Azolyl-substituted 1,2,3-triazoles

Article abstract of DOI:10.1134/S1070428016030209

Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-ph

Full text of DOI:10.1134/S1070428016030209

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 3, pp. 414–420. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.A. Golovanov, I.S. Odin, V.V. Bekin, A.V. Vologzhanina, I.S. Bushmarinov, S.S. Zlotskii, Yu.L. Gerasimov, P.P. Purygin, 2016,
published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 3, pp. 434–440.
Azolyl-Substituted 1,2,3-Triazoles
a
a
a
b
b
A. A. Golovanov , I. S. Odin , V. V. Bekin , A. V. Vologzhanina , I. S. Bushmarinov ,
c
d
d
S. S. Zlotskii , Yu. L. Gerasimov , and P. P. Purygin
a
Togliatti State University, ul. Belorusskaya 14, Togliatti, 445667 Russia
e-mail: aleksandgolovanov@yandex.ru
b
Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
c
Ufa State Petroleum Technological University, ul. Kosmonavtov 1, Ufa, 450062 Bashkortostan, Russia
d
Korolev Samara State Aerospace University, Moskovskoe shosse 34, Samara, 443086 Russia
Received December 16, 2015
Abstract—Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones
afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-
prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones reacted with
hydrazine hydrate and phenylhydrazine to give 72–93% of 4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-
1
H-1,2,3-triazoles which underwent dehydrogenation on heating in boiling acetic acid with formation of the
corresponding pyrazole derivatives. The molecular structures of (E)-3-phenyl-1-(5-phenyl-1H-1,2,3-triazol-4-
yl)prop-2-en-1-one and 4-[3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-tri-
azole were studied by X-ray analysis. 4-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles
showed toxicity against Daphnia magna.
DOI: 10.1134/S1070428016030209
1
,2,3-Triazole derivatives exhibit a broad spectrum
after removal of the solvent and acidification, we
isolated 89–98% of isomeric chalcones 3a–3h and 4a–
4e (Scheme 1). Compounds 3 and 4 are colorless or
light yellow crystalline finely crystalline substances
with sharp melting points, which are stable on storage.
The cycloaddition was regioselective; according to the
of biological activity [1–3]; for example, cinnamoyl-
substituted 1,2,3-triazoles and 1,2,3-benzotriazoles
azachalcones) efficiently inhibit transglutaminase
4, 5]. These compounds can be used to obtain
triazolyl-substituted heterocyclic systems [6–9] which
were reported to possess pronounced antimicrobial
activity [10, 11]. Therefore, synthesis of new 1,2,3-tri-
azole derivatives and study of their properties are
topical problems.
(
[
1
TLC and H NMR data, compounds 3 and 4 were
formed as a single isomer. Analogous regioselectivity
was observed previously in the reactions of some
activated acetylenes with azides [14, 15].
Cinnamoyl-substituted 1,2,3-triazoles can be syn-
thesized by cycloaddition of azides to unsaturated
ketones [4, 12]. In the preliminary communication [13]
we showed the possibility for preparing azolyl-substi-
tuted 1,2,3-triazoles from 1,5-disubstituted (E)-pent-2-
en-4-yn-1-ones 1. Herein we report the synthesis of
a series of 5-aryl-4-(azol-5-yl)-1,2,3-triazoles from
ketones 1 and the results of studying their structure and
toxicity.
The structure of compounds 3a–3h and 4a–4e was
confirmed by elemental analyses and IR, NMR, and
mass spectra. The IR spectra of 3 and 4 contained
absorption bands typical of stretching vibrations of
–
1
carbonyl (1665–1652 and 1675–1637 cm , respec-
tively) and endocyclic NH group (3232–3174 and
–
1
1
3
200–3090 cm , respectively). In the H NMR spectra
of 3 and 4, protons on the trans-configured double
bond resonated as doublets at δ 7.60–7.93 ppm (J =
15–16 Hz), and the NH signal appeared as a broadened
singlet at δ 7.5–12.4 (3) or 10.9–16.0 ppm (4). The
Aryl acetylenylvinyl ketones 1a–1h, as well as
vinylacetylenyl ketones 2a–2g, are reactive dipolaro-
1
3
philes which reacted with KN in DMF at room tem-
carbonyl carbon signal was observed in the C NMR
3
perature. The reactions were complete in less than 1 h;
spectra at δ 181–190 ppm.
