The Dimroth rearrangement of 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides

Article abstract of DOI:10.1007/s10593-020-02819-w

[Figure not available: see fulltext.] The rearrangement of 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides was investigated. The process was optimized by varying the solvent, temperature, and the type of base. The optimal reaction conditions were found, and new 1-unsubstituted 5-arylamino-1,2,3-triazole-4-carbothioamides were synthesized. It has been shown that 1-aryl-1,2,3-triazoles containing a nitro group in the para position undergo rearrangement upon heating under reflux in n-butanol in the absence of a base. The rearrangement of compounds containing halogen, hydrogen, methyl, or methoxy groups in the aryl moiety requires the use of a base. The structure of the obtained compounds was confirmed by the data of NMR spectroscopy and mass spectrometry.

Full text of DOI:10.1007/s10593-020-02819-w

DOI 10.1007/s10593-020-02819-w
Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
The Dimroth rearrangement
of 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides
Vladimir G. Ilkin1, Lidiya N. Dianova1, Vasiliy A. Bakulev1,
Vera S. Berseneva1, Dmitry A. Saveliev1, Tetyana V. Beryozkina1*
1 Ural Federal University named after the first President of Russia B. N. Yeltsin,
19 Mira St., Yekaterinburg 620002, Russia; e-mail: tetber@mail.ru
Submitted April 11, 2020
Accepted April 29, 2020
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(10), 1335–1340
The rearrangement of 5-amino-1-aryl-1,2,3-triazole-4-carbothioamides was investigated. The process was optimized by varying the sol-
vent, temperature, and the type of base. The optimal reaction conditions were found, and new 1-unsubstituted 5-arylamino-1,2,3-triazole-
4-carbothioamides were synthesized. It has been shown that 1-aryl-1,2,3-triazoles containing a nitro group in the para position undergo
rearrangement upon heating under reflux in n-butanol in the absence of a base. The rearrangement of compounds containing halogen,
hydrogen, methyl, or methoxy groups in the aryl moiety requires the use of a base. The structure of the obtained compounds was con-
firmed by the data of NMR spectroscopy and mass spectrometry.
Keywords: azides, thioamides, 1,2,3-triazoles, Dimroth rearrangement.
The ability of 1,2,3-triazoles to undergo various trans-
formations and rearrangements of the ring has always
attracted numerous researchers.1 Among 1,2,3-triazole deri-
vatives, many compounds exhibit various biological activi-
ties, stimulating interest in the synthesis of novel
derivatives of this heterocycle. The 1,2,3-triazole ring
creates a structural basis for the manifestation of anti-
bacterial, anti-inflammatory, neuroleptic, antiviral, and
pesticidal activity by triazole derivatives.2 On the other
hand, thioamides are of interest as unique reagents3 used in
organic synthesis and possessing anticancer activity.4 We
assume that the combination of the NH fragment5 and the
thioamide group in the 1,2,3-triazole molecule can lead to
the manifestation of new chemical properties, to the use of
such 1,2,3-triazoles as ligands for the preparation of highly
active palladium catalysts for cross-coupling reactions in
aqueous media,6 and to the emergence of new types of
biological activity of synthesized hybrid molecules.2
enamines9 and compounds with an active methylene
group,8,10 reactions of NH-1,2,3-triazoles with electrophilic
reagents,8,11 inter-12 and intramolecular reactions of diazo
compounds with aldimines,8 and transformation of other
heterocyclic compounds.13 However, these methods are not
applicable to the synthesis of NH-1,2,3-triazole-4-carbo-
thioamides.
We turned our attention to the Dimroth rearrangement of
5-amino-1-aryl-1,2,3-triazoles leading to the formation of
NH-triazoles.14 The term "Dimroth rearrangement" was
introduced in 196314b for the isomerization of 1-substituted
1,2,3-triazoles A to 5-amino-substituted 1,2,3-triazoles C
proceeding via the opening of the triazole ring and
conversion to diazoacetamidines B followed by recycli-
zation via the heteroelectrocyclic mechanism12b,15 with the
participation of the nitrogen atom of the amino group of
compound B (Fig. 1). This rearrangement was first
described by O. Dimroth1a and was subsequently reflected
in many publications, including a series of reviews.14,16
It was shown that the introduction of strong electron-
withdrawing substituents into positions 1 and 4 of the
triazole ring facilitates the rearrangement.14,16 Until this
The most common methods for the synthesis of
1,2,3-triazoles include copper-catalyzed cycloaddition of
azides to acetylenes,7 oxidative cyclization of
functionalized hydrazones,8 reactions of azides with
0009-3122/20/56(10)-1335©2020 Springer Science+Business Media, LLC
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Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
Table 1. Optimization of the conditions of the rearrangement of
1-aryl-1,2,3-triazole 1а* in 5-arylamino-1,2,3-triazole 4а
Figure 1. A simplified mechanism of the Dimroth rearrangement
in the series of 5-amino-1,2,3-triazoles.
study, there were no data in the literature on the Dimroth
rearrangement of 1,2,3-triazole-4-carbothioamides.
