Reaction of 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides/isothiocyanates with 3-amino-5-methylisoxazole

Article abstract of DOI:10.1080/10426507.2010.548840

1-Aryl-1H-1,2,3-triazole-4-carbonyl chlorides were selected as starting materials for the Boulton-Katritzky rearrangement. When 3-amino-5- methylisoxazole was acylated by 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides, 1-aryl-5-methyl-N-(5-methylisoxazol-3

Full text of DOI:10.1080/10426507.2010.548840

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Phosphorus, Sulfur, and Silicon and the
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Reaction of 1-Aryl-1H-1,2,3-Triazole-4-
Carbonyl Chlorides/Isothiocyanates with
3-Amino-5-Methylisoxazole
Nazariy T. Pokhodylo a & Vasyl S. Matiychuk a
a Department of Organic Chemistry, Ivan Franko National University
of Lviv, Lviv, Ukraine
Published online: 24 Aug 2011.
To cite this article: Nazariy T. Pokhodylo & Vasyl S. Matiychuk (2011) Reaction of 1-Aryl-1H-1,2,3-
Triazole-4-Carbonyl Chlorides/Isothiocyanates with 3-Amino-5-Methylisoxazole, Phosphorus, Sulfur,
and Silicon and the Related Elements, 186:9, 1895-1901, DOI: 10.1080/10426507.2010.548840
To link to this article: http://dx.doi.org/10.1080/10426507.2010.548840
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Phosphorus, Sulfur, and Silicon, 186:1895–1901, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.548840
REACTION OF 1-ARYL-1H-1,2,3-TRIAZOLE-4-CARBONYL
CHLORIDES/ISOTHIOCYANATES WITH
3-AMINO-5-METHYLISOXAZOLE
Nazariy T. Pokhodylo and Vasyl S. Matiychuk
Department of Organic Chemistry, Ivan Franko National University of Lviv,
Lviv, Ukraine
GRAPHICAL ABSTRACT
N
S
O
Me
O
O
N
Me
N
N
N
H
N
N
N
N
O
O
Cl
N
H
N
N
N
N
R1
R1
3a-l
R1
R2
6a-g
R2
5a-e
R2
Abstract 1-Aryl-1H-1,2,3-triazole-4-carbonyl chlorides were selected as starting materi-
als for the Boulton–Katritzky rearrangement. When 3-amino-5-methylisoxazole was acylated
by 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides, 1-aryl-5-methyl-N-(5-methylisoxazol-3-yl)-
1H-1,2,3-triazole-4-carboxamides 5 were obtained and no further rearrangement occurred.
On the other hand, when 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides were first converted
into isothiocyanates by the reaction with KSCN and then were allowed to react with 3-amino-
5-methylisoxazole 4 in one pot, intermediate thioureas were formed and spontaneously trans-
formed in statu nascendi into 1,2,4-thiadiazole derivatives 6.
Keywords 1H-1; 2; 3-triazole; isoxazole; 1; 2; 4-thiadiazole; Boulton–Katritzky rearrangement
INTRODUCTION
The scope of the application of the Boulton–Katritzky rearrangement1 in organic syn-
thesis is gradually increasing due to the fact that such reactions are used for the preparation of
unique imidazoles,2 pyrazoles,3 1,2,3-triazoles,4 1,3,4-triazoles,5 tetrazoles,6 oxadiazoles,7
thiadiazoles,8 and their derivatives. The Boulton–Katritzky rearrangement was thoroughly
reviewed by Ruccia et al.9a and Vivona et al.,9b and several other reviews focused on
molecular rearrangements of azoles.10
In 1967, Boulton et al. suggested a new rearrangement of azoles (see Scheme 1),
which included azole–azole interconversions limited to heterocycles containing the N–O
bond, such as isoxazoles, 1,2,4-oxadiazoles, and 1,2,5-oxadiazoles, where the nucleophilic
side chain at C-3 (X Y-ZH) was a hetero-allyl moiety. The reactivity of substrates depends
Received 30 October 2010; accepted 13 December 2011.