C
4
14

AZOLYL-SUBSTITUTED 1,2,3-TRIAZOLES
415
Scheme 1.
O
O
(
(
1) KN , DMF, ~20°C
2) HCl
β
3
R2
N
R2
α
N
R1
N
H
R1
1
a–1h
3a–3h
O
O
β
(
(
1) KN , DMF, ~20°C
2) HCl
3
N
R
R
α
N
Ph
N
Ph
H
2
a–2e
4a–4e
R3
N
N
3
N
N
R NHNH , EtOH, ~78°C
2
3
a, 3b, 3d–3f
1
HN
R = Ph
R2
Ph
5
a–5f
Ph
N
N
N
N
AcOH, ~120°C
5
b, 5e
3
HN
R = Ph
R2
Ph
6
a, 6b
1
2
1
2
1
1
, 3, R = R = Ph (a); R = Ph, R = 4-MeC
6
H
4
(b), 4-MeOC
6
H
4
(c), 4-ClC
(h); 2, 4, R = Ph (a), 4-ClC (b), 3-BrC
(b), 4-ClC (c), 4-BrC (d), thiophen-2-yl (e); R = Ph, R = H (f); 6, R = 4-MeC
6 4
-BrC H (b).
6
H
4
(d), 4-BrC
6
H (e), thiophen-2-yl (f); R = 4-MeC H ,
4
6
4
2
1
2
2
R = Ph (g); R = R = 4-BrC
R = Ph (a); R = Ph, R = 4-MeC
6
H
4
6
H
4
4
H
6 4
(c), 4-Me
2 6 4
NC H (d), thiophen-2-yl (e); 5, R =
3 2
3
3
2
2
6
H
4
6
H
4
6
H
6 4
H (a),
4
1
3
1
Compounds 3 fairly readily reacted with hydrazine
hydrate and phenylhydrazine hydrochloride on heating
in boiling ethanol to afford 72–93% of 4-(4,5-dihydro-
C and H NMR spectra of 6a and 6b indicated the
absence in their molecules of CH and C H groups.
3
sp
2
According to [17], triazoles 6 can exist as several
1
H-pyrazol-5-yl)-1H-1,2,3-triazoles 5a–5f. Com-
tautomers.
1
pounds 5 displayed in the H NMR spectra signals
from two diastereotopic protons on C of the pyrazole
ring (δ 3.18–3.51 ppm) and 5-H (δ 5.71–7.69 ppm), as
well as a broadened singlet from the triazole NH
proton (δ ~15.3 ppm). The H NMR spectrum of 5a
showed two NH signals at δ 14.95 and 15.51 ppm,
presumably due to the presence of two tautomers.
The described procedure for the synthesis of azolyl-
substituted 1,2,3-triazoles is characterized by high
yields and selectivity and easy workup (no chromato-
graphic separation is necessary), and it can be regarded
as an alternative to the previously proposed method of
synthesis of analogous nonfused biheterocycles [16].
Heating of compounds 5b and 5e in boiling acetic
acid on exposure to air resulted in their dehydrogena-
tion with formation of pyrazolyl-substituted 1,2,3-tri-
azoles 6a and 6b (yield 82–89%). Their structures
were confirmed by high-resolution mass spectra. The
The structure of 4a was studied by X-ray powder
diffraction (Fig. 1). The results confirmed E con-
figuration of the exocyclic double bond and s-cis
conformation of the enone fragment. Molecules 4a
in crystal are linked through strong hydrogen bonds
4
1
8
4
N –H···O (r
2.83 Å) to form infinite chains.
N···O
7
N
6
N
8
N
9
1
2
C
5
C
C
1
1
2
17
C
C
C
1
3
1
16
18
C
1
0
C
C
C
C
3
C
4
O
21
1
4
C
15
C
C
2
0
19
C
C
Fig. 1. Structure of the molecule of (E)-3-phenyl-1-(5-phe-
nyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-one (4a) in crystal.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

4
16
GOLOVANOV et al.
5
4
N
14
dihydropyrazole ring adopts an envelope conformation
where the N atom deviates by 0.087(6) Å from the
N
C
1
2
1
15
16
C
C
2
2
3
C
N
2
1
0
9
C
13
plane formed by the other atoms [the mean deviation
of atoms is 0.005(3) Å]. The dihydropyrazole and
triazole ring planes form a dihedral angle of 75.3(2)°.
The aryl substituents on the dihydropyrazole ring are
almost coplanar [the dihedral angles are 7.9(2)° for the
C
C
1
2
3
C
C
2
C
C
18
1
5
C
17
N
C
C
2
4
C
2
4
4
-methylphenyl ring and 15.1(2)° for the phenyl ring].
N
C
1
The phenyl ring on C is turned through an angle of
3
C
3
4.1(2)° with respect to the 1,2,3-triazole ring plane.
6
1
1
C
C
The toxicity of compounds 3b and 5b–5d was
7
8
studied against Daphnia magna (laboratory culture)
which is commonly used for quantitative assays of
toxic effect of many organic compounds [18]. Lethal
concentrations (LC ), lowest lethal concentrations
C
C
1
0
C
9
C
5
0
1
2
C
(LC ), and minimal concentrations inhibiting and
Lo
completely suppressing reproduction of Daphnia
magna were determined (Table 1). Compounds 3b and
Fig. 2. Structure of the molecule of 4-[3-(4-methylphenyl)-1-
phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-tri-
azole (5b) according to the X-ray diffraction data. Non-
hydrogen atoms are shown as thermal vibration ellipsoids
with a probability of 50%.
5
b–5d were characterized by close LC values. Their
50
lethal effect was observed starting from a concentra-
tion of 0.01 mg/L, and the total death, from a concen-
tration of 0.5–1.0 mg/L. All compounds showed nega-
tive effect on the reproduction of Daphnia magna and
increased the fetal period.
The molecular structure of 4-[3-(4-methylphenyl)-
-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-
,2,3-triazole (5b) is shown in Fig. 2. Molecule 5b
1
1
EXPERIMENTAL
possesses an asymmetric carbon atom, and this com-
pound crystallized in non-centrosymmetric space
group (Fdd2), indicating the presence of both enan-
tiomers (racemic compound). The dihydropyrazole
ring is characterized by bond alternation, and the bond
1
13
The H and C NMR spectra were recorded on
Bruker AM-300 (300 and 75.47 MHz, respectively)
and Jeol ECX-400A spectrometers (400 and 100 MHz,
respectively) using tetramethylsilane as internal
standard. The IR spectra were measured in KBr on
an FSM-1201 spectrometer with Fourier transform.
The elemental analyses were obtained on a Perkin
Elmer Model 2400 CHN analyzer. The electron impact
mass spectra (70 eV) were recorded on a Shimadzu
GCMS-QP2010Ultra instrument equipped with a 30-m
Rtx-5MS capillary column. The high-resolution mass
spectra (HESI) were obtained on a Q Exactive mass
spectrometer. The progress of reactions was monitored,
and the purity of the isolated compounds was checked,
3
1
4
5
2
angles are typical of sp - (N , C , C ) and sp -hybrid-
2
3
ized atoms (N , C ). The bond lengths in the triazole
ring and bond angles therein indicate delocalization of
2
5
electron density. The C –C bond between the hetero-
cycles [1.493(6) Å] is close to standard carbon–carbon
bond, whereas the bonds between the aryl substituents
and the heterocycles are somewhat shortened. The
other bond lengths and bond angles in molecule 5b are
similar to the corresponding reference values. The
1
,2,3-triazole ring is planar within 0.003(3) Å. The
Table 1. Toxicity parameters of compounds 3b and 5b–5d against Daphnia magna (mg/L)
Compound
no.
Minimal concentration
inhibiting reproduction
Minimal concentration
suppressing reproduction
LC50
Minimal lethal concentration
3
5
5
5
b
b
c
1.66±0.85
1.75±0.25
1.77±0.75
1.15±0.13
0.5
1.0
0.5
0.1
0.005
0.005
0.010
0.005
2.0
2.0
1.6
2.0
d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

AZOLYL-SUBSTITUTED 1,2,3-TRIAZOLES
417
by TLC on Sorbfil plates (ethyl acetate–cyclohexane,
:1). The melting points were determined in open
capillaries.