In order to investigate the possibility of the rearrange-
ment of 1,2,3-triazole-4-carbothioamides and obtaining 5-aryl-
amino-1H-1,2,3-triazole-4-carbothioamides not described in
the literature, we synthesized a series of thioamides of
1-aryl-1,2,3-triazole-4-carboxylic acid 117,18 from the
corresponding thioamides 2 and azides 3 (Scheme 1) and
investigated their transformation into isomeric compounds.
Tempera-
Time, Isolated yield,
Entry Base (mmol)
Solvent**
ture,
°C
h
%
1
2
Et3N
EtOH (95%)
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
DMF
75
10
6
49
80
85
87
90
90
50
85
92
90
DBU (1.0)
100
100
100
100
100
140
100
118
118
3
DBU (3.0)
6
4
DBU (4.0)
6
Scheme 1. Synthesis of thioamides of 1-aryl-1,2,3-triazole-
4-carboxylic acid 1
DBU (6.0)
5
6
6
DBU (10.0)
6
7
‒
‒
‒
‒
‒
8
n-BuOH
6
9
n-BuOH
2
10
n-BuOH
6
* Amount of compound 1a – 0.5 mmol.
** Amount of EtOH, 1,4-dioxane, n-BuOH – 3 ml; DMF – 1 ml.
phenyl)amino-1,2,3-triazoles 4a,f,j,k were obtained in 71–
92% yields (Table 2).
We found that 1-aryl-1,2,3-triazoles 1b–e,g–i,l
containing either electron-donating substituents or H, Cl,
and F in the para position of the aryl moiety do not
rearrange to isomeric triazoles by heating under reflux in
We found that the formation of 5-arylamino-1,2,3-
triazole 4а does not occur by long heating of [5-amino-
1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl](pyrrolidin-1-yl)-
methanethione (1а) in EtOH. The addition of Et3N changed
the situation and led to the formation of triazole 4а in 49%
yield (Table 1, entry 1).
Table 2. Yields of 5-arylamino-1,2,3-triazoles 4а‒l
as a result of the rearrangement of 1-aryl-1,2,3-triazoles 1а‒l
Replacing EtOH with the higher boiling 1,4-dioxane
and using DBU (in the amount of 1.0, 3.0, 4.0, and 6.0 mmol)
increased the yield of target product 4a to 90% (Table 1,
entries 2–5). Obviously, the use of 6.0 mmol of DBU is
optimal, since a further increase in its amount does not lead
to an increase in the yield of triazole 4а (Table 1, entry 6).
We also found that the target product 4а was formed upon
heating of 1-aryl-1,2,3-triazole 1а in DMF, but the product
yield was lower and amounted to 50% (Table 1, entry 7). It
is interesting to note that the Dimroth rearrangement of
1-aryl-1,2,3-triazole 1а also occurs when the reaction is
carried out in n-BuOH at 100°C with an 85% yield of
compound 4а (Table 1, entry 8). A further increase in
temperature led to a decrease in the reaction time and an
increase in the yield of triazole 4а to 92% (Table 1, entry
9). Apparently, carrying out the reaction in n-BuOH at
118°C for 2 h is optimal for the synthesis of triazole 4а
(Table 1, entry 9). Alternatively, a technique using
1,4-dioxane as a solvent and DBU (6.0 mmol) as a base at
100°C can be recommended (Table 1, entry 5).
Compound
NR1R2
R3
NO2
H
Yield, %
92
Pyrrolidin-1-yl
Pyrrolidin-1-yl
Pyrrolidin-1-yl
Pyrrolidin-1-yl
Pyrrolidin-1-yl
Morpholin-4-yl
Morpholin-4-yl
Morpholin-4-yl
Morpholin-4-yl
Piperidin-1-yl
Azepan-1-yl
4a
4b
4c
4d
4e
4f
4g
4h
4i
71
Me
OMe
Cl
91
83
90
NO2
H
85
87
Ме
F
93
95
NO2
NO2
Н
61
4j
4k
4l
We have shown that the procedure for rearranging
1-(4-nitrophenyl)-1,2,3-triazoles 1a,f,j,k in n-BuOH is well
suited for all compounds. In these reactions, 5-(4-nitro-
88
88
NH2
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Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
n-BuOH. Therefore, to obtain triazoles 4b–e,g–i,l, we used
3b‒e (5.87‒6.48 mmol) was added. The reaction mixture
was kept at 50°C for 2 h, then cooled. The formed
precipitate was filtered off, washed with cooled EtOH until
the filtrate decolorized, or crystallized from EtOH
(compounds 1b,c,h). The resulting product was dried in an
oven at 80°C.
an alternative procedure for the rearrangement of 1-aryl-
1,2,3-triazoles 4b–e,g–i,l in 1,4-dioxane in the presence of
6.0 mmol of DBU (Table 2). The reaction is fully completed
in 6 h and leads to the formation of triazoles 4b–e,g–i,l in
high yields. Presumably, the addition of DBU stabilizes the
final product, which has a higher acidity than the starting
1-substituted triazole, which favors an easier rearrangement
and higher yields of triazoles 4b–e,g–i,l.
