Synthesis of β-azolyl- and β-azolylcarbonylenamines and their reactions with aromatic azides

Article abstract of DOI:10.1007/s10593-019-02525-2

[Figure not available: see fulltext.] Synthesis of 4-acetyl-substituted azoles (1,2,3-triazole, 1,2,3-thiadiazole, and 1,2-oxazole) is reported. Organocatalytic reactions of 4-acetyl-1,2,3-triazoles with aryl azides were used to obtain bis-1,2,3-triazoles

Full text of DOI:10.1007/s10593-019-02525-2

DOI 10.1007/s10593-019-02525-2
Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
Synthesis of β-azolyl- and β-azolylcarbonylenamines
and their reactions with aromatic azides
Yuri M. Shafran1, Tetyana V. Beryozkina1,
Ilya V. Efimov1, Vasiliy A. Bakulev1*
1 Ural Federal University named after the first President of Russia B. N. Yeltsin,
19 Mira St., Yekaterinburg 620002, Russia; e-mail: v.a.bakulev@urfu
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(8), 704–715
Submitted March 13, 2019
Accepted April 16, 2019
Synthesis of 4-acetyl-substituted azoles (1,2,3-triazole, 1,2,3-thiadiazole, and 1,2-oxazole) is reported. Organocatalytic reactions of
4-acetyl-1,2,3-triazoles with aryl azides were used to obtain bis-1,2,3-triazoles containing directly linked ring systems. The reactions of
4-acetylazoles with DMF–DMA led to the formation of enamines. It was found that the acetyl and methyl groups in 4-acetyl-5-methyl-
1,2,3-thiadiazole competed for the role of reactive site. The obtained enamines reacted with aryl azides, forming bisheterocycles that
were linked by a carbonyl group. The structures of the synthesized compounds were proved by NMR spectroscopy, mass spectrometry,
and X-ray structural analysis.
Keywords: bistriazoles, enamines, enaminones, 1,2-oxazoles, 1,2,3-thiadiazoles, 1,2,3-triazoles.
Molecules containing chains of azole rings and other
heterocycles (known as stick-like molecules) are attractive
objects of study in medicinal chemistry,1 organic
synthesis,2 materials chemistry,3 and organic electronics.4
For these reasons, it is important to continue research in the
synthesis of bisazoles on the basis of 1,2,3-triazole, 1,2,3-
thiadiazole, and 1,2-oxazole, either directly bonded or
linked by a carbonyl group. The most common method for
obtaining 1,2,3-triazoles via the reactions of acetylenes
with azides5 has limited applicability to the synthesis of
azolyltriazoles due to the limited availability of azolyl-
acetylenes. On the other hand, a more promising route to
these compounds relies on the reactions of azides with the
significantly more available enamines.6 In addition,
compounds containing an azolyl enamine moiety are of
interest to medicinal chemists as potential lead compounds
for the discovery of new biologically active compounds.7
Taking into account all of this, our research was aimed at
developing a convenient method for the preparation of
3-azolyl enamines, and their reactions with aromatic azides
were studied.
We have previously shown that the reactions of β-azolyl
enamines with aromatic and aliphatic azides provide an
effective method for the synthesis of (1,2,3-triazolyl-4-yl)-
5-azoles (4–5-bonding).8 Thus, we planned to prepare
bisazoles where position 4 of azole and position 5 of 1,2,3-
triazole were linked either by a single bond (structure A,
Scheme 1) or through a carbonyl group (structure A'),
using the reactions of aromatic and aliphatic azides with
α-azolyl enamines (structure B) and 3-azolyl enaminones
(structure B'). It should be noted that the synthesis of
α-azolyl enamines B and their reactions with azides have not
been described in the literature prior to the current study,
while bicyclic ensembles A that were synthesized by
another method (from 1,2,3-triazolylacetylenes) have been
represented by only a few examples.9 The synthesis of
enamines B was proposed starting from secondary amines,
using reactions with the acetylazoles C.
The starting materials C selected from 1,2,3-triazole
series were 1-substituted 4-acetyl-5-methyl-1,2,3-triazoles
1a–n and 4-acetyl-1,2,3-triazoles 1o–r, as well as 1,2,3-
thiadiazole 1s and 4-acetyl-1,2-oxazole 1t (Fig. 1).
0009-3122/19/55(8)-0704©2019 Springer Science+Business Media, LLC
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Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
Scheme 1. The planned routes of synthesis for bisazoles А and A'
Scheme 2. Synthesis of bistriazoles 3a–g (structures A)
For the purpose of obtaining enamines B, we treated
4-acetyl-1,2,3-triazoles 1a,b with boiling morpholine and
pyrrolidine under various conditions (in the presence of
CaO or p-TsOH, without solvent or in PhMe solution while
removing the solvent by distillation) over several hours. In
none of these experiments, the starting ketones 1a,b
participated in the reaction. Nevertheless, we added aryl
azides 2 to the studied reaction mixtures with the
expectation that even minimal amounts of enamines B,
which would be in equilibrium with the starting ketones C,
would participate in the reaction, forming bistriazoles A.
Indeed, refluxing ketones 1a–d for many hours with a large
excess of aryl azides 2a,b,e under various combinations of
reaction conditions (in morpholine or pyrrolidine, without
additives, or in the presence of CaO or TiCl4) led to the
formation of the target compounds 3a–g in 40‒70% yields
(Scheme 2).
The structure of compounds 3а–g as bicyclic ensembles
was established by NMR experiments as well as by
monocrystal X-ray structural analysis of compound 3d
(Fig. 2).
It should be noted that we could not obtain the
analogous triazoles from ketones of 1,2,3-thiadiazole
(compound 1s) and isoxazole (compound 1t) series. Thus,
as a result of generating the previously unknown 1-(1,2,3-
triazol-4-yl) enamines B followed by their reactions with
aromatic azides 2a,b,e, a new method has been developed
for obtaining bicyclic 1,2,3-triazoles that are not accessible
by other methods.
In order to synthesize alternative bisheterocyclic
structures A' containing an azole moiety and triazole ring
linked by a carbonyl group, we performed studies aimed at
advancing the methodology for the preparation of
enaminones B' and studied their interaction with azides.
We have previously synthesized enamines of 1,2,3-triazole
series by reactions of 5-methyl-1,2,3-triazoles with the
Bredereck's reagent (1-tert-butoxy-N,N,N',N'-tetramethyl-
methanediamine) in high boiling point solvents.8b The
attempts to obtain the respective enaminones from 5-methyl-
1,2,3-triazoles by using the considerably less costly
dimethylformamide dimethylacetal (DMF–DMA) were
unsuccessful.8
Taking into account the high cost of the Bredereck's
reagent, we repeated the attempts to synthesize enaminones
by reactions of 5-methyl-1,2,3-triazoles with DMF–DMA
in various solvents with the addition of Lewis acids or
various bases, including N-methylimidazole,8c as well as
under solvent-free conditions. Acceptable yields of
enaminones 4a–r were achieved only after prolonged heating
of ketones 1b–i,k–t at 80‒110°С in DMF–DMA solution
without additives (Scheme 3). The optimal procedure
included the removal of unreacted DMF–DMA by
distillation, with an option for reuse of the recovered
reagent. Depending on the solubility of the obtained
Figure 2. The molecular structure of bistriazole 3d with atoms
represented by thermal vibration ellipsoids of 50% probability.
Figure 1. Structures of the starting acetylazoles 1a–t and azides 2a–l.
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Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
Scheme 3. Synthesis of enaminones 4a–s
products in organic solvents, purification was performed
NMe2
Me
O
either by column chromatography or recrystallization from
organic solvents. The obtained azolyl enaminones 4a–r
were crystalline compounds with high melting points. The
employed method provided access to a wide range of
enamines containing various azole rings in their structure.
Taking into account the value of 1,2,3-triazolyl enaminones
as unique building blocks for organic synthesis, as well as
their potential as lead structures for drug discovery
research, we put particular emphasis on the preparation of
1-aryl-1,2,3-triazolyl enaminones 4b–j,n–p with a wide
variety of substituents in the phenyl ring, as well as the
1-n-butyl- and 1-allyltriazoles 4k,l. At the same time, the
reactions of pentafluoro derivative 1j with DMF–DMA
gave an intractable product mixture that could not be
separated preparatively into individual compounds.
According to HPLC–HRMS analysis, its major components
were products arising from the substitution of one or two
fluorine atoms in the initially formed 1-(5-methyl-
1-(perfluorophenyl)-1H-1,2,3-triazol-4-yl-l)prop-2-en-1-one
with methoxy groups by the action of MeOH, which was
liberated from DMF–DMA reagent during the synthesis.
Apparently, the general method for the preparation of
enaminones was unsuitable in the case of ketone containing
a pentafluorophenyl group, due to the reactivity of fluorine
atoms of the polyfluorinated phenyl ring in the basic
medium containing DMF–DMA.