The X-ray powder diffraction pattern of compound
a was obtained on a Bruker D8 AdvanceVario diffrac-
Table 2. Divergence factors for structure refinement of com-
pound 4a
2
Factor
Pawley refinement
Rietveld refinement
K
1
–
8.00
1.79
6.01
1.16
5.84
0.65
2.20
4
Rwp, %
1.81
7.67
1.36
11.270
0.04
2.40
tometer equipped with a Ge(111) monochromator and
a
R′wp, %
a LynxEye position-sensitive detector (CuK radiation,
α1
R
p
, %
λ = 1.540596 Å; scan range 2θ 3.8–80°, scan step
a
0
.01048°). All calculations were performed using
R′
p
, %
Bruker TOPAS software [19]. The X-ray powder pat-
tern was indexed by the SVD technique [20] imple-
mented in TOPAS. Orthorhombic crystal system; unit
cell parameters: a = 26.44840(30), b = 13.01737(10),
RBragg, %
GOF
a
Background-corrected values.
3
c = 8.249606(51) Å; V = 2840.25(4) Å . The Pbca
eter (CCD area detector, λCuK radiation, multilayer
space group was determined from systematic extinc-
tion. The volume of the independent part of the unit
cell corresponded to one formula unit. The structure
was solved in the direct space by the parallel tem-
pering algorithm implemented in FOX [21]. The
structure proposed on the basis of the NMR data and
calculated for the gas phase by the PM3 method
α
optics microfocus tube, 2θmax = 130°). A correction for
absorption was applied using SADABS [24]. The
structure was solved by the charge flipping algorithm;
all non-hydrogen atoms were localized by difference
syntheses of electron density and were refined against
2
hkl
F
in anisotropic approximation; all hydrogen atoms
were placed into geometrically calculated positions
which were refined in isotropic approximation accord-
ing to the riding model [U (H) = 1.5U (C) for methyl
(
Hyperchem) was used as model. The Rietveld refine-
ment was performed with restraints on bond lengths
and bond angles. The positions of hydrogen atoms
were refined according to the riding model, using the
same isotropic thermal parameter for each type of
atoms in each molecule. A symmetric modification of
the previously reported soft restraints on bond lengths
iso
eq
group or 1.2U (X) for the other atoms, where U(X) is
eq
the equivalent temperate factor of the atom to which
the given hydrogen atom is attached]. The unit cell
also contained disordered ethanol molecules whose
contribution to the total intensity was taken into
account without refinement of atom positions using
SQUEEZE/PLATON [25]. The molecular formula,
molecular weight, and density were calculated with the
solvent molecules included. Final divergence factors:
R = 0.063 [for 3399 reflections with I > 2σ(I)], wR =
[22] was applied; the lack of overshots (with account
taken of mean-square deviations) in bond length dis-
tribution over a wide range of restraint strengths
(
parameter K ) indicated the validity of the refined
1
structural model. Corrections for preferred sample
orientations (Järvinen fourth-order spherical harmo-
nics, texture index 1.06) and anisotropic line broaden-
ing were applied. The line asymmetry was refined
according to the axial divergence model [23]. The
F
2
0
.143 (for 3723 independent reflections, Rint = 0.073);
goodness of fit 1.07, Flack parameter 0.2(5). All
calculations were performed using SHELXTL [26] and
OLEX2 [27].
simulated diffractogram (K = 8.00, mean-square
1
The crystallographic data for compounds 4a and 5b
were deposited to the Cambridge Crystallographic
Data Center, CCDC entry nos. 1 015 704 (4a)
and 1 009 919 (5b), and are available at
www.ccdc.cam.ac.uk/data_request/cif.
deviation for bond lengths 0.014 Å) conformed well to
the experimental pattern, and the divergence factors
were comparable with those for the Pawley refinement
of line intensities (Table 2).
A 0.5 ×0.06×0.06-mm light yellow single crystal
Ketones 1 [28] and 2 [29] and compounds 3–5 [13]
were synthesized by known methods. Compounds 3a,
(
needle) of 5b was obtained by slow crystallization
from ethanol; C H N O (M 379.47); orthorhombic
2
5
24
5
0.5
3
b, 3d, and 5a–5c were described in [13].
crystal system (120 K) with the following unit cell
parameters: a = 18.2477(5), b = 86.222(2), c =
(E)-1-(4-Methoxyphenyl)-3-(5-phenyl-1H-1,2,3-
triazol-4-yl)prop-2-en-1-one (3c). Yield 90%, light
3
5
.7239(2) Å; V = 9005.7(2); dcalc = 1.1194 mg/mm ;
space group Fdd2; Z = 16. A set of 15965 reflections
was collected at 120 K on a Bruker Apex II diffractom-
yellow crystals, mp 133–134°C (from benzene–petro-
leum ether). IR spectrum, ν, cm : 3193 (NH), 1656
–
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

4
18
GOLOVANOV et al.
1
13
(
C=O). H NMR spectrum (300 MHz, CDCl ), δ, ppm:
Harom). C NMR spectrum (75 MHz, DMSO-d ), δ ,
6 C
3
3
.79 s (3H, CH O), 6.86–7.63 m (7H, Harom), 7.88 d
ppm: 122.6–136.1, 187.9 (C=O). Mass spectrum:
m/z 431.9348 [M + H] . Found, %: C 47.50; H 2.83;
3
3
+
(
1H, β-H, J = 15.4 Hz), 8.03–8.11 m (3H, α-H, Harom),
1
3
1
0.07 br.s (1H, NH). C NMR spectrum (75 MHz,
N 9.25. C H Br N O. Calculated, %: C 47.14;
1
7
11
2
3
CDCl ), δ , ppm: 55.5 (OCH ), 114.0–163.9, 188.4
H 2.56; N 9.70. M + H 431.9343.
E)-3-Phenyl-1-(5-phenyl-1,2,3-triazol-4-yl)prop-
-en-1-one (4a). Yield 89%, colorless crystals,
mp 140–141°C (from aq. MeOH). IR spectrum, ν,
3
C
3
+
(
C=O). Mass spectrum: m/z 306.1243 [M + H] .
(
Found, %: C 70.50; H 5.12. C H N O . Calculated,
18
15
3
2
2
%: C 70.80; H 4.96. M + H 306.1243.
–
1
1
(E)-1-(4-Bromophenyl)-3-(5-phenyl-1H-1,2,3-tri-
cm : 3178 (NH), 1652 (C=O). H NMR spectrum
azol-4-yl)prop-2-en-1-one (3e). Yield 98%, light yel-
(300 MHz, DMSO-d ), δ, ppm: 7.27–7.87 m (11H,
6
3
low crystals, mp 133–134°C (from benzene–petroleum
β-H, Harom), 7.91 d (1H, α-H, J = 15.8 Hz), 10.98 br.s.
–
1
13
ether). IR spectrum, ν, cm : 3207 (NH), 1661 (C=O).
(1H, NH). C NMR spectrum (75 MHz, DMSO-d6),
1
H NMR spectrum (300 MHz, CDCl ), δ, ppm: 7.43–
δ , ppm: 123.3–145.1, 183.9 (C=O). Mass spectrum,
3
C
3
+
7
1
.91 m (10H, β-H, Harom), 8.00 d (1H, α-H, J =
m/z (I , %): 275 (35) [M] , 246 (26), 131 (51), 115
rel
1
3
5.4 Hz), 8.70 br.s (1H, NH). C NMR spectrum
(23), 103 (80), 89 (47), 77 (100), 63 (28), 51 (39).
+
(
75 MHz, CDCl ), δ , ppm: 124.1–136.3, 188.9 (C=O).
Found: m/z 276.1124 [M + H] . C H N O. Calculat-
3
C
17 13
3
+
Mass spectrum: m/z 354.0240 [M + H] . Found, %:
ed: M + H 276.1133.
E)-3-(4-Chlorophenyl)-1-(5-phenyl-1,2,3-triazol-
-yl)prop-2-en-1-one (4b). Yield 94%, light yellow
crystals, mp 171–172°C (from benzene–petroleum
C 57.26; H 3.40; Br 22.45. C H BrN O. Calculated,
1
7
12
3
(
%: C 57.64; H 3.42; Br 22.56. M + H 354.0243.
4
(
E)-3-(5-Phenyl-1H-1,2,3-triazol-4-yl)-1-(thio-
–
1
phen-2-yl)prop-2-en-1-one (3f). Yield 91%, light yel-
ether). IR spectrum, ν, cm : 3137 (NH), 1637 (C=O).