Address correspondence to Nazariy T. Pokhodylo, Department of Organic Chemistry, Ivan Franko National
University of Lviv, Kyryla i Mefodiya St. 6, Lviv 79005, Ukraine. E-mail: pokhodylo@gmail.com
1895

1896
N. T. POKHODYLO AND V. S. MATIYCHUK
on the nucleophilicity of the side chain and continuous π-electron system extended over
the reaction center in the transition state. Such reactions usually occur on heating with or
without a base, sometimes in the presence of copper powder.9,10 Generally, the scope of the
Boulton–Katritzky rearrangement has not been fully elaborated yet.
A
A
X
X
zY
B
B
Y
DH
D N
N
ZH
A, B, D, X, Y, Z = C, N, O, S
Scheme 1
RESULTS AND DISCUSSION
3-Aminoisoxazoles are one of the most suitable and available precursors of com-
pounds applied in the Boulton–Katritzky rearrangement due to the lability of the isoxazole
ring and the fact that the fragment required for rearrangement can be readily formed via
acylation, heterocumulenes additions, or azocoupling reactions. In the current paper, we fo-
cused on the reactions between 1H-1,2,3-triazole-4-carbonyl chlorides and isothiocyanates
with 3-amino-5-methylisoxazole for the preparation of new 1,2,4-oxadiazole and 1,2,4-
thiadiazole derivatives containing 1H-1,2,3-triazole fragment. Previously, the reactions
of 3-amino-5-methylisoxazole have been studied with phenyl isothiocyanate,11 adaman-
tanecarbonyl isothiocyanate12 and 3-aryl-1-phenyl-4-pyrazolecarbonyl isothiocyanates13
and ethoxycarbonyl isothiocyanate.14 Moreover, 3-aminoisoxazole15,16a and 3-amino-5-
methoxyisoxazole16 were used for synthesis of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-
methoxyiminoacetic acid as a side chain of the of cephem antibiotics. In all cases, 1,2,4-
thiadiazole derivatives were prepared in good yields by a simple procedure.
Herein, the reactions of 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides with 3-amino-
5-methylisoxazole were studied. We presumed that such kind of reactions could be con-
venient for the synthesis of new derivatives of 1-aryl-1H-1,2,3-triazole-4-carboxylic acids,
which were in focus of research as potential biologically active substances.17 First, 1-
aryl-1H-1,2,3-triazole-4-carbonyl chlorides 3a–e were allowed to react with 3-amino-5-
methylisoxazole 4 in acetonitrile at 70 ◦C for 5 h in the presence of two equivalents of Et3N.
However, only compounds 5 were obtained and, no rearrangement products were isolated.
We were unsuccessful in our attempts to apply amides 5 in the Boulton–Katritzky rearrange-
ment. Increases in temperature and the application of various bases and solvents (e.g., the
following base/solvent systems were tested: Et3N/acetonitrile, Et3N/dioxane, Potassium-
tert-butoxide (t-BuOK)/dimethyl sulfoxide (DMSO), potassium hydroxide (KOH)/ ethanol
(EtOH), pyridine) did not effect the formation of compounds type A, and as a result,
compounds 5 or a complex mixture of tarry products were isolated. We suggest that the
equilibrium between isoxazoles 5 and 1,2,4-oxadiazoles A is totally shifted to isoxazoles
5 due to electron withdrawing character of the 1,2,3-triazole ring, which stabilizes the
carbamoyl group in 5.
Continuing the research, 1-aryl-1H-1,2,3-triazole-4-carbonyl chlorides 3f–l were
converted in situ into corresponding isothiocyanates, which were allowed to react with
3-amino-5-methylisoxazole 4 in one pot. Stirring of 1,2,3-triazole-4-carbonyl chlorides

REACTION OF 1-ARYL-1H-1,2,3-TRIAZOLE-4-CARBONYL CHLORIDES . . .
