Structure of reaction products of substituted [1,3]thiazolo[3,2-b][1,2,4] triazol-6(5H)-ones with amines and hydrazines

Article abstract of DOI:10.1134/S1070428013110201

Reactions of 2-(4-methylphenyl)[1,3]triazolo[3,2-b][1,2,4]thiazol-6(5H)-one and 5-benzylidene-2-(4- methylphenyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)- one with amines and hydrazines of diverse structures were studied. The structure of the reaction pro

Full text of DOI:10.1134/S1070428013110201

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 11, pp. 1680−1685. © Pleiades Publishing, Ltd., 2013.
Original English Text © A.A. Rzhevskii, N.P. Gerasimova, Zh.V. Chirkova, S.I. Filimonov, S.I. Firgang, G.A. Stashina, K.Yu. Suponitsky, 2013, published in
Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 11, pp. 1697−1702.
Structure of Reaction Products of Substituted
[1,3]Thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones with Amines
and Hydrazines
A. A. Rzhevskiia, N. P. Gerasimovaa, Zh. V. Chirkovaa, S. I. Filimonova,
S. I. Firgangb, G. A. Stashinab, and K. Yu. Suponitskyc
aYaroslavl’State Technical University, Yaroslavl, 150023 Russia
e-mail: filimonovsi@ystu.ru
bZelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia
cNesmeyanov Institute of Organoelemental Compounds, Russian Academy of Sciences, Moscow, Russia
Received June 7, 2013
Abstract—Reactions of 2-(4-methylphenyl)[1,3]triazolo[3,2-b][1,2,4]thiazol-6(5H)-one and 5-benzylidene-2-(4-
methylphenyl)[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one with amines and hydrazines of diverse structures were
studied. The structure of the reaction products was established.
DOI: 10.1134/S1070428013110201
The development of preparation methods of new
derivatives of 1,2,4-triazolethiones is an urgent problem
since these compounds possess a wide range of physi-
ological activity exhibiting analgesic, vasodilatory, anti-
tumor, bactericidal, and sedative action [1–3].
3,3a-dihydro-2H-pyrazolo[3’,4’:4,5][1,3]thiazolo[3,2-b]
[1,2,4]triazoles [11].
We formerly proved for the first time by XRD method
by an example of 5-(4-methylphenyl)-2,4-dihydro-3Н-
1,2,4-triazole-3-thione that the cyclocondensation of
triazolethiones with haloacetic acids proceeded regiospe-
cifically with the formation of 2-(4-methylphenyl)[1,3]
thiazolo[3,2-b][1,2,4]triazol-6(5H)-one (I) and not the
isomeric 3-(4-methylphenyl)[1,3]thiazolo[2,3-c][1,2,4]
triazol-5(6H)-one [12]. In the present study we examined
the structures of the products of the reactions of [1,3]
thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones and 5-benzyli-
dene[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones with
diverse amines (primary and secondary, cycloaliphatic
and heterocyclic) and hydrazines. As model compounds
substances I, II were used.
Aspecial interest is directed to the chemical properties
of [1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones obtained
by a cyclocondensation of 1,2,4-triazole-3-thiones with
haloacetic acids, and also of the reaction products of the
latter with aldehydes, 5-benzylidene[1,3]thiazolo[3,2-b]
[1,2,4]triazol-6(5H)-ones. The published data on the
reactions of these heterocyclic systems with amines of
various structures are ambiguous. It is reported in [4, 5]
on the opening of the lactam ring of the [1,3]thiazolo[3,2-
b][1,2,4]triazol-6(5H)-ones under the action of aromatic
amines and hydrazines with the formation of the cor-
responding thioacetamides. In the reaction of 5-benzyli-
dene[1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones with
secondary amines no opening of te lactam ring occurs,
and the products of Michael 1,4-addition are formed
where an intramolecular hydrogen bond exists between
the nitrogen atom of the added amine and the proton of the
enol hydroxy group [6–10]. Aprolonged heating of [1,3]
thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones with substituted
hydrazines in acetic acid resulted in tricyclic compounds,
The reactions of compound I in dioxane with amines
(piperidine, morpholine, cyclohexylamine, pyridin-3-
ylmethanamine) and hydrazine hydrate at room tempera-
ture, and with 3-(trifluoromethyl)aniline at boiling led to
the rupture of the С–N bond of the lactam ring and to the
formation of the corresponding amides of thioacetic acid
IIIа–IIIf in 77–91% yields. The reactions of compound II
with hydrazines, primary and secondary amines at room
temperature in dioxane afforded three different com-
1680

STRUCTURE OF REACTION PRODUCTS
1681
H
N
H
n-Tol
n-Tol
n-Tol
N
N
N
N
OH
O
N
S
O
N
N
N
H
N
R
n-Tol
R
S
S
N
R
N
NH
O
N
R
S
IIIa_IIIf
Va, Vb
IVa, IVb
VIа, VIb
H
N
n-Tol
H
N
N
n-Tol
n-Tol
n-Tol
N
N
N
O
N
O
O
N
N
S
O
N
N
N
OH
S
OH
S
S
VII
I
VIII
II
III, R = N(CH2CH2)2CH2 (a), N(CH2CH2)2O (b), NHCH(CH2)5 (c), Py-3-CH2NH (d), NHNH2 (e), 3-CF3C6H4NH (f); IV, R =
N(CH2CH2)2CH2 (a), N(CH2CH2)2O (b); V, R = NHCH(CH2)5 (a), Py-3-CH2NH (b); VI, R = H (a), 4-CH3OC6H4 (b).