(5-Amino-1-phenyl-1H-1,2,3-triazol-4-yl)(pyrrolidin-
1-yl)methanethione (1b) was obtained from 3-(pyrrolidin-
1-yl)-3-thioxopropionitrile (2a) (1.00 g, 6.48 mmol) and
phenyl azide (3b) (772 mg, 6.48 mmol). Yield 1.27 g
(72%), colorless powder, mp 154‒156°С. IR spectrum,
ν, cm–1: 3364, 3229, 3178, 2969, 2938, 1597, 1378, 1340,
The structure of compounds 4a–l was confirmed by
1H and 13C NMR spectroscopy and mass spectrometry. EI
mass spectra of all compounds contain a molecular ion
peak. The molecular formula of compound 4e was
confirmed by the high-resolution mass spectrum. The
1Н NMR spectra of all compounds 4a–l contain signals of
NH protons downfield at 11.18‒15.07 ppm, which is
typical for the spectra of NH-1,2,3-triazoles18 and signals of
the NH protons of arylamino groups at 8.76‒10.11 ppm
which are absent in the spectra of isomeric triazoles 1a–l.
Analysis of the 13C NMR spectrum of compound 4i made it
possible to identify the signals of the carbon atoms of the
aryl substituent and the signals at 130.3 and 147.3 ppm
corresponding to the C-4 and C-5 atoms of the 1,2,3-tri-
azole ring.
1
1288, 1254, 1151, 1018, 973, 916, 825, 730. H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.90‒2.00
(2Н, m, СН2); 2.02‒2.05 (2Н, m, СН2); 3.87 (2Н, t, J = 8.0,
СН2); 4.21 (2Н, t, J = 8.0, СН2); 7.37 (2Н, s, NH2); 7.55‒7.77
(5Н, m, Н Ph). 13C NMR spectrum (100 MHz, DMSO-d6),
δ, ppm: 23.3; 26.5; 53.8; 54.9; 124.6 (2C); 126.1; 129.3;
129.8 (2C); 134.7; 146.6; 180.2. Mass spectrum, m/z
(Irel, %): 273 [M]+ (97), 244 (26), 176 (100), 175 (54), 132
(41), 119 (52), 99 (19), 77 (81). Found, %: C 57.03;
H 5.62; N 25.36. C13H15N5S. Calculated, %: C 57.12;
H 5.53; N 25.62.
To conclude, as a result of the study of the Dimroth re-
arrangement of 1-aryl-1,2,3-triazoles to 5-arylamino-1,2,3-
triazoles, it was shown that in the case of 1-(4-nitrophenyl)-
1,2,3-triazoles, the reaction proceeds by heating under
reflux in n-butanol. The transformation of 1-phenyl-1,2,3-
triazole, as well as 1-aryl-1,2,3-triazoles with electron-
donating substituents and halogens at position 4, requires
heating under reflux in 1,4-dioxane in the presence of
DBU.
[5-Amino-1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl]-
(pyrrolidin-1-yl)methanethione (1c) was obtained from 3-(pyr-
rolidin-1-yl)-3-thioxopropionitrile (2a) (1.00 g, 6.48 mmol)
and 4-methylphenyl azide (3c) (863 mg, 6.48 mmol). Yield
1.38 g (74%), colorless powder, mp 153‒155°С. IR spect-
rum, ν, cm–1: 3408, 3224, 3035, 2967, 2912, 2849, 1600,
1580, 1513, 1488, 1435, 1373, 1320, 1224, 1206, 1155,
1
1110, 1015, 974, 943, 813. H NMR spectrum (400 MHz,
Experimental
DMSO-d6), δ, ppm (J, Hz): 1.90‒2.05 (4Н, m, 2СН2); 3.86
(2Н, t, J = 8.0, СН2); 4.21 (2Н, t, J = 8.0, СН2); 7.29 (2Н,
s, NH2); 7.42‒7.47 (4Н, m, Н Ph). 13C NMR spectrum
(100 MHz, DMSO-d6), δ, ppm: 20.7; 23.2; 26.5; 53.8; 54.9;
124.6 (2C); 126.2; 130.3 (2C); 132.2; 139.0; 146.6; 180.6.
Mass spectrum, m/z (Irel, %): 287 [M]+ (69), 258 (29), 190
(100), 146 (25), 133 (45), 91 (70). Found, %: C 58.20;
H 5.62; N 24.68. C14H17N5S. Calculated, %: C 58.51;
H 5.96; N 24.37.
