Synthesis of 1,2,3-triazoles linked into chains with other carbo- and heterocycles by a reaction between β-azolyl enamines and azides

Article abstract of DOI:10.1007/s10593-018-2249-3

[Figure not available: see fulltext.] The reactions of β-azolyl enamines with azides proceeded under solvent-free conditions in the absence of base at 110°С by one of the possible routes, selectively forming 1,4-disubstituted 1,2,3-triazoles. The proposed reaction mechanism includes cycloaddition of the starting reagents, leading to 1,2,3-triazoline intermediates, followed by elimination of dimethylamine and the formation of aromatic triazole ring.

Full text of DOI:10.1007/s10593-018-2249-3

DOI 10.1007/s10593-018-2249-3
Chemistry of Heterocyclic Compounds 2018, 54(2), 167–172
Synthesis of 1,2,3-triazoles linked into chains with other carbo- and
heterocycles by a reaction between β-azolyl enamines and azides
1
1
Ilya V. Efimov , Nikolai A. Beliaev ,
1
1
Vasiliy A. Bakulev , Tetyana V. Beryozkina *
1
Ural Federal University named after the first President of Russia B. N. Yeltsin,
1
9 Mira St., Yekaterinburg 620002, Russia; е-mail: tetber@mail.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
018, 54(2), 167–172
Submitted October 27, 2017
Accepted November 28, 2017
2
The reactions of β-azolyl enamines with azides proceeded under solvent-free conditions in the absence of base at 110°С by one of the
possible routes, selectively forming 1,4-disubstituted 1,2,3-triazoles. The proposed reaction mechanism includes cycloaddition of the
starting reagents, leading to 1,2,3-triazoline intermediates, followed by elimination of dimethylamine and the formation of aromatic
triazole ring.
Keywords: azides, enamines, linear chains of ring systems, 1,2,3-triazoles, triazolines.
Heterocyclic compounds containing chains of several
linked rings have shown various types of biological
between azides and enamines, which also led to
regiospecific formation of 1,4-disubstituted 1,2,3-triazoles
1–8
9–11
activity, are used for the purposes of organic synthesis,
as a result of the high reactivity of enamines toward azides,
1
2–17
33,34
in materials chemistry,
and are recognized as
relative to other alkenes in analogous reactions.
Our
promising objects for organic chemistry research. They can
be considered as rod-like molecules, representing a new
class of materials for organic electronics.18,19
preferred method for the synthesis of azolyl-1,2,3-triazoles
was based on the use of β-azolyl enamines,3
3–35
due to their
better availability compared to azolylacetylenes. The
reactions of β-azolyl enamines with aromatic and aliphatic
azides have not been described in the literature, except for
The copper-catalyzed cycloaddition of azides to
acetylenes (CuAAC) discovered by Meldal and
Sharpless2
0,21
has attracted the interest of many synthetic
our preliminary report.
33
chemists toward studying the properties of 1,2,3-triazole
In order to develop an effective and convenient
preparative method for the synthesis of bicyclic 1,2,3-
triazoles linked in linear chains with 1,2,3-thiadiazole,
isoxazole, 1,2,3-triazole, or 1,2,4-oxadiazole rings, we
studied the reactions of β-azolyl enamines 1a–e with
aromatic azides 2а–е, ethoxycarbonylacetazide (2f), and
benzyl azide (2g) (Scheme 1). The starting enamines 1a–e
were synthesized from the respective 5-methylazoles by a
derivatives.1
,22–24
The use of CuAAC reactions has
provided access to a large number of various compounds
2
belonging to this class, including bioconjugates,
3
4
5
chemosensors, ligands, and anion receptors. These
developments have led to increased role of 1,2,3-triazoles
1
3,22–24
in medicine, technology, and organic synthesis.
The main methods for the synthesis of 1,2,3-triazoles
2
0,21,25
include the addition of azides to acetylenes,
the
reaction with dimethylformamide dimethyl acetal
according to previously published procedures.3
4,35
Their
reaction of azides with compounds containing activated
2
6,27
methylene groups,
intramolecular cyclization of
structures were assigned as trans-isomers on the basis of
spin-spin coupling constants (J = 13.0–13.6 Hz) of the
vicinal protons in H NMR spectra of compounds 1a–e.