Az
4a–r
O
DMF–DMA
O
Az
Me
100–120°C
1.5–50 h
1b–i,k–t
N
N
S
NMe2
4s (42%)
O
NMe2
4 a R1 = Ph (75%), b R1 = 4-O2NC6H4 (83%),
c R1 = 2-O2NC6H4 (68%), d R1 = 4-MeC6H4 (70%),
e R1 = 4-i-PrC6H4 (95%), f R1 = 3-ClC6H4 (56%),
N
N
Me
N
R1
g R1 = 3-FC H4 (81%), h R1 = 2-Cl-4-MeC6H3 (97%),
6
i R1 = 2-O2N-5-ClC6H3 (40%),
j R1 = 4-BrC6H4CH2 (46%),
k R1 = n-Bu (79%), l R1 = allyl (39%)
O
NMe2
N
N
1
1
N
R1
4 m
o
n
R = Ph (75%), R = 4-O2NC6H4 (87%),
1
1
p
R = 2-O NC6H4 (58%), R = 4-MeC6H4 (80%)
2
Cl
O
O
NMe2
NMe2
N
N
It should be noted that the reactions of 4-acetyl-1,2,3-tri-
azoles 1o–r lacking substituents at position 5, as well as
4-acetyl-5-methylazoles 1b–n and 1,2-oxazole 1t contain-
ing a 4-acetyl group along with 5-methyl group produced
individual compounds 4a–p,r with the participation of
acetyl group only. An alternative transformation with the
participation of 5-methyl group was observed only in the
reaction of 1,2,3-thiadiazole 1s with DMF–DMA, forming
not only enaminone 4q, but also a product with enamine
moiety at position 5 ‒ compound 4s. The location of the
enamine moiety in the molecules of compounds 4q,s was
determined on the basis of two-dimensional 1H–13C HMBC
N
Me
4q (23%)
Me
(82%)
S
O
4r
selectivity of reactions between DMF–DMA and the acetyl
group in triazoles 1b–r and isoxazole 1t and the
ambivalence of acetyl and methyl groups in 1,2,3-thia-
diazole 1s. By comparing the chemical shifts of methyl and
acetyl group protons in the starting ketones 1b–t with the
chemical shifts of methyl group protons in enaminones 4a–r,
it was possible to define a rule, according to which the
electrophilic DMF–DMA reagent reacted exclusively with
the methyl group giving a more downfield proton NMR
signal.
and H–13C HSQC experiments. Besides that, monocrystal
1
X-ray structural analysis was performed for enaminone 4q,
allowing to conclusively prove the structures of both
isomers (Fig. 3). It should be noted that, according to the
results of X-ray structural analysis, enaminone 4q existed
in the form of Е-isomer. This was in agreement with the
high spin-spin coupling constant (J = 12.6 Hz) between the
alkene group protons in its 1Н NMR spectrum. This constant
for enaminones 4q,r belonging to 1,2,3-triazole and
isoxazole series was equally large (12.3‒12.6 Hz),
providing strong evidence that these compounds are also in
the E-form.
Thus, we have achieved a substantial progress in
developing a general and effective method for the synthesis
of azolyl enaminones in good yields, using the reactions of
5-acetyl-substituted 1,2,3-triazoles containing various
aryl substituents at position 1, as well as other azoles with
DMF–DMA.
It should be noted that the proton signals of 5-methyl
1
and 4-acetyl groups in Н NMR spectrum of the starting
1,2,3-thiadiazole 1s were practically equivalent and
therefore could not be assigned. At the same time, the
chemical shifts of protons in the respective methyl groups
in the series of 1,2,3-triazoles 1b–r differed by only 0.10 to
0.25 ppm, while for isoxazole 1t this difference reached
0.57 ppm. This observation was in agreement with the
Figure 3. The molecular structure of enaminone 4q with atoms
represented by thermal vibration ellipsoids of 50% probability.
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Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
The possibility of using the obtained enaminones 4 for
to the CFCl3 signal. Mass spectra with EI ionization were
recorded on a GCMS-QP 2010 Ultra mass spectrometer
(70 eV). Elemental analysis (C, H, and N) was performed
on a PerkinElmer 2400 II automatic analyzer. HPLC-MS
analysis of the compounds with electrospray ionization was
performed using an Agilent 6540 UHD Accurate-Mass
Q-TOF LC/MS tandem quadrupole time-of-flight exact
mass-selective detector. Analytical chromatographic
separations were performed using an Agilent 1290 Infinity
UPLC instrument equipped with a Zorbax Extend-C18
RRHT, 2.1 × 50 mm column, the particle size of stationary
phase was 1.8 µm (Agilent 727700-902) at thermostat
temperature of 50°C. The reaction progress and purity of
the obtained compounds were controlled by TLC method
on Sorbfil UV-254 plates, using visualization under UV
light. KSKG silica gel with 40–100 µm particle size was
used for the column chromatography. The volatile
components were evaporated, and solutions were concen-
trated at reduced pressure. The solid and liquid phases were
separated by centrifugation at 3000 rpm. Melting points
were determined on a Stuart SMP10 melting point
apparatus.
the synthesis of bisheterocyclic systems in which the azole
moiety and the 1,2,3-triazole ring are linked via a carbonyl
group was demonstrated using the reactions of enaminones
4a,b,n,m,r, with aryl azides 2a,b,d,g,h,i. As a result,
4-(1,2,3-triazole-4-carbonyl)azoles 5a–i were obtained in
good yields (Scheme 4). The structures of compounds 5a–i
1
were proved on the basis of Н and 13С NMR spectra. The
1
characteristic Н NMR signals were those of the newly
formed 1,2,3-triazole ring protons at 8.52‒9.96 ppm, while
13С NMR spectra contained the characteristic С=О group
signals at 175.3‒180.4 ppm.
Scheme 4. Synthesis of triazolylcarbonylazoles 5a–i
All solvents were prepared according to the standard
procedures. The petroleum ether fraction with 70–100°С
bp was used.
Methyltriazolyl ketones 1a,10a 1b,c,e,m,10b 1d,10c 1l,10d
1o,10e 1r,10f 1s,10g,h 1t10i, azides 2a–h,j–l11, and enaminones
4a,b10a were synthesized according to literature procedures.
Azide 2i was obtained from a commercial source.
Synthesis of methyl triazolyl ketones 1f,h,i (General
method). A solution of the appropriate azide 2d,h,k
(10.0 mmol) and acetylacetone (2.0 g, 20.0 mmol) in DMF
(20 ml) was treated by adding Et3N (2.02 g, 20.0 mmol)
and DBU (0.76 g, 5.00 mmol), while for the synthesis of
compound 1h only Et3N (20.0 mmol) was used as base.
The reaction mixture was stirred at room temperature for
12 h. The solution was then diluted with H2O (20 ml), the
precipitate that formed was filtered off after 10 min, washed
with H2O (10 ml), and dried in a vacuum desiccator over
P4O10.
Thus, as a result of this study, a new aproach was
developed for the synthesis of previously difficult to obtain
bis-1,2,3-triazole system containing two rings with direct
bonding between the carbon atoms at positions 4 and 5, as
well as bisheterocyclic structures where the 1,2,3-triazole
ring and a second azole ring are linked via a carbonyl
group. The synthesis of the first type of bisheterocycles
apparently involved a new type of enamines – α-(1,2,3-triazol-
4-yl) enamines. In addition, a dual reactivity of 4-acetyl-
5-methyl-1,2,3-thiadiazole in reactions with DMF–DMA
was identified. The second 1,2,3-triazole ring in the
bisheterocyclic structures of both types was assembled
mostly by using the same aryl azides as in the synthesis of
the starting acetylazoles. For this reason, the developed
approach was highly productive even with a limited range
of available reactants.
1-{5-Methyl-1-[4-(propan-2-yl)phenyl]-1Н-1,2,3-triazol-
4-yl}ethanone (1f) was obtained from azide 2d. Yield
1
2.262 g (93%), light-beige powder, mp 81‒83°C. H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 1.27 (6H, d, J = 6.9,
CH(CH3)2); 2.51 (3H, s, 5-CH3); 2.64 (3H, s, CH3СО);
2.94–3.13 (1H, m, CH(CH3)2); 7.33–7.68 (4H, m, H Ar).
13C NMR spectrum (DMSO-d6), δ, ppm: 9.7; 23.6; 27.5;
33.2; 125.3; 127.5; 132.8; 137.6; 142.7; 150.5; 193.3. Mass
spectrum, m/z (Irel, %): 243 [M]+ (30), 200 (40), 158 (100).
Found, %: C 69.01; H 6.65; N 17.13. C14H17N3O.
Calculated, %: C 69.11; H 7.04; N 17.27.
1-[1-(3-Fluorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
ethanone (1g). A solution of azide 2f (1.371 g, 10 mmol)
and acetylacetone (1.201 g, 12.00 mmol) in CHCl3 (6 ml)
was treated with Et3N (1.011 g, 10.00 mmol) and DBU
(0.166 g, 1.10 mmol). The solution was maintained in a
sealed vessel for 2 h at 60°C. The volatile components
were removed by evaporation to dryness, the oily residue
was extracted with boiling petroleum ether. Yield 1.58 g
Experimental
1Н, 13С, and 19F NMR spectra were acquired on a Bruker
Avance II 400 spectrometer (400, 100, and 376 MHz,
respectively) in DMSO-d6, CDCl3, or DMF-d7 solutions.
The residual signals of DMSO, CHCl3, and DMF were
used as internal standards for 1Н and 13С NMR spectra. The
chemical shifts of 19F NMR signals were measured relative
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Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
(72%), light-beige powder, mp 89‒91°C. 1H NMR
(5), 263 [M–N2]+ (2), 221 (45), 208 (10), 194 (10), 43
(100). Found, %: C 45.02; H 2.05; N 14.71. C11H6F5N3O.
Calculated, %: C 45.37; H 2.08; N 14.43.
spectrum (CDCl3), δ, ppm (J, Hz): 2.52–2.64 (3H, m,
5-CH3); 2.66–2.78 (3H, m, CH3СО); 7.25 (3H, d, J = 7.6,
H-4,5,6 Ar); 7.48–7.61 (1H, m, H-2 Ar). 13C NMR
spectrum (CDCl3), δ, ppm (J, Hz): 10.0; 27.7; 113.0 (d,
J = 24.8); 117.1 (d, J = 20.9); 120.9 (d, J = 3.5); 131.1 (d,
J = 8.9); 135.7–138.1 (m); 143.6; 162.7 (d, J = 250.0);
194.1. 19F NMR spectrum (CDCl3), δ, ppm: –109.54. Mass
spectrum, m/z (Irel, %): 219 [M]+ (14), 191 [M–N2]+ (4),
176 (18), 148 (81), 43 (100). Found, %: C 59.96; H 4.55;
N 19.08. C11H10FN3O. Calculated, %: C 60.27; H 4.60;
N 19.17.
