Synthesis and properties of substituted [3-(2-hydroxyphenyl)-1H-1,2,4- triazol-1-yl]acetonitriles

Article abstract of DOI:10.1134/S1070428010070201

Alkylation of 3-substituted 5-(2-hydroxyphenyl)-1H-1,2,4-triazoles with chloroacetonitrile gave hitherto unknown N-cyanomethyl derivatives whose structure was determined by X-ray analysis and ¹H and ¹³C NMR spectroscopy. Condensation

Full text of DOI:10.1134/S1070428010070201

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 7, pp. 1079–1084. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.Yu. Shasheva, N.I. Vikrishchuk, L.D. Popov, V.I. Minkin, M.E. Kletskii, M.Yu. Antipin, A.D. Vikrishchuk, I.E. Mikhailov, 2010,
published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 7, pp. 1080–1085.
Synthesis and Properties of Substituted [3-(2-Hydroxyphenyl)-
1H-1,2,4-triazol-1-yl]acetonitriles
E. Yu. Shashevaa, N. I. Vikrishchuka, L. D. Popova, V. I. Minkina, M. E. Kletskiia,
M. Yu. Antipinb, A. D. Vikrishchukc, and I. E. Mikhailovc
a Southern Federal University, ul. Zorge 7, Rostov-on-Don, 344090 Russia
e-mail: natvi2004@mail.ru
b Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences,
ul. Vavilova 28, Moscow, 119991 Russia
c Southern Research Center, Russian Academy of Sciences, Rostov-on-Don, Russia
Received January 21, 2009
Abstract—Alkylation of 3-substituted 5-(2-hydroxyphenyl)-1H-1,2,4-triazoles with chloroacetonitrile gave
1
hitherto unknown N-cyanomethyl derivatives whose structure was determined by X-ray analysis and H and
13C NMR spectroscopy. Condensation of substituted [3-(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]acetonitriles
at the activated methylene group with acetone led to the formation of new 3-methyl-2-triazolylbut-2-enenitrile
derivatives.
DOI: 10.1134/S1070428010070201
Hydroxyphenyl-substituted 1,2,4-triazoles I are
formed via recyclization of 4-oxo-1,3-benzoxazinium
perchlorates II [1, 2] by the action of hydrazine hy-
drate (Scheme 1) [3]. Their molecules possess several
nucleophilic centers, and therefore their reactions with
various electrophilic reagents attract interest. Substitut-
ed 1,2,4-triazoles are biologically active substances;
antitumor [4, 5], antifungal [6], sedative [7], tranquiliz-
ing [8], analgesic, and antihypoxic agents [8] were
found among 1,2,4-triazole derivatives.
gas phase, according to which the most energetically
favorable is tautomer A (the energies of formation of
tautomers A–C are –609655.52, –609644.72, and
–609655.02 kcal/mol, respectively).
In the present work we examined reactions of
1,2,4-triazoles I with chloroacetonitrile. Taking into
account that triazoles I in solution could give rise to
equilibrium mixtures of tautomers A–C, the alkylation
process may involve different nitrogen atoms in
molecule I with formation of isomeric structures D–F
(Scheme 2). By treatment of 1,2,4-triazoles Ia–Id with
chloroacetonitrile in acetone in the presence of potas-
sium carbonate according to standard procedure (1.5 h
under reflux) we obtained compounds IIIa–IIId
(Scheme 3) whose structure was determined on the
basis of their elemental compositions and IR, NMR,
and mass spectra. The structure of triazole IIIc was
unambiguously proved by X-ray analysis (Fig. 1).
Scheme 1.
R
H
O
O
N
N2H4 ·H2O
AcOH
NH
N
ClO4
N
H
O
R
IIa–IIf
Ia–If
R = Me (a), PhCH=CH (b), 4-MeOC6H4CH=CH (c), 2-(2-thienyl)-
vinyl (d), 4-BrC6H4CH=CH (e), 4-FC6H4CH=CH (f).