Table 1 Synthesis of 1H-1,2,3-triazole derivatives 5a–e, 6a–g
1897
Entry
Compound
R1
R2
Yielda (%)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
6a
6b
6c
6d
6e
6f
Me
Ме
Ме
Ме
Ме
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
4-Et
4-i-Pr
4-Bu
3,4-Me2
2-Me-5-Cl
H
3-Me
4-Me
4-Cl
93
95
79
97
80
88
76
94
97
84
88
95
10
11
12
4-Br
3-CF3
4-MeO
6g
aIsolated yields of compounds 5a–e, 6a–g.
◦
3f–l with KSCN in acetonitrile at 60 C for 30 min followed by the addition of 3-
amino-5-methylisoxazole 4 afforded 1,2,4-thiadiazoles in high yields (76%–97%, Table
1). The mechanism of such reactions includes two stages: a rapid formation of intermediate
thioureas B and their spontaneous transformation in statu nascendi into thiadiazoles 6 by
the attack of the nucleophilic thiocarbonyl group on the N–O bond of the isoxazole ring.
This is confirmed by the fact that no traces of thioureas B were found after the reaction
(see Scheme 2). The yields of the products 6a–g weakly depended on the nature of aro-
matic substituent and were high in general. Furthermore, iso-propyl moiety caused no steric
problems while adding amine 4 to the isothiocyanate group.
For 3a-
e
Me
H2N
Me
O
O
O
N
N
N
N
O
N
N
N
O
Cl
N
H
4
N
N
N
N
N
R1
R1
5a
N
Et3N
MeCN
Me
R1
O
R2
-e
R2
3a
-l
R2
A
3a; R1 = Me, R2 = 4-Et
3d; R1 = Me, R2 = 3,4-Me2
3e; R1 = Me, R2 = 2-Me-5-Cl
3b; R1 = Me, R2 = 4-i-Pr
3c; R1 = Me, R2 = 4-Bu
For 3f-l
N
N
S
O
O
S
H2N
Me
KSCN
MeCN
N
Me
N
H
N
N
N
4
O
N
H
O
N
NH
N
R1
R1
N
N
O
R2
6a
-g
Me
3f; R1 = i-Pr, R2 = H
3g; R1 = i-Pr, R2 = 3-Me
3h; R1 = i-Pr, R2 = 4-Me
B
R2
3j; R1 = i-Pr, R2 = 4-Br
3i; R1 = i-Pr, R2 = 4-Cl
3k; R1 = i-Pr, R2 = 3-CF3
3l; R1 = i-Pr, R2 = 4-MeO
Scheme 2

1898
N. T. POKHODYLO AND V. S. MATIYCHUK
The obtained compounds 5 and 6 were colorless crystalline compounds. Their com-
position was proved by elemental analysis, and their structures were confirmed by 1H NMR.
1
In the H NMR spectra of compounds 5a–e, characteristic singlets of methyl (2.43–2.44
ppm) and isoxazole (6.43, 6.68–6.69 ppm) protons were found. On the contrary, two singlet
peaks of methyl (2.21–2.22 ppm) and methylene (3.96–3.97 ppm) protons of the acetone
fragment in 3 position of the thiadiazole ring were observed for compounds 6a–g.
It is noteworthy that products containing 1,2,4-thiadiazole ring have been the subject
of increasing interest because of progressive biological activity studies of this class of com-
pounds.18 There are many methods for preparation of disubstituted 1,2,4-thiadiazoles but
only a few of them are suitable for wide variation of substituents required by combinatorial
and medicinal chemistry. The synthetic path to 1,2,4-thiadiazoles presented in the article
made possible structure variations of 6a–g by simple replacement of substituents in the
aryl, triazole, or isoxazole rings allowing the discovery of new drug candidates.