IR spectra were registered on a Bruker Alpha Fourier
transform spectrometer (ATR, ZnSe) in 4000‒500 cm–1
1
range. H and 13C NMR spectra were acquired on Bruker
Avance II 400 (400 and 100 MHz, respectively) and Bruker
Avance Neo (600 and 150 MHz, respectively)
spectrometers in DMSO-d6 and CDCl3. Chemical shifts
were determined relative to the residual signals of the
1
corresponding solvent (DMSO-d6: 2.50 ppm for H nuclei,
[5-Amino-1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl]-
(pyrrolidin-1-yl)methanethione (1d) was obtained from
3-(pyrrolidin-1-yl)-3-thioxopropionitrile (2a) (1.00 g,
6.48 mmol) and 4-methoxyphenyl azide (3d) (966 mg,
6.48 mmol). Yield 1.81 g (92%), colorless powder, mp 170‒
172°С, Rf 0.88 (EtOAc ‒ petroleum ether, 2:1). IR spect-
rum, ν, cm–1: 3374, 3252, 2971, 1660, 1585, 1521, 1379,
1
40.1 ppm for 13C nuclei; CDCl3: 7.26 ppm for H nuclei,
77.1 ppm for 13C nuclei). Mass spectra were recorded on a
GCMS-QP 2010 Ultra mass spectrometer (EI ionization,
70 eV). High-resolution mass spectra were recorded on an
Orbitrap Elite spectrometer (Thermo Fisher Scientific) with
electrospray ionization. Elemental analysis was performed
on a PerkinElmer Series II 2400 CHN-analyzer. Melting
points were determined on a Stuart SMP10 apparatus.
Monitoring of the reaction progress and assessment of the
purity of synthesized compounds were done by TLC on
Sorbfil UV-254 plates, visualization under UV light.
1
1340, 1301, 1251, 1152, 1027, 1016, 980, 829. H NMR
spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.97‒2.11
(4H, m, 2СН2); 3.87 (3Н, s, ОСН3); 4.03 (2H, t, J = 6.0,
СН2); 4.36 (2H, t, J = 6.0, СН2); 6.33 (2Н, s, NH2); 7.06
(2Н, d, J = 9.0, H Ar); 7.42 (2Н, d, J = 9.0, H Ar).
13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 23.9; 27.1;
54.3; 55.3; 55.8; 115.4; 126.4; 127.5; 127.6; 146.7; 160.7;
181.4. Mass spectrum, m/z (Irel, %): 303 [M]+ (22), 275
(33), 274 (41), 260 (33), 206 (100), 191 (57), 149 (55), 77
(52), 70 (53). Found, %: C 55.73; H 5.57; N 23.33.
C14H17N5OS. Calculated, %: C 55.43; H 5.65; N 23.08.
[5-Amino-1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl]-
(pyrrolidin-1-yl)methanethione (1e) was obtained from
5-Amino-1-aryl-1,2,3-triazole-4-carbothioamides 1a,f,i–l
were obtained and characterized by us earlier.19
Synthesis of 5-amino-1-aryl-1,2,3-triazole-4-carbo-
thioamides 1b–e,g,h (General method). The corresponding
thioamide 2a,b (1.00 g, 5.87‒6.48 mmol) was added to a
freshly prepared solution of EtONa (150 mg Na and 20 ml
EtOH), and the resulting mixture was stirred at room
temperature for 10 min. Then, the corresponding aryl azide
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Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
3-(pyrrolidin-1-yl)-3-thioxopropionitrile (2a) (1.00 g,
under reduced pressure, the residue was triturated with
H2O, filtered off, and dried in an oven at 80°С.
6.48 mmol) and 4-chlorophenyl azide (3е) (995 mg,
6.48 mmol). Yield 1.70 g (85%), colorless powder, mp 182‒
{5-[(4-Nitrophenyl)amino]-1H-1,2,3-triazol-4-yl}-
(pyrrolidin-1-yl)methanethione (4a). Yield 585 mg
(92%), yellow powder, mp 224‒225°С, Rf 0.53 (EtOAc ‒
petroleum ether, 2:1). IR spectrum, ν, cm–1: 3296, 2981,
2954, 2924, 2905, 1596, 1577, 1538, 1442, 1287, 1168,
1106. 1H NMR spectrum (400 MHz, CDCl3), δ, ppm
(J, Hz): 2.05‒2.14 (4H, m, 2CH2); 4.02‒4.05 (2H, m, CH2);
4.14‒4.20 (2H, m, CH2); 7.63 (2H, d, J = 8.8, H Ar); 8.21
(2H, d, J = 8.8, H Ar); 10.72 (1H, s, NH); 11.18 (1H, br. s,
NH). 13C NMR spectrum (100 MHz, CDCl3), δ, ppm: 23.8;
26.9; 54.7; 55.2; 116.1 (2С); 125.7 (2С); 131.6; 140.9;
146.5; 149.4; 180.9. Mass spectrum, m/z (Irel, %): 318 [M]+
(43), 289 (6), 285 (7), 202 (6), 70 [C4H8N]+ (100). Found,
%: C 48.85; H 4.55; N 26.45. C13H14N6O2S. Calculated, %:
C 49.05; H 4.43; N 26.40.
