A novel one-pot synthesis method of 3,4,5-triaryl-substituted 1,2,4-triazoles

Article abstract of DOI:10.1007/s10593-019-02545-y

[Figure not available: see fulltext.] A novel method for the preparation of 3,4,5-triaryl-substituted 1,2,4-triazoles by the reaction of hydrazides with secondary amides in polyphosphoric ester has been developed. The new method is characterized by mild conditions and ease of synthesis, including the stages of isolation and purification of the product. Additionally, product structures were confirmed by counter synthesis. It was shown that the proposed method is suitable for producing 1,2,4-triazoles with phenolic substituents without the stages of the protection and deprotection of the hydroxyl group. Using the new method, five 3,4,5-substituted 1,2,4-triazoles were obtained for the first time.

Full text of DOI:10.1007/s10593-019-02545-y

DOI 10.1007/s10593-019-02545-y
Chemistry of Heterocyclic Compounds 2019, 55(9), 834–838
A novel one-pot synthesis method of
3,4,5-triaryl-substituted 1,2,4-triazoles
Igor K. Yakuschenko1, Natal'ya N. Pozdeeva1,
Svyatoslav Ya. Gadomsky1*
1 Institute of Problems of Chemical Physics of the Russian Academy of Sciences,
1 Akademika Semenova Ave., Chernogolovka 142432, Moscow region, Russia;
е-mail: gadomsky@icp.ac.ru
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(9), 834–838
Submitted December 19, 2018
Accepted after revision June 13, 2019
A novel method for the preparation of 3,4,5-triaryl-substituted 1,2,4-triazoles by the reaction of hydrazides with secondary amides in
polyphosphoric ester has been developed. The new method is characterized by mild conditions and ease of synthesis, including the stages of
isolation and purification of the product. Additionally, product structures were confirmed by counter synthesis. It was shown that the
proposed method is suitable for producing 1,2,4-triazoles with phenolic substituents without the stages of the protection and deprotection of
the hydroxyl group. Using the new method, five 3,4,5-substituted 1,2,4-triazoles were obtained for the first time.
Keywords: hydrazides, polyphosphoric ester, secondary amides, 3,4,5-substituted 1,2,4-triazoles, one-pot synthesis.
The large number of reviews and original publications
devoted to 3,4,5-substituted derivatives of 1,2,4-triazoles,1–6
testifies to the exceptional importance of these compounds
as objects of investigation in many branches of science.
Triazoles have a proven wide spectrum of biological
activity (they exhibit antitumor,3,7 antiviral, anticonvulsant,
antifungal, and antibacterial properties3–5), and have proven
to be corrosion inhibitors.1 There are also a number of
publications in which compounds based on 1,2,4-triazoles
are considered as promising luminophores in the
manufacture of organic electroluminescent devices.8–10 In
this regard, the development of novel methods for
producing 3,4,5-substituted derivatives of 1,2,4-triazoles is
of great interest.
Scheme 1
amides, such as thioamide,12 chloromethylene amide,13
imidate,14 and others11 can enter the reaction. Thus, almost
all of the one-pot approaches described in the literature for
the synthesis of 3,4,5-substituted derivatives of 1,2,4-tri-
azoles consist of two main steps: 1) the condensation of the
amide with hydrazide (at ~10°C) in the presence of an
activator such as POCl3, PCl5, or oxalyl chloride;11
2) cyclization at >100°C and with the replacement of the
solvent in the reactor (as a rule, with PhMe or saturated
aqueous NaHCO311).
Significant successes in the development of a one-pot
approach were achieved by Spanish authors,15 who used
trifluoromethanesulfonic anhydride as an activating
additive. The principal difference of the proposed method
is that the composition of the reaction medium remains
unchanged for both steps of the process (Scheme 1).