EXPERIMENTAL
All melting points were determined in capillary tubes in a Thiele apparatus and
1
are uncorrected. H NMR spectra were recorded on a Varian Mercury 400 instrument
1
1
(400 MHz for H). The H chemical shifts were reported in parts per million relative to
tetramethylsilane or deuterated solvent as an internal reference. Mass spectra were run using
Agilent 1100 series LC/MSD with an API-ES/APCI ionization mode. The evolution of the
reactions and purity of the synthesized compounds were monitored chromatographically on
Silufol UV-254 plates. 1-Aryl-1H-1,2,3-triazole-4-carbonyl chlorides 3a–l were prepared
according to the procedures described in the literature.19
General Procedure for 1-Aryl-5-Methyl-N-(5-Methylisoxazol-3-yl)-
1H-1,2,3-Triazole-4-Carboxamides (5a–e) Synthesis
The appropriate acid chloride 3 (5 mmol) was added to the solution of 3-
aminoisoxazole 4 (5 mmol) in acetonitrile 20 mL. The mixture was heated under reflux for
30 min, cooled, and diluted with water 50 mL. The precipitate was filtered off, washed on
a filter with water (up to 50 mL), dried in air, and purified by crystallization from ethanol
EtOH.
1-(4-Ethylphenyl)-5-methyl-N-(5-methylisoxazol-3-yl)-1H-1,2,3-triazole-4-carbo
xamide (5a). Yield: 0.29 g (93%); white crystals; mp 133–134 ◦С. 1H NMR (DMSO-d6):
δ 1.31 (t, J = 7.6 Hz, 3H, Et), 2.44 (s, 3H, Me), 2.60 (s, 3H, Me), 2.77 (q, J = 7.5 Hz,
2H, НAr-3,5), 6.69 (s, 1H, isoxazole), 7.45 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H,
НAr-2,6), 10.79 (s, 1H, NH). MS (CI): m/z (%) = 312 (100%) [M+H+]. Anal. Calcd. for
C16H17N5O2 (311.34): C 61.72, H 5.50, N 22.49. Found: C 61.44, H 5.71, N 22.36.
5-Methyl-1-[4-(1-methylethyl)phenyl]-N-(5-methylisoxazol-3-yl)-1H-1,2,3-tria
zole-4-carboxamide (5b). Yield: 0.31 g (95%); white crystals; mp 132–133 ◦С. 1H NMR
(DMSO-d6): δ 1.30 (d, J = 4.2 Hz, 6H, i-Pr), 2.43 (s, 3H, Me), 2.58 (s, 3H, Me), 3.00–3.07
(m, 1H, i-Pr), 6.68 (s, 1H, isoxazole), 7.45–7.49 (m, 4H, НAr), 10.78 (s, 1H, NH). MS
(CI): m/z (%) = 326 (100%) [M+H+]. Anal. Calcd. for C17H19N5O2 (325.36): C 62.75, H
5.89, N 21.52. Found: C 62.45, H 5.72, N 21.37.
1-(4-Butylphenyl)-5-methyl-N-(5-methylisoxazol-3-yl)-1H-1,2,3-triazole-4-car
boxamide (5c). Yield: 0.27 g (79%); white crystals; mp 144–145 ◦С. 1H NMR (DMSO-d6):
δ 0.97 (t, J = 7.3 Hz, 3H, Bu), 1.40 (sext., J = 8.2 Hz, 2H, Bu), 1.62–1.72 (m, 2H, Bu),

REACTION OF 1-ARYL-1H-1,2,3-TRIAZOLE-4-CARBONYL CHLORIDES . . .
1899
2.44 (s, 3H, Me), 2.60 (s, 3H, Me), 2.73 (t, J = 7.6 Hz, 2H, Bu), 6.69 (s, 1H, isoxazole),
7.43 (d, J = 8.4 Hz, 2H, НAr-3,5), 7.49 (d, J = 8.4 Hz, 2H, НAr-2,6), 10.76 (s, 1H, NH).