1
low crystals, mp 172.5–173.5°C (from aq. EtOH). IR
H NMR spectrum (300 MHz, DMSO-d ), δ, ppm:
6
–
1
1
3
spectrum, ν, cm : 3187 (NH), 1656 (C=O). H NMR
7.45–7.54 m (5H, Harom), 7.75 d (1H, β-H, J =
spectrum (300 MHz, DMSO-d ), δ, ppm: 7.26–7.72 m
16.1 Hz), 7.79–7.94 m (5H, α-H, Harom), 15.94 br.s
6
3
13
(
8
7H, β-H, Harom), 7.87 d (1H, α-H, J = 15.4 Hz), 7.93–
.02 m (2H, Harom), 15.73 br.s (1H, NH). C NMR
(1H, NH). C NMR spectrum (75 MHz, DMSO-d ),
6
1
3
δ , ppm: 124.5–141.8, 183.2 (C=O). Mass spectrum,
C
+
+
spectrum (75 MHz, DMSO-d ), δ , ppm: 123.5–144.8,
m/z (I , %): 310.0745 [M + H] , 309 (17) [M] , 280
6
C
rel
+
1
81.0 (C=O). Mass spectrum: m/z 282.0699 [M + H] .
(28), 165 (38), 137 (36), 101 (100), 89 (87), 75 (64),
63 (49), 51 (50). Found, %: C 65.93; H 3.95; N 13.60.
C H ClN O. Calculated, %: C 65.92; H 3.90;
Found, %: C 63.93; H 3.95; N 14.84. C H N OS.
1
5
11
3
Calculated, %: C 70.80; H 4.96; N 14.94. M + H
82.0702.
E)-3-[5-(4-Methylphenyl)-1,2,3-triazol-4-yl]-1-
1
7
12
3
2
N 13.57. M + H 310.0743.
(
(E)-3-(3-Bromophenyl)-1-(5-phenyl-1,2,3-triazol-
4-yl)prop-2-en-1-one (4c). Yield 95%, colorless crys-
tals, mp 169–170°C (from benzene–petroleum ether).
phenylprop-2-en-1-one (3g). Yield 87%, light yellow
crystals, mp 125–126°C (from aq. EtOH). IR spec-
–
1
1
–1
trum, ν, cm : 3187 (NH), 1656 (C=O). H NMR spec-
trum (300 MHz, DMSO-d ), δ, ppm: 2.41 s (3H, CH ),
IR spectrum, ν, cm : 3132 (NH), 1675 (C=O).
1
H NMR spectrum (300 MHz, DMSO-d ), δ, ppm:
6
3
6
3
3
7
1
.25–7.61 m (8H, NH, Harom), 7.89 d (1H, β-H, J =
5.4 Hz), 7.92–7.97 m (3H, α-H, Harom). C NMR
7.35–7.65 m (5H, Harom), 7.73 d (1H, β-H, J =
1
3
16.1 Hz), 7.79–7.95 m (5H, α-H, Harom), 15.96 br.s
13
spectrum (75 MHz, DMSO-d ), δ , ppm: 21.4 (CH ),
(1H, NH). C NMR spectrum (75 MHz, DMSO-d6),
6
C
3
1
24.8–139.8, 190.0 (C=O). Mass spectrum:
δ , ppm: 124.3–141.4, 182.9 (C=O). Mass spectrum:
m/z 354.0237 [M + H] . Found, %: C 57.51; H 3.34;
C
+
+
m/z 290.1291 [M + H] . Found, %: C 74.52; H 5.41;
N 14.23. C H N O. Calculated, %: C 74.72; H 5.23;
N 11.81. C H BrN O. Calculated, %: C 57.65;
1
8
15
3
17 12
3
N 14.52. M + H 290.1289.
H 3.41; N 11.86. M + H 354.0238.