However, after the completion of the first step of the
synthesis, the reactor must be transferred to the microwave
reactor system for the further cyclization step, that is, the
proposed method also consists of two successive stages. In
In a review article from 2010,11 all the routes from
literature for producing 1,2,4-triazoles are presented. The
most universal approach to the synthesis of such structures
is the reaction of an amide with hydrazide,11 proceeding
with the formation of an intermediate N-acylamidrazone,
which then undergoes cyclodehydration to the target
triazole (Scheme 1).
The two-step process (Scheme 1) complicates its
implementation as a one-pot reaction, since the conditions
of each step are significantly different.11 An additional
complexity of this approach is that only activated forms of
0009-3122/19/55(9)-0834©2019 Springer Science+Business Media, LLC
834

Chemistry of Heterocyclic Compounds 2019, 55(9), 834–838
Scheme 3
addition, the very use of the microwave reactor system and
the need for a reaction in an inert atmosphere can be
considered as significant disadvantages of the method.15
In connection with the abovesaid considerations, the
main objective of this study was to search for the most
universal conditions for the implementation of the process
in Scheme 1, that is, conditions under which both the
condensation reaction (step 1, Scheme 1) and cyclo-
dehydration reaction (step 2, Scheme 1) are possible. The
most optimal for these purposes was the use of
polyphosphoric ester (PPE) as the reaction medium. Given
the moderately acidic properties of the polyphosphoric
ester, it could be expected that the amide, according to
Scheme 2, will be reversibly protonated to a carbocation
having sufficient electrophilicity to react with hydrazide.
In addition, polyphosphoric ester is ideally suited for the
final stage indicated in Scheme 1, since it is a good solvent
for cyclodehydration reactions.16,17 Moreover, it was
shown17 that the use of polyphosphoric ester is preferable
to the use of polyphosphoric acid, since in the presence of
polyphosphoric ester the cyclization reaction proceeds
under milder conditions (at temperatures of 100–120°С
instead of 180–250°С)17 and with high yields of the final
products.
Scheme 2
In the present work, various reactions of hydrazides 1a–e
with amides 2a–c were carried out in polyphosphoric ester
(Scheme 3, Table 1). In all cases, the target triazoles 3a–e
were formed with acceptable yields and under mild
temperature conditions. Moreover, it was found that an
increase in temperature above 100°C significantly increases
the contribution of side processes, and the reaction of the
formation of the target triazole proceeds either with a
significantly lower yield or does not proceed at all.
It is very likely that optimizing the synthesis temperature
would lead to a significant increase in the yields of reaction
products, however, additional studies are required for this.
In order to verify the universality of the proposed
approach and confirm the resulting structures, a counter
synthesis of compound 3a was carried out. Both syntheses
were carried out under the same conditions – in poly-
phosphoric ester. The main difference was the distribution
of R1–R4 substituents between the starting amide and
hydrazide (the R substituents in the hydrazide molecule for
one reaction coincided with the R substituents in the amide
molecule for the other reaction, Table 1). The analysis of
the obtained products showed that the same compound is
formed as a result of two different reactions (1a + 2a and
1b + 2b) with similar yields, which confirms both the
claimed structure of the products and the viability of the
proposed synthesis method.
structure by other known methods11,15 is substantially
complicated by side processes involving the phenolic
moiety. Therefore, in such cases, it is also necessary to
carry out additional stages of the protection and
deprotection of the hydroxyl group, in addition to the main
reaction to obtain triazole. However, due to the fact that the
developed method involves the synthesis under fairly mild
conditions, in the present work, compound 3b was obtained
Table 1. Yields of triazoles 3a–e
and temperature conditions of the reaction of hydrazides 1a–e
with amides 2a–c in polyphosphoric ester
Tempe-
Hydrazide R1
R2 Amide R3
R4 rature, Triazole Yield, %
°С
H
H
OMe
OMe
H
H
H
t-Bu 104
t-Bu 125
47
–
1a
1a
1b
1b
1c
1d
1a
1a
1e
2a
2a
2b
2b
2a
2c
2c
2c
2b
3a
3a
3a
3a
3b
3c
3d
3d
3e
t-Bu
t-Bu
H
OMe
OMe
H
H
H
80
102
80
62
54
31
82
52
14
34
H
OH
H
t-Bu
Ph
Ph
Ph
H
Br
H
87
H
OMe
OMe
H
H
80
H
H
104
80
An additional advantage of the developed method was
shown on the example of compound 3b containing one
hydroxyl group (substituent R2). Synthesis of a similar
NMe2
OMe
835

Chemistry of Heterocyclic Compounds 2019, 55(9), 834–838
1
directly using hydrazide with a free hydroxyl group. In
164°С23). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz):
4.51 (2H, s, NH2); 7.66 (2H, d, J = 8.5, H Ar); 7.76 (2H, d,
J = 8.5, H Ar); 9.85 (1H, s, NH). Found, %: C 39.40;
H 3.58; N 13.37. C7H7BrN2O. Calculated, %: C 39.10;
H 3.28; N 13.03.
addition, compound 3b was also obtained from triazole 3a
(treatment with 40% HBr), which is another confirmation
of the structure of the obtained compounds 3a,b.
To conclude, a novel one-pot method for the synthesis
of 3,4,5-triaryl-substituted 1,2,4-triazoles was developed in
the present work (5 compounds were obtained). The
method is based on the reaction of amides with hydrazides
in polyphosphoric ester at 80–125°C. The fundamental
difference between the proposed one-pot approach and
those described in the literature is the absence of a two-step
process (no solvent replacement in the reactor is required
during the reaction or transfer of the reactor to the
microwave unit). In addition, the proposed method has
such advantages as ease of execution, mildness of the
synthesis conditions, and ease of isolation of the target
products. The structure of triazoles obtained by the
proposed one-pot method was proved by counter synthesis.
Due to the mild synthesis conditions, it was possible to
obtain triazole with a hydroxyl group without additional
stages of the protection and deprotection of this group.
4-(Dimethylamino)benzoic acid hydrazide (1e). Yield
13.4 g (75%), colorless crystals, mp 176–177°С (EtOH)
(mp 169–170°С23). H NMR spectrum (DMSO-d6), δ, ppm
1
(J, Hz): 2.95 (6H, s, N(CH3)2); 4.33 (2H, s, NH2); 6.68 (2H,
d, J = 9.0, H Ar); 7.75 (2H, d, J = 9.0, H Ar); 9.38 (1H, s,
NH). Found, %: C 59.83; H 7.08; N 24.21. C9H13N3O.
Calculated, %: C 60.32; H 7.31; N 23.45.
4-tert-Butyl-N-(4-methylphenyl)benzamide (2a). Yield
12.3 g (92%), colorless crystals, mp 129–130°С (i-PrOH)
(mp 129–130°С24). H NMR spectrum (DMSO-d6), δ, ppm
1
(J, Hz): 1.32 (9H, s, C(CH3)3); 2.28 (3H, s, CH3); 7.15 (2H,
d, J = 8.5, H Ar); 7.53 (2H, d, J = 8.5, H Ar); 7.65 (2H, d,
J = 8.5, H Ar); 7.88 (2H, d, J = 8.5, H Ar); 10.07 (1H, s,
NH). Found, %: C 81.45; H 8.22; N 5.34. C18H21NO.
Calculated, %: C 80.86; H 7.92; N 5.24.
2-Methoxy-N-(4-methylphenyl)benzamide (2b). Yield
9.4 g (78%), colorless crystals, mp 62–62.5°С (PhMe)
(mp 66–67°С (EtOH)20). H NMR spectrum (DMSO-d6),
1
Experimental
IR spectra were registered on a PerkinElmer Spectrum
δ, ppm (J, Hz): 2.27 (3H, s, CH3); 3.90 (3H, s, OCH3); 7.06
(1H, t, J = 7.5, H Ar); 7.12–7.19 (3H, m, H Ar); 7.47–7.52
(1H, m, H Ar); 7.61–7.65 (3H, m, H Ar); 10.00 (1H, s,
NH). Found, %: C 74.32; H 6.11; N 6.04. C15H15NO2.
Calculated, %: C 74.67; H 6.27; N 5.81.
1
100 apparatus in KBr pellets. H and 13C NMR spectra
were acquired on a Bruker DRX-500 (500 and 126 MHz,
respectively) in DMSO-d6 or СDCl3, with TMS as internal
standard. Mass spectra were recorded on a Finnigan MAT
INCOS 50 mass spectrometer with direct sample injection
(EI ionization, 70 eV). Elemental analysis was performed
on a Vario MICRO cube CHNS-analyzer. Melting points
were determined on a Boetius heating bench.
N-(4-Methylphenyl)biphenyl-4-carboxamide (2c). Yield
12.5 g (87%), colorless crystals, mp 233.5–234°С (DMF)
(mp 217.5–218.5 °С25). H NMR spectrum (DMSO-d6),
1
δ, ppm (J, Hz): 2.29 (3H, s, CH3); 7.17 (2H, d, J = 8.5,
H Ar); 7.41–7.45 (1H, m, H Ar); 7.49–7.53 (2H, m, H Ar);
7.69 (2H, d, J = 8.4, H Ar); 7.76 (2H, d, J = 7.2, H Ar);
7.83 (2H, d, J = 8.4, H Ar); 8.06 (2H, d, J = 8.4, H Ar);
10.21 (1H, s, NH). Found, %: C 82.82; H 6.04; N 5.20.
C20H17NO. Calculated, %: C 83.59; H 5.96; N 4.87.
Polyphosphoric ester,18 hydrazides 1a–e,19 and amides
2a–c20 were obtained according to literature methods.
2-Methoxybenzoic acid hydrazide (1a). Yield 12.1 g
(73%), colorless crystals, mp 82–82.5°C (PhMe) (mp 78–
1
80°С (PhMe)21). H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 3.86 (3H, s, OCH3); 4.52 (2H, s, NH2); 7.02 (1H,
dd, J = 10.0, J = 2.0, H Ar); 7.11 (1H, d, J = 10.0, H Ar);
7.45 (1H, dd, J = 10.0, J = 2.0, H Ar); 7.68 (1H, d, J = 10.0,
H Ar); 9.20 (1H, s, NH). Found, %: С 57.96; H 6.24;
N 16.78. C8H10N2O2. Calculated, %: C 57.82; H 6.07; N 16.86.
4-tert-Butylbenzoic acid hydrazide (1b). Yield 15.7 g
(82%), colorless crystals, mp 130–130.5°С (PhMe) (mp 117–
120°С (i-PrOH)19,22). 1H NMR spectrum (DMSO-d6),
δ, ppm (J, Hz): 1.33 (9H, s, C(CH3)3); 4.20 (2H, s, NH2);
7.45 (2H, d, J = 8.0, H Ar); 7.26 (1H, s, NH); 7.69 (2H, d,
J = 8.0, H Ar). Found, %: С 68.56; H 8.41; N 14.23.
C11H16N2O. Calculated, %: C 68.72; H 8.39; N 14.57.
2-Hydroxybenzoic acid hydrazide (1c). Yield 10.6 g
(70%), colorless crystals, mp 150–150.5°С (EtOH)
Synthesis of compounds 3a–e (General method).
Solvent (15 ml): CHCl3 (for triazole 3e), PhCl (for triazoles
3b,c), or no solvent for triazoles 3a,d was added to a
suspension of hydrazide 1a–e (0.01 mol) and amide 2a–c
(0.01 mol) in polyphosphoric ester (20 g). The mixture was
stirred at 80–125°С (Table 1) for 3 h. Then the reaction
mixture was cooled and treated with H2O (100 ml).
Aqueous NaOH was added to the mixture to pH 8.
Methods by which the target products 3a–e were isolated
varied and are indicated for each compound.
3-(4-tert-Butylphenyl)-5-(2-methoxyphenyl)-4-(4-methyl-
phenyl)-4H-1,2,4-triazole (3a). The reaction mixture was
extracted with CHCl3. After removal of solvent, the residue
was dissolved by heating in twice the volume of tert-butyl
methyl ether. The resulting solution was kept at 5–7°С for
24 h. The precipitate was filtered off and dried at reduced
pressure over P2O5. Yield 1.87 g (47% from compounds 1a
and 2a), 2.46 g (62% from compounds 1b and 2b),
colorless crystals, mp 199.5–200.3°С (TBME). IR spect-
rum, ν, cm–1: 3037, 2967, 2885, 2841, 2295, 2045, 1918,
1793, 1680, 1611, 1584, 1533, 1516, 1475, 1439, 1423,
1364, 1303, 1276, 1249, 1164, 1108, 1046, 1027, 973, 937,
1
(mp 148–150°С (EtOH)21). H NMR spectrum (DMSO-d6),
δ, ppm (J, Hz): 4.63 (2H, s, NH2); 6.83–6.88 (1H, m,
H Ar); 6.88–6.91 (1H, m, H Ar); 7.35–7.40 (1H, m, H Ar);
7.80 (1H, dd, J = 7.9, J = 1.6, H Ar); 10.05 (1H, s, NH);
12.48 (1H, s, OH). Found, %: C 54.89; H 5.03; N 18.91.
C7H8N2O2. Calculated, %: C 55.26; H 5.30; N 18.41.
4-Bromobenzoic acid hydrazide (1d). Yield 17.2 g
(80%), colorless crystals, mp 159–160°С (MeOH) (mp 162–
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Chemistry of Heterocyclic Compounds 2019, 55(9), 834–838
923, 912, 844, 769, 755. 1H NMR spectrum (CDCl3), δ, ppm
152 (50), 139 (10), 115 (10), 104 (18), 91 (85). Found, %:
C 69.80; H 4.52; N 8.57. C27H20BrN3. Calculated, %:
C 69.53; H 4.32; N 9.01.
(J, Hz): 1.29 (9H, s, C(CH3)3); 2.32 (3H, s, CH3); 3.43 (3H,
s, OCH3); 6.73 (1H, d, J = 8.2, H Ar); 6.93 (2H, d, J = 8.2,
H Ar); 6.97–7.01 (1H, m, H Ar); 7.07 (1H, d, J = 8.2,
H Ar); 7.30 (2H, d, J = 8.2, H Ar); 7.33–7.37 (1H, m,
H Ar); 7.38–7.41 (2H, m, H Ar); 7.51 (2H, dd, J = 7.5,
J = 1.8, H Ar). 13C NMR spectrum (CDCl3), δ, ppm: 21.1
(CH3); 31.1 (C(CH3)3); 34.7 (C(CH3)3); 54.8 (OCH3);
110.6; 116.9; 120.5; 124.3; 125.2; 126.7; 128.2; 129.5;
131.6; 132.2; 132.9; 138.6; 152.5; 153.6; 154.1; 157.1.
Mass spectrum, m/z (Irel, %): 397 [М]+ (100), 382 (10), 366
(35), 306 (15), 291 (25), 250 (15), 202 (10), 180 (9), 131
(20), 116 (25), 105 (18), 91 (40), 77 (20), 65 (35). Found,
%: C 77.65; H 6.86; N 10.72. C26H27N3O. Calculated, %:
C 78.56; H 6.85; N 10.57.