diazoimines according to the heteroelectrocyclic
mechanism,2
8,29
reactions of α-diazoacetonitriles with
1
3
0,31
amines and hydrogen halides,
and electrophilic
Aromatic azides 2a–е were obtained by treatment of
aromatic diazonium salts with sodium azide,3 while
2-azidoacetate (2f) and benzyl azide (2g) were obtained by
6
substitution reactions in 1,2,3-triazoles synthesized by
other methods.32 Our attention was focused on the reaction
0
009-3122/18/54(2)-0167©2018 Springer Science+Business Media, LLC
167

Chemistry of Heterocyclic Compounds 2018, 54(2), 167–172
Scheme 1
Az
NMe2
N R
Az
H
4
5
–Me2NH
45–92%
N1 R
N
N
N
3
N
2
+

T-1
Az
–

3a–m
N
N
+
NMe2
N
R
Heating
1
a–e
2a–g
Az
Az
Me2N
H
–Me2NH
N R
N R
N
N
N
N
T-2
3'a–m
CO2Et
Ph
CO2Et
Ar
CO2Me
CO Me
Ph
2
N
N
N
N
N
1
a Az =
, b Az =
, c Az =
, d Az =
, e Az =
N
N
N
S
O
O
N
Ar
O
1
Ar = 2,6-Cl2C6H3
1
Ar = 4-FC6H4
2
a R = Ph, b R = 4-MeC H , c R = 4-O NC H , d R = 4-ClC H , e R = 4-FC H , f R = CH CO Et, g R = Bn
6
4
2
6
4
6
4
6
4
2
2
CO2Et
Ph
Ar2
CO2R1
CO2Me
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
S
O
O
N
F
N
N
N
N
R
R
R
Bn
2
1
3
a R = Ph
b R = 4-MeC6H4
c R = CH2CO2Et
3 d R = Ph
e R = 4-ClC6H4
f R = 4-FC6H4
g R = 4-O2NC6H4
h R = CH2CO2Et
3i–k Ar = Ph, R = Et
i R = Ph
2
2
6 3
3l Ar = 2,6-Cl C H
R1 = Me
R = 4-O2NC6H4
j R = 4-ClC H4
6
3m
k R = Bn
a reaction of 2-bromoacetate and benzyl bromide with
sodium azide.37
Table 1. Optimization of conditions for the reaction of enamine
е with azide 2с* and yields of triazole 3g
1
In order to find the optimum conditions for the
preparation of azolyl-1,2,3-triazoles, we studied the
reaction of β-(oxadiazol-5-yl)enamine 1e with 4-nitro-
phenyl azide (2с) in different solvents and at different
temperatures (Table 1). As indicated by Table 1, the type of
solvent had a minor effect on the yield of azolyltriazole 3g.
It was shown that increasing the temperature of the
process (entries 2, 3) shortened the reaction time and at the
same time improved the yield of triazole 3g. We found that
rapid heating of the starting material mixture to 110°С
under solvent-free conditions and maintaining for 20 min at
this temperature followed by rapid cooling allowed to
increase the target product yield to 92%. Thus, the
optimum reaction conditions involve the use of starting
materials in equivalent amounts and performing the
reaction in the absence of solvent at 110°С. The same
conditions were used in all our subsequent experiments for
the preparation of 1,2,3-triazoles 3a–m. We demonstrated
that all of the synthesized enamines 1a–e smoothly reacted
with azides 2a–g providing 45–92% yields of 1,2,3-
triazoles 3a–m containing 1,2,3-thiadiazole, isoxazole,
Entry
Solvent
DMSO
DMF
Temperature, °С
Time, h
10
Yield, %
1
2
3
4
5
70
40
70
65
70
92
110
110
110
110
2.5
DMSO
m-Xylene
Melt
0.5
0.66
0.33
* Experiments 1–4 were performed with 0.33 mmol of the starting com-
pounds in 1 ml of the indicated solvent, while experiment 5 was
performed with the same amount of the starting materials under solvent-
free conditions.
substituted 1,2,3-triazoles 3' representing isomers of
compounds 3. When comparing our studied reaction of
azolyl enamines and azides with the CuAAC reaction,
which also led to the formation of 1,4-disubstituted 1,2,3-
triazoles, it can be concluded that β-azolyl enamines can be
viewed as synthetic equivalents of monosubstituted
acetylenes.
1
,2,3-triazole, or oxadiazole rings in their molecules
Scheme 1).
It should be noted that analysis by TLC and Н NMR
spectroscopy did not reveal the formation of 1,5-di-
The structures of the obtained 4-(azol-5-yl)-1,2,3-tri-
1
(
azoles 3a–m were confirmed by the results of Н and
1
13
С NMR spectroscopy, as well as by X-ray structural
analysis of compound 3i (Fig. 1). It should be noted that a
1
68

Chemistry of Heterocyclic Compounds 2018, 54(2), 167–172
39
structural analysis. The process leading to the formation
of aromatic 1,2,3-triazoles was concluded by the
elimination of dimethylamine molecule.
