One-pot microwave-assisted solvent free synthesis of simple alkyl 1,2,3-triazole-4-carboxylates by using trimethylsilyl azide

Article abstract of DOI:10.1002/jhet.36

A fast one-pot microwave-assisted solvent free synthesis of simple alkyl 1,2,3-triazole-4-carboxylate derivatives by 1,3-dipolar cycloaddition reactions with trimethylsilyl azide (Me₃Si-N₃) on the alkylpropiolates and DMAD in high yi

Full text of DOI:10.1002/jhet.36

January 2009
One-Pot Microwave-Assisted Solvent Free Synthesis of
Simple Alkyl 1,2,3-Triazole-4-carboxylates by Using
Trimethylsilyl Azide
131
Avat Arman Taherpoura* and Khojasteh Kheradmanda,b
aChemistry Department, Science Faculty, Arak I.A. University, PO Box 38135-567 Arak, Iran
bYoung Researchers Club Branch of Arak, Islamic Azad University, PO Box 38135-567 Arak, Iran
*E-mail: avatarman.taherpour@gmail.com
Received February 4, 2008
DOI 10.1002/jhet.36
Published online 11 February 2009 in Wiley InterScience (www.interscience.wiley.com).
A fast one-pot microwave-assisted solvent free synthesis of simple alkyl 1,2,3-triazole-4-carboxylate
derivatives by 1,3-dipolar cycloaddition reactions with trimethylsilyl azide (Me3Si-N3) on the alkylpro-
piolates and DMAD in high yields is described.
J. Heterocyclic Chem., 46, 131 (2009).
INTRODUCTION
harsh conditions, that is, high temperature and longer
reaction times. In the original description, the explored
examples showed that although these were relatively
clean processes, they could take from 12 to 48 h at high
temperatures (ꢀ110ꢁC) [19]. Several examples of Cu(I)-
catalyzed alkyne-azide 1,3-dipolar cycloaddition under
milder conditions have been described. The mechanistic
proposal of the Cu(I)-catalyzed alkyne-azide 1,3-dipolar
cycloaddition was reported and found to involve polar
transition states, favorable for microwave activation [25].
These Huisgen 1,3-dipolar cycloaddition of azides and
alkynes resulting in 1,2,3-triazoles is one of the most
powerful click reactions [14,24–26]. An example of
microwave-assisted azide-alkyne cycloaddition was
reported by Katritzky and Singh [11]. The reactions
involved primary azides and acetylenic amide. Recently,
the synthesis of simple alkyl 1,2,3-triazole-4-carboꢂxylate
derivatives was reported by reaction between N3 and
alkylpropyolates [27–30]. The total reaction time was 48
h [29,30]. In another report, the reaction time for synthe-
sis of 2, 4, and 6 was 90 h [30].
The synthesis of important compounds with many
applications in chemistry and medicinal area has been
observed in the literature. Microwave-assisted synthesis
has been utilized as a powerful and effective technique to
promote a group of chemical reactions [1–9]. Since the
first publications on the use of microwave irradiation in
organic chemistry, the accelerated process described have
been a lure for chemists to further apply new reactions to
this technology [10]. Huisgen’s 1,3-dipolar cycloaddition
of alkynes and azides yielding triazoles is, undoubtedly,
the premier example of click chemistry reactions [11–21].
This type of reaction is an effective and excellent reaction
for preparation of 1,2,3-triazoles. 1,2,3-Triazoles are
known to be relatively resilient to metabolic degradation
and have known utility in several medicinal chemistry
campaigns as isosteres for phenyl rings and carboxyl func-
tionalities [19]. The triazoles may display a wide range of
biological activity as anti-HIV and antimicrobial agents,
as well as selective b3 adrenergic receptor agonist and
antiallergic agents [20–23]. Additionally, 1,2,3-triazoles
are found in herbicides, fungicides, and dyes [14,24].
Because of these interesting activities, fast and new
methods for the synthesis of these compounds should be
significant. In general, 1,2,3-triazole formation requires
Here, was reported a fast one-pot microwave-assisted
(60 W, 10 min) solvent free synthesis of simple alkyl
1,2,3-triazole-4-carboxylate (2, 4, and 6) derivatives by
1,3-dipolar cycloaddition reactions with trimethylsilyl
C
V
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A. A. Taherpour and K. Kheradmand
Vol 46
Methyl-1H-1,2,3-triazole-4-carboxylate (2). White crystals,
mp 127–128ꢁC (lit. 126–128ꢁC) [27–30]. FTIR (KBr): 3150
(NAH), 3138, 3005, 2937, 1708 (C¼¼O), 1660, 1538, 1480,
(DMSO): 8.56 (s, 1H), 3.83 (s, 3H). 13C NMR: 161, 138.8,
130.1, and 51.83. MS: m/z (relative intensity), Mw ¼ 127; 127
(Mþ, 8.8), 95 (70.6), 96 (100), 78 (17.6), and 63 (18.5).
C4H5N3O2, CHN-analysis; calculated: C (37.80%), H (3.97%),
and N (33.06%), experiment: C (37.73%), H (3.95%), and N