MS (CI): m/z (%) = 340 (100%) [M+H+]. Anal. Calcd. for C18H21N5O2 (339.39): C
63.70, H 6.24, N 20.64. Found: C 63.91, H 6.08, N 20.74.
1-(3,4-Dimethylphenyl)-5-methyl-N-(5-methylisoxazol-3-yl)-1H-1,2,3-triazole-4-
1
carboxamide (5d). Yield: 0.30 g (97%); white crystals; mp 143–144 ◦С. H NMR
(DMSO-d6): δ 2.36 (s, 6H, Me), 2.43 (s, 3H, Me), 2.57 (s, 3H, Me), 6.68 (s, 1H, isoxazole),
7.27 (dd, J = 7.8, 2.3 Hz, 1H, НAr-6), 7.34 (d, J = 2.0 Hz, 1H, НAr-2), 7.36 (d, J = 8.2 Hz,
1H, НAr-5), 10.75 (s, 1H, NH). MS (CI): m/z (%) = 312 (100%) [M+H+]. Anal. Calcd.
for C16H17N5O2 (311.34): C 61.72, H 5.50, N 22.49. Found: C 61.86, H 5.33, N 22.31.
1-(5-Chloro-2-methylphenyl)-5-methyl-N-(5-methylisoxazol-3-yl)-1H-1,2,3-tria
zole-4-carboxamide (5e). Yield: 0.26 g (80%); white crystals; mp 207–208 ◦С. 1H NMR
(DMSO-d6): δ 1.93 (s, 3H, Me), 2.43 (s, 3H, Me), 2.51 (s, 3H, Me), 6.43 (s, 1H, isoxazole),
7.51 (d, J = 8.4 Hz, 1H, НAr-3), 7.54 (d, J = 1.7 Hz, 1H, НAr-6), 7.57 (dd, J = 8.2, 2.0 Hz,
1H, НAr-4), 10.87 (s, 1H, NH). MS (CI): m/z (%) = 332 (100%) [M+H+]. Anal. Calcd.
for C15H14ClN5O2 (331.76): C 54.30, H 4.25, N 21.11. Found: C 54.21, H 4.43, N 21.00.
General Procedure for 5-(1-Methylethyl)-N-[3-(2-Oxopropyl)-1,2,4-
Thiadiazol-5-yl]-1-Aryl-1H-1,2,3-Triazole-4-Carboxamides (6a–g)
Synthesis
To a solution of acid chloride 3 0.001 mol in acetonitrile 10 mL, KSCN 0.0011 mol
was added under vigorous stirring. The mixture was stirred at 60 ◦C for 30 min and 0.098
g (0.001 mol) of 3-aminoisoxazole 4 was added. The mixture was left for stirring at 60 ◦C
for 1 h, then cooled to room temperature, and diluted with water (20 mL). The precipitate
formed was filtered off and recrystallized.
5-(1-Methylethyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-1-phenyl-1H-1,2,3-
◦
1
triazole-4-carboxamide (6a). Yield: 0.32 g (88%); white crystals; mp 146–147 С. H
NMR (DMSO-d6): δ 1.38 (d, J = 7.0 Hz, 6H, i-Pr), 2.22 (s, 3H, Me), 3.24–3.33 (m, 1H,
i-Pr), 3.97 (s, 2H, CH2), 7.64–7.72 (m, 5H, НPh), 13.32 (s, 1H, NH). MS (CI): m/z (%) =
371 (100%) [M+H+]. Anal. Calcd. for C17H18N6O2S (370.43): C 55.12, H 4.90, N 22.69.
Found: C 55.25, H 4.71, N 22.48.