Thus, by studying the reaction of azolyl enamines with
aromatic and aliphatic azides we have developed an
effective and convenient preparative method for
regioselective and atom-economical synthesis of 4-azolyl-
1
,2,3-triazoles.
Experimental
IR spectra were recorded on a Bruker Alpha FTIR
1
spectrometer equipped with a ZnSe ATR accessory. Н and
1
3
С NMR spectra were acquired on a Bruker Avance II 400
spectrometer (400 and 100 MHz, respectively). Solvents:
Figure 1. The molecular structure of triazole 3i with atoms
represented by thermal vibration ellipsoids of 50% probability.
1
1
:1 DMSO-d
compounds 3a,i,j,l,m), СDCl
compounds 3b,k), or DMSO-d
6
–CCl
4
system ( Н NMR spectra of
1 13
3
( Н and С NMR spectra of
(the rest of the spectra);
6
characteristic feature of all obtained triazoles 3a–m was the
TMS was used as internal standard. Mass spectra were
recorded on a Shimadzu GCMS-QP2010 Ultra mass
spectrometer (EI ionization, 70 eV). Elemental analysis (C,
H, N) was performed on a PerkinElmer 2400 II automatic
analyzer. Melting points were determined on a Stuart
SMP3 apparatus. Reaction progress and purity of the
obtained compounds were controlled by a TLC method on
Sorbfil UV-254 plates using 1:1 EtOAc–hexane system.
Column chromatography was performed on silica gel with
60–120 μm particle size.
1
presence of H NMR signal due to the Н-5 proton of
1
3
triazole ring in the range of 8.21–10.12 ppm and C NMR
signals due to the С-4 carbon atom in the range of 134.7–
1
39.9 ppm.
1
The integral values for H NMR signals belonging to
the enamine moiety allowed us to determine the extent
to which enamines 1a,b were converted to the
corresponding triazoles in reactions with azides 2a–d,
when heated in DMSO-d solution at 110°С for 120 min
6
34,35
36,37
(
Table 2). As shown in Table 2, the conversion of both
The starting enamines 1a–e
and azides 2a–g
enamines decreased along with weaker electron-
withdrawing properties of substituents in the aryl azide
were obtained according to standard literature procedures.
Enamines 1а–e were obtained by using commercially
available dimethylformamide dimethyl acetal (Sigma-
Aldrich).
Preparation of 4-(azol-5-yl)-1,2,3-triazoles 3a–m
(General method). A mixture of azolyl enamine 1a–e
(1 mmol) and azide 2a–g (1 mmol) was stirred at 110°С for
0.33–6 h. The reaction mixture was then cooled to room
temperature and diluted with hexane. The obtained
precipitate was filtered off, dried, and recrystallized from
EtOH (compound 3i was purified by column chromato-
graphy, eluent 1:1 EtOAc–hexane).
molecule (NO > Cl > H > Me). Thus, we can conclude
2
that the introduction of electron-withdrawing substituents
in azide molecules increases the rate of reactions with
enamines.
The reactions of aromatic azides with enamines are
recognized as reactions with inverse electron demand, since
the introduction of electron-withdrawing substituents in the
molecule of azide (the dipole component) and electron-
donating substituents in the molecule of enamine (the
dipolarophile component) facilitates the cycloaddition
reaction.38 This interpretation is in agreement with our
obtained data on the conversion of β-azolyl enamines
achieved in reactions with aromatic azides. The expected
mechanism of the reaction between enamines 1 and azides
Ethyl
5-(1-phenyl-1Н-1,2,3-triazol-4-yl)-1,2,3-thia-
diazole-4-carboxylate (3a). Yield 0.22 g (73%), light-
–
1
beige powder, mp 180–182°С. IR spectrum, ν, cm : 3156,
1
1706 (C=O), 1462, 843, 755. H NMR spectrum, δ, ppm
2
involves 1,3-dipolar cycloaddition with the formation of
nonaromatic 1,2,3-triazoline intermediate Т-1, but not Т-2
Scheme 1).
,2,3-Triazolines are generally unstable compounds.