(33.01%).
azide II (Me3Si-N3) on the alkylpropyolates (1,3) and
DMAD (5) in high yields.
1432, 1352, 1212, 1116, 1023, 843, 779 cmꢂ1 1H NMR dH
.
RESULTS AND DISCUSSION
The results show that the trimethylsilyl (Me3Si-) was
removed at the final simple alkyl 1,2,3-triazole-4-car-
boxylate (2, 4, and 6) products. No details are given
about the by-products and only the final products are
considered.
The 13C NMR results show 4, 5, and 3 C-atom types
for 2, 4, and 6, respectively. See results in the Experi-
mental section. The [Mþ] for 2, 4, and 6, were 127, 141,
and 185, respectively. The percentages of C, H, and N
are explained in the Experimental section. In accordance
with the results that were shown in the Experimental sec-
tion the MS (and CI) spectrums and CHN analysis dem-
onstrated that the trimethylsilyl (Me3Si-) was removed
from the products during the synthesis process.
Ethyl-1H-1,2,3-triazole-4-carboxylate (4). White crystals,
mp 102–104ꢁC (lit. 102–104ꢁC) [27–30]. FTIR (KBr): 3224
(NAH), 3167, 2986, 1723 (C¼¼O), 1661, 1533, 1466, 1375,
1332, 1238, 1202, 1114, 1029, 843, 780 cmꢂ1 1H NMR dH
.
(DMSO): 8.46 (s, 1H), 4.27–4.35 (q, 2H, 7.0 Hz) and 1.27–
1.32 (t, 3H, 7.0 Hz). 13C NMR: 160.4, 138.2, 131.4, 60.4, and
14.0. MS: m/z (relative intensity); Mw ¼ 141; CI ¼ 141
(6.82), 113 (47.73), 95 (100), 71, 68 (78.5), and 44 (34.1).
C5H7N3O2, CHN-analysis; calculated: C (42.55%), H (5.00%),
and N (29.77%), experiment: C (42.50%), H (5.03%), and N
(29.74%).
Dimethyl-1H-1,2,3-triazole-4,5-carboxylate
(6). White
crystals, mp 116–118ꢁC (lit. 117–118ꢁC) [27–30]. FTIR
(KBr): 3239 (NAH), 3100, 2996, 2861, 1742 (C¼¼O), 1658,
1519, 1437, 1389, 1304, 1228, 1190, 1084, 990, 833, 767
EXPERIMENTAL
1
cmꢂ1. H NMR dH (DMSO): 3.87 (s). 13C NMR: 160.2, 131.0,
The simple imides that were synthesized (2, 4, and 6), are
known compounds and those physical data, infrared and 1H
NMR spectra were essentially identical with those of authentic
samples [27–30]. The FTIR spectra was recorded as KBr pel-
and 52.4. MS: m/z (relative intensity); Mw ¼ 185; 187 (M2Hþ,
38.2), 154 (67.65), 124 (58.8), 93, 58, and 43 (100).
C6H7N3O4, CHN-analysis; calculated: C (38.92%), H (3.81%),
and N (22.70%), experiment: C (38.98%), H (3.85%), and N
(22.66%).
1
lets on a Shimadzu FTIR 8000 spectrometer. H NMR spectra
was determined on a 300 MHz Bru¨ker spectrometer. The sol-
vent for NMR recording was DMSO. It should be noted that a
limited amount of compounds is required for this experiment.
Therefore some small quality of vapor is evolved during irradi-
ation. The power generated by the microwave oven was mea-
sured before the experiments by the method described in the
literature [31].
Caution: For safety reasons all of the experiments should be
performed in an efficient hood in order to avoid contact with
vapors, as some quantity of substances can be vaporized
during irradiation.
The simple one-pot microwave assisted solvent free synthe-
sis of useful alkyl 1,2,3-triazole-4-carboxylate derivatives (2,
4, and 6) by Huisgen 1,3-dipolar cycloaddition reactions with
trimethylsilyl azide (Me3Si-N3) on the alkylpropyolates 1,3
and DMAD (5), in high yields is described. Comparison of
this procedure with the other methods confirms the facility and
rapidity of this method for synthesis of the alkyl 1,2,3-triazole-
4-carboxylate derivatives.
Acknowledgments. The authors gratefully acknowledge Profes-
sor Curt Wentrup and the colleagues in Chemistry Department of
The University of Queensland-Australia, for their useful sugges-
tions. The authors are grateful to the Research Council of Science
and Research Campus and Arak branch of I.A. University for
supporting this study.
Typical experimental procedure for synthesis of methyl-
1H-1,2,3-triazole-4-carboxylate (2). A mixture of methyl-pro-
piolate 1 (1 g, 1 mL, 0.012 mol) and trimethylsilyl azide
(Me3Si-N3) II (1.2 g, 1.5 mL, 0.012 mol) was made in a dried
heavy wall Pyrex tube. The tube was sealed and then exposed
to microwave oven. After 10 min irradiation at 60 W power,
the mixture was cooled to room temperature. The residue of
compounds was evaporated under air and reduced pressure. An
off-white solid was afforded. The product 2 can be re-crystal-
lized from chloroform þ acetone and petroleum ether. These
stages afforded 0.049 g product (workup yield 82% and GC
yield ꢃ100%).
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One-Pot Microwave-Assisted Solvent Free Synthesis of Simple Alkyl
1,2,3-Triazole-4-carboxylates by Using Trimethylsilyl Azide
133
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet