthalen-
2-yl)vinyl]-1H-1,2,4-triazole (5g) (54 mg, 46%) was obtained
as a white solid. Mp 176–177◦C. δH 7.97 (1H, s, H-1 naph),
7.95 (1H, d, J 16.1, H-2 vinyl-5), 7.84–7.88 (3H, m, H-5, -4, -8
naph), 7.75 (1H, d, J 8.8, H-3 naph), 7.62 (1H, d, J 16.1, H-2
vinyl-3), 7.50–7.53 (4H, m, H-6, -7 naph and o-H Ph), 7.01 (1H,
d, J 16.7, H-1 vinyl-5), 6.95 (1H, d, J 16.5, H-1 vinyl-3), 6.92
(2H, d, J 8.8, m-H Ph), 3.98 (3H, s, CH3), 3.84 (3H, s, CH3O).
δC 160.9 (C), 159.8 (C), 153.2 (C), 137.5 (CH), 133.7 (C), 133.5
(C), 133.3 (CH), 133.0 (C), 129.3 (C), 128.7 (CH), 128.6 (CH),
128.4 (CH), 128.2 (CH), 127.7 (CH), 126.8 (CH), 126.7 (CH),
123.2 (CH), 115.4 (CH), 114.2 (CH), 110.8 (CH), 55.3 (OCH3),
35.2 (CH3). HRMS: C24H21N3O requires [M + H]+ 367.1685;
found 367.1684. Elemental analysis requires C 78.45, H 5.76,
N 11.44; found C 78.57, H 5.79, N 11.41%.
Reaction of 3,5-Dibromo-1-methyl-1H-1,2,4-triazole (1)
with 4-Vinylbiphenyl (2d)
Method A. From 4-vinylbiphenyl (300 mg) (2d) and using
hexane/AcOEt 9:1 as the eluent, 5-[2-(biphenyl-4-yl)vinyl]-
3-bromo-1-methyl-1H-1,2,4-triazole (3d) (138 mg, 49%) was
obtained as a white solid. Mp 166–167◦C. δH 7.79 (1H, d, J
15.7, H-2 vinyl), 7.61–7.65 (6H, m, H Ar), 7.46 (2H, t, J 7.3,
H Ar), 7.38 (1H, t, J 7.3, p-H Ar), 6.84 (1H, d, J 15.7, H-1
vinyl), 3.93 (3H, s, CH3). δC 154.6 (C), 142.5 (C), 140.1 (C),
139.2 (C), 138.5 (CH), 134.0 (C), 128.9 (CH), 127.9 (CH), 127.8
(CH), 127.6 (CH), 127.0 (CH), 109.2 (CH), 35.4 (CH3). HRMS:
C17H14BrN3 requires[M + H]+ 339.0371;found339.0369. Ele-
mental analysis requires C 60.02, H 4.15, Br 23.49, N 12.35;
found C 59.86, H 4.26, Br 23.60, N 12.51%.
5-(4-Methoxystyryl)-1-methyl-3-[4-(trifluoromethyl)styryl]-
1H-1,2,4-triazole (5h)
Method C. From 3-bromo-5-(4-methoxystyryl)-1-methyl-1H-
1,2,4-triazole (90 mg) (3e) and 4-(trifluoromethyl)styrene
(104 mg) (2c), 5-(4-methoxystyryl)-1-methyl-3-[4-(trifluoro-
methyl)styryl]-1H-1,2,4-triazole(5h)(92 mg, 79%)wasobtained
as a white solid. Mp 127–128◦C. δH 7.74 (1H, d, J 15.7, H-2
vinyl-5), 7.62–7.66 (5H, m, o- and m-H Arꢀ, H-2 vinyl-3), 7.54
(2H, d, J 8.8, o-H Ar), 7.13 (1H, d, J 16.5, H-1 vinyl-3), 6.94
(2H, d, J 8.8, m-H Ar), 6.76 (1H, d, J 15.7, H-1 vinyl-5), 3.95
(3H, s, CH3O), 3.85 (3H, s, CH3). δC 161.0 (C), 160.2 (C),
154.0 (CF3), 137.8 (C), 133.2 (C), 133.1 (C), 132.1 (CH), 129.1
(CH), 128.4 (CH), 127.2 (CH), 125.9 (CH), 125.8 (CH), 125.6
(C), 120.4 (CH), 114.6 (CH), 55.6 (OCH3), 35.5 (CH3). HRMS:
Reaction of 3,5-Dibromo-1-methyl-1H-1,2,4-triazole (1)
with 4-Methoxystyrene (2e)
Method A. From 4-methoxystyrene (222 mg) (2e) and using
hexane/AcOEt 9:1 as the eluent, 3-bromo-5-(4-methoxystyryl)-
1-methyl-1H-1,2,4-triazole (3e) (132 mg, 54%) was obtained as
a white solid. Mp 137–138◦C. δH 7.71 (1H, d, J 16.1, H-2 vinyl),

Microwave-Controlled Preparation of Alkenyl-(1H)-1,2,4-triazoles
1605
C21H18F3N3O requires [M + H]+ 385.1402; found 385.1400.
Elemental analysis requires C 65.45, H 4.71, F 14.79, N 10.90;
found C 65.40, H 4.56, F 14.90, N 11.03%.
requires [M + H]+ 277.1215; found 277.1221. Elemental anal-
ysis requires C 73.63, H 5.45, N 15.15; found C 73.59, H 5.49,
N 15.22%.
4-[2-(Naphthalen-1-yl)vinyl]-1-phenyl-1H-1,2,3-
triazole (8d)
3-[2-(Biphenyl-4-yl)vinyl]-5-(4-methoxystyryl)-1-methyl-
1H-1,2,4-triazole (5i)
Method D. From 1-iodonaphthalene (360 mg) (7d), 4-[2-
Method C. From 3-bromo-5-(4-methoxystyryl)-1-methyl-1H-
1,2,4-triazole(90 mg)(3e)and4-vinylbiphenyl(108 mg)(2d), 3-
[2-(biphenyl-4-yl)vinyl]-5-(4-methoxystyryl)-1-methyl-1H-1,2,
4-triazole (5i) (148 mg, 61%) as a pale yellow solid. Mp 185–
186◦C. δH 7.77 (1H, d, J 15.7, H-2 vinyl-5), 7.67 (1H, d, J 16.5,
H-2 vinyl-3), 7.60–7.64 (6H, m, o-HAr, m-HAr, o-HArꢀ), 7.53–
7.55 (2H, d, J 8.8, o-H Ph-OMe), 7.44 (2H, d, J 7.3, m-H Arꢀ),
7.35 (1H, t, p-HArꢀ), 7.10 (1H, d, J 16.1, H-1 vinyl-3), 6.94 (2H,
d, J 8.8, m-H Ph-OMe), 6.76 (1H, d, J 15.7, H-1 vinyl-5), 3.94
(3H, s, CH3O), 3.85 (3H, s, CH3). δC 160.6 (C), 160.5 (2 × C),
153.6 (C), 140.9 (C), 140.6 (C), 137.3 (CH), 135.6 (C), 133.0
(CH), 128.8 (CH), 128.3 (C), 127.4 (CH), 127.3 (CH), 126.9
(CH), 117.7 (CH), 114.3 (CH), 109.7 (CH), 108.3 (CH), 55.3
(OCH3), 35.1 (CH3). HRMS: C26H23N3O requires [M + H]+
393.1841; found 393.1844. Elemental analysis requires C 79.36,
H 5.89, N 10.68; found C 79.52, H 5.98, N 10.51%.
(naphthalen-1-yl)vinyl]-1-phenyl-1H-1,2,3-triazole
(8d)
(186 mg, 54%) was obtained as a white solid. Mp 171–172◦C.
δH 8.3 (1H, d, J 8, H-5 naph), 8.2 (1H, d, J 16.1, H-2 vinyl), 8.1
(1H, s, H-5), 7.8–7.9 (5H, m), 7.4–7.5 (6H, m), 7.2 (1H, d, J 16.1,
H-1 vinyl). δC 146.9 (C), 137.0 (C), 134.3 (C), 133.7 (C), 131.3
(C), 129.8 (CH), 128.7 (CH), 128.6 (CH), 128.5 (CH), 128.4
(CH), 126.3 (CH), 125.9 (CH), 125.6 (CH), 123.8 (CH), 123.6
(CH), 120.5 (CH), 119.1 (CH), 118.5 (CH). HRMS: C20H15N3
requires [M + H]+ 297.1266; found 297.1271. Elemental anal-
ysis requires C 80.78, H 5.08, N 14.13; found C 80.89, H 4.97,
N 14.03%.
Accessory Publication
Temperature–time profile of all the reactions conducted with a
Discover® CEM microwave reactor are available on the Journal’s
website.
4-(3,5-Dimethylstyryl)-1-phenyl-1H-1,2,3-triazole (8a)
Acknowledgements
Method D. From 1-iodo-3,5-dimethylbenzene (300 mg) (7a), 4-
(3,5-dimethylstyryl)-1-phenyl-1H-1,2,3-triazole (8a) (238 mg,
74%) was obtained as a white solid. Mp 126–127◦C. δH 7.98
(1H, s, H-5), 7.77 (2H, d, J 7.3, o-H Ar), 7.53 (2H, t, J 6.6,
m-H Ar), 7.44 (1H, d, J 6.6, p-H Ar), 7.35 (1H, d, J 16.4, H-2
vinyl), 7.25 (2H, s, o-H Arꢀ), 7.11 (1H, d, J 16.6, H-1 vinyl),
6.94 (1H, s, p-HArꢀ), 2.34 (6H, s, 2 × CH3). δC 147.2 (C), 138.4
(CH), 137.2 (C), 136.8 (C), 131.7 (CH), 130.1 (CH), 130.0 (CH),
128.9(CH), 124.7(CH), 120.7(CH), 118.3(CH), 116.2(C), 21.5
(CH3). HRMS: C18H17N3 requires [M + H]+ 275.1422; found
275.1425. Elemental analysis requires C 78.52, H 6.22, N 15.26;
found C 78.66, H 6.10, N 15.17%.
Financial support from the DGICYT of Spain through project CTQ2007–
60037/BQU and from the Consejería de Educación y Ciencia, JCCM through
projects PCI08–0040 and PII2I09–0100–9633 is gratefully acknowledged.
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