1-[1-(2-Chloro-4-methylphenyl)-5-methyl-1H-1,2,3-tri-
azol-4-yl]ethanone (1h) was obtained from azide 2h.
Yield 2.01 g (80%), colorless powder, mp 114‒115°C.
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.34 (3H,
s, 4-CH3 Ar); 2.44 (3H, s, 5-CH3); 2.65 (3H, s, CH3СО); 7.38–
7.49 (1H, m, H-5 Ar); 7.58 (1H, d, J = 8.0, H-6 Ar); 7.66
(1H, d, J = 1.0, H-3 Ar). 13C NMR spectrum (DMSO-d6),
δ, ppm: 9.0; 20.6; 27.5; 129.1; 129.2; 129.6; 129.9; 130.6;
139.0; 142.3; 143.3; 193.2. Mass spectrum, m/z (Irel, %):
251 [M]+ (4), 250 [M]+ (2), 249 [M]+ (12), 221 [M–N2]+
(4), 206 (23), 178 (50), 43 (100). Found, %: C 57.36;
H 4.80; N 16.75. C12H12ClN3O. Calculated, %: C 57.72;
H 4.84; N 16.83.
1-[1-(4-Bromobenzyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
ethanone (1k). A solution of azide 2j (2.364 g, 10.00 mmol)
and acetylacetone (1.202 g, 12.00 mmol) in anhydrous
1,4-dioxane (4 ml) was treated by adding Et3N (1.215 g,
12.00 mmol) and DBU (0.154 g, 1.01 mmol). The solution
was heated for 23 h at 95°С, and the volatile components
were removed by evaporation. The residue was triturated
with cold H2O. The obtained oil was dried to remove
residual H2O and EtOH. The crude product was isolated by
fractional crystallization from petroleum ether. Yield
0.539 g (18%), light-brown amorphous material, mp 86‒
1
87°C. H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.45
(3H, s, CH3СО); 2.67 (3H, s, 5-CH3); 5.45 (2H, s, CH2);
7.05 (2H, d, J = 8.4, H Ar); 7.47 (2H, d, J = 8.4, H Ar).
13C NMR spectrum (CDCl3), δ, ppm: 9.1; 27.7; 51.0;
122.8; 128.9; 132.3; 133.0; 136.7; 144.1; 194.2. Mass
spectrum, m/z (Irel, %): 296 [M]+ (2), 295 [M]+ (14), 294
[M]+ (3), 293 [M]+ (14), 266 (25), 265 [M–N2]+ (4), 264
(25), 252 (19), 250 (21), 224 (8), 222 (7), 54 (100). Found,
%: C 49.12; H 4.08; N 14.35. C12H12BrN3O. Calculated, %:
C 49.00; H 4.11; N 14.29.
1-[(5-Methyl-1-prop-2-en-1-yl)-1H-1,2,3-triazol-4-yl]-
ethanone (1n). A solution of diazoacetylacetone (1.261 g,
10.00 mmol) and allylamine (1.427 mg, 25.00 mmol) in
CHCl3 (6 ml) was maintained at room temperature for 24 h.
The volatile components were evaporated to dryness. The
obtained oily residue was treated with H2O (8 ml) and
concentrated HCl (0.8 ml). The product was extracted with
Et2O, and the extract was evaporated to dryness. Yield
1.082 g (66%), colorless oil that was suitable for sub-
sequent syntheses without additional purification. An
analytically pure sample was obtained by converting
ketone 1n into the corresponding semicarbazone 1n',
followed by its decomposition to ketone 1n in acidic
medium (see the Supplementary information file). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 2.53 (3H, d, J = 0.8,
CH3); 2.67 (3H, d, J = 1.4, CH3); 4.93 (1H, d, J = 5.4,
CH2CH=CH2); 5.01–5.12 (1H, m, CН2CH=CH2); 5.30 (2H,
dd, J = 10.3, J = 0.6, CH2CH=CH2); 5.87–5.95 (1H, m,
CH2CH=CH2). 13C NMR spectrum (CDCl3), δ, ppm: 8.9;
27.6; 50.1; 119.1; 130.5; 136.9; 143.8; 194.3. Mass
spectrum, m/z (Irel, %): 165 [M]+ (43), 136 (30), 122 (21),
54 (100). Found, %: C 58.19; H 6.58; N 25.52. C8H11N3O.
Calculated, %: C 58.17; H 6.71; N 25.44.
Synthesis of methyl triazolyl ketones 1p,q (General
method). A solution of (3E)-4-(dimethylamino)but-3-en-
2-one (1.131 g, 10.00 mmol) and the appropriate azide 2с,l
(10.00 mmol) in PhMe (4 ml) was heated at 50‒105°С for
6‒23 h. After cooling, the volatile components were
evaporated to dryness and the residue was separated on a
chromatography column (eluent PhH (for compound 1p) or
CHCl3 (for compound 1q)). The fractions containing the
product were combined, evaporated to dryness, and the
residue was crystallized from petroleum ether.
1-[1-(5-Chloro-2-nitrophenyl)-5-methyl-1H-1,2,3-tri-
azol-4-yl]ethanone (1i) was obtained from azide 2k. Yield
2.47 g (88%), light-yellow powder, mp 141‒142°C. 1H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 2.49 (3H, s, 5-CH3);
2.66 (3H, s, CH3СО); 8.01–8.12 (1H, m, H-6 Ar); 8.19–
8.28 (1H, m, H-3 Ar); 8.39 (1H, dd, J = 8.8, J = 1.5, H-4
Ar). 13C NMR spectrum (DMSO-d6), δ, ppm: 9.1; 27.6;
127.8; 128.5; 129.6; 132.5; 139.2; 139.7; 142.4; 193.1.
Mass spectrum, m/z (Irel, %): 282 [M]+ (8), 281 [M]+ (4),
280 [M]+ (26), 252 [M–N2]+ (9), 43 (100). Found, %: C 47.12;
H 3.53; N 20.06. C11H9ClN4O3. Calculated, %: C 47.07;
H 3.23; N 19.96.
1-[5-Methyl-1-(pentafluorophenyl)-1H-1,2,3-triazol-4-yl]-
ethanone (1j). A mixture of azide 2g (525 mg, 2.50 mmol)
and acetylacetone (250 mg, 2.50 mmol) in CHCl3 (3 ml)
was treated by adding Et3N (252 mg, 2.49 mmol) and DBU
(103 mg, 0.68 mmol). The reaction mixture was maintained
at room temperature for 1.5 h, followed by evaporation of
the volatile components to dryness. The product was
extracted from the precipitate with boiling petroleum ether,
the extract was concentrated to a minimum volume, and the
residue was crystallized from petroleum ether. The precipi-
tate was separated and dried. The yield of the crude product
was 415 mg (57%), colorless crystalline powder, suitable
for using in the subsequent synthetic steps. Analytically
pure product was obtained by column chromatography
1
(eluent PhH), mp 82‒83°C. H NMR spectrum (CDCl3),
δ, ppm: 2.52 (3H, s, CH3СО); 2.76 (3H, s, CH3). 13C NMR
spectrum (CDCl3), δ, ppm (J, Hz): 8.9; 27.6; 136.5–
137.2 (m); 139.4 (ddd, J = 13.9, J = 8.9, J = 4.0); 140.0;
141.5–142.2 (m); 144.5 (dt, J = 13.4, J = 7.2); 143.1; 193.5.
19F NMR spectrum (CDCl3), δ, ppm (J, Hz): –143.56÷
–144.13 (2F, m), –147.42 (1F, t, J = 21.5), –158.31÷
–159.08 (2F, m). Mass spectrum, m/z (Irel, %): 291 [M]+
1-[1-(4-Methylphenyl)-1H-1,2,3-triazol-4-yl]ethanone
(1p) was obtained from azide 2l, the reaction was
708

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
performed at 105°С for 23 h. Yield 965 mg (48%),
347 [M]+ (4), 319 [M–N2]+ (13), 290 (10), 274 (10), 244
(24), 77 (100). Found, %: C 58.54; H 3.75; N 28.54.
C17H13N7O2. Calculated, %: C 58.79; H 3.77; N 28.23.
1-(4-Bromobenzyl)-5-methyl-3'-(4-nitrophenyl)-1H,3'H-
4,4'-bis-1,2,3-triazole (3f). The reaction was performed for
33 h at 95°С. Yield 616 mg (70%), colorless powder,
colorless crystals, mp 115‒116°C. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.42 (3H, s, CH3); 2.73 (3H, s,
CH3); 7.33 (2H, d, J = 8.1, H Ar); 7.61 (2H, d, J = 8.4,
H Ar); 8.44 (1H, s, H triazole). 13C NMR spectrum
(CDCl3), δ, ppm: 21.1; 27.2; 120.7; 123.3; 130.4; 134.1;
139.8; 148.4; 192.8. Mass spectrum, m/z (Irel, %): 201 [M]+
(13), 173 [M–N2]+ (3), 158 (83), 144 (7), 130 (100). Found,
%: C 65.66; H 5.56; N 21.00. C11H11N3O. Calculated, %:
C 65.66; H 5.51; N 20.88.
1
mp 191‒195°C. H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.19 (3H, s, CH3); 5.63 (2H, s, CH2); 7.16 (2H, d,
J = 8.4, H Ar); 7.58 (2H, d, J = 8.4, H Ar); 7.76 (2H, d,
J = 9.0, H Ar); 8.26 (1H, s, H triazole); 8.36 (2H, d,
J = 9.0, H Ar). 13C NMR spectrum (DMSO-d6), δ, ppm:
8.0; 50.3; 121.3; 124.7; 126.2; 129.1; 131.7; 131.8; 133.9;
134.2; 134.6; 141.2; 147.4. Mass spectrum, m/z (Irel, %):
442 [M]+ (2), 441 [M]+ (5), 440 [M]+ (2), 439 [M]+ (5), 414
[M–N2]+ (10), 413 [M–N2]+ (48), 412 [M–N2]+ (22), 411
[M–N2]+ (48), 382 (11), 338 (21), 90 (100). Found, %:
C 49.16; H 2.97; N 22.35. C18H14BrN7O2. Calculated, %:
C 49.11; H 3.21; N 22.27.