(J, Hz): 1.47 (3H, t, J = 7.1, OCH
2
CH ); 4.54 (2H, q,
3
J = 7.1, OCH
2
CH ); 7.45–7.59 (1H, m, H Ph); 7.63 (2H, d,
3
(
J = 7.8, H Ph); 7.94 (2H, d, J = 7.8, H Ph); 9.33 (1H, s,
13
1
H-5). C NMR spectrum, δ, ppm: 14.4 (OCH
2
СH
3
); 62.6
Some compounds of this type have been isolated and
identified by using NMR spectroscopy and X-ray
(OСH CH ); 120.9 (C Ph); 123.6 (С-5); 129.7 (C Ph);
2
3
3
8
130.0 (C Ph); 136.5 (C Ph); 136.8 (С-4); 146.5 (C-5');
1
3
%
52.6 (C-4'); 161.4 (C=O). Mass spectrum, m/z (Irel, %):
+
01 [M] (4), 217 (27), 104 (100), 77 (80), 69 (68). Found,
Table 2. The degree of conversion for enamines 1a,b in reactions
with azides 2a–d in DMSO-d over 120 min, %
6
: C 51.84; H 4.05; N 23.61. C13
H
11
N
5
O S. Calculated, %:
2
C 51.82; H 3.68; N 23.24.
6 4 3
Azide 4-RC H N
Ethyl 5-[1-(4-methylphenyl)-1Н-1,2,3-triazol-4-yl]-
Enamine
2
a
2b
2c
2d
1
,2,3-thiadiazole-4-carboxylate (3b). Yield 0.16 g (52%),
(
R = H)
(R = Me)
(R = NO
78
2
)
(R = Cl)
1
light-beige powder, mp 205–207°С. H NMR spectrum,
1
a
20
6
15
2
41
13
δ, ppm (J, Hz): 1.52 (3H, t, J = 7.1, OCH
2
CH
3
3
); 2.45 (3H,
1
b
63
s, ArСН ); 4.58 (2H, q, J = 7.1, OCH CH
3
2
); 7.36 (2H, d,
1
69

Chemistry of Heterocyclic Compounds 2018, 54(2), 167–172
J = 8.5, H Ar); 7.69 (2H, d, J = 8.5, H Ar); 9.22 (1H, s, H-5).
5-[1-(4-Nitrophenyl)-1Н-1,2,3-triazol-4-yl]-3-phenyl-
1
3
C NMR spectrum, δ, ppm: 14.4 (OCH
2
СH
3
); 21.3
1,2,4-oxadiazole (3g). Yield 0.30 g (92%), colorless
–1
(
ArСН ); 62.6 (OCH СH ); 120.8 (C Ar); 123.5 (С-5);
3
2
3
powder, mp 288–290°С. IR spectrum, ν, cm : 3120, 1639,
1
1
1
30.5 (C Ar); 134.1 (C Ar); 136.7 (C Ar); 139.9 (C-4);
1522, 1337, 1039, 853, 745. H NMR spectrum, δ, ppm
46.4 (C-5'); 152.7 (С-4'); 161.4 (С=О). Mass spectrum, m/z
(J, Hz): 7.52–7.64 (3H, m, H Ph); 8.12–8.15 (2H, m,
H Ph); 8.43 (2H, d, J = 9.3, H Ar); 8.50 (2H, d, J = 9.3,
H Ar); 10.12 (1H, s, H-5). 13C NMR spectrum, δ, ppm:
122.0; 126.0 (C-5); 126.3; 127.3; 127.7; 129.9; 132.4;
134.9; 140.7; 147.9; 168.7 (С-3'); 169.1 (C-5'). Mass
+
(
(
I
rel, %): 315 [M] (5), 287 (37), 270 (53), 242 (40), 91
100). Found, %: C 53.47; H 3.87; N 22.48. C14
H
13
N
5
O S.
2
Calculated, %: C 53.32; H 4.16; N 22.21.
Ethyl 5-[1-(2-ethoxyethyl-2-oxo)-1Н-1,2,3-triazol-4-yl]-
+
1
,2,3-thiadiazole-4-carboxylate (3c). Yield 0.14 g (45%),
spectrum, m/z (Irel, %): 334 [M] (8), 189 (18), 143 (25),
1
yellow oil. H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t,
128 (19), 118 (37), 103 (34), 91 (23), 77 (100), 76 (82), 75
J = 7.1, OCH
2H, q, J = 7.1, OCH
CH ); 5.58 (2H, s, NCH
2
CH
3
); 1.38 (3Н, t, J = 7.1, OCH
CH ); 4.48 (2H, q, J = 7.1,
); 9.05 (1H, s, H-5).