5-(1-Methylethyl)-1-(3-methylphenyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-
1H-1,2,3-triazole-4-carboxamide (6b). Yield: 0.29 g (76%); white crystals; mp 152–153
◦С. 1H NMR (DMSO-d6): δ 1.38 (d, J = 7.0 Hz, 6H, i-Pr), 2.21 (s, 3H, Me), 2.49 (s, 3H,
Me), 3.23–3.32 (m, 1H, i-Pr), 3.97 (s, 2H, CH2), 7.29 (d, J = 7.6 Hz, 1H, НAr-4), 7.33
(s, 1H, НAr-2), 7.46 (d, J = 7.7 Hz, 1H, НAr-6), 7.52 (t, J = 7.7 Hz, 1H, НAr-5), 13.28
(s, 1H, NH). MS (CI): m/z (%) = 385 (100%) [M+H+]. Anal. Calcd. for C18H20N6O2S
(384.45): C 56.23, H 5.24, N 21.86. Found: C 56.16, H 5.38, N 21.78.
5-(1-Methylethyl)-1-(4-methylphenyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-
yl]-1H-1,2,3-triazole-4-carboxamide (6c). Yield: 0.36 g (94%); white crystals; mp
148–149 ◦С. 1H NMR (DMSO-d6): δ 1.36 (d, J = 7.0 Hz, 6H, i-Pr), 2.21 (s, 3H, Me), 2.48
(s, 3H, Me), 3.22–3.32 (m, 1H, i-Pr), 3.96 (s, 2H, CH2), 7.38 (d, J = 8.3 Hz, 2H, НAr-3,5),
7.43 (d, J = 8.2 Hz, 2H, НAr-2,6), 13.27 (s, 1H, NH). MS (CI): m/z (%) = 385 (100%)
[M+H+]. Anal. Calcd. for C18H20N6O2S (384.45): C 56.23, H 5.24, N 21.86. Found: C
56.40, H 5.09, N 21.83.
1-(4-Chlorophenyl)-5-(1-methylethyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-
1H-1,2,3-triazole-4-carboxamide (6d). Yield: 0.39 g (97%); white crystals; mp 151–152

1900
N. T. POKHODYLO AND V. S. MATIYCHUK
1
◦С. H NMR (DMSO-d6): δ 1.37 (d, J = 7.0 Hz, 6H, i-Pr), 2.22 (s, 3H, Me), 3.22–3.32
(m, 1H, i-Pr), 3.97 (s, 2H, CH2), 7.59 (d, J = 8.7 Hz, 2H, НAr-3,5), 7.67 (d, J = 8.6 Hz,
2H, НAr-2,6), 13.32 (s, 1H, NH). MS (CI): m/z (%) = 405 (100%) [M+H+]. Anal. Calcd.
for C17H17ClN6O2S (404.87): C 50.43, H 4.23, N 20.76. Found: C 50.32, H 4.56, N 20.42.
1-(4-Bromophenyl)-5-(1-methylethyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-
1H-1,2,3-triazole-4-carboxamide (6e). Yield: 0.38 g (84%); white crystals; mp 144–145
1
◦С. H NMR (DMSO-d6): δ 1.36 (d, J = 7.0 Hz, 6H, i-Pr), 2.21 (s, 3H, Me), 3.21–3.30
(m, 1H, i-Pr), 3.96 (s, 2H, CH2), 7.52 (d, J = 8.4 Hz, 2H, НAr-3,5), 7.81 (d, J = 8.5 Hz,
2H, НAr-2,6), 13.33 (s, 1H, NH). MS (CI): m/z (%) = 449, 451 (100%) [M+H+]. Anal.
Calcd. for C17H17BrN6O2S (449.32): C 45.44, H 3.81, N 18.70. Found: C 45.36, H 3.97,
N 18.54.