1,5-Dimethyl-3'-phenyl-1H,3'H-4,4'-bis-1,2,3-triazole
(3c). Method I. A mixture of ketone 1а (278 mg, 2.00 mmol),
azide 2а (1.073 g, 9.00 mmol), and CaO (221 mg, 3.94 mmol)
in anhydrous morpholine (2 ml) was stirred at 120°C for
72 h. The volatile components were evaporated to dryness,
the residue was separated on a chromatography column
(using a sequence of eluents: CHCl3‒EtOAc, 2:1; CHCl3‒
EtOAc, 1:1; CHCl3‒EtOAc, 1:2). The last portions of
eluate containing the product were combined and
evaporated to dryness. The oily residue was treated with
petroleum ether and left overnight at cold temperature.
Method II. A solution of ketone 1а (278 mg, 2.00 mmol)
and azide 2a (550 mg, 4.61 mmol) in anhydrous
pyrrolidine (2 ml) was stirred at 70‒80°С for 8 h. The
volatile components were evaporated to dryness. The crude
product was purified in the way described in method I.
Yield 71 mg (15%, method I), 192 mg (40%, method II),
light-yellow powder, mp 86‒91°С. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.02 (3H, s, CH3); 3.95 (3H, s,
NCH3); 7.40‒7.43 (5H, m, Н Ph); 7.91 (1H, s, H triazole).
13C NMR spectrum (CDCl3), δ, ppm: 8.0; 34.7; 124.8;
128.9; 129.2; 132.4; 132.8; 134.4; 136.6. Mass spectrum,
m/z (Irel, %): 240 [M]+ (11), 212 [M–N2]+ (23), 183 (56),
169 (14), 56 (100). Found, %: C 59.62; H 4.75; N 34.87.
C12H12N6. Calculated, %: C 59.99; H 5.03; N 34.98.
Synthesis of bistriazoles 3d,e,g (General method). A
solution of the appropriate ketone 1a,g (2.00 mmol) and
azide 2b,e (5.00 mmol) in anhydrous morpholine (2 ml)
was stirred at 95‒120°C for 12‒48 h. The volatile compo-
nents were evaporated to dryness, the residue was purified
by column chromatography (eluent CHCl3, followed by
CHCl3‒EtOAc, 1:1 (for compound 3d); CHCl3, followed
by CHCl3‒EtOAc, 1:3 (for compound 3e); petroleum ether,
petroleum ether ‒ Et3N, 93:1; petroleum ether ‒ Et3N ‒
EtOAc, 93:1:186 (for compound 3g)).
1,5-Dimethyl-3'-(4-nitrophenyl)-1H,3'H-4,4'-bis-1,2,3-tri-
azole (3d). The reaction was performed for 48 h at 110°C.
The product was isolated by column chromatography and
then additionally purified by crystallization from EtOH.
Yield 285 mg (50%), colorless powder, mp 160‒165°С.
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.32 (3H,
1-[1-(2-Nitrophenyl)-1H-1,2,3-triazol-4-yl]ethanone
(1q) was obtained from azide 2с, the reaction was
performed at 55°С for 6 h. Yield 1.3 g (56%), colorless
crystals, mp 133‒134°C. 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.75 (3H, s, CH3); 7.61 (1H, dd, J = 7.8, J = 1.3,
H Ar); 7.80 (2H, t, J = 8.0, H Ar); 7.84 (1H, t, J = 8.0, H Ar);
8.15 (1H, dd, J = 8.1, J = 1.4, H Ar); 8.38 (1H, s, H triazole).
13C NMR spectrum (CDCl3), δ, ppm: 27.4; 125.9; 127.2;
128.0; 129.6; 131.6; 134.2; 144.3; 148.2; 192.3. Mass
spectrum, m/z (Irel, %): 232 [M]+ (1), 204 [M–N2]+ (2), 145
(3), 43 (100). Found, %: C 51.88; H 3.78; N 24.31.
C10H8N4O3. Calculated, %: C 51.73; H 3.47; N 24.13.
Synthesis of bistriazoles 3a,b,f (General method). A
suspension of TiCl4 (1.32 g, 7.00 mmol) in anhydrous
1,4-dioxane (6 ml) was cooled to –7÷–10°С and treated by
the addition of anhydrous morpholine (5.94 ml, 68.90 mmol).
The reaction mixture was stirred for 5 min at room tempe-
rature, then the appropriate ketone 1a,b,k (2.00 mmol) and
azide 2a,b (5.00 mmol) were added. The reaction mixture
was stirred for 7‒36 h at 95‒105°С. The solids were
separated, washed with hot 1,4-dioxane (2×7 ml) and
CHCl3. The liquid phases were combined and evaporated
to dryness. The residue was treated with 1 N HCl, then
with H2O. The crude product was purified by column
chromatography (eluent CHCl3 ‒ petroleum ether, 1:1 (for
compound 3a); petroleum ether, CHCl3 ‒ petroleum ether,
gradient from 1:1 to 2:1 (for compound 3b); petroleum
ether, CHCl3 ‒ petroleum ether, 1:1, CHCl3, then CHCl3‒
EtOAc, 1:1 (for compound 3f)).
5-Methyl-1,3'-diphenyl-1H,3'H-4,4'-bis-1,2,3-triazole
(3а). The reaction was performed at 95°С for 36 h. Yield
1
290 mg (48%), colorless oil. H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 2.07 (3H, s, CH3); 7.40‒7.45 (2H, m,
H Ar); 7.45–7.51 (3H, m, H Ar); 7.50‒7.60 (5H, m, H Ar);
8.03 (1H, s, H triazole). 13C NMR spectrum (CDCl3), δ, ppm:
9.3; 124.9; 125.0; 128.7; 129.4; 129.5; 129.7; 129.9; 133.0;
133.2; 134.7; 135.7; 136.6. Mass spectrum, m/z (Irel, %): 302
[M]+ (4), 274 [M–N2]+ (14), 245 (32), 204 (15), 143 (73),
77 (100). Found, %: C 67.79; H 4.29; N 27.94. C17H14N6.
Calculated, %: C 67.54; H 4.67; N 27.80.
5-Methyl-3'-(4-nitrophenyl)-1-phenyl-1H,3'H-4,4'-bis-
1,2,3-triazole (3b). The reaction was performed at 105°С
for 7 h. Yield 340 mg (49%), light-pink powder, mp 211‒
1
213°С. H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
2.33 (3H, s, CH3); 7.62‒7.65 (5H, m, Н Ph); 7.87 (2H, d,
J = 9.0, H Ar); 8.33 (1H, s, H triazole); 8.40 (2H, d,
J = 9.1, H Ar). 13C NMR spectrum (DMSO-d6), δ, ppm:
9.6; 125.3; 125.6; 126.7; 129.4; 130.2; 130.4; 132.3; 134.7;
134.8; 135.9; 141.7; 148.0. Mass spectrum, m/z (Irel, %):
709

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
s, CH3); 4.00 (3H, s, NCH3); 7.78 (2H, d, J = 9.1, H Ar);
301 [M]+ (16), 229 (22), 98 (100). Found, %: C 55.91;
H 5.21; N 23.47. C14H15N5O3. Calculated, %: C 55.81;
H 5.02; N 23.24.
8.07 (1H, s, Н triazole); 8.36 (2H, d, J = 9.1, H Ar).
13C NMR spectrum (DMSO-d6), δ, ppm: 7.9; 34.5; 124.4;
125.8; 129.1; 133.6; 133.7; 140.0; 141.3; 147.2. Mass
spectrum, m/z (Irel, %): 285 [M]+ (9), 257 [M–N2]+ (42),
228 (10), 214 (7), 201 (9), 182 (20), 56 (100). Found, %:
C 50.91; H 3.89; N 34.18. C12H11N7O2. Calculated, %:
C 50.53; H 3.89; N 34.37.
3'-(4-Chlorophenyl)-1,5-dimethyl-1H,3'H-4,4'-bis-1,2,3-
triazole (3e). The reaction was performed for 26 h at 120°С.
The product obtained after column chromatography was
crystallized from heptane. Yield 203 mg (41%), light-
brown powder, mp 120‒123°С. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.17 (3Н, s, CH3); 4.00 (3H, s,
NCH3); 7.43–7.47 (4H, m, J = 8.9, H Ar); 7.90 (1H, s,
Н triazole). 13C NMR spectrum (CDCl3), δ, ppm: 8.2; 34.9;
126.3; 128.8; 129.4; 132.2; 134.3; 135.1; 135.3. Mass
spectrum, m/z (Irel, %): 276 [M+2]+ (6), 275 [M+1]+ (3),
274 [M]+ (17), 246 [M–N2]+ (5), 217 (20), 183 (23), 56
(100). Found, %: C 52.11; H 3.97; N 30.39. C12H11ClN6.
Calculated, %: C 52.47; H 4.04; N 30.59.
3-(Dimethylamino)-1-[5-methyl-1-(methylphenyl)-1H-
1,2,3-triazol-4-yl]prop-2-en-1-one (4d). The reaction was
performed at 110°С over 22 h. The product was purified by
column chromatography (eluent EtOAc), then crystallized
from i-PrOH. Yield 568 mg (70%), light-yellow needles,
1
mp 190‒193°C. H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.41 (3H, s, CH3); 2.51 (3H, s, CH3); 2.90 (3H, br. s,
NCH3); 3.15 (3H, br. s, NCH3); 6.08 (1H, d, J = 12.6,
CH=CHN(CH3)2); 7.42 (2H, d, J = 8.2, H Ar); 7.45–7.50
(2H, m, H Ar); 7.75 (1H, d, J = 12.6, CH=CHN(CH3)2).
13C NMR spectrum (DMSO-d6), δ, ppm: 9.6; 20.6; 92.7;
125.1; 130.0; 133.1; 135.7; 139.4; 143.9; 153.0; 180.9.
Mass spectrum, m/z (Irel, %): 270 [M]+ (36), 242 [M–N2]+
(2), 227 (5), 198 (37), 132 (100). Found, %: C 66.52;
H 6.74; N 20.57. C15H18N4O. Calculated, %: C 66.64;
H 6.71; N 20.73.
3-(Dimethylamino)-1-{5-methyl-1-[4-(propan-2-yl)-
phenyl]-1H-1,2,3-triazol-4-yl}prop-2-en-1-one (4e). The
reaction was performed at 110°С for 20 h. The crude
product was purified by crystallization from PhH. Yield
850 mg (95%), light-yellow powder, mp 190‒192°C.
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.28 (6H, d,
J = 6.9, CH(CH3)2); 2.61 (3H, s, 5-CH3); 2.96–2.99 (4H, m,
NCH3, CH(CH3)2); 3.14 (3H, s, NCH3); 6.27 (1H, d,
J = 12.6, CH=CHN(CH3)2); 7.34 (2H, d, J = 8.7, H Ar);
7.38 (2H, d, J = 8.6, H Ar); 7.85 (1H, d, J = 12.6,
CH=CHN(CH3)2). 13C NMR spectrum (CDCl3), δ, ppm:
10.2; 23.8; 33.9; 37.4; 45.0; 125.2; 127.5; 144.4; 150.6;
153.3; 182.7. Mass spectrum, m/z (Irel, %): 298 [M]+ (49),
270 [M–N2]+ (3), 226 (62), 184 (19), 160 (81), 98 (100).
Found, %: C 68.53; H 7.31; N 19.07. C17H22N4O.
Calculated, %: C 68.43; H 7.43; N 18.78.
1-[1-(3-Chlorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-(dimethylamino)-prop-2-en-1-one (4f). The reaction
was performed at 100°С for 24 h. The product was purified
by column chromatography (eluent EtOAc), then crystal-
lized from a PhH – petroleum ether mixture. Yield 488 mg
(56%), light-yellow powder, mp 128‒129°C. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 2.63 (3H, s, CH3); 2.95
(3H, s, NCH3); 3.14 (3H, s, NCH3); 6.24 (1H, d, J = 12.6,
CH=CHN(CH3)2); 7.30–7.40 (1H, m, H Ar); 7.44–7.56
(3H, m, H Ar); 7.83 (1H, d, J = 12.6, CH=CHN(CH3)2).
13C NMR spectrum (CDCl3), δ, ppm: 10.3; 37.4; 45.1;
93.6; 123.4; 125.6; 129.8; 130.5; 135.3; 136.3; 136.9;
144.7; 153.5; 182.4. Mass spectrum, m/z (Irel, %): 292 [M]+
(14), 291 [M]+ (8), 290 [M]+ (43), 273 (10), 218 (46), 152
(66), 98 (100). Found, %: C 57.92; H 4.99; N 19.62.
C14H15ClN4O. Calculated, %: C 57.83; H 5.20; N 19.27.
3-(Dimethylamino)-1-[1-(3-fluorophenyl)-5-methyl-1H-
1,2,3-triazol-4-yl]prop-2-en-1-one (4g). The reaction was
performed at 100°С for 7.5 h. The crude product was
washed with petroleum ether and crystallized from PhH –
petroleum ether mixture. Yield 667 mg (81%), light-brown
powder, mp 157‒158°C. 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.67 (3H, s, CH3); 2.98 (3H, s, NCH3); 3.17 (3H, s,
NCH3); 6.27 (1H, d, J = 12.4, CH=CHN(CH3)2); 7.26 (3H,
1-Butyl-5-methyl-3'-(4-nitrophenyl)-1H,3'H-4,4'-bis-
1,2,3-triazole (3g). The reaction was performed at 95°С
over 12 h. The product isolated by column chromatography
was crystallized from PhH ‒ petroleum ether mixture.
Yield 400 mg (61%), light-yellow amorphous material,
1
mp 91‒93°С. H NMR spectrum (CDCl3), δ, ppm (J, Hz):
0.95 (3H, t, J = 7.4, N(CH2)3CH3); 1.28–1.46 (2H, m,
N(CH2)2CH2CH3); 1.80–1.95 (2H, m, NCH2CH2CH2CH3);
2.25 (3H, s, CH3); 4.27 (2H, t, J = 7.3, NCH2(CH2)2CH3);
7.74 (2H, d, J = 9.0, H Ar); 7.90 (1H, s, H triazole); 8.29
(2H, d, J = 8.9, H Ar). 13C NMR spectrum (CDCl3),
δ, ppm: 8.3; 13.4; 19.7; 31.6; 48.2; 124.5; 125.7; 129.0;
131.9; 132.4; 134.4; 141.5; 147.8. Mass spectrum, m/z
(Irel, %): 327 [M]+ (7), 299 [M–N2]+ (25), 298 (100).
Found, %: C 55.03; H 5.45; N 29.87. C15H17N7O2.
Calculated, %: C 55.04; H 5.23; N 29.95.
Synthesis of enaminones 4с–s (General method). A
mixture of the appropriate ketone 1 (3.00 mmol) and
DMF–DMA (4.3 g, 4.8 ml, 36.00 mmol) was heated at 100‒
120°С (the temperature of the oil bath) for 1.5‒50 h. The
excess of DMF–DMA was evaporated, the crude
enaminone was purified by crystallization from EtOH,
PhH, or petroleum ether, or by column chromatography
(eluent EtOAc, a mixture of EtOAc ‒ petroleum ether,
CHCl3‒EtOAc, or CHCl3‒EtOH).
3-(Dimethylamino)-1-[5-methyl-1-(2-nitrophenyl)-
1H-1,2,3-triazol-4-yl]prop-2-en-1-one (4c). The reaction
was performed over 22 h at 110°С. The crude product was
treated by petroleum ether, H2O, then crystallized from
EtOH. Yield 615 mg (68%), light-yellow powder, mp 228‒
1
229°С (decomp.). H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.48 (3H, d, J = 6.6, CH3); 2.91 (3H, s, NCH3);
3.17 (3H, s, NCH3); 6.07 (1H, d, J = 12.6, CH=CHN(CH3)2);
7.78 (1H, d, J = 12.6, CH=CHN(CH3)2); 7.91–7.94 (2H, m,
H Ar); 7.98–8.08 (1H, m, H Ar); 8.31 (1H, dd, J = 8.4,
J = 1.3, H Ar). 13C NMR spectrum (DMSO-d6), δ, ppm:
9.0; 92.9; 99.5; 125.6; 128.0; 129.6; 132.1; 134.6; 137.5;
143.8; 145.5; 153.3; 180.6. Mass spectrum, m/z (Irel, %):
710

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
s, H Ar); 7.44–7.62 (1H, m, H Ar); 7.85 (1H, d, J = 12.4,
145.0; 153.4; 182.6. Mass spectrum, m/z (Irel, %): 351 [M]+ (4),
350 [M]+ (20), 349 [M]+ (4), 348 [M]+ (22), 333 (13), 331
(14), 276 (6), 98 (100). Found, %: C 51.38; H 4.84;
N 16.09. C15H17BrN4O. Calculated, %: C 51.59; H 4.91;
N 16.04.
CH=CHN(CH3)2). 13C NMR spectrum (CDCl3), δ, ppm
(J, Hz): 10.2; 37.4; 44.8, 93.3, 112.9 (d, J = 25.0); 116.5 (d,
J = 21.0); 120.9 (d, J = 3.0); 130.9 (d, J = 9.0); 136.2;
137.1 (d, J = 10.0); 144.6; 153.4; 162.7 (d, J = 258.0);
182.3. 19F NMR spectrum (CDCl3), δ, ppm: –110.0. Mass
spectrum, m/z (Irel, %): 275 [M+1]+ (7), 274 [M]+ (36), 257
(8), 202 (41), 176 (12), 162 (14), 136 (100). Found, %:
C 61.38; H 5.72; N 20.65. C14H15FN4O. Calculated, %:
C 61.30; H 5.51; N 20.43.
1-(1-Butyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-(dimethyl-
amino)prop-2-en-1-one (4k). The reaction was performed
at 110°С for 50 h. The crude product was crystallized from
petroleum ether. Yield 562 mg (79%), light-yellow powder,
1
mp 93‒95°C. H NMR spectrum (CDCl3), δ, ppm (J, Hz):
1-[1-(2-Chloro-4-methylphenyl)-5-methyl-1H-1,2,3-
triazol-4-yl]-3-(dimethylamino)prop-2-en-1-one (4h).
The reaction was performed at 120°С for 24 h. The crude
product was treated with petroleum ether and crystallized
from PhH – petroleum ether mixture. Yield 886 mg (97%),
light-yellow powder, mp 160‒162°C. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.43 (3H, s, CH3); 2.46 (3H, s, CH3);
2.96 (3H, s, NCH3); 3.15 (3H, s, NCH3) 6.28 (1H, d, J = 12.6,
CH=CHN(CH3)2); 7.22–7.28 (2H, m, H Ar); 7.40 (1H, d,
J = 0.4, H Ar); 7.85 (1H, d, J = 12.6, CH=CHN(CH3)2).
13C NMR spectrum (CDCl3), δ, ppm: 9.5; 21.1; 37.3; 44.9;
93.8; 128.5; 128.8; 130.9; 131.0; 131.4; 138.0; 142.5;
143.9; 153.4; 182.6. Mass spectrum, m/z (Irel, %): 306
[M+2]+ (22), 305 [M+1]+ (13), 304 [M]+ (66), 287 (9), 241
(15), 234 (25), 232 (71), 166 (100). Found, %: C 58.93;
H 5.25; N 18.66. C15H17ClN4O. Calculated, %: C 59.11;
H 5.62; N 18.38.