1
184°С, Rf 0.49 (EtOAc ‒ petroleum ether, 1:4). H NMR
spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 1.90‒2.05
(4H, m, 2СН2); 3.86 (2H, t, J = 6.7, СН2); 4.20 (2H, t,
J = 6.7, СН2); 7.42 (2Н, s, NH2), 7.63 (2Н, d, J = 8.7,
H Ar); 7.70 (2Н, d, J = 8.7, H Ar). 13C NMR spectrum
(100 MHz, CDCl3), δ, ppm: 23.2; 26.5; 53.8; 54.9; 126.1;
126.6 (2С); 129.8 (2С); 133.5; 133.8; 146.7; 180.1. Found,
m/z: 308.0738 [M+H]+. C13H14ClN5S. Calculated, m/z:
308.0731.
(5-Amino-1-phenyl-1H-1,2,3-triazol-4-yl)(morpholin-
4-yl)methanethione (1g) was obtained from 3-(morpholin-
4-yl)-3-thioxopropionitrile (2b) (1.00 g, 5.87 mmol) and
phenyl azide (3b) (700 mg, 5.87 mmol). Yield 1.28 g
(75%), colorless powder, mp 155‒157°С. IR spectrum,
ν, cm–1: 3366, 3221, 2863, 1602, 1505, 1433, 1272, 1234,
[5-(Phenylamino)-1H-1,2,3-triazol-4-yl](pyrrolidin-
1-yl)methanethione (4b). Yield 384 mg (71%), yellow
crystals, mp 164‒166°С (EtOAc), Rf 0.78 (EtOAc ‒
petroleum ether, 2:1). ). IR spectrum, ν, cm–1: 3163, 3081,
2965, 2873, 1591, 1562, 1529, 1380, 1248, 1010, 971, 739,
686. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm
(J, Hz): 1.95‒1.99 (4Н, m, 2СН2); 3.85‒3.88 (2Н, m, СН2);
4.03‒4.05 (2Н, m, СН2); 6.87‒6.91 (1Н, m, Н Ar); 7.27‒
7.31 (2Н, m, Н Ar); 7.46‒7.48 (2Н, m, Н Ar); 9.85 (1Н, s,
1
1113, 1018, 970, 868, 766. H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm (J, Hz): 3.70‒3.80 (4Н, m, 2СН2); 4.24‒
4.47 (4Н, m, 2СН2); 7.02 (2Н, br. s, NH2); 7.56‒7.66 (5Н,
m, Н Ph). 13C NMR spectrum (100 MHz, DMSO-d6), δ, ppm:
49.4; 53.3; 66.0; 66.2; 124.5 (2С); 125.6; 129.2; 129.6
(2С); 134.4; 146.4; 184.1. Mass spectrum, m/z (Irel, %): 289
[M]+ (80), 176 (100), 132 (38), 119 (66), 77 (83). Found,
%: C 53.95; H 5.53; N 24.29. C13H15N5OS. Calculated, %:
C 53.96; H 5.23; N 24.20.
1
NH); 14.85 (1Н, s, NH). H NMR spectrum (100 MHz,
[5-Amino-1-(p-tolyl)-1H-1,2,3-triazol-4-yl](morpholin-
4-yl)methanethione (1h) was obtained from 3-(morpholin-
4-yl)-3-thioxopropionitrile (2b) (1.00 g, 5.87 mmol) and
4-methylphenyl azide (3c) (782 mg, 5.87 mmol). Yield
1.26 g (71%), colorless powder, mp 166‒168°С. IR spect-
rum, ν, cm–1: 3381, 3265, 3002, 2913, 2858, 1602, 1519,
1472, 1429, 1380, 1235, 1168, 1104, 1023, 936, 820.
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 2.42
(3H, s, CH3); 3.70‒3.83 (4Н, m, 2СН2); 4.32‒4.39 (4Н, m,
2СН2); 6.97 (2Н, s, NH2); 7.42‒7.48 (4Н, m, Н Ar).
13C NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 20.7;
49.3; 53.6; 66.4 (2C); 124.6 (2C); 125.7; 130.2 (2C);
132.1; 139.2; 146.6; 184.3. Mass spectrum, m/z (Irel, %):
303 [M]+ (53), 190 (100), 146 (22), 133 (58), 91 (73).
Found, %: C 55.12; H 5.34; N 23.43. C14H17N5OS.
Calculated, %: C 55.43; H 5.65; N 23.08.
Synthesis of 5-arylamino-1,2,3-triazoles 4a,f,j,k
(General method). A solution of 5-amino-1-aryl-1,2,3-tri-
azole 1a,f,j,k (2.00 mmol) in n-BuOH (10 ml) was heated
under reflux for 2–6 h. The solvent was evaporated under
reduced pressure, the residue was crystallized from EtOH.
The formed precipitate was filtered off and dried in an oven
at 80°С.
Synthesis of 5-arylamino-1,2,3-triazoles 4b–e,g–i,l
(General method). DBU (913 mg, 6.00 mmol) was added
to a solution of the corresponding 5-amino-1-aryl-1,2,3-tri-
azole 1b–e,g–i,l (2.00 mmol) in anhydrous 1,4-dioxane
(12 ml), and the mixture was heated under reflux for 6 h.