5-(1-Methylethyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl]-1-[3-(trifluoromethyl)
phenyl]-1H-1,2,3-triazole-4-carboxamide (6f). Yield: 0.38 g (88%); white crystals; mp
◦
1
184–185 С. H NMR (DMSO-d6): δ 1.38 (d, J = 7.0 Hz, 6H, i-Pr), 2.21 (s, 3H, Me),
3.21–3.30 (m, 1H), 3.96 (s, 2H, CH2), 7.85–7.93 (m, 2H, НAr-4,5), 7.94 (s, 1H, НAr-2),
7.99 (d, J = 7.3 Hz, 1H, НAr-6), 13.37 (s, 1H, NH). MS (CI): m/z (%) = 439 (100%)
[M+H+]. Anal. Calcd. for C18H17F3N6O2S (438.43): C 49.31, H 3.91, N 19.17. Found: C
49.53, H 3.87, N 19.02.
1-(4-Methoxyphenyl)-5-(1-methylethyl)-N-[3-(2-oxopropyl)-1,2,4-thiadiazol-5-yl
]-1H-1,2,3-triazole-4-carboxamide (6g). Yield: 0.38 g (95%); white crystals; mp 163–164
1
◦С. H NMR (DMSO-d6): δ 1.35 (d, J = 7.0 Hz, 6H, i-Pr), 2.21 (s, 3H, Me), 3.23–3.32
(m, 1H, i-Pr), 3.89 (s, 3H, MeO), 3.96 (s, 2H, CH2), 7.13 (d, J = 8.9 Hz, 2H, НAr-3,5),
7.43 (d, J = 8.9 Hz, 2H, НAr-3,5), 13.26 (s, 1H, NH). MS (CI): m/z (%) = 401 (100%)
[M+H+]. Anal. Calcd. for C18H20N6O3S (400.45): C 53.99, H 5.03, N 20.99. Found: C
54.12, H 5.20, N 20.81.
REFERENCES
1. A. J. Boulton, A. R. Katritzky, and A. Majid Hamid, J. Chem. Soc. (S), 2005–2007 (1967).
2. A. P. Piccionello, A. Pace, S. Buscemi, N. Vivona, and M. Pani, Tetrahedron, 64, 4004–4010
(2008).
3. M. Ruccia, N. Vivona, G. Cusmano, and G. Macaluso, J. Chem. Soc., Perkin Trans. I, 589–591
(1977).
4. (a) N. Vivona, G. Macaluso, V. Frenna, and M. Ruccia, J. Heterocyclic Chem., 20, 931–934
(1983); (b) A. Fontana, S. Guernelli, P. Lo Meo, E. Mezzina, S. Morganti, R. Noto, E. Rizzato,
D. Spinelli, and R. Zappacosta, Tetrahedron, 64, 733–740 (2008); (c) N. N. Makhova and A. N.
Blinnikov, Mendeleev Commun., 9, 17–19 (1999).
5. D. N. Kozhevnikov, N. N. Kataeva, V. L. Rusinov, O. N. Chupakhin, and G. G. Aleksandrov,
Mendeleev Commun., 15, 31–33 (2005).
6. H. Kano and E. Yamazaki, Tetrahedron, 20, 461–464 (1964).
7. V. G. Andrianov, V. G. Semenikhina, and A. V. Eremeev, Chem. Heterocycl. Compd., 30, 475–477
(1994).
8. T. Iwakawa and A. Murabayashi, Heterocycles, 51, 811–819 (1999).
9. (a) M. Ruccia, N. Vivona, and D. Spinelli, Adv. Heterocycl. Chem., 29, 141–169 (1981); (b) N.
Vivona, S. Buscemi, V. Frenna, and G. Cusmano, Adv. Heterocycl. Chem., 56, 49–154 (1993).
10. (a) G. L’abbe, J. Heterocycl. Chem., 21, 627–638 (1984); (b) A. Pace, I. Pibiri, S. Buscemi, and
N. Vivona, Heterocycles, 63, 2627–2648 (2004).
11. N. Vivona, G. Cusmano, and G. Macaluso, J. Chem. Soc., Perkin Trans. I, 1616–1619 (1977).

REACTION OF 1-ARYL-1H-1,2,3-TRIAZOLE-4-CARBONYL CHLORIDES . . .