1-[1-(5-Chloro-2-nitrophenyl)-5-methyl-1H-1,2,3-tri-
azol-4-yl]-3-(dimethylamino)prop-2-en-1-one (4i). The
reaction was performed at 150°С for 12 h. The crude product
was purified by column chromatography (eluent CHCl3‒
EtOAc, 1:1, then EtOAc), followed by crystallization from
PhH ‒ petroleum ether mixture. Yield 403 mg (40%), light-
yellow crystals, mp 192‒194°C (decomp.). 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.54 (3H, s, CH3); 2.96 (3H, s,
NCH3); 3.16 (3H, s, NCH3); 6.23 (1H, d, J = 12.5,
CH=CHN(CH3)2); 7.50 (1H, d, J = 2.0, H Ar); 7.72 (1H,
dd, J = 8.8, J = 1.9, H Ar); 7.85 (1H, d, J = 12.5,
CH=CHN(CH3)2); 8.16 (1H, d, J = 8.8, H Ar). 13C NMR
spectrum (CDCl3), δ, ppm: 9.6; 37.4; 45.1; 93.5; 127.1;
129.9; 130.3; 131.6; 138.1; 140.4; 143.8; 144.3; 153.7;
181.9. Mass spectrum, m/z (Irel, %): 337 [M]+ (5), 336 [M]+
(3), 335 [M]+ (15), 265 (7), 263 (22), 98 (100). Found, %:
C 50.05; H 4.11; N 20.59. C14H14ClN5O3. Calculated, %:
C 50.08; H 4.20; N 20.86.
0.90 (3H, t, J = 7.4, (CH2)3CH3); 1.25–1.33 (2H, m,
(CH2)2CH2CH3); 1.77–1.85 (2H, m, CH2CH2CH2CH3); 2.56
(3H, s, CH3); 2.90 (3H, d, J = 2.2, NСН3); 3.09 (3H, br. s,
NСН3); 4.21 (2H, t, J = 7.3, CH2(CH2)2CH3); 6.16 (1H, d,
J = 12.7, CH=CHN(CH3)2); 7.76 (1H, d, J = 12.7,
CH=CHN(CH3)2). 13C NMR spectrum (CDCl3), δ, ppm:
9.1; 13.4; 19.6; 31.7; 37.3; 44.9; 47.2; 93.5; 135.2; 144.3;
153.1; 182.8. Mass spectrum, m/z (Irel, %): 236 [M]+ (44), 219
(26), 193 (6), 164 (20), 151 (16), 42 (100). Found, %:
C 61.20; H 8.28; N 23.51. C12H20N4O. Calculated, %:
C 60.99; H 8.53; N 23.71.
3-(Dimethylamino)-1-[5-methyl-1-(prop-2-en-1-yl)-
1H-1,2,3-triazol-4-yl]prop-2-en-1-one (4l). The reaction
was performed at 100°С for 5 h. The crude product was
purified by column chromatography (eluted with the
sequence of CHCl3, 1:1 CHCl3‒EtOAc mixture, and
EtOH). The ethanol eluate contained the product and was
evaporated to dryness. The residue was purified by
chromatography using a second column (eluent PhH‒Et3N,
93:1, then CHCl3‒Et3N, 93:1), followed by crystallization
from petroleum ether. Yield 258 mg (39%), light-yellow
1
powder, mp 75‒77°C. H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.55 (3H, s, CH3); 2.91 (3H, s, NCH3); 3.10 (3H, s,
NCH3); 4.89 (2H, d, J = 5.3, CH2CH=CH2); 5.02 (1H, d,
J = 17.1, CH2CH=CH2); 5.24 (1H, d, J = 10.4,
CH2CH=CH2); 5.87–5.95 (1H, m, CH2CH=CH2); 6.18 (1H,
d, J = 12.6, CH=CHN(CH3)2); 7.78 (1H, d, J = 12.6,
CH=CHN(CH3)2). 13C NMR spectrum (CDCl3), δ, ppm:
8.9; 37.2; 44.9; 49.8; 93.3; 118.3; 131.0; 135.6; 144.4; 153.1;
182.4. Mass spectrum, m/z (Irel, %): 220 [M]+ (74), 203 (46),
177 (7), 148 (30), 98 (100). Found, %: C 59.86; H 6.97;
N 25.28. C11H16N4O. Calculated, %: C 59.98; H 7.32;
N 25.44.
3-(Dimethylamino)-1-(1-phenyl-1H-1,2,3-triazol-4-yl)prop-
2-en-1-one (4m). The reaction was performed at 120°С for
1-(1-[4-Bromobenzyl)-5-methyl-1H-1,2,3-triazol-4-yl]-
3-(dimethylamino)prop-2-en-1-one (4j). The reaction was
performed at 105°С for 3.5 h. The crude product was
purified by column chromatography (eluent CHCl3, then
CHCl3‒EtOAc, 1:1, then EtOAc). The fractions containing
the product were evaporated to dryness, the residue was
crystallized from PhH ‒ petroleum ether mixture. Yield
482 mg (46%), light-yellow powder, mp 158‒160°C. 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 2.49 (3H, s, CH3); 2.94
(3H, br. s, NCH3); 3.13 (3H, br. s, NCH3); 5.44 (2H, s,
CH2); 6.21 (1H, d, J = 12.6, CH=CHN(CH3)2); 7.02 (2H, d,
J = 8.4, H Ar); 7.44 (2H, d, J = 8.4, H Ar); 7.80 (1H, d,
J = 12.6, CH=CHN(CH3)2). 13C NMR spectrum (CDCl3),
δ, ppm: 9.1; 50.8; 93.7; 122.4; 128.8; 132.2; 133.6; 135.6;
6 h. The crude product was purified by column
chromatography (eluted with the sequence of CHCl3,
EtOAc, and EtOH). Yield 545 mg (75%), light-yellow
1
needles, mp 188‒189°C. H NMR spectrum (DMSO-d6),
δ, ppm (J, Hz): 2.93 (3H, s, NCH3); 3.17 (3H, s, NCH3);
6.01 (1H, d, J = 12.5, CH=CHN(CH3)2); 7.50 (1H, t, J = 7.4,
H Ar); 7.60 (2H, t, J = 7.8, H Ar); 7.84 (1H, d, J = 12.5,
CH=CHN(CH3)2); 7.97 (2H, d, J = 7.9, H Ar); 9.20 (1H, s,
H triazole). 13C NMR spectrum (DMSO-d6), δ, ppm: 37.1;
44.5; 91.8; 120.2; 123.8; 128.8; 129.8; 136.4; 149.8; 153.7;
178.5. Mass spectrum, m/z (Irel, %): 242 [M]+ (71), 225 (8),
185 (7), 173 (21), 171 (27), 98 (100). Found, %: C 64.68;
H 5.99; N 22.78. C13H14N4O. Calculated, %: C 64.45;
H 5.82; N 23.13.
711

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
3-(Dimethylamino)-1-[1-(4-nitrophenyl)-1H-1,2,3-tri-
d, J = 8.5, H Ar); 7.54 (1H, br. s, CH=CHN(CH3)2); 7.61 (2H,
d, J = 8.6, H Ar). 13C NMR spectrum (CDCl3), δ, ppm: 12.7;
37.0; 45.0; 76.8; 77.1; 77.4; 127.9; 128.6; 130.3; 135.7; 160.2.
Mass spectrum, m/z (Irel, %): 292 [M]+ (8), 291 [M]+ (5), 290
[M]+ (24), 273 (12), 246 (11), 98 (100). Found, %: C 61.98;
H 5.55; N 9.97. C15H15ClN2O2. Calculated, %: C 61.97;
H 5.20; N 9.64.
azol-4-yl]prop-2-en-1-one (4n). The reaction was
performed at 120°С for 18 h. The crude product was
washed with Et2O, then with petroleum ether, and dried.
Yield 750 mg (87%), light-yellow crystals, mp 281‒284°C
(decomp.). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
2.95 (3H, s, NCH3); 3.19 (3H, s, NCH3); 5.99 (1H, d,
J = 12.5, CH=CHN(CH3)2); 7.86 (1H, d, J = 12.5,
CH=CHN(CH3)2); 8.22–8.37 (2H, m, H Ar); 8.39‒8.52
(2H, m, H Ar); 9.36 (1H, s, H triazole). 13C NMR spectrum
(DMSO-d6), δ, ppm: 31.1; 92.5; 121.5; 124.8; 125.9; 141.3;
147.5; 150.7; 154.4; 178.7. Mass spectrum, m/z (Irel, %): 287
[M]+ (64), 242 (10), 216 (21), 215 (57), 98 (100). Found,
%: C 54.31; H 4.92; N 24.44. C13H13N5O3. Calculated, %:
C 54.35; H 4.56; N 24.38.
3-(Dimethylamino)-1-[1-(2-nitrophenyl)-1H-1,2,3-tri-
azol-4-yl]prop-2-en-1-one (4o). The reaction was per-
formed at 120°С for 2.5 h. The crude product was purified
by column chromatography (eluent EtOAc, then EtOAc‒
EtOH, 10:1), then crystallized from PhH ‒ EtOAc ‒
petroleum ether mixture. Yield 500 mg (58%), light-yellow
powder, mp 156‒157°C. 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.98 (3H, s, NCH3); 3.19 (3H, s, NCH3); 6.18 (1H,
d, J = 10.8, CH=CHN(CH3)2); 7.59 (1H, dd, J = 7.8,
J = 1.1, H Ar); 7.70 (1H, td, J = 7.9, J = 1.3, H Ar); 7.78
(1H, td, J = 7.7, J = 1.3, H Ar); 7.99 (1H, br. s,
CH=CHN(CH3)2); 8.08 (1H, dd, J = 8.1, J = 1.3, H Ar);
8.36 (1H, s, H triazole). 13C NMR spectrum (CDCl3),
δ, ppm: 37.4; 45.1; 93.0; 125.7; 126.4; 127.7; 130.0; 131.0;
133.9; 144.5; 150.3; 154.4; 179.9. Mass spectrum, m/z
(Irel, %): 287 [M]+ (27), 215 (36), 98 (100). Found, %:
C 54.06; H 4.76; N 24.68. C13H13N5O3. Calculated, %:
C 54.35; H 4.56; N 24.38.