The IR spectra of N-cyanomethyl-1,2,4-triazoles
IIIa–IIId contained medium-intensity absorption
bands in the region 1690–1550 cm–1, which were
assigned to vibrations of the triazole and benzene
rings, while no absorption typical of cyano group
(2100–2200 cm–1) was observed. In the 1H NMR spec-
tra of IIIa–IIId, protons in the exocyclic methylene
group resonated as a singlet at δ 5.62–5.81 ppm, which
The formation of just 5-(2-hydroxyphenyl)-1H-
1,2,4-triazoles A rather than other isomeric structures
B and C (Scheme 2) was proved previously [9] and
was confirmed by the 13C NMR data and DFT
B3LYP/6-31G* quantum-chemical calculations for the
1079

SHASHEVA et al.
1080
Scheme 2.
R
R
H
H
O
H
O
O
N
N
N
N
N
NH
R
N
H
N
H
N
A
B
C
R'Cl
R'Cl
R'Cl
R
R
N
H
H
H
O
O
O
N
N
N
N
N
N
R
R'
N
N
R'
R'
D
E
F
R = Me, ArCH=CH, HtCH=CH; R′ = CH2CN.
was absent in the spectra of initial triazoles Ia–Id. In
the downfield region of the spectrum we observed only
one singlet at δ 10.66–10.86 ppm, belonging to the
phenolic hydroxy group.
spin coupling with the 6-H proton in the hydroxyphen-
yl group; its signal was a doublet at δC 160.73 ppm
(3J = 4.2 Hz). The C5 atom in the triazole ring gave rise
to a multiplet at δC 154.16 ppm due to long-range
couplings with the 5-CH and CH2 protons (2J = 5.2,
3J = 1.9 Hz).
Scheme 3.
R
H
O
OMe
ClCH2CN
N
K2CO3, Me2CO
N
Ia–Id
CH2CN
C5, δC 154.16 ppm, m
2J = 5.2 Hz
3J = 1.9 Hz
N
IIIa–IIId
OH
N
R = Me (a), PhCH=CH (b), 4-MeOC6H4CH=CH (c),
2-(2-thienyl)vinyl (d).
N
CH2CN
N
C3, δC 160.73 ppm, d
3J = 4.2 Hz
The structure of N-cyanomethyl-1,2,4-triazole IIIc
was also studied by 13C NMR spectroscopy. The C3
atom in the triazole ring displayed long-range spin–
IIIc
The X-ray diffraction data for a single crystal of
IIIc indicated formation of intramolecular hydrogen
bond between the N3 atom in the triazole ring and
hydrogen atom in the phenolic hydroxy group
[d(H···N) = 1.77 Å], which stabilized coplanar ar-
rangement of the 2-hydroxyphenyl substituent and
1,2,4-triazole ring plane (Fig. 1). The principal bond
lengths and bond angles in molecule IIIc are given in
table.
C4
C3
C5
C6
O1
C2
C1
C14
C13
N3
C10
C15
C16
C7
N1
C12
C19
C11
N2
N4
C17 O2
C8
C9
C18
It is known that alkylation of 1,2,4-triazoles in
alkaline medium usually gives the corresponding
1-alkyl-substituted derivatives [10], i.e., products like
D are commonly formed from tautomer A. In our case,
products with structure F were isolated exclusively
(Scheme 2). Presumably, in the reactions of triazoles
Fig. 1. Structure of the molecule of {3-(2-hydroxyphenyl)-5-
[2-(4-methoxyphenyl)vinyl]-1H-1,2,4-triazol-1-yl}acetoni-
trile (IIIc) according to the X-ray diffraction data.
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SYNTHESIS AND PROPERTIES OF SUBSTITUTED [3-(2-HYDROXYPHENYL)-...
1081
Principal bond lengths (d) in the molecule of {3-(2-hydroxy-
phenyl)-5-[2-(4-methoxyphenyl)vinyl]-1H-1,2,4-triazol-1-
yl}acetonitrile (IIIc) according to the X-ray diffraction data
and quantum-chemical calculations (italic numbers)
Ia–Id with chloroacetonitrile the direction of electro-
philic attack changes due to effect of substituent in the
triazole ring. Insofar as the alkylation of Ia–Id was
carried out in alkaline medium (Scheme 3) in the pres-
ence of 4 equiv of potassium carbonate, the substrates
reacted as the corresponding anions IVa–IVd, and just
the structure of the latter should be responsible for the
direction of electrophilic attack. In order to verify this
assumption we performed quantum-chemical calcula-
tions of the electronic and steric structure and relative
stabilities of conformers of anion IVa in terms of
the density functional theory (DFT) using B3LYP/
6-311++G** basis set. The results showed that struc-
tures IVa and IVa′ (Fig. 2) occupy minima on the
potential energy surface (PPE). Conformers IVa and
IVa′ are almost equally stable: the difference in their
energies calculated with correction for zero-point
vibration energy was ΔEZPE = 1.26 kcal/mol, and the
total energies were –368654.15 and –368655.36 kcal×
mol–1 for compounds IVa and IVa′, respectively. The
least harmonic vibration frequencies were ω1 = 65
(IVa) and 66 cm–1 (IVa′). The calculated negative
charge (natural bond orbital approximation) on the N2
atom in anion IVa (–0.385 a.u.) is slightly greater than
the charge on N1 (–0.374 a.u.). This factor may be
responsible for the alkylation at N2. Anion IVa′ is
characterized by the opposite charge distribution over
N1 and N2, but strong intramolecular hydrogen bond
between the N1 atom and hydroxy group (H···N1
1.537 Å) is likely to hamper electrophilic substitution
at that center, so that the alkylation also occurs at N2.
The alkylation of IVa and IVa′ at position 4 of the
triazole ring (N3) is hardly probable; this reaction
direction is not consistent with the recent data on the
alkylation of 1,2,4-triazoles [10].
Bond
d, Å
Bond
d, Å
Bond
d, Å
N4–C9 1.144(4) C5–C6 1.389(4) C13–C14 1.386(3)
1.160 1.402 1.404
C8–C9 1.467(4) C4–C5 1.380(4) C14–C15 1.391(3)
1.474 1.388 1.394
N2–C8 1.445(3) C3–C4 1.394(4) C15–C16 1.385(4)
1.450 1.404 1.400
N1–N2 1.365(3) C2–C3 1.400(3) C16–C17 1.391(4)
1.364 1.417 1.407
N1–C1 1.326(3) O1–C3 1.361(3) C17–C18 1.378(4)
1.331
1.351
1.383
N3–C1 1.371(3) O1–H
0.9405 C13–C18 1.403(4)
1.371
1.412
N3–C10 1.333(3) C10–C11 1.442(3) O2–C16 1.367(3)
1.331 1.450 1.359
N2–C10 1.361(3) C11–C12 1.328(3) O2–C19 1.431(3)
1.367 1.352 1.359
C1–C2 1.458(3) C11–H 0.9300 C19–H 0.9600
1.463
C2–C7 1.409(3) C12–C13 1.459(3) C8–H
0.9700
1.407 1.459
C6–C7 1.378(4) C12–H 0.9300 C14–H 0.9300
1.387
1,2,4-triazoles IIIe and IIIf and isobutylene deriva-
tives Va and Vb. The latter were formed as a result of
condensation of acetone at the activated exocyclic
methylene group in triazoles III. According to the
1H NMR data, the product ratios were IIIe :Va =
0.40:0.60 and IIIf:Vb = 0.32:0.68. By heating mix-
tures IIIe/Va and IIIf/Vb in boiling acetone in the
presence of potassium carbonate for an additional 1 h
The alkylation of triazoles Ie and If containing
a fluorine or bromine atom in the arylvinyl fragment
gave mixtures of the corresponding N-cyanomethyl-
1.637 Ǻ
–0.437
–0.377
1.663 Ǻ
–0.374
–0.385
Fig. 2. Structures of conformers IVa and IVa′ and charges on some atoms, according to quantum-chemical calculations.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

SHASHEVA et al.
1082
Scheme 4.
R
R
H
H
O
O
Me
CN
N
N
K2CO3, Me2CO
Me2CO
N
N
Me
Id, If
+
ClCH2CN
CH2CN
N
N
IIIe, IIIf
Va, Vb
IIIe, Va, R = 4-BrC6H4CH=CH; IIIf, Vb, R = 4-FC6H4CH=CH.
we obtained pure compounds Va and Vb (Scheme 4).
Isobutylene derivative Vc (R = 4-MeOC6H4CH=CH)
having an electron-donating group in the arylvinyl
fragment was obtained by heating triazole Ic in boiling
acetone in the presence of potassium carbonate over
a period of 1.5 h.
B3LYP/6-31G* basis set. The calculations revealed
some differences in the thermodynamics of the trans-
formation I→III (Scheme 5) for triazoles having dif-
ferent arylvinyl substituents. The substitution reaction
Ic →IIIc (R = 4-MeOC6H4CH=CH) is exothermic,
while analogous transformation If → IIIf (R =
4-FC6H4CH=CH) is endothermic (Fig. 3). The same
results were obtained by ab initio calculations with
6-31G* basis set. Presumably, this is the reason why
we failed to isolate fluoro derivative IIIf as individual
substance. The subsequent addition of acetone to com-
pounds III with formation of adducts VI is exothermic
in both cases (Fig. 4).
With a view to elucidate specificities of the
structure and mechanism of formation of isobutylene
derivatives Va–Vc (Scheme 5), compounds Ic (R =
4-MeOC6H4CH=CH) and If (R = 4-FC6H4CH=CH)
and products of their transformations were analyzed
by DFT quantum-chemical calculations using
1
0.8
Scheme 5.
0.6
0.4
0.2
R
OH
Me
CN
N
OH
Me
ClCH2CN
Me2CO
2
N
0.0
I
III
N
–0.2
–0.4
–0.6
VI
V
–0.8
–1.0
–H2O
Reaction coordinate
Comparison of the results of quantum-chemical cal-
Fig. 3. Thermodynamic effects in the transformations I→III
(Scheme 5) according to quantum-chemical calculations:
(1) R = 4-FC6H4CH=CH, (2) R = 4-MeOC6H4CH=CH.
culations on N-cyanomethyl-1,2,4-triazole IIIc with the
X-ray diffraction data (see table) showed a good agree-
ment between the calculated and experimental geo-
metric parameters, indicating proper choice of the cal-
culation scheme.
0.0
–0.4
–0.8
–1.2
The structure of compounds Va–Vc was confirmed
1
by the data of elemental analysis and IR and H NMR
spectroscopy. The IR spectra of Va–Vc contained
absorption bands in the region 1730–1500 cm–1 due to
stretching vibrations of the C=C bond in the isobutyl-
ene fragment, C=C bond conjugated with the phenyl
group, and double bonds in the azole and benzene
rings. Unlike N-cyanomethyl-1,2,4-triazoles IIIa–IIIf,
2
–1.6
1
–2.0
–2.4
1
Reaction coordinate
compounds Va–Vc displayed in the H NMR spectra
two three-proton singlets from methyl groups in the
region δ 1.79–2.34 ppm, while no singlet at δ 5.62–
5.81 ppm was present (CH2).
Fig. 4. Thermodynamic effects in the transformations III→V
(Scheme 5) according to quantum-chemical calculations:
(1) R = 4-FC6H4CH=CH, (2) R = 4-MeOC6H4CH=CH.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

SYNTHESIS AND PROPERTIES OF SUBSTITUTED [3-(2-HYDROXYPHENYL)-...