pounds IV–VI, whose structure was established from the
combination of IR, NMR, and mass spectra. No reaction
occurred with aromatic amines even at prolonged boiling.
group of the enol form may appear in the same region
1
(3200–3100 cm–1), and in the Н NMR spectrum the
proton signals of these groups are observed in a weak
field (14.0–14.5 ppm) and easily exchange with water
present in the deuterated solvent. Attempting to clear
the structure of compound IVa we registered 2D spectra
ROESY and HMBC, but due to the formation of a strong
intramolecular hydrogen bond between the nitrogen atom
of the piperidine fragment and the enol proton of the OH
group we failed to obseve the expected cross-peaks of the
aliphatic protons (the proton signals from the СН2 group
were observed as five broadened singlets). This hydrogen
bond is absent in compound Va indicating the formation
of the corresponding amide derivative as confirms the
presence in the 1Н NMR spectrum of the signals of the
amide hydrogen (7.88 ppm) in the form of a broadened
doublet (J 3.3 Hz). The structure of compound Va was un-
ambiguously proved by XRD analysis. The general view
of the molecule of compound Va is shown in the figure.
1
In the Н NMR spectra of compounds IIIа–IIIf a
characteristic downfield signal is observed from the
proton of the NH group of the triazole ring in the region
14.0–14.5ppm, which due to the prototropic ring tautom-
erism [13] appears as two contiguous broadened singlets.
In the spectra of compounds IIIа, IIId, IIIf, Va, Vb, VIa
an expected signal of the amide proton is observed. Under
the electron impact compounds III–VI give as a rule the
most intensive ions corresponding to the fragment of the
lactam ring [319+ (II)], or to the thiazole fragment formed
at the rupture of the S–C bond (191+).
In order to refine the data on the structure of addition
products of amines and hydrazines the alkaline hydro-
lysis was performed of compounds I, II providing the
corresponding derivatives of thioacetic acids VII, VIII.
1
The Н NMR spectra of compounds VII, VIII contain
characteristic signals of CH2 and =CH– groups in the
regions 3.94 and 8.09 ppm respectively, and also of the
protons of NH groups in the region 14.0–14.5 ppm and
СООН in the region 12.5–13.0 ppm.
All aromatic rings in the molecule are planar, the
cyclohexane fragment is present in the usual chair con-
formation. The toluene and triazole fragments are located
in the same plane and are conjugated, as indicates the
length of the C2–C3 bond (see the table) that is somewhat
shorter than the average value for the conjugated systems
(1.476 Å) [14]. The distribution of the bond lengths in the
triazole shows precisely that the proton is bound to the
The structure of the reaction products obtained with
the substrate II was difficult to establish unambiguously
using only spectral data since in the IR spectra the bands
of the NH groups of the triazole ring and of the OH
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

RZHEVSKII et al.