3-(Dimethylamino)-1-[1-(4-methylphenyl)-1H-1,2,3-tri-
azol-4-yl]prop-2-en-1-one (4p). The reaction was
performed at 120°С for 22 h. The crude product was
treated with Et2O, the solids were separated and
crystallized from PhH ‒ petroleum ether mixture. Yield
615 mg (80%), light-yellow powder, mp 213‒215°C.
1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.40 (3H, s,
CH3); 2.97 (3H, s, NCH3); 3.16 (3H, s, NCH3); 6.19 (1H, d,
J = 9.6, CH=CHN(CH3)2); 7.30 (2H, d, J = 8.2, H Ar); 7.57–
7.74 (2H, m, H Ar); 7.94 (1H, br. s, CH=CHN(CH3)2); 8.43
(1H, s, H triazole). 13C NMR spectrum (CDCl3), δ, ppm:
21.1; 37.4; 45.1; 92.9; 120.4; 122.9; 130.3; 134.5; 139.1;
150.2; 154.1; 180.5. Mass spectrum, m/z (Irel, %): 256 [M]+
(86), 228 [M–N2]+ (4), 187 (24), 185 (35), 98 (100). Found,
%: C 65.40; H 6.50; N 21.75. C14H16N4O. Calculated, %:
C 65.61; H 6.29; N 21.86.
1-[3-(4-Chlorophenyl)-5-methyl-1,2-oxazol-4-yl]-3-(di-
methylamino)prop-2-en-1-one (4r). The reaction was
performed at 100°С for 1.5 h. The volatile components
were removed by evaporation to dryness. The crude
product was purified by column chromatography (eluent –
CHCl3 followed by CHCl3‒EtOAc, gradient from 12.5:1 to
4:1), then crystallized from MeOH. Yield 715 mg (82%),
light-yellow powder, mp 88‒89°C. 1H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.63 (6H, s, N(CH3)2); 3.06 (3H,
s, CH3); 4.95 (1H, d, J = 12.3, CH=CHN(CH3)2); 7.40 (2H,
Synthesis of 3-(dimethylamino)-1-(5-methyl-1,2,3-thia-
diazol-4-yl)prop-2-en-1-one (4q) and 1-{5-[2-(dimethyl-
amino)ethenyl]-1,2,3-thiadiazol-4-yl}ethanone (4s). A
solution of ketone 1s (213 mg, 1.50 mmol) in DMF–DMA
(1.06 ml, 23.0 mmol) was heated in a sealed vessel at 80°C
for 1 h. The volatile components were removed by
evaporation to dryness, the residue was separated by
column chromatography (eluting first with CHCl3, then
with CHCl3‒EtOAc, gradient from 4:1 to 1:10). Enamine
4s (Rf 0.68, EtOAc) was isolated from the first fractions,
yield 125 mg (42%), yellow-green needles, mp 120‒122°C
(decomp.), while the last fractions gave enaminone 4q
(Rf 0.34, EtOAc), yield 68 mg (23%), light-yellow needles,
mp 131‒132°C.
1
Compound 4q. H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 2.93 (6H, d, J = 16.5, N(CH3)2); 3.16 (3H, s, CH3);
6.37 (1H, d, J = 12.6, CH=CHN(CH3)2); 7.84 (1H, d,
J = 12.6, CH=CHN(CH3)2). 13C NMR spectrum (CDCl3),
δ, ppm: 11.0 (NCH3); 37.5 (NCH3); 45.2 (CH3); 95.2 (C-β);
154.4 (C-4); 156.5 (C-5); 157.8 (C-α); 181.7 (C=O). Mass
spectrum, m/z (Irel, %): 197 [M]+ (11), 154 (19), 98 (100).
Found, %: C 48.66; H 5.31; N 21.32. C8H11N3OS.
Calculated, %: C 48.71; H 5.62; N 21.30.
Compound 4s. 1H NMR spectrum (CDCl3), δ, ppm (J, Hz):
2.74 (3H, s, CH3); 2.97 (6H, s, N(CH3)2); 6.46 (1H, d,
J = 13.3, CH=CHN(CH3)2); 7.06 (1H, d, J = 13.3,
CH=CHN(CH3)2). 13C NMR spectrum (DMSO-d6), δ, ppm:
29.1 (CH3); 40.9 (N(CH3)2); 85.1 (C-β); 149.3 (C-4); 154.6
(C-5); 162.4 (C-α); 191.4 (C=O). Mass spectrum, m/z (Irel, %):
197 [M]+ (38), 169 [M–N2]+ (18), 127 (91), 42 (100).
Found, m/z: 220.0514 [M+Na]+. C8H11N3NaOS. Calcu-
lated, m/z: 220.0515. Found, %: C 49.04; H 5.71; N 21.64.
C8H11N3OS. Calculated, %: C 48.71; H 5.62; N 21.30.
Synthesis of 4-triazolylcarbonyl-1,2,3-triazoles 5a–i
(General method). A solution of enaminone 4a,b,m,n,r
(1.0 mmol) and the appropriate azide 2a,b,d,g,h,i (1.5‒
7.0 mmol) in 1,4-dioxane (5‒10 ml) was heated at 55‒110°С
for 1.5‒48 h. The solvent was removed by evaporation, the
crude product was purified by column chromatography or
by recrystallization.
(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-yl)[1-(4-nitro-
phenyl)-1H-1,2,3-triazol-4-yl]methanone (5a) was obtained
from enaminone 4a (256 mg, 1.0 mmol) and azide 2b
(328 mg, 2.0 mmol). The reaction was performed at 110°С
for 16 h. After cooling the reaction mixture, the solids were
separated, refluxed in EtOH (6 ml) for 10 min, the
precipitate was separated and then washed with a small
amount of EtOH. Yield 323 mg (86%), light-brown
1
powder, mp 235‒238°C. H NMR spectrum (DMSO-d6),
δ, ppm (J, Hz): 2.65 (3H, s, CH3); 7.58–7.77 (5H, m,
Н Ph); 8.39 (2H, d, J = 9.1, H Ar); 8.47 (2H, d, J = 9.1,
H Ar); 9.94 (1H, s, H triazole). 13C NMR spectrum
712

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
(DMSO-d6), δ, ppm: 9.9; 121.8; 125.3; 125.4; 128.7; 129.7;
–118.20. Mass spectrum, m/z (Irel, %): 365 [M–N2]+ (9),
308 (5), 291 (4), 262 (7), 77 (100). Found, %: C 55.16;
H 3.16; N 25.14. C18H12FN7O3. Calculated, %: C 54.96;
H 3.08; N 24.93.
130.2; 135.0; 140.1; 140.5; 142.2; 145.6; 147.4; 177.0. Mass
spectrum, m/z (Irel, %): 347 [M–N2]+ (11), 319 [M–N2]+ (2),
290 (7), 244 (8), 77 (100). Found, %: C 57.55; H 3.63;
N 26.10. C18H13N7O3. Calculated, %: C 57.60; H 3.49;
N 26.12.
[3-(4-Chlorophenyl)-5-methyl-1,2-oxazol-4-yl](1-phenyl-
1H-1,2,3-triazol-4-yl)methanone (5e) was obtained from
enaminone 4r (291 mg, 1.0 mmol) and azide 2a (833 mg,
7.0 mmol). The reaction was performed at 90°С for 20 h.
The crude product was purified by column chromatography
(eluent CHCl3, then CHCl3‒EtOAc, 4:1), followed by
crystallization from PhH ‒ petroleum ether mixture. Yield
[5-Methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-
[1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl]methanone (5b)
was obtained from enaminone 4b (301 mg, 1.0 mmol) and
azide 2b (492 mg, 3.0 mmol). The reaction was performed
at 100°С for 16.5 h. The crude product was purified by
column chromatography (eluent PhH, PhH‒HOAc, 55:1,
then CHCl3‒EtOAc, 1:1), then crystallized from 1,4-dioxane‒
i-PrOH mixture. Yield 273 mg (65%), light-beige powder,
1
231 mg (63%), colorless crystals, mp 97‒99°C. H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 2.66 (3H, s, CH3); 7.33
(2H, d, J = 8.6, H Ar); 7.45–7.62 (5H, m, Н Ph); 7.65–7.77
(2H, m, H Ar); 8.52 (1H, s, H triazole). 13C NMR spectrum
(CDCl3), δ, ppm: 13.5; 115.7; 120.7; 125.1; 127.9; 128.9;
129.7; 130.1; 135.9; 136.2; 147.9; 161.3; 173.8; 181.1.
Mass spectrum, m/z (Irel, %): 366 [M]+ (3), 365 [M]+ (2),
364 [M]+ (9), 336 [M–N2]+ (6), 335 (13), 265 (6), 43 (100).
Found, %: C 62.94; H 3.34; N 15.04. C19H13ClN4O2.
Calculated, %: C 62.56; H 3.59; N 15.36.
[3-(4-Chlorophenyl)-5-methyl-1,2-oxazol-4-yl][1-(4-nitro-
phenyl)-1H-1,2,3-triazol-4-yl]methanone (5f) was obtained
from enaminone 4r (291 mg, 1.0 mmol) and azide 2b
(492 mg, 3.0 mmol). The reaction was performed at 55°С
for 4 h. The crude product was purified by column
chromatography (eluent CHCl3‒EtOAc, 1:1), then
crystallized twice from a mixture of DMF–H2O and EtOH.
Yield 160 mg (39%), colorless crystals, mp 152‒154°C.