The solvent was evaporated under reduced pressure, AcOH
(2–4 ml) was added to the residue, and the mixture was
kept stirring at room temperature for 1 h. The product was
extracted with EtOAc, washed with aqueous NaHCO3,
H2O, and dried over Na2SO4. The solvent was evaporated
DMSO-d6), δ, ppm: 23.4; 26.3; 54.1; 54.8; 116.2 (2C);
120.3; 129.1 (2C); 129.8; 141.0; 149.2; 180.7. Mass
spectrum, m/z (Irel, %): 273 [M]+ (100), 203 (13), 104 (13),
77 (27). Found, %: C 57.35; H 5.57; N 25.93. C13H15N5S.
Calculated, %: C 57.12; H 5.53; N 25.62.
{5-[(4-Methylphenyl)amino]-1H-1,2,3-triazol-4-yl)}-
(pyrrolidin-1-yl)methanethione (4c). Yield 552 mg
(91%), yellow powder, mp 164‒166°С, Rf 0.77 (EtOAc ‒
petroleum ether, 1:2). 1H NMR spectrum (600 MHz,
DMSO-d6), δ, ppm (J, Hz): 1.91‒2.00 (4Н, m, 2СН2); 2.24
(3Н, s, СН3); 3.84‒3.87 (2Н, m, СН2); 4.05 (2Н, br. s,
СН2); 7.10 (2Н, d, J = 8.5, H Ar); 7.35 (2Н, d, J = 8.5,
H Ar); 9.79 (1H, br. s, NH); 14.77 (1H, br. s, NH).
13C NMR spectrum (150 MHz, DMSO-d6), δ, ppm: 20.0;
23.1; 26.1; 53.9; 54.5; 116.3 (2С); 128.9; 129.3 (2С);
129.6; 138.5; 149.5; 180.8. Mass spectrum, m/z (Irel, %):
287 [M]+ (100), 190 (39), 91 (42). Found, %: C 58.17;
H 5.82; N 24.37. C14H17N5S. Calculated, %: C 58.51;
H 5.96; N 24.37.
{5-[(4-Methoxyphenyl)amino]-1H-1,2,3-triazol-4-yl}-
(pyrrolidin-1-yl)methanethione (4d). Yield 503 mg
(83%), yellow crystals, mp 163‒165°С (EtOAc), Rf 0.61
(EtOAc ‒ petroleum ether, 1:2). IR spectrum, ν, cm–1:
3279, 3207, 2956, 1598, 1562, 1511, 1489, 1442, 1231,
1290, 1130, 1024, 822, 692. 1H NMR spectrum (600 MHz,
DMSO-d6), δ, ppm (J, Hz): 1.94‒2.01 (4Н, m, 2СН2); 3.71
(3Н, s, ОСН3); 3.84‒3.87 (2Н, m, СН2); 4.04‒4.06 (2Н, m,
СН2); 6.89 (2Н, d, J = 12.0, H Ar); 7.40 (2Н, d, J = 12.0,
H Ar); 9.69 (1Н, s, NH); 14.70 (1Н, s, NH). 13C NMR
spectrum (150 MHz, DMSO-d6), δ, ppm: 23.3; 26.3; 54.1;
54.8; 55.2; 114.4 (2C); 118.0 (2C); 129.2; 134.4; 149.6;
153.6; 180.6. Mass spectrum, m/z (Irel, %): 303 [M]+ (70),
274 (47), 260 (36), 206 (100). Found, %: C 55.25; H 5.67;
1338

Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
N 23.35. C14H17N5OS. Calculated, %: C 55.43; H 5.65;
N 23.08.
{5-[(4-Chlorophenyl)amino]-1H-1,2,3-triazol-4-yl}-
petroleum ether, 1:2). IR spectrum, ν, cm–1: 3279, 3206,
2956, 1599, 1562, 1511, 1489, 1442, 1290, 1231, 1164, 1024,
1
972, 822, 692. H NMR spectrum (400 MHz, DMSO-d6),
(pyrrolidin-1-yl)methanethione (4e). Yield 558 mg
(90%), light-yellow crystals, mp 166‒168°С (EtOН),
Rf 0.49 (EtOAc ‒ petroleum ether, 1:2). IR spectrum, ν, cm–1:
3357, 3189, 2938, 1597, 1564, 1489, 1438, 1406, 1313,
δ, ppm: 3.61‒3.83 (4Н, m, 2СН2); 3.93‒4.07 (2Н, m, СН2);
4.21‒4.38 (2Н, m, СН2); 7.07‒7.12 (2Н, m, Н Ar); 7.43‒
7.46 (2Н, m, Н Ar); 8.76 (1Н, s, NH); 14.74 (1Н, br. s,
NH). 13C NMR spectrum (100 MHz, DMSO-d6), δ, ppm
(J, Hz): 49.1; 52.6; 65.8; 66.1; 115.2 (d, J = 22.0); 117.5
(d, J = 7.0); 130.3; 137.9 (d, J = 2.0); 147.3; 156.3 (d,
J = 235.0, CF); 185.2. Mass spectrum, m/z (Irel, %): 307
[M]+ (100), 221 (14), 160 (16), 122 (19), 95 (24), 86 (66).