СH ); 14.5
CH ); 62.4
); 128.3 (С-5); 135.3 (С-4); 146.6 (C-5'); 152.5
2
CH
3
); 4.20
(39). Found, %: C 57.65; H 2.90; N 25.52. C16
H
10
N
6
O .
3
(
2
3
Calculated, %: C 57.49; H 3.02; N 25.14.
OCH
2
3
2
Ethyl 2-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)-1Н-1,2,3-
triazol-1-yl]acetate (3h). Yield 0.21 g (70%), colorless
1
3
C NMR spectrum, δ, ppm: 14.4 (OCH
2
3
–1
(
(
(
(
OCH
OСH
2
СH
CH
3
); 51.3 (NСН
2
); 62.2 (OСH
2
3
powder, mp 160–162°С. IR spectrum, ν, cm : 3070, 1707,
1
2
3
1513, 1220, 852. H NMR spectrum, δ, ppm (J, Hz): 1.32
C-4'); 160.9 (C=O); 167.4 (C=O). Mass spectrum, m/z
(3H, t, J = 7.1, OCH
2
CH
); 5.49 (2H, s, NCH
8.08–8.14 (2H, m, H Ph); 9.03 (1H, s, H-5). C NMR
spectrum, δ, ppm: 13.8 (OCH CH ); 50.6 (NCH ); 61.5
3
); 4.26 (2H, q, J = 7.1,
+
I
rel, %): 311 [M] (6), 283 (44), 211 (26), 125 (17). Found,
: C 42.28; H 4.30; N 22.71. C11 S. Calculated, %:
C 42.44; H 4.21; N 22.50.
-Phenyl-5-(1-phenyl-1Н-1,2,3-triazol-4-yl)-1,2,4-oxa-
diazole (3d). Yield 0.21 g (69%), colorless powder,
OCH
2
CH
3
2
); 7.52–7.58 (3H, m, H Ph);
13
%
H
13
N
5
O
4
2
3
2
3
(OCH
2
CH ); 126.1 (C-5); 126.9 (2C Ph); 128.7 (2C Ph);
3
128.8; 131.1; 132.9; 166.0 (C=O); 167.9 (C-3'); 168.7
–
1
+
mp 183–184°С. IR spectrum, ν, cm : 3136, 1640, 1303,
(C-5'). Mass spectrum, m/z (Irel, %): 299 [M] (4), 240 (19),
1
1
040, 745. H NMR spectrum, δ, ppm: 7.48–7.67 (6H, m,
H Ph); 8.03–8.09 (2H, m, H Ph); 8.09–8.16 (2H, m, H Ph);
.82 (1H, s, H-5). 13C NMR spectrum, δ, ppm: 120.6; 125.8
223 (35), 145 (28), 135 (63), 77 (100). Found, %: C 56.51;
H 4.72; N 23.17. C14
H 4.38; N 23.40.
H
13
N
5
O . Calculated, %: C 56.18;
3
9
(
С-5); 125.9; 127.1; 129.2; 129.4; 129.9; 131.7; 133.8;
Ethyl 3-phenyl-5-(1-phenyl-1Н-1,2,3-triazol-4-yl)-1,2-
oxazole-4-carboxylate (3i). Yield 0.20 g (56%), colorless
1
35.8; 168.1 (C-3'); 168.8 (C-5'). Mass spectrum, m/z
+
–1
(
(
I
rel, %): 289 [M] (5), 144 (31), 128 (12), 118 (17), 103
prisms, mp 153–154°С. IR spectrum, ν, cm : 3180, 2926,
1
16), 77 (100), 51 (50). Found, %: C 66.61; H 3.47;
1714, 1618, 1131. H NMR spectrum, δ, ppm (J, Hz): 1.16
N 24.61. C16
H
11
N
5
O. Calculated, %: C 66.43; H 3.83;
(3H, t, J = 7.1, OCH
2
CH ); 4.25 (2H, q, J = 7.1,
3
N 24.21.