1682
General view of the molecule N-cyclohexyl-2-{[5-(4-
methylphenyl)-1H-1,2,4-triazol-3-yl]sulfanyl}-3-phenylprop-
2-enamide (Va) the atoms presented as thermal ellipsoids of
50% probability
Bond
Length, Å
Bond
Length, Å
N4–C18
C10–C18
C10–C11
C11–C12
C2–C3
1.330(2)
1.509(2)
1.345(2)
1.472(2)
1.467(2)
N1–C1
N2–C1
N2–N3
N3–C2
N1–C2
1.363(2)
1.325(2)
1.364(2)
1.349(2)
1.334(2)
atom N3, as has been localized from the difference map of
the electron density. The fragment N4–C18(O1)–C10=C11 is
planar and is not conjugated with the benzene ring, the tor-
sion angle С10С11С12С13 is –143.0(2)°. The conjugation
is however absent also in this planar fragment: The bond
С10–С18 (see the table) is considerably longer then the
average value for the conjugated systems (1.464 Å [14]).
The N4 and O1 atoms of the amide group are involved
in the formation of hydrogen bonds. The intramolecular
hydrogen bond N4–H4⋯N1 [N⋯N 3.022(2), H⋯N 2.18 Å,
NHN angle 156°] apparently stabilizes the conformation
observed in the crystal structure of compound Va. The
bond N3–H3⋯O1 [N⋯O 2.732(2), H⋯O 1.83 Å, NHO
angle 176°] connects the molecules into chains parallel
to the b axis. The other intermolecular interactions in the
crystals are governed by the van der Waals forces.
Lengths of some bonds in compound Va
reactions with amines form reaction products of diverse
structures in keepimg with the nature and the structure
of the reagent. In the reaction of 5-benzylidene[1,3]
thiazolo[3,2-b][1,2,4]triazol-6(5H)-one (II) with sec-
ondary amines stable structures IV are formed without
the opening of the lactam ring; these structures may be
regarded as intramolecular zwitter-ions. In reactions
with primary amines and hydrazines the lactam ring is
openedwith the formation of the corresponding amides V
and pyrazolidones VI. Amides III are formed also in the
reactions between amines of various nature and hydrazine
and [1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-one (I).
In the 1Н NMR spectrum of compound VIа obtained
by the reaction of compound II with hydrazine hydrate
гиdраtоm signals of four protons are observed in a wide
range of chemical shifts (4.3–9.7 ppm), and three among
them are connected in pairs by common vicinal coupling
constants. It indicates the formation of a pyrazolidone
EXPERIMENTAL
NMR spectra were registered on a spectrometer Bruker
DRX-500 [500.13 (1H), 125.75 MHz (13C)] in DMSO-d6
at 30°С.As internal reference for measuring the chemical
shifts was used the signal of tetramethylsilane (Institute
of Organic Chemistry, Russian Academy of Sciences,
Moscow). The registering of 2D spectra was carried out
by standard Bruker procedures.
ring with the prevalence of the keto form. In the spectrum
of compound VIb only signals of two protons appear as
a doublet and a triplet, and the downfield signal is ab-
sent. It means that in the formed pyrazolidone ring the
para-methoxyphenyl substituent is attached to the amide
nitrogen atom.
Mass spectra were measured on a GC-MS instrument
Finnigan MAT INCOS 50, electron impact, ionizing
electrons energy 70 eV, ionizing chamber temperature
100–220°С (Institute of Organic Chemistry, Russian
Academy of Sciences, Moscow).
It is presumable from the existing spectral data that
the formation of compounds VIа, VIb occurs primarily
by 1,4-addition of hydrazine along Michael reaction fol-
lowed by the opening of the lactam ring and simultaneous
cyclization to pyrazolidone. The first stage of the reaction
apparently proceeds analogously to the conversion of
compound II into IV.
IRspectrawererecordedonaFourierspectrophotometer
Perkin Elmer in the range 700–4000 cm–1 from mulls of
substances in mineral oil between KBr plates.
XRD analysis was carried out in the Institute of
Organoelemental Compounds, Russian Academy
Thus it was shown by the example of compounds I,
II that [1,3]thiazolo[3,2-b][1,2,4]triazol-6(5H)-ones in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

STRUCTURE OF REACTION PRODUCTS
1683
of Sciences, Moscow. The experimental intensity
of reflections were measured on a diffractometer
Smart Apex2 CCD, λ(MoKα) 0.71073 Å, graphite
monochromator, ω-scanning at 100 K. The processing
of the arrays of the measured intensities was performed
along the programAPEX2. The structures were solved by
the direct method and refined by full-matric least-squares
method in the anisotropic approximation for nonhydrogen
atoms with respect to F2hkl. The hydrogen atoms were
placed in the geometrically calculated positions and
refined in the rider model [Uiso(H) = nUeq(C)], where
n = 1.5 for carbon atoms of methyl groups, 1.2 for the
other carbon atoms. The solution and refining of the
structure were carried out by SHELXTL software. The
X-ray structural analysis data have been deposited in
the Cambridge Crystallographic Data Center (CCDC
no. 972922).