1901
12. I. G. Semenova, Yu. E. Klimko, and O. G. Yurchenko, Abstracts of Papers, Mezhdunarodnaya
konferentsiya [Khimiya azotovmisnikh geterotsikliv] [Reaction of adamantoyl isothiocyanate
with 3-amino-5-methylisoxazole]. Int. Conf. on Nitrogen Containing Heterocycles, Kharkov,
2000.
13. M. V. Vovk, N. V. Mel’nichenko, V. A. Chornous, and M. K. Bratenko, Russ. J. Org. Chem., 38,
599–601 (2002).
14. G. Macaluso, G. Cusmana, S. Buscemi, V. Prenna, N. Vivona, and M. Ruccia, Heterocycles, 24,
3433–3439 (1986).
15. T. Glinka, K. Huie, A. Cho, M. Ludwikow, J. Blais, D. Griffith, S. Hecker, and M. Dudley,
Bioorg. Med. Chem., 11, 591–600 (2003).
16. (a) K. Tatsuta, S. Miura, H. Gunji, T. Tamai, R. Yoshida, and T. Inagaki, Tetrahedron Lett., 34,
6423–6426 (1993); (b) K. Tatsuta, S. Miura, H. Gunji, T. Tamai, R. Yoshida, T. Inagaki, and Y.
Kurita, Bull. Chem. Soc. Jpn., 67, 1701–1707 (1994).
17. (a) K. Kubo, M. Tobisu, E. Honda, T. Taniguchi, Y. Fukase, M. Kawamura, and M. Nakayama,
Eur. Patent, 1 867 331 A1 (2007); (b) V. Calderone, F. L. Fiamingo, G. Amato, I. Giorgi, O. Livi,
A. Martelli, and E. Martinotti, Eur. J. Med. Chem., 43, 2618–2626 (2008); (c) S. Ito, A. Satoh,
Y. Nagatomi, Y. Hirata, G. Suzuki, T. Kimura, A. Satow, S. Maehara, H. Hikichi, M. Hata, H.
Kawamoto, and H. Ohta, Bioorg. Med. Chem., 16, 9817–9829 (2008).
18. (a) A. Castro, T. Castan˜o, A. Encinas, W. Porcal, and C. Gil, Bioorg. Med. Chem., 14, 1644–1652
(2006); (b) K.-Y. Jung, S.-K. Kim, Z.-G. Gao, A. S. Gross, N. Melman, K. A. Jacobson, and Y.-C.
Kim, Bioorg. Med. Chem., 12, 613–623 (2004); (c) A. Borghini, D. Pietra, P. Domenichelli, and
A. M. Bianucci, Bioorg. Med. Chem., 13, 5330–5337 (2005); (d) A. Castro, A. Encinas, C. Gil,
S. Bra¨se, W. Porcal, C. Pe´rez, F. J. Moreno, and A. Mart´ınez, Bioorg. Med. Chem., 16, 495–510
(2008); (e) P. Bhattacharya, J. T. Leonard, and K. Roy, Bioorg. Med. Chem., 13, 1159–1165
(2005); (f) J. M. Keith, R. Apodaca, W. Xiao, M. Seierstad, K. Pattabiraman, J. Wu, M. Webb,
M. J. Karbarz, S. Brown, S. Wilson, B., Scott, C.-S. Tham, L. Luo, J. Palmer, M. Wennerholm,
S. Chaplan, and J. G. Breitenbucher, Bioorg. Med. Chem. Lett., 18, 4838–4843 (2008).
19. (a) N. D. Obushak, N. T. Pokhodylo, N. I. Pidlypnyi, and V. S. Matiichuk, Russ. J. Org. Chem.,
44, 1522–1527 (2008); (b) N. T. Pokhodylo, O. Ya. Shyyka, V. S. Matiichuk, and N. D. Obushak,
Russ. J. Org. Chem., 46, 417–421 (2010).