(
E)-1-(4-Bromophenyl)-3-[5-(4-bromophenyl)-
(E)-3-[4-(Dimethylamino)phenyl]-1-(5-phenyl-
1,2,3-triazol-4-yl)prop-2-en-1-one (4d). Yield 82%,
bright red crystals, mp 143–144°C (from benzene–pe-
1
9
H-1,2,3-triazol-4-yl]prop-2-en-1-one (3h). Yield
1%, colorless crystals, mp 166–167°C (from ben-
zene–petroleum ether). IR spectrum, ν, cm : 3174
NH), 1652 (C=O). H NMR spectrum (300 MHz,
–
1
–1
troleum ether). IR spectrum, ν, cm : 3090 (NH), 1637
1
1
(
(C=O). H NMR spectrum (400 MHz, DMSO-d ), δ,
6
DMSO-d ), δ, ppm: 7.27–7.67 m (8H, β-H, Harom, NH),
ppm: 2.96 s [6H, (CH ) N], 6.69–7.83 m (12H, β-H,
6
3 2
3
13
7
.93 d (1H, α-H, J = 15.4 Hz), 7.98–8.01 m (2H,
Harom, NH). C NMR spectrum (100 MHz, DMSO-d ),
6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

AZOLYL-SUBSTITUTED 1,2,3-TRIAZOLES
419
δ , ppm: 40.2 [(CH ) N], 112.4–152.6, 183.7 (C=O).
Mass spectrum: m/z 319.1549 [M + H] . Found, %:
Found, %: C 70.20; H 5.63. C H N . Calculated, %:
C 70.57; H 5.24.
C
3 2
17 15
5
+
C 71.49; H 5.76; N 17.35. C H N O. Calculated, %:
1
9
18
4
Compounds 6a and 6b (general procedure).
A solution of 0.5 mmol of compound 5b or 5e in 5–
7 mL of glacial acetic acid was heated for 6–8 h under
reflux. The mixture was cooled and poured onto ice
under stirring. The precipitate was filtered off, washed
with 50% ethanol, and dried first in air and then under
reduced pressure (30 mm) at 75–80°C.
C 71.68; H 5.70; N 17.60. M + H 319.1555.
E)-1-(5-Phenyl-1,2,3-triazol-4-yl)-3-(thiophen-
-yl)prop-2-en-1-one (4e). Yield 86%, light yellow
crystals, mp 151–152°C (from benzene–petroleum
(
2
–
1
ether). IR spectrum, ν, cm : 3200 (NH), 1660 (C=O).
1
H NMR spectrum (300 MHz, DMSO-d ), δ, ppm:
6
3
7
1
.03–7.44 m (6H, Harom), 7.60 d (1H, β-H, J =
4-[3-(4-Methylphenyl)-1-phenyl-1H-pyrazol-5-
yl]-5-phenyl-1H-1,2,3-triazole (6a). Yield 82%, color-
3
5.8 Hz), 8.00 d (1H, α-H, J = 15.8 Hz), 8.02–8.81 m
1
3
1
(
(
(
[
(
2H, Harom), 12.18 br.s (1H, NH). C NMR spectrum
less crystals, mp 95–97°C (crude). H NMR spectrum
75 MHz, DMSO-d ), δ , ppm: 122.2–145.0, 183.2
6
C
(300 MHz, DMSO-d ), δ, ppm: 2.35 s (3H, CH ),
6
3
C=O). Mass spectrum, m/z (I , %): 282.0704
rel
7.15–7.85 m (15H, Harom), 15.62 br.s (1H, NH).
+
+
1
3
M + H] ; 281 (15) [M] , 252 (41), 137 (68), 109
C NMR spectrum (75 MHz, DMSO-d ), δ , ppm:
6
C
100), 89 (89), 77 (49), 65 (91), 51 (46). Found, %:
2
0.9 (CH ), 107.3, 123.6, 125.3 (2C), 126.5 (2C),
3
C 63.92; H 3.98; N 14.59. C H N OS. Calculated, %:
1
5
11
3
127.3 (2C), 128.7, 128.8 (2C), 129.3, 129.5, 137.6
+
C 64.04; H 3.94; N 14.94. M + H 282.0697.
-[3-(4-Bromophenyl)-1-phenyl-4,5-dihydro-1H-
pyrazol-5-yl]-5-phenyl-1H-1,2,3-triazole (5d). Yield
4%, colorless crystals, mp 112–113°C (from aq.
(
2C), 139.2, 151.3. Found: m/z 378.1707 [M + H] .
C H N . Calculated: M + H 378.1714.