1083
Apart from activated methylene group, 1,2,4-tri-
azoles IIIa–IIIf possess a cyano group whose func-
tionalization could lead to novel polyheterocyclic
systems. However, our attempt to effect condensations
of N-cyanomethyl-1,2,4-triazoles at the cyano group
with o-phenylenediamine or carboxylic acid hydra-
zides under standard conditions were unsuccessful, and
the initial reactants were recovered from the reaction
mixtures.
b. Potassium hydroxide, 0.56 g (10 mmol), was
added to a solution of 1.75 g (10 mmol) of compound
Ia in 3 ml of DMF, the mixture was heated for 1.5 h on
a water bath and diluted with water, and the precipitate
was filtered off and purified by recrystallization. Yield
2.57 g (38%), colorless crystals, mp 140–142°C (from
butan-1-ol). IR spectrum, ν, cm–1: 1660, 1620, 1590
1
(C=Carom, C=N). H NMR spectrum, δ, ppm: 2.59 s
(3H, CH3), 5.62 s (2H, CH2), 6.92–7.78 m (4H, Harom),
10.80 s (1H, OH). Found, %: C 61.30; H 4.80; N 25.60.
C11H10N4O. Calculated, %: C 61.68; H 4.67; N 26.17.
EXPERIMENTAL
[3-(2-Hydroxyphenyl)-5-(2-phenylvinyl)-1H-
1,2,4-triazol-1-yl]acetonitrile (IIIb). Yield 1.69 g
(56%). Colorless crystals, mp 170–172°C (from
1-BuOH). IR spectrum, ν, cm–1: 1610, 1600, 1590
The IR spectra were recorded on a Specord 75IR
spectrometer from samples dispersed in mineral oil.
1
The H and 13C NMR spectra were measured on
a Varian Unity-300 instrument (300 MHz) at 20°C
using DMSO-d6 as solvent. The mass spectra (electron
impact, 70 eV) were obtained on a VG 7070E mass
spectrometer.
1
(C=Carom, C=N). H NMR spectrum, δ, ppm: 5.81 s
(2H, CH2), 6.92 d and 7.78 d (2H, CH=CH, J =
8.6 Hz), 6.89–7.98 m (9H, Harom), 10.74 s (1H, OH).
Mass spectrum, m/z (Irel, %): 302 (99) [M]+, 233 (5),
204 (3), 155 (4), 147 (10), 128 (34), 115 (72), 105
(35), 91 (67), 76 (76), 63 (51), 51 (94), 38 (62). Found,
%: C 71.90; H 4.20; N 18.10. C18H14N4O. Calculated,
%: C 71.52; H 4.64; N 18.54. M 302.22.
The synthesis of perchlorates IIa–IIf was described
previously [1, 2], and 1,2,4-triazoles Ia–If were pre-
pared according to the procedure reported in [3].
2-(3-Methyl-1H-1,2,4-triazol-5-yl)phenol (Ia)
was obtained by heating 2-methyl-4-oxo-1,3-benzoxa-
zinium perchlorate with hydrazine hydrate in glacial
acetic acid according to the procedure described in
[2]. 13C NMR spectrum, δC, ppm: 12.92 q (Me, J =
129.2 Hz), 114.51 m (Carom), 117.6 m (Carom), 120.05 m
(Carom), 127.08 d (Carom, J = 5.6 Hz), 131.58 m (Carom),
155.09 q (C3, J = 7.3 Hz), 157.10 m (Carom), 158.55 m
(C5, 2J = 5.2 Hz).