m/z (Irel, %): 318 [M]+ (20), 191 (94), 128 (54), 118 (63),
117 (50), 86 (100), 56 (58). Found, %: C 59.47; H 5.62;
N 17.55. C15H18N4O2S. Calculated, %: С 56.59; H 5.70,
N 17.60. M 318.40.
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-N-cyclohexylacetamide (IIIc). Yield 3 g
(91%), mp 207–209°C. IR spectrum, ν, cm–1: 3300 (NH),
1638 (C=О), 1549 (NHC=О). 1Н NMR spectrum, δ, ppm:
1.06 m (1Н, CH2), 1.18 d.t (4Н, CH2, J 10.0 Hz), 1.49 br.d
(1H, CH2, J 11.5 Hz), 1.55–1.63 m (4H, СH2), 2.36 s (3H,
CH3), 3.52 br.s (1H, CHN), 3.82 s (2H, CH2S), 7.31 br.s
(2Н, H3'",5'" ), 7.84 d (2Н, H2'",6'", J 7.9 Hz), 7.97 br.s (1H,
NH), 14.31 br.s (1H, NH). Mass spectrum, m/z (Irel, %):
330 [M]+ (18), 248 (21), 232 (32), 191 (25), 140 (100),
118 (53), 99 (81), 82 (89). Found, %: C 61.27; H 6.82;
N 16.55. C15H18N4O2S. Calculated, %: С 61.79; H 6.71;
N 16.95. M 330.46.
Compounds IIIа–IIIf, IVа, IVb, Vа, V, VIа, VIb.
General procedure. Into a flask equipped with a stirrer
to a solution of 10 mmol of compound I or II in 50 mL
of dioxane was added 12 mmol of primary secondary
amine or hydrazine. The reaction mixture was stirred for
1 h at room temperature (in the case of aromatic amine,
2 h at boiling), then the mixture was poured in water, the
separated precipitate was filtered off, washed with water
on the filter, and dried.
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-N-(pyridin-3-ylmethyl)acetamide (IIId).
Yield 2.95 g (87%), mp 141–144°C. IR spectrum, ν, cm–1:
1
3320 (NH), 1622 (C=О). Н NMR spectrum, δ, ppm:
2.36 s (3H, CH3), 3.95 s (2H, SCH2), 4.33 d (2H, NCH2,
J 5.9 Hz), 7.22 d.d (1Н, H5', J 4.5, J 7.5 Hz), 7.31 d (2Н,
H3'"',5'"', J 8.0 Hz), 7.62 br.d (1Н, H4', J 7.5 Hz), 7.83 d (2Н,
H2'"',6'"', J 8.0 Hz), 8.42 d (1H, H6', J 4.5 Hz), 8.47 br.s
(1H, H2'), 8.77 br.t (1H, NH, J 5.9 Hz), 14,35 s (1H, NH).
Mass spectrum, m/z (Irel, %): 339 [M]+ (98), 325 (21), 266
(15), 231 (22), 205 (73), 192 (74), 191 (20), 172 (21),
162 (32), 149 (54), 135 (55), 118 (84), 108 (53), 107 (56),
92 (62), 91 (100), 88 (27), 65 (84). Found, %: C 59.96;
H 4.96; N 20.55. C11H13N5OS. Calculated, %: С 60.16;
H 5.05; N 20.63. M 339.42.
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-1-(piperidin-1-yl)ethanone (IIIа). Yield
2.43 g (77%), mp 178.5–181.5°C (decomp.). IR spectrum,
1
ν, cm–1: 3159 (NH), 1622 (C=О). Н NMR spectrum,
δ, ppm: 1.43 br.s (2Н, СН2), 1.55 br.s (4Н, СН2), 2.35 s
(3H, CH3), 3.45 br.s (4Н, NCH2), 4.20 br.s (2H, SСH2),
7.31 br.d (2Н, H3'",5'", J 8.0 Hz), 7.85 d (2Н, H2'",6'"
,
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]sul-
fanyl}acetohydrazide (IIIe). Yield 2.18 g (83%), mp
72–75°C. IR spectrum, ν, cm–1: 3307 (NH), 1659 (C=О).