3-(Biphenyl-4-yl)-5-(2-methoxyphenyl)-4-(4-methyl-
phenyl)-4H-1,2,4-triazole (3d) was separated from the
aqueous phase as an oil and mixed with EtOH (3 ml). The
resulting mixture was kept at 5–7°С for 24 h. The
precipitate was filtered off and dried at reduced pressure
over P2O5. Yield 2.17 g (52%), colorless crystals, mp 190–
191°С (EtOH). IR spectrum, ν, cm–1: 3343, 3067, 3038,
2976, 2290, 2072, 2046, 1955, 1904, 1797, 1654, 1584,
1516, 1474, 1422, 1327, 1254, 1213, 1161, 1121, 1046,
1025, 845, 770, 762, 752, 733. 1H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 2.33 (3H, s, CH3); 3.44 (3H, s, OCH3); 6.75
(1H, d, J = 8.0, H Ar); 6.95 (2H, d, J = 8.0, H Ar); 6.99–
7.03 (1H, т, J = 7.5, H Ar); 7.08–7.10 (2H, d, J = 8.0,
H Ar); 7.33–7.45 (4H, m, H Ar); 7.52–7.55 (5H, m, H Ar);
7.58 (2H, d, J = 7.5, H Ar). 13C NMR spectrum (CDCl3),
δ, ppm: 21.1 (CH3); 54.8 (OCH3); 110.7; 116.7; 120.5;
126.1; 126.6; 126.9; 127.0; 127.1; 127.7; 128.8; 129.0;
129.6; 131.7; 132.2; 132.9; 138.7; 140.1; 141.9; 153.9;
157.2. Mass spectrum, m/z (Irel, %): 417 [M]+ (100), 399
(8), 387 (25), 287 (35), 181 (20), 152 (15), 91 (5), 77 (5),
65 (5). Found, %: C 80.55; H 5.62; N 9.97. C28H23N3O.
Calculated, %: C 80.55; H 5.55; N 10.06.
2-[5-(4-tert-Butylphenyl)-4-(4-methylphenyl)-4H-1,2,4-
triazol-3-yl]phenol (3b) was isolated in the same way as
triazole 3a, however, EtOAc was used for extraction, and
PhH was used as the recrystallization solvent. Yield 1.19 g
(31%), colorless crystals, mp 212–212.5°С (PhH).
Synthesis of triazole 3b from triazole 3а. A mixture of
compound 3a (0.012 mol), 48% aqueous HBr (35 ml), and
glacial AcOH (25 ml) was stirred at 120–130°С for 20 h.
After cooling, the reaction mixture was diluted with H2O
(50 ml), pH was adjusted to ~5 by the addition of 10 M
aqueous NaOH, the formed precipitate was filtered off and
washed with H2O. It was recrystallized from Me2CO. Yield
3.42 g (74%). IR spectrum, ν, cm–1: 2956, 1624, 1591,
1511, 1484, 1457, 1407, 1295, 1257, 1201, 1165, 1138,
1110, 1045, 1016, 932, 897, 835, 823, 799, 770, 744, 711,
4-[5-(2-Methoxyphenyl)-4-(4-methylphenyl)-4H-1,2,4-
triazol-3-yl]-N,N'-dimethylaniline (3e) was isolated in the
same way as triazole 3a, however, Me2CO was used for
recrystallization. Yield 1.31 g (34%), colorless crystals,
mp 233–234°С (Me2CO). IR spectrum, ν, cm–1: 1608, 1581,
1560, 1540, 1513, 1478, 1446, 1402, 1355, 1332, 1279,
1249, 1225, 1202, 1186, 1125, 1202, 1186, 1125, 1095,
1063, 1046, 1022, 990, 943, 834, 822, 803, 793, 764, 747,
1
675, 627, 613, 578, 509, 486, 474, 412, 378. H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.35 (9H, s, C(CH3)3);
2.50 (3H, s, CH3); 6.58 (1H, dd, J = 7.6, J = 7.6, H Ar);
7.11 (1H, d, J = 8.5, H Ar); 7.17 (1H, d, J = 8.5, H Ar);
7.19–7.23 (2H, m, H Ar); 7.30–7.37 (4H, m, H Ar); 7.49
(1H, d, J = 7.5, H Ar); 7.52 (1H, d, J = 8.5, H Ar); 7.80 (1H,
d, J = 8.5, H Ar). 13C NMR spectrum (CDCl3), δ, ppm: 21.9
(CH3); 31.6 (C(CH3)3); 35.4 (C(CH3)3); 111.1; 118.8;
120.6; 123.9; 126.1; 127.3; 128.8; 130.0; 131.5; 133.3;
134.5; 141.2; 153.6; 154.5; 155.7; 158.9. Mass spectrum,
m/z (Irel, %): 383 [М]+ (100), 386 (60), 221 (8), 116 (9), 91
(25), 77 (7), 65 (8). Found, %: C 77.89; H 6.62; N 10.83.