Found, %: C 51.18; H 4.56; N 22.78. C13H14FN5OS.
Calculated, %: C 50.80; H 4.59; N 22.79.
1
1112, 1009, 837, 747, 682. H NMR spectrum (400 MHz,
DMSO-d6), δ, ppm (J, Hz): 1.94–2.00 (4H, m, 2СН2); 3.85
(2H, t, J = 6.4, СН2); 4.03 (2H, t, J = 6.5, СН2); 7.31 (2H,
d, J = 8.4, H Ar); 7.51 (2H, d, J = 8.3, H Ar); 9.90 (1H, s,
NH); 14.88 (1H, s, NH). 13C NMR spectrum (100 MHz,
DMSO-d6), δ, ppm: 23.4; 26.2; 53.8; 54.9; 117.7 (2С); 123.6;
128.8 (2С); 130.1; 140.0; 148.7; 180.6. Found, m/z: 308.0734
[M+H]+. C13H14ClN5S. Calculated, m/z: 308.0731.
{5-[(4-Nitrophenyl)amino]-1H-1,2,3-triazol-4-yl}-
(piperidin-1-yl)methanethione (4j). Yield 405 mg (61%),
yellow crystals, mp 185‒187°С, Rf 0.56 (EtOAc ‒
petroleum ether, 1:2). IR spectrum, ν, cm–1: 3355, 3188,
2937, 1596, 1564, 1487, 1436, 1405, 1311, 1110, 1007,
(Morpholin-4-yl){5-[(4-nitrophenyl)amino]-1H-1,2,3-
triazol-4-yl}methanethione (4f). Yield 568 mg (85%),
yellow powder, mp 249‒250°С, Rf 0.28 (EtOAc ‒
petroleum ether, 2:1). IR spectrum, ν, cm–1: 3184, 3115,
2898, 2859, 1600, 1573, 1529, 1486, 1634, 1432, 1296,
1
836, 746, 682. H NMR spectrum (600 MHz, DMSO-d6),
δ, ppm (J, Hz): 1.58‒1.68 (6Н, m, 3СН2); 3.73 (2Н, br. s,
СН2); 4.26 (2Н, br. s, СН2); 7.48 (2Н, d, J = 9.0, H Ar);
8.15 (2Н, d, J = 9.0, H Ar); 9.42 (1Н, s, NH); 15.03 (1Н,
br. s, NH). 13C NMR spectrum (150 MHz, DMSO-d6),
δ, ppm: 23.5; 25.3; 26.6; 49.9; 53.0; 114.8 (2С); 125.7
(2С); 133.8; 139.0; 143.6; 148.7; 184.0. Mass spectrum,
m/z (Irel, %): 332 [M]+ (39), 271 (18), 84 (100). Found, %:
C 50.94; H 4.59; N 25.16. C14H16N6O2S. Calculated, %:
C 50.59; H 4.85; N 25.28.
1
1259, 1102. H NMR spectrum (400 MHz, DMSO-d6),
δ, ppm (J, Hz): 3.58‒3.68 (2H, m, CH2); 3.72‒3.77 (2H, m,
CH2); 3.84‒3.90 (2H, m, CH2); 4.25‒4.34 (2H, m, CH2);
7.50 (2H, d, J = 8.4, H Ar); 8.15 (2H, d, J = 8.4, H Ar);
9.45 (1H, s, NH); 15.07 (1H, br. s, NH). 13C NMR
spectrum (100 MHz, DMSO-d6), δ, ppm: 49.1; 52.6; 65.7;
66.2; 114.9 (2С); 125.6 (2С); 133.5; 139.1; 144.2; 148.4;
185.1. Mass spectrum, m/z (Irel, %): 334 [M]+ (68), 289
(10), 264 (13), 248 (12), 202 (18), 86 [C4H8NO]+ (100).
Found, %: C 46.78; H 4.01; N 25.25. C13H14N6O3S.
Calculated, %: C 46.70; H 4.22; N 25.14.
(Azepan-1-yl){5-[(4-nitrophenyl)amino]-1H-1,2,3-tri-
azol-4-yl}methanethione (4k). Yield 609 mg (88%),
yellow powder, mp 217‒218°С, Rf 0.75 (EtOAc ‒
petroleum ether, 2:1). IR spectrum, ν, cm–1: 3254, 2937,
2917, 2853, 1600, 1567, 1536, 1289, 1109. 1H NMR
spectrum (400 MHz, CDCl3), δ, ppm (J, Hz): 1.60‒1.74
(4H, m, 2CH2); 1.88‒2.06 (4H, m, 2CH2); 4.06‒4.09 (2H,
m, CH2); 4.24‒4.27 (2H, m, CH2); 7.57 (2H, d, J = 9.0,
H Ar); 8.21 (2H, d, J = 9.0, H Ar); 9.86 (1H, s, NH); 11.23
(1H, br. s, NH). 13C NMR spectrum (100 MHz, CDCl3),
δ, ppm: 25.5; 26.5; 27.1; 29.5; 55.1; 55.9; 116.1 (2С);
125.8 (2С); 132.5; 141.1; 146.8; 148.9; 184.9. Mass
spectrum, m/z (Irel, %): 346 [M]+ (100), 313 (23), 285 (67),
98 (92). Found, %: C 52.02; H 4.88; N 23.90.