1Н NMR spectrum, δ, ppm: 2.37 s (3H, CH3), 3.82 s
J 8.0 Hz), 14.26 s (1H, NH). Mass spectrum, m/z (Irel, %):
316 [M]+ (24), 191 (23), 126 (100), 118 (19), 116 (16),
112 (20), 97 (81), 91 (17), 83 (92). Found, %: C 60.65;
H 6.26; N 17.68. C16H20N4OS. Calculated, %: С 60.73;
H 6.37; N 17.71. M 316.43.
(1H, SCH2), 4.26 br.s (2H, NH2), 7.30 d (2Н, H3'",5'"
,
J 8.0 Hz), 7.84 d (2Н, H2'",6'", J 8.0 Hz), 9.26 br.s (1H,
NH), 14.23 s (1H, NH). Mass spectrum, m/z (Irel, %):
263 [M]+ (95), 232 (63), 204 (55), 192 (61), 191 (100),
118 (66), 117 (46), 91 (50), 65 (26). Found, %: C 50.08;
H 4.86; N 26.53. C11H13N5OS. Calculated, %: С 50.18;
H 4.98; N 26.60. M 263.32.
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-1-(morpholin-4-yl)ethanone (IIIb). Yield
2.58 g (81%), mp 215–217°C. IR spectrum, ν, cm–1:
1
3157 (NH), 1623 (C=О). Н NMR spectrum, δ, ppm:
2.35 s (3H, CH3), 3.46 t (2Н, СН, J 4.5 Hz), 3.56 t (4Н,
СН2, J 4.5 Hz), 3.62 t (2Н, СН2, J 4.5 Hz), 4.20 br.s
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-N-[3-(trifluoromethyl)phenyl]acetamide
(IIIf). Yield 3.57 g (91%), mp 168–170°C (benzene–
ethanol). IR spectrum, ν, cm–1: 3268, 3208 (NH), 1682
(2H, СH2), 7.32 br.s (2Н, H3'",5'"), 7.86 d (2Н, H2'",6'"
,
J 8.0 Hz), 14.03 s, 14.32 s (1H, NH). 13С NMR spec-
trum, δ, ppm: 20.86, 45.90, 65.90, 125.58, 125.85, 129.23,
129.46, 138.76, 151.81, 160.39, 165.53. Mass spectrum,
1
(C=О), 1556 (NH–C=О). Н NMR spectrum, δ, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

RZHEVSKII et al.
1684
2.35 s (3H, CH3), 4.12 br.s (2H, SСH2), 7.38 br.s (2Н,
H3'"',5'"'), 7.42 br.d (1H, H4', J 7.9 Hz), 7.57 t (1Н, H5',
(1H, С=CH), 7.73 d (2Н, H2',6', J 7.4 Hz), 7.82 d (2Н,
H2''',6''', J 7.7 Hz), 7.88 d (1H, NH, J 3.3 Hz) 14.45 s (1H,
NH). Mass spectrum, m/z (Irel, %): 418 [M]+ (15), 320
[M – (NH – C6H11)]+ (12), 292 [M – (CONH –C6H11)]
(17), 228 (100), 191 (97), 161 (10), 146 (24), 134 (66),
118 (46), 98 (49). Found, %: C 68.75; H 6.19; N 13.33.
C24H26N4OS. Calculated, %: С 68.87; H 6.26; N 13.39.
M 418.57.
J 7.9 Hz), 7.78 br.d (1Н, H6', J 7.9 Hz), 7.83 d (2Н, H2'"',6'"'
,
J 8.0 Hz), 8.08 s (1Н, H2'), 10.63 br.s (1H, NH), 14.13
and 14.39 br.s (1H, NH). Mass spectrum, m/z (Irel, %):
392 [M]+ (20), 232 [M – (NH–C7H4F3)]+ (18), 205 (100),
172 (21), 160 (17), 118 (51), 118 (25), 117 (25), 91 (15).
Found, %: C 54.98; H 3.76; N 14.24. C18H15F3N4OS.
Calculated, %: С 55.10; H 3.85; N 14.28. M 392.41.