C25H25N3O. Calculated, %: C 78.30; H 6.57; N 10.96.
1
685, 643, 609, 587, 536, 501, 436, 388. H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 2.31 (3H, s, CH3); 2.95 (6H, s,
N(CH3)2); 3.42 (3H, s, OCH3); 6.58 (2H, d, J = 9.0, H Ar);
6.72 (1H, d, J = 8.0, H Ar); 6.93 (2H, d, J = 9.0, H Ar);
6.98 (1H, t, J = 7.5, H Ar); 7.06 (2H, d, J = 8.0, H Ar); 7.31–
7.36 (3H, m, H Ar); 7.50 (1H, d, J = 8.0, H Ar).
13C NMR spectrum (CDCl3), δ, ppm: 21.1 (CH3); 40.0
(N(CH3)2); 54.8 (OCH3); 110.6; 111.4; 114.6; 117.1; 120.4;
126.7; 129.4; 129.6; 131.4; 132.2; 133.3; 138.3; 150.7;
153.1; 154.6; 157.2. Mass spectrum, m/z (Irel, %): 384 [M]+
(100), 366 (45), 353 (27), 337 (7), 278 (7), 251 (13), 237
(14), 207 (12), 192 (13), 180 (12), 165 (5), 145 (50), 132
(10), 105 (25), 91 (35), 78 (14), 65 (15). Found, %:
3-(Biphenyl-4-yl)-5-(4-bromophenyl)-4-(4-methyl-
phenyl)-4H-1,2,4-triazole (3с) was isolated in the same
way as triazole 3a, PhH was used for recrystallization.
Yield 3.81 g (82%), colorless crystals, mp 256.5–258°С
(PhH). IR spectrum, ν, cm–1: 3340, 3056, 2922, 1904, 1653,
1608, 1597, 1563, 1515, 1472, 1405, 1323, 1262, 1234,
C
74.56; H 6.15; N 14.60. C24H24N4O. Calculated, %:
C 74.97; H 6.29; N 14.57.
1
1165, 1106, 1070, 1011, 971. H NMR spectrum (CDCl3),
The work was carried out on the topic '"'Design,
fundamental research on the structure, properties, and
mechanisms of the biological action of new small
molecules and supramolecular systems to create innovative
targeted drugs for the treatment of socially significant
diseases'' of the State Assignment of the Ministry of Science
and Higher Education of the Russian Federation to
Institute of Problems of Chemical Physics of the Russian
Academy of Sciences (State registration number 0089-2019-
0014).
δ, ppm (J, Hz): 2.44 (3H, s, CH3); 7.08 (2H, d, J = 8.0,
H Ar); 7.25–7.27 (1H, d, J = 8.0, H Ar); 7.32 (2H, d,
J = 8.0, H Ar); 7.36 (1H, d, J = 7.5, H Ar); 7.40–7.47 (4H,
m, H Ar); 7.49–7.58 (7H, m, H Ar). 13C NMR spectrum
(CDCl3), δ, ppm: 21.3 (CH3); 120.4; 125.6; 127.0; 127.3;
128.9; 129.5; 130.2; 131.7; 132.4; 133.8; 134.1; 135.6;
139.2; 140.2; 142.3; 144.4; 154.0; 154.8. Mass spectrum,
m/z (Irel, %): 465 [M]+ (100), 385 (8), 285 (10), 284 (40),
270 (40), 256 (15), 234 (10), 193 (11), 179 (80), 165 (15),
837

Chemistry of Heterocyclic Compounds 2019, 55(9), 834–838
13. Lindstrom, J.; Johansson, M. H. Synth. Commun. 2006, 36,
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