1H NMR spectrum (DMF-d7), δ, ppm (J, Hz): 2.69 (3H, s,
CH3); 7.46–7.60 (2H, m, H Ar); 7.61–7.75 (2H, m, H Ar);
8.40 (2H, d, J = 9.1, H Ar); 8.57 (2H, d, J = 9.1, H Ar); 9.81
(1H, s, H triazole). 13C NMR spectrum (DMF-d7), δ, ppm:
12.6; 115.8; 121.6; 125.6; 127.7; 128.0; 128.9; 130.4;
135.3; 140.8; 147.9; 148.0; 161.2; 174.1; 180.4. Mass spect-
rum, m/z (Irel, %): 411 [M]+ (2), 410 [M]+ (1), 409 [M]+ (5),
381 [M–N2]+ (6), 380 (7), 43 (100). Found, %: C 56.04;
H 3.20; N 16.92. C19H12ClN5O4. Calculated, %: C 55.69;
H 2.95; N 17.09.
[1-(2-Chloro-4-methylphenyl)-1H-1,2,3-triazol-4-yl]-
(1-phenyl-1H-1,2,3-triazol-4-yl)methanone (5g) was
obtained from enaminone 4m (242 mg, 1.0 mmol) and
azide 2h (336 mg, 2.0 mmol). The reaction was performed
at 100°С for 16 h. The crude product was purified by
column chromatography (eluting with a sequence of PhH,
CHCl3, and 1:1 mixture of CHCl3‒Me2CO), then
crystallized from PhH ‒ petroleum ether mixture. Yield
287 mg (79%), light-yellow powder, mp 202‒203°C.
1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.44 (3H,
s, CH3); 7.44 (1H, d, J = 8.0, H Ar); 7.56 (1H, t, J = 7.4,
H Ar); 7.61–7.73 (4H, m, H Ar); 8.05 (2H, d, J = 7.6,
H Ar); 9.57 (1H, s, H triazole); 9.75 (1H, s, H triazole).
13C NMR spectrum (DMSO-d6), δ, ppm: 20.5; 66.4; 120.9;
127.8; 128.0; 128.2; 128.3; 128.9; 129.4; 129.9; 130.7;
131.4; 132.1; 136.1; 142.6; 144.8; 146.0; 175.3. Mass
spectrum, m/z (Irel, %): 338 [M–N2]+ (3), 337 [M–N2]+ (2),
336 [M–N2]+ (9), 308 (16), 273 (27), 245 (16), 205 (8), 77
(100). Found, %: C 59.08; H 3.76; N 23.03. C18H13ClN6O.
Calculated, %: C 59.27; H 3.59; N 23.04.
1
mp 226‒229°C. H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 2.72 (3H, s, CH3); 8.04 (2H, d, J = 8.9, H Ar); 8.40
(2H, d, J = 9.2, H Ar); 8.48 (2H, d, J = 9.1, H Ar); 8.52
(2H, d, J = 9.0, H Ar); 9.96 (1H, s, H triazole). 13C NMR
spectrum (DMSO-d6), δ, ppm: 10.1; 121.7; 125.1; 125.4;
126.7; 128.9; 139.7; 140.4; 140.7; 145.4; 142.3; 147.3;
148.2; 176.7. Mass spectrum, m/z (Irel, %): 392 [M–N2]+
(37), 318 (11), 290 (15), 244 (35), 117 (100). Found, %:
C 51.53; H 2.99; N 26.90. C18H12N8O5. Calculated, %:
C 51.43; H 2.88; N 26.66.
(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-yl)[1-(pentafluoro-
phenyl)-1H-1,2,3-triazol-4-yl]methanone (5c) was obtained
from enaminone 4a (256 mg, 1.0 mmol) and azide 2g
(418 mg, 2.0 mmol). The reaction was performed at 60°С
for 1.5 h. The crude product was purified by column
chromatography (eluent CHCl3), then crystallized from
heptane. Yield 252 mg (60%), colorless crystals, mp 147‒
1
149°C. H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.73
(3H, s, CH3); 7.48 (2H, dd, J = 7.4, J = 2.0, H Ar); 7.54–
7.69 (3H, m, H Ar); 9.42 (1H, s, H triazole). 13C NMR
spectrum (CDCl3), δ, ppm: 10.4; 125.3; 129.8; 130.4;
132.5; 135.1; 136.8; 139.4; 140.2; 141.4; 142.5; 144.0;
145.0; 176.2. 19F NMR spectrum (CDCl3), δ, ppm (J, Hz):
–144.69÷–145.25 (2F, m); –148.89 (1F, t, J = 21.4);
–158.82÷–159.32 (2F, m). Mass spectrum, m/z (Irel, %):
392 [M–N2]+ (9), 335 (8), 317 (6), 234 (7), 77 (100).
Found, %: C 51.55; H 2.48; N 19.72. C18H9F5N6O.
Calculated, %: C 51.44; H 2.16; N 20.00.
[1-(2-Fluoro-4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-
(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)methanone (5d)
was obtained from enaminone 4a (256 mg, 1.0 mmol) and
azide 2i (273 mg, 1.5 mmol). The reaction was performed at
104°С for 1.5 h. The crude product was purified by
column chromatography (eluent PhH‒HOAc, 53:1, then
PhH‒EtOAc‒HOAc, 53:53:1), followed by refluxing of the
product in EtOH for 5 min and separation of the solids.
Yield 163 mg (42%), light-yellow powder, mp 215‒217°C
(decomp.). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
2.65 (3H, s, CH3); 7.69 (5H, s, Н Ph); 8.34–8.37 (2H, m,
H Ar); 8.57 (1H, d, J = 10.8, H Ar); 9.79 (1H, d, J = 1.7,
H triazole). 13C NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
10.0; 113.4 (d, J = 13.5); 120.7 (d, J = 2.0); 125.5; 126.2;
129.3 (d, J = 9.0); 129.8; 130.3; 131.7 (d, J = 4.0); 134.9;
140.3; 143.1 (d, J = 283.0); 148.2 (d, J = 9.0); 152.0;
154.5; 176.5. 19F NMR spectrum (DMSO-d6), δ, ppm:
713

Chemistry of Heterocyclic Compounds 2019, 55(8), 704–715
[1-(2-Fluoro-4-nitrophenyl)-1H-1,2,3-triazol-4-yl]-
deposited at the Cambridge Crystallographic Data Center
(deposits CCDC 1901947 and CCDC 1901951,
respectively).
(1-phenyl-1H-1,2,3-triazol-4-yl)methanone (5h) was
obtained from enaminone 4m (242 mg, 1.0 mmol) and
azide 2i (273 mg, 1.5 mmol). The reaction was performed
at 100°С for 2.5 h. The crude product was purified by
column chromatography (eluting with the sequence of PhH,
CHCl3, and 1:1 CHCl3‒EtOH mixture). The solids were
then briefly treated with boiling EtOH, filtered off, and
dried. Yield 155 mg (41%), light-yellow powder, mp 247‒
Supplementary information file containing descriptions
of the procedures used for the preparation and purification
1
of compounds 1b,c,d,m,n,o,s,t, as well as H–13C HMBC
1
and H–13C HSQC spectra of compound 4s is available
from the journal website at http://link.springer.com/
journal/10593.
1
248°C (decomp.). H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 7.57 (1H, t, J = 7.3, H Ar); 7.65 (2H, t, J = 7.7,
H Ar); 8.04 (2H, d, J = 7.7, H Ar); 8.26–8.42 (2H, m,
H Ar); 8.57 (1H, d, J = 10.9, H Ar); 9.75 (2H, s,
H triazole). 13C NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 113.4 (d, J = 25.0): 120.8; 126.8; 127.9; 129.2 (d,
J = 11.0); 129.5; 129.9; 131.5 (d, J = 6.0); 136.1; 145.2;
146.1; 148.4 (d, J = 8.3); 152.1; 154.6; 175.1. 19F NMR
spectrum (DMSO-d6), δ, ppm: –118.05. Mass spectrum, m/z
(Irel, %): 379 [M]+ (1), 351 [M–N2]+ (8), 323 (18), 282 (6),
277 (8), 77 (100). Found, %: C 53.79; H 2.43; N 25.90.
C17H10FN7O3. Calculated, %: C 53.83; H 2.66; N 25.85.
[1-(4-Isopropylphenyl)-1H-1,2,3-triazol-4-yl][1-(4-nitro-
phenyl)-1H-1,2,3-triazol-4-yl]methanone (5i) was obtained
from enaminone 4n (287 mg, 1.0 mmol) and azide 2d
(515 mg, 3.2 mmol). The reaction was performed at 90‒
100°С for 48 h. The crude product was purified by column
chromatography (eluent PhH, then PhH‒Me2CO‒HOAc,
121:53:1). The first fractions of the eluate contained
unreacted azide (360 mg). The fractions of eluate that
contained the product were combined and evaporated to
dryness. The residue was treated with boiling EtOH for
5 min, and the solids were separated. Yield 72 mg (18%),
This work received financial support from the Russian
Foundation for Basic Research (grant 18-03-00715) and
by the directive No. 211 of the Government of the Russian
Federation (contract No. 02.A03.21.0006).
References
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1
light-yellow powder, mp 246‒250°C (decomp.). H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 1.26 (6H, d, J = 6.9,
CH(CH3)2); 2.98–3.06 (1H, m, CH(CH3)2); 7.52 (2H, d,
J = 8.4, H Ar); 7.95 (2H, d, J = 8.4, H Ar); 8.39 (2H, d,
J = 9.0, H Ar); 8.50 (2H, d, J = 9.0, H Ar); 9.71 (1H, s,
H triazole); 9.96 (1H, s, H triazole). 13C NMR spectrum
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128.0; 128.7; 134.0; 140.4; 145.7; 145.9; 147.4; 150.1;
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(100). Found, m/z: 404.1471 [M+H]+. C20H18N7O3.
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X-ray structural analysis of compounds 3d and 4q
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hydrogen atoms. The hydrogen atoms were placed in the
calculated positions and included in the refinement
according to the riding model. The complete X-ray
structural datasets for compounds 3d and 4q were
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