C15H18N6O2S. Calculated, %: C 52.01; H 5.24; N 24.26.
5-(Phenylamino)-1H-1,2,3-triazole-4-carbothioamide
(4l). Yield 387 mg (88%), colorless powder, mp 256‒258°С,
Rf 0.36 (EtOAc ‒ petroleum ether, 3:1). IR spectrum, ν, cm–1:
3278, 3205, 2956, 1600, 1563, 1514, 1490, 1444, 1291,
(Morpholin-4-yl)[5-(phenylamino)-1H-1,2,3-triazol-4-yl]-
methanethione (4g). Yield 498 mg (87%), yellow powder,
mp 163‒165°С, Rf 0.53 (EtOAc ‒ petroleum ether, 1:2).
IR spectrum, ν, cm–1: 3279, 2980, 2848, 1594, 1561, 1494,
1433, 1382, 1296, 1232, 1115, 999, 752. 1H NMR
spectrum (600 MHz, DMSO-d6), δ, ppm: 3.66‒3.77 (4Н,
m, 2СН2); 4.00 (2Н, br. s, СН2); 4.31 (2Н, br. s, СН2); 6.86
(1Н, br. s, H Ar); 7.25‒7.27 (3Н, m, H Ar); 7.43 (1Н, br. s,
H Ar); 8.77 (1Н, br. s, NH); 14.76 (1Н, br. s, NH).
13C NMR spectrum (150 MHz, DMSO-d6), δ, ppm: 49.2;
52.8; 65.7; 65.9; 115.9 (2С); 119.9; 128.7 (2С); 130.8;
141.4; 147.8; 185.3. Found, %: C 53.96; H 4.88; N 23.89.
C13H15N5OS. Calculated, %: C 53.96; H 5.23; N 24.20.
{5-[(4-Methylphenyl)amino]-1H-1,2,3-triazol-4-yl}-
(morpholin-4-yl)methanethione (4h). Yield 503 mg
(93%), yellow powder, mp 142‒144°С, Rf 0.51 (EtOAc ‒
petroleum ether, 1:2). 1H NMR spectrum (600 MHz,
DMSO-d6), δ, ppm (J, Hz): 2.23 (3H, s, СН3); 3.62‒3.71
(4Н, m, 2СН2); 3.99‒4.38 (4Н, m, 2СН2); 7.07 (2Н, d,
J = 12.0, H Ar); 7.32 (2Н, d, J = 12.0, H Ar); 8.79 (1Н, s,
NH); 14.68 (1Н, br. s, NH). 13C NMR spectrum (150 MHz,
DMSO-d6), δ, ppm: 20.2; 49.3; 52.9; 66.1 (2С); 116.2 (2С);
128.7; 129.4 (2С); 130.0; 139.1; 147.8; 185.2. Mass
spectrum, m/z (Irel, %): 303 [M]+ (100), 190 (36), 133 (20),
91 (36), 81 (36). Found, %: C 55.77; H 5.63; N 23.04.
C14H17N5OS. Calculated, %: C 55.43; H 5.65; N 23.08.
1
1233, 1165, 1025, 973, 830, 699. H NMR spectrum (600
MHz, DMSO-d6), δ, ppm (J, Hz): 7.38–7.42 (3H, m, Ph);
7.52 (2H, t, J = 7.8, H Ph); 8.48 (1H, s, NH); 10.11 (1H,
br. s, NH2); 11.66 (1H, br. s, NH2); 14.71 (1H, s, NH).
13C NMR spectrum (150 MHz, DMSO-d6), δ, ppm: 125.3
(2С); 127.4; 128.2; 129.8 (2С); 134.6; 155.0; 156.0. Mass
spectrum, m/z (Irel, %): 219 [M]+ (100), 191 (24), 163 (22),
131 (27), 104 (31), 77 (70). Found, %: C 49.44; H 4.08;
N 31.73. C9H9N5S. Calculated, %: C 49.30; H 4.14;
N 31.94.
{5-[(4-Fluorophenyl)amino]-1H-1,2,3-triazol-4-yl}-
(morpholin-4-yl)methanethione (4i). Yield 583 mg
(95%), yellow powder, mp 164‒166°С, Rf 0.38 (EtOAc ‒
This work was supported by the Russian Foundation for
Basic Research (grant 18-03-00715).
1339

Chemistry of Heterocyclic Compounds 2020, 56(10), 1335–1340
(c) Zhang, C.; Morinaka, K.; Kose, M.; Ubukata, T.;
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