2-{[3-(4-Methylphenyl)-1H-1,2,4-triazol-5-yl]
sulfanyl}-N-(pyridin-3-ylmethyl)-3-phenylprop-2-
enamide (Vb). Yield 3.25 g (76%), mp 203–206°C (de-
comp.). IR spectrum, ν, cm–1: 3253 (NH), 1634 (C=О),
1538 (NH-C=О). 1Н NMR spectrum, δ, ppm: 2.37 s (3H,
CH3), 4.35 d (2H, NCH2, J 6.0 Hz), 7.01 d.d (1Н, H5'',
J 4.8, J 7.7 Hz), 7.33 d (2Н, H3''',5''', J 8.0 Hz), 7.40 t (1Н,
H4', J 7.6 Hz), 7.45 d (1Н, H4'', J 7.7 Hz), 7.46 t (2Н,
H3',5', J 7.6 Hz), 7.75 d (2Н, H2'',6'', J 7.6 Hz), 7.80 d (2Н,
H2''',6''', J 8.0 Hz), 7.89 s (1Н, CH=C), 8.31 br.d (1H, H6'',
J 4.7 Hz), 8.40 br.s (1H, H2''), 8.91 t (1H, NH, J 6.0 Hz),
14.22 br.s (1H, NH). Mass spectrum, m/z (Irel, %): 427
[M]+ (36), 395 (15), 336 (17), 319 (24), 237 (100), 191
(57), 134 (47), 118 (44), 92 (79), 80 (40). Found, %:
C 67.35; H 4.88; N 16.32. C24H21N5OS. Calculated, %:
С 67.43; H 4.95; N 16.38. M 427.53.
2-(4-Methylphenyl)-5-[phenyl(piperidin-1-yl)
methyl][1,3]thiazolo[3,2-b][1,2,4]triazol-6-ol (IVa).
Yield 3.75 g (93%), mp 195–197°C (decomp.). IR spec-
trum, ν, cm–1: 3149 (OH), 1599 (C=N). 1Н NMR spec-
trum, δ, ppm: 1.34 br.s (2H, CH2), 1.53 br.s (2H, CH2),
1.59 br.s (2H, CH2) , 2.36 s (3H, CH3), 3.30 br.s (2H,
CH2), 3.64 br.s (2H, SCH2), 6.92 s (1H, NCH), 7.33 d
(2Н, H3',5', J 8.0 Hz), 7.37 t (1H, H4'', J 7.7 Hz), 7.46 t
(2Н, H3'',5'', J 7.7 Hz), 7.63 d (2Н, H2'',6'', J 7.7 Hz), 7.86 d
(2Н, H2',6', J 8.0 Hz). 13С NMR spectrum, δ, ppm: 21.0,
24.08, 24.92, 25.34, 42.37, 48.18, 66.41, 125.91, 129.66,
129.30, 128.53, 128.43, 128.34, 130.65, 134.61, 140.02,
165.28. Mass spectrum, m/z (Irel, %): 404 [M]+ (12), 371
(25), 319 (51), 293 (22), 214 (100), 191 (41). Found, %:
C 68.17; H 5.90; N 13.82. C23H24N4OS. Calculated, %:
С 68.29; H 5.98; N 13.85. M 404.54.
4-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-5-phenylpyrazolidin-3-one (VIа). Yield
3.02 g (86%), mp 168.5–171°C (decomp.). IR spectrum,
ν, cm–1: 3236 (NH), 1668 (C=О). 1Н NMR spectrum, δ,
ppm: 2.37 s (3H, CH3), 4.38 d (1H, H4, J 6.2 Hz), 4.70 d.d
(1H, Н5, J 6.2, J 7.6 Hz), 5.98 d (1Н, Н1, J 7.6 Hz), 7.28 t
(1H, H4', J 7.6 Hz), 7.35 t (2Н, H3',5', J 7.6 Hz), 7.36 d
(2H, H3''',5''', J 7.8 Hz), 7.57 d (2Н, H2',6', J 7.6 Hz), 7.84 d
(2Н, H2''',6''', J 7.8 Hz), 9.70 br.s (1H, H2), 14.20 s, 14.46 s
(1H, NH). Mass spectrum, m/z (Irel, %): 351 [M]+ (3),
320 [M – (NH – NH2)]+ (12), 319 (6), 228 (9), 191 (100),
160 (42), 131 (28), 118 (36), 103 (40), 91 (25). Found,
%: C 61.45; H 4.76; N 19.87. C18H17N5OS. Calculated,
%: С 61.52; H 4.88; N 19.93. M 351.43.