4
24 19
5
4
-[3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-
8
5
-yl]-5-phenyl-1H-1,2,3-triazole (6b). Yield 89%,
–
1
1
MeOH). IR spectrum, ν, cm : 3258 (NH), 1596
colorless crystals, mp 122–123°C (crude). H NMR
1
(C=N). H NMR spectrum (300 MHz, DMSO-d ), δ,
6
spectrum (300 MHz, DMSO-d ), δ, ppm: 7.17–7.92 m
6
2
3
1
3
ppm: 3.21 d.d (1H, 4-H, J = 17.0, J = 7.7 Hz), 3.23–
(
(
15H, Harom), 15.39 br.s (1H, NH). C NMR spectrum
2
3
.38 m (1H, 4-H), 5.77 d.d (1H, 5-H, J = 12.1,
75 MHz, DMSO-d ), δ, ppm: 107.7, 119.1, 121.3,
6
3
J = 7.7 Hz), 6.69–7.68 m (14H, Harom), 15.26 br.s (1H,
123.7, 126.5, 126.7, 127.4, 127.5 (2C), 127.8, 128.5,
128.8, 131.4, 131.5; 131.7, 139.1, 150.2. Found:
1
3
NH). C NMR spectrum (75 MHz, DMSO-d ), δ ,
ppm: 40.4 (C ), 55.7 (C ), 113.0–146.5. Found:
m/z 444.0818 [M + H] . C H BrN . Calculated:
6
C
4
5
+
m/z 442.0662 [M + H] . C H BrN . Calculated:
2
3
16
5
+
2
3
18
5
M + H 442.0663.
M + H 444.0820.
-Phenyl-4-[1-phenyl-3-(thiophen-2-yl)-4,5-dihy-
dro-1H-pyrazol-5-yl]-1H-1,2,3-triazole (5e). Yield
2%, colorless crystals, mp 95–96°C (from aq. MeOH).
The toxicity of compounds 3b and 5b–5d against
Daphnia magna laboratory culture was studied accord-
ing to standard procedure [30] at 21–22°C on exposure
to daylight. The test medium was prepared from water
with addition of 1% of beaker’s east as nutrient and
a solution of 3b or 5b–5d in DMSO. Water was used
as control. The number of dead and survived species,
the length of the oviposition period, and the time
of appearance of young species from brood chambers
and their number were determined. All experiments
were carried out in triplicate. The LC values (72 h)
5
7
–
1
IR spectrum, ν, cm : 3335 (NH), 1595 (C=N).
1
H NMR spectrum (300 MHz, DMSO-d ), δ, ppm:
.26 m (1H, 4-H), 3.44 d.d (1H, 4-H, J = 17.2, J =
6
2
3
3
1
2.8 Hz), 5.70–5.77 m (1H, 5-H), 6.62–7.77 m (13H,
1
3
Harom), 15.27 br.s (1H, NH). C NMR spectrum
(
1
4
5
75 MHz, DMSO-d ), δ , ppm: 40.4 (C ), 55.6 (C ),
6 C
+
12.9–144.1. Found: m/z 372.1284 [M + H] .
5
0
C H N S. Calculated: M + H 372.1279.
were calculated by the Shtabskii criterion, and the
validity of reproduction differences was estimated
by the Wilcoxon‒Mann‒Whitney test [31].
2
1
17
5
5
-Phenyl-4-[3-phenyl-4,5-dihydro-1H-pyrazol-5-
yl]-1H-1,2,3-triazole (5f). Yield 85%, colorless crys-
tals, mp 129–130°C (from aq. MeOH). IR spectrum, ν,
This study was performed under financial support
by the Russian Science Foundation (project no. 15-13-
10 034). I.S. Bushmarinov thanks the Council for
Grants at the President of the Russian Federation for
support of the study of the validity of geometric
parameters obtained by X-ray powder diffraction
(project no. MK-7267.2015.3).
–
1
1
cm : 3428 (NH), 3268 (NH), 1588 (C=N). H NMR
spectrum (300 MHz, DMSO-d ), δ, ppm: 3.15–3.24 m
6
(
5
1H, 4-H), 3.38–3.47 m (1H, 4-H), 5.13–5.21 m (1H,
-H), 7.36–7.73 m (11H, Harom, NH), 15.10 br.s (1H,
1
3
NH). C NMR spectrum (75 MHz, DMSO-d ), δ ,
ppm: 38.1 (C ), 54.9 (C ), 127.1–141.5, 148.3 (C=N).
6
C
4
5
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 3 2016

4
20
GOLOVANOV et al.
16. Verkhozina, O.N., Kizhnyaev, V.N., Vereshchagin, L.I.,
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