-[1-(4-Chlorophenyl)-1Н-1,2,3-triazol-4-yl]-3-phenyl-
,2,4-oxadiazole (3e). Yield 0.24 g (75%), colorless
OCH
2
CH ); 7.46–7.76 (8H, m, H Ph); 8.00 (2H, d, J = 8.0,
3
13
5
H Ph); 9.42 (1H, s, H-5). C NMR spectrum, δ, ppm: 13.6
1
(ОCH
2
СH
3
); 61.4 (ОCH
2
СH ); 108.5 (С-4'); 120.8; 125.4
3
–
1
powder, mp 250–252°С. IR spectrum, ν, cm : 3120, 1638,
(C-5); 127.5; 128.4; 129.0; 129.6; 130.1; 130.3; 135.2;
136.0; 160.9 (C=O); 162.3 (C-3'); 163.7 (C-5'). Mass
1
1
487, 833, 742. H NMR spectrum, δ, ppm: 7.50–7.69 (5H,
+
m, H Ar); 8.03–8.18 (4H, m, H Ar); 9.87 (1H, s, H-5).
spectrum, m/z (Irel, %): 360 [M] (4), 286 (17), 259 (17),
1
3
C NMR spectrum, δ, ppm: 122.4; 125.8 (C-5); 126.3;
144 (95), 143 (94), 116 (22), 104 (25), 77 (100). Found, %:
1
27.1; 129.3; 129.9; 131.8; 133.9; 134.0; 134.7; 168.2
C 66.69; H 4.61; N 15.79. C20
C 66.66; H 4.48; N 15.55.
H
16
N
4
O . Calculated, %:
3
(
[
(
(
С-3'); 168.8 (C-5'). Mass spectrum, m/z (Irel, %): 325
37 + 35 +
M( Cl)] (8), 323 [M( Cl)] (22), 180 (30), 179 (20), 178
100), 177 (38), 176 (31), 164 (17), 150 (28), 128 (23), 118
59), 113 (19), 111 (59), 77 (60), 76 (18), 75 (45). Found,
Ethyl
5-[1-(4-chlorophenyl)-1Н-1,2,3-triazol-4-yl]-
3-phenyl-1,2-oxazole-4-carboxylate (3j). Yield 0.24 g
(61%), light-beige powder, mp 130–133°С. IR spectrum,
–
1
1
%
: C 59.12; H 2.72; N 21.60. C16
C 59.36; H 3.11; N 21.63.
-[1-(4-Fluorophenyl)-1Н-1,2,3-triazol-4-yl]-3-phenyl-
,2,4-oxadiazole (3f). Yield 0.24 g (78%), beige powder,
H
10ClN
5
O. Calculated, %:
ν, cm : 3173, 1718, 1500, 1135, 824. H NMR spectrum,
δ, ppm (J, Hz): 1.17 (3H, t, J = 7.1, OCH
q, J = 7.1, OCH CH ); 7.26–7.56 (3H, m, H Ar); 7.56–
7.85 (4H, m, H Ar); 8.03–8.06 (2H, m, H Ar); 9.46 (1H, s,
2
CH ); 4.25 (2H,
3
5
2
3
1
–
1
13
mp 225–227°С. IR spectrum, ν, cm : 3125, 1639, 1511,
H-5). C NMR spectrum, δ, ppm: 13.5 (ОCH
2
СH ); 61.3
3
1
1
225, 827, 744. H NMR spectrum, δ, ppm: 7.34–7.44 (2H,
(ОCH
2
СH ); 108.5 (C-4'); 122.4; 125.3 (C-5); 127.4;
3
m, H Ar); 7.53–7.62 (3H, m, H Ar); 8.08–8.16 (4H, m,
128.3; 128.9; 129.9; 130.1; 133.8; 134.8; 135.2; 160.8
13
H Ar); 9.82 (1H, s, H-5). C NMR spectrum, δ, ppm:
(C=O); 162.1 (C-3'); 163.5 (С-5'). Mass spectrum, m/z
3
7
+
35
+
1
1
16.8 (d, J = 23.0); 123.6 (d, J = 9.0); 125.8 (C-5); 126.3;
27.1; 129.3; 131.8; 132.4 (d, J = 3.0); 133.9; 162.1 (d,
(Irel, %): 396 [M( Cl)] (4), 394 [M( Cl)] (10), 368
(27), 366 (39), 217 (33), 145 (42), 113 (27), 111 (100), 77
(38), 76 (18), 75 (41). Found, %: C 60.86; H 3.64;
J = 244.0, С–F); 168.1 (C-3'); 168.8 (C-5'). Mass spectrum,
+
m/z (Irel, %): 307 [M] (18), 162 (100), 161 (47), 160 (41),
N 14.28. C20
N 14.19.
H15ClN
4
O . Calculated, %: C 60.84; H 3.83;
3
1
46 (17), 134 (46), 128 (26), 119 (16), 118 (73), 95 (92),
7 (71), 76 (15), 75 (46). Found, %: 62.48; H 3.08; N 22.82.