{3-(2-Hydroxyphenyl)-5-[2-(4-methoxyphenyl)-
vinyl]-1H-1,2,4-triazol-1-yl}acetonitrile (IIIc). Yield
1.83 g (55%). Colorless crystals, mp 175°C (from tol-
uene). IR spectrum, ν, cm–1: 1670, 1610, 1510 (C=C,
1
C=Carom, C=N). H NMR spectrum, δ, ppm: 3.82 s
(3H, OCH3), 5.69 s (2H, CH2), 6.89–8.00 m (10H,
H
arom, CH=CH), 10.86 s (1H, OH). 13C NMR spec-
trum, δC, ppm: 37.27 t (1C, CH2, J = 151.1 Hz),
56.18 q (1C, OCH3, J = 144.6 Hz), 108.46 d (1C,
CH=CH, J = 7.1 Hz), 114.32 d (1C, Carom, J = 7.7 Hz),
115.23 t (1C, CH, J = 8.81 Hz), 115.24 m (1C, Carom),
116.05 m (1C, Carom), 117.96 m (1C, Carom), 120.43 m
(1C, Carom), 127.55 t (1C, Carom, J = 6.8 Hz), 128.57 m
(1C, Carom), 130.49 m (2C, Carom), 132.31 m (1C,
[3-(2-Hydroxyphenyl)-5-methyl-1H-1,2,4-triazol-
1-yl]acetonitrile (IIIa). a. Triazole Ia, 1.75 g
(10 mmol), was dissolved in 30 ml of acetone, 5.52 g
(40 mmol) of calcined potassium carbonate was added,
the mixture was heated for 20–25 min and cooled,
0.76 g (10 mmol) of chloroacetonitrile was added, and
the mixture was heated for 1.5 h under reflux and
diluted with water. The precipitate was filtered off and
recrystallized. Yield 3.92 g (58%), colorless crystals,
mp 140–142°C (from 1-BuOH). IR spectrum, ν, cm–1:
1660, 1620, 1595 (C=Carom, C=N). 1H NMR spectrum,
δ, ppm: 2.59 s (3H, CH3), 5.62 s (2H, CH2), 6.92–
7.78 m (4H, Harom), 10.80 s (1H, OH). Mass spectrum,
m/z (Irel, %): 214 (77) [M]+, 186 (5), 145 (36), 119
(15), 105 (49) , 91 (34) ,76 (56), 63 (32), 50 (35), 42
(70), 39 (100). Found, %: C 62.00; H 4.90; N 25.80.
C11H10N4O. Calculated, %: C 61.68; H 4.67; N 26.17.
M 214.14.
C
arom), 139.57 m (1C, CH=CH), 154.16 m (1C, C5, 2J =
3
5.2, J = 1.9 Hz), 157.28 m (1C, COMe), 160.73 d
(1C, C3, J = 4.21 Hz), 161.55 m (1C, COH). Mass
spectrum, m/z (Irel, %): 331 (100) [M]+, 317 (5), 301
(7), 292 (20), 159 (18), 145 (24), 119 (25), 105 (31),
77 (38), 51 (33). Found, %: C 68.10; H 5.20; N 16.30.
C19H16N4O2. Calculated, %: C 68.67; H 4.82; N 16.87.
M 331.23.
{3-(2-Hydroxyphenyl)-5-[2-(2-thienyl)vinyl]-1H-
1,2,4-triazol-1-yl}acetonitrile (IIId). Yield 1.51 g
(49%). Colorless crystals, mp 169–171°C (from tol-
uene). IR spectrum, ν, cm–1: 1630, 1590, 1520 (C=C,
Compounds IIIb–IIId were synthesized in a simi-
lar way.
1
C=Carom, C=N). H NMR spectrum, δ, ppm: 5.71 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

SHASHEVA et al.
1084
(2H, CH2), 6.81–7.99 m (9H, Harom, CH=CH), 10.66 s
(1H, OH). Found, %: C 62.10; H 3.20; N 18.30.
C16H12N4OS. Calculated, %: C 62.34; H 3.90; N 18.18.
IR spectrum, ν, cm–1: 1730 (Me2C=C); 1640, 1610,
1510 (C=C, C=Carom, C=N). H NMR spectrum, δ,
ppm: 2.34 s and 2.48 s (3H each, Me), 3.82 s (3H,
OMe), 6.91–8.00 m (10H, Harom, CH=CH), 10.87 s
(1H, OH). Found, %: C 71.10; H 5.00; N 15.20.