7
Ethyl 5-(1-benzyl-1Н-1,2,3-triazol-4-yl)-3-phenyl-1,2-
oxazole-4-carboxylate (3k). Yield 0.22 g (62%), colorless
C
16
H
10FN O. Calculated, %: C 62.54; H 3.28; N 22.79.
5
1
70

Chemistry of Heterocyclic Compounds 2018, 54(2), 167–172
–
1
powder, mp 161–163°С. IR spectrum, ν, cm : 3116, 1624,
References
1
1
067, 696. H NMR spectrum, δ, ppm (J, Hz): 0.66 (3H, t,
J = 7.1, OCH CH ); 3.77 (2H, q, J = 7.1, OCH CH ); 5.25
2H, s, NCH ); 6.88–7.11 (8H, m, H Ph); 7.18–7.20 (2H,
m, H Ph); 8.21 (1H, s, H-5). C NMR spectrum, δ, ppm:
3.6 (ОCH СH ); 54.4 (NСН ); 61.1 (ОCH СH ); 108.0
С-4'); 126.4; 127.9; 128.0; 128.4; 129.0; 129.2; 129.3;
29.7; 134.0; 136.0; 161.8 (C=O); 162.6 (C-3'); 164.8
1
2
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Patent 2012101261.
2
3
2
3
(
2
1
3
1
2
3
2
2
3
3. Li, W.-T.; Wu, W.-H.; Tang, C.-H.; Tai, R.; Chen, S.-T. ACS
Comb. Sci. 2011, 13, 72.
(
4
. Olesen, P. H.; Sørensen, A. R.; Ursø, B.; Kurtzhals, P.;
1
+
Bowler, A. N.; Ehrbar, U.; Hansen, B. F. J. Med. Chem. 2003,
(
C-5'). Mass spectrum, m/z (Irel, %): 374 [M] (5), 91 (100),
7 (17), 65 (15). Found, %: C 67.07; H 5.15; N 14.61.
. Calculated, %: C 67.37; H 4.85; N 14.96.
4
6, 3333.
7
5
. Lu, R. J.; Pickens, J. C.; Tucker, J. A.; Zinevitch, T.;
Sviridov, S.; Konoplev, V. WO Patent 2007103456.
C
21
H
18
N
4
O
3
Methyl 3-(2,6-dichlorophenyl)-5-[1-(4-nitrophenyl)-
6
7
. Leclerc, J.-P.; Li, C. S.; Ramtohul, Y. K. WO Patent 2010025553.
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Hanaki, H.; Sharpless, K. B.; Omura, S. Heterocycles 2006, 69, 55.
1
Н-1,2,3-triazol-4-yl]-1,2-oxazole-4-carboxylate (3l). Yield
0
.38 g (82%), cream-colored powder, mp 205–207°С.
–1
IR spectrum, ν, cm : 3188, 1732, 1522, 1504, 1346, 780.
8. Sapountzis, I.; Ettmayer, P.; Klein, C.; Mantoulidis, A.;
Steegmaier, M.; Steurer, S.; Waizenegger, I. WO Patent
1
H NMR spectrum, δ, ppm (J, Hz): 3.71 (3H, s, OCH
3
);
2009003998.
7
.59 (3H, s, H Ar); 8.37 (2H, d, J = 9.1, H Ar); 8.49 (2H, d,
1
3
9. Patil, P.; Madhavachary, R.; Kurpiewska, K.; Kalinowska-
J = 9.1, H Ar); 9.75 (1H, s, H-5). C NMR spectrum, δ, ppm:
Tłuścik, J.; Dömling, A. Org. Lett. 2017, 19, 642.
5
1
1
[
(
2.5 (OCH ); 108.9 (C-4'); 121.6; 125.5; 126.4; 126.7;
3
1
1
1
0. Sinn, S.; Biedermann, F.; De Cola, L. Chem.–Eur. J. 2017, 23, 1965.
1. Kaur, T.; Gautam, R. N.; Sharma, A. Chem.–Asian J. 2016, 11, 2938.
2. Liu, Y.; Yan, W.; Chen, Y.; Petersen, J. L.; Shi, X. Org. Lett.
28.3; 132.7; 134.3; 135.1; 140.2; 147.3; 158.9 (C=O);
60.0 (C-3'); 163.9 (C-5'). Mass spectrum, m/z (Irel, %): 459
35
+
M( Cl)] (4), 399 (19), 398 (15), 396 (42), 213 (65), 211
100), 189 (25), 146 (18), 143 (45), 76 (43). Found, %:
2
008, 10, 5389.
13. Watkinson, M. Top. Heterocycl. Chem. 2012, 28, 109.
14. Potratz, S.; Mishra, A.; Bäuerle, P. Beilstein J. Org. Chem.
2012, 8, 683.
C 49.41; H 2.53; N 14.93. C19
H
2
11Cl N
5
O . Calculated, %:
5
C 49.59; H 2.41; N 15.22.
1
5. van Steenis, D. J. V. C.; David, O. R. P.; van Strijdonck, G. P. F.;
Methyl 1-benzyl-(4-fluorophenyl)-1Н,3'Н-4,4'-bis(1,2,3-
triazole)-5'-carboxylate (3m). Yield 0.22 g (59%),
colorless powder, mp 160–162°С. IR spectrum, ν, cm :
van Maarseveen, J. H.; Reek, J. N. H. Chem. Commun. 2005, 4333.
–1
16. Kulhánek, J.; Ludwig, M.; Bureš, F.; Tydlitát, J. Chem.
Heterocycl. Compd. 2017, 53, 46. [Khim. Geterotsikl. Soedin.
1
3
070, 1707, 1513, 1220, 852. H NMR spectrum, δ, ppm
J, Hz): 3.33 (3H, s, OCH ); 5.22 (2Н, br. s, NCH ); 6.55–
.84 (2H, m, H Ar); 6.90 (5H, br. s, H Ar); 7.09 (2H, br. s,
2
017, 53, 46.]
(
3
2
1
7. Kostyuchenko, A. S.; Drozdova, E. A.; Fisyuk, A. S. Chem.
Heterocycl. Compd. 2017, 53, 92. [Khim. Geterotsikl. Soedin.
2017, 53, 92.]
6
1
3
H Ar); 8.23 (1H, s, H-5). C NMR spectrum, δ, ppm (J, Hz):
5
1
2.5 (OCH
3
); 53.3 (NCH
2
); 116.5 (d, J = 23.0); 127.4;
18. Horčic, M.; Kozmík, V.; Svoboda, J.; Novotná, V.; Pociecha, D.
J. Mater. Chem. C 2013, 1, 7560.
28.2; 128.3; 128.6 (d, J = 9.0); 128.8; 132.3; 132.5 (d,
1
9. Kim, M.-H.; Nam, Y.-K.; Choi, E.-J. J. Inf. Disp. 2017, 18, 31.
J = 4.0); 133.0; 135.7; 136.1; 160.7 (C=O); 162.5 (d, J = 246.0,
+
20. Tornøe, C. W.; Chistensen, C.; Meldal, M. J. Org. Chem.
C–F). Mass spectrum, m/z (Irel, %): 378 [M] (3), 228 (59), 226
2
002, 67, 3057.
(
C
36), 158 (18), 95 (100). Found, %: C 60.44; H 3.85; N 22.06.
2
1. Rostovtsev, V. V.; Green, L. G., Fokin V. V.; Sharpless, B. K.
Angew. Chem., Int. Ed. 2002, 41, 2596.
H15FN O
19 6 2
. Calculated, %: C 60.31; H 4.00; N 22.21.
X-ray structural study of compound 3i. Crystals of
compound 3i (C20 , M 360.12) suitable for X-ray
2
2
2. Crowley, J. D.; McMorran, D. A. Top Heterocycl. Chem. 2012, 28, 31.
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H
16
N
4
O
3
structural analysis were obtained by slowly evaporating an
ethanol solution of compound 3i. A fragment of colorless
crystal was studied on an Xcalibur 3 monocrystal X-ray
diffractometer according to the standard procedure (MoKα
radiation, graphite monochromator, ω-scanning with a step
of 1°, 295(2) K). The structure was solved and refined by
using the SHELXTL software suite. The structure was
solved by direct method with the ShelXS program and
refined by full-matrix method of least squares by F with
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2
2
2
6. Mignani, S.; Zhou, Y.; Lecourt, T.; Micouin, L. Top
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4
0
7. Krivopalov, V. P.; Shkurko, O. P. Russ. Chem. Rev. 2005, 74,
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2
3
9. Bakulev, V. A. Rus. Chem. Rev. 1995, 64, 99. [Usp. Khim.
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995, 64, 107.]
"
rider" model. The complete dataset obtained by X-ray
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[
Khim. Geterotsikl. Soedin. 1984, 1266.]
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580192).
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This work received financial support from the Russian
Science Foundation (grant 15-13-10031).
1
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