C21H18N4O3. Calculated, %: C 70.97; H 5.38; N 15.05.
1
2-{5-[2-(4-Bromophenyl)vinyl]-3-(2-hydroxy-
phenyl)-1H-1,2,4-triazol-1-yl}-3-methylbut-2-ene-
nitrile (Va). 2-{3-[2-(4-Bromophenyl)vinyl]-1H-1,2,4-
triazol-5-yl}phenol (Id), 3.43 g (10 mmol), was dis-
solved in 30 ml of acetone, 5.52 g (40 mmol) of
calcined potassium carbonate was added, the mixture
was heated for 15 min under reflux and cooled, 0.76 g
(10 mmol) of chloroacetonitrile was added, and the
mixture was heated for 2.5 h under reflux and diluted
with water. The colorless precipitate was filtered off
and recrystallized. Yield 2.74 g (65%), mp 196–198°C
(from MeCN). IR spectrum, ν, cm–1: 1690 (Me2C=C);
This study was performed under financial support
by the program “Development of Scientific Potential at
Higher School” (project no. 2.1.1./2371).
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4. Tkisler, A., Usunanali, E., and Demirbas, A., Ind. J.
Pharm. Sci., 2000, vol. 62, p. 371.
2-{5-[2-(4-Fluorophenyl)vinyl]-3-(2-hydroxy-
phenyl)-1H-1,2,4-triazol-1-yl}-3-methylbut-2-ene-
nitrile (Vb) was synthesized in a similar way. Yield
2.14 g (59%), colorless crystals, mp 198–200°C (from
MeCN). IR spectrum, ν, cm–1: 1690 (C=C); 1640,
5. Chernyshev, V.M., Zemlyakov, N.D., Taranushich, V.A.,
and Rakitov, E.A., Zh. Prikl. Khim., 1999, vol. 72,
p. 1688.
6. Vartanyan, R.S., Sintez osnovnykh lekarstvennykh
sredstv (Synthesis of Main Medicinals), Moscow: Med.
Inform. Agentstvo, 2005, p. 744.
1
1560, 1500 (C=C, C=Carom, C=N). H NMR spectrum,
7. Arzamastsev, A.P., Farmatsevticheskaya khimiya
(Pharmaceutical Chemistry), Moscow: GEOTAR-
Media, 2005, p. 484.
δ, ppm: 1.79 s and 2.34 s (3H each, Me), 6.79–7.97 m
(10H, Harom, CH=CH), 10.57 s (1H, OH). Found, %:
C 70.10; H 4.20; N 15.30. C21H17FN4O. Calculated, %:
C 70.00; H 4.72; N 15.56.
8. Ryabukhin, Yu.I., Doctoral (Chem.) Dissertation,
Rostov-on-Don, 1991.
2-{3-(2-Hydroxyphenyl)-5-[2-(4-methoxyphenyl)-
vinyl]-1H-1,2,4-triazol-1-yl}-3-methylbut-2-ene-
nitrile (Vc). Compound IIIc, 10 mmol, was dissolved
in 30 ml of acetone, 5.52 g (40 mmol) of potassium
carbonate was added, the mixture was heated for 1.5 h
under reflux and diluted with water, and the precipitate
was filtered off and recrystallized. Yield 1.61 g (43%),
light brown crystals, mp 186–187°C (from 1-BuOH).
9. Kompan, O.E., Gerr, R.G., Struchkov, Yu.T., Falee-
va, L.N., Ryabukhin, Yu.I., and Olekhnovich, L.P.,
Khim. Geterotsikl. Soedin., 1989, p. 109.
10. Grimmett, M.R., Comprehensive Organic Chemistry,
Barton, D. and Ollis, W.D., Eds., Oxford: Pergamon,
1979, vol. 4. Translated under the title Obshchaya
organicheskaya khimiya, Moscow: Khimiya, 1985,
vol. 8, p. 453.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010