2-(4-Methylphenyl)-5-[morpholin-4-yl(phenyl)
methyl][1,3]thiazolo[3,2-b][1,2,4]triazol-6-ol (IVb).
Yield 3.90 g (96%), mp 166–168°C (decomp.). IR spec-
trum, ν, cm–1: 3159 (OH), 1599 (C=N). 1Н NMR spec-
trum, δ, ppm: 2.38 s (3H, CH3), 3.37 br.s (2H, NCH2),
3.46 br.s (2H, NCH2), 3.64 br.s (2H, OCH2), 3.73 br.d
(2H, OCH2), 6.94 s (1H, NCH), 7.30 d (2Н, H3',5'
J 8.0 Hz), 7.36 t (1H, H4'', J 7.6 Hz), 7.44 t (2Н, H3'',5''
J 7.6 Hz), 7.63 d (2Н, H2'',6'', J 7.6 Hz), 7.84 d (2Н, H2',6'
,
,
,
J 8.0 Hz). Mass spectrum, m/z (Irel, %): 406 [M]+ (44), 373
(16), 320 (100), 293 (18), 216 (34), 191 (33), 160 (23),
134 (42), 131 (20), 117 (21), 102 (12), 90 (5). Found, %:
C 59.88; H 5.38; N 13.75. C22H22N4O2S. Calculated, %:
С 65.00; H 5.46; N 13.78. M 406.51.
2-(4-Methoxyphenyl)-4-{[3-(4-methylphenyl)-1H-
1,2,4-triazol-5-yl]sulfanyl}-5-phenylpyrazolidin-3-one
(VIb). Yield 2.49 g (55%), mp 212–214°C. IR spectrum,
ν, cm–1: 3197 (NH), 1659 (C=О). 1Н NMR spectrum, δ,
ppm: 2.37 s (3H, CH3), 3.76 s (3H, OCH3), 5.20 d.d (1H,
Н4, J 6.4, J 7.2 Hz), 5.41 d (1H, H5, J 7.2 Hz), 6.99 d (2H,
H3',5', J 8.9 Hz), 7.15 d (1H, H1, J 6.4 Hz), 7.19 d (2H,
H3''',5''', J 8.0 Hz), 7.27 t (2H, H3'',5'', J 7.7 Hz), 7.29 t (1H,
H4'', J 7.7 Hz), 7.35 d (2Н, H2'',6'', J 7.7 Hz), 7.79 d (2Н,
H2',6', J 8.9 Hz), 7.84 d (2Н, H2''',6''', J 8.0 Hz), 14.42 s
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-3-phenyl-N-cyclohexylprop-2-enamide
(Vа). Yield 3.39 g (81%), mp 201–204°C (decomp.).
IR spectrum, ν, cm–1: 3320 (NH), 1625 (C=О), 1541
1
(NH–C=О). Н NMR spectrum, δ, ppm: 1.06 m (1Н,
CH2), 1.18 d.t (4Н, CH2, J 7.0, J 10.0 Hz), 1.49 br.d (1H,
CH2, J 11.5), 1.55–1.63 m (4H, CH2), 2.35 s (3H, CH3),
3.52 br.s (1H, NCH), 7.32 d (2Н, H3''',5''', J 7.7 Hz), 7.38 t
(1H, H4', J 7.4 Hz), 7.46 t (2Н, H3',5', J 7.4 Hz), 7.67 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

STRUCTURE OF REACTION PRODUCTS
1685
(1H, NH). Mass spectrum, m/z (Irel, %): 457 [M]+ (2),
REFERENCES
319 (19), 267 (72), 250 (25), 191 (56), 131 (67), 122 (62),
107 (51), 103 (100), 91 (57), 80 (65). Found, %:C 65.46;
H 4.96; N 15.26. C25H23N5O2S. Calculated, %: С 65.63;
H 5.07; N 15.31. M 457.56.
1. Uzgören-Baran, A., Tel, B.C., Sarýgöl, D., Öztürk, E.Ý.,
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3. Doğdaş, E., Tozkoparan, B., Kaynak, F.B., Eriksson, L.,
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8. Tozkoparan, B., Aktay, G., Yesilada, E., and Ertan, M.,
Arz.-Forsch. (Drug, Res.)., 2001, 51, vol. I, p. 470.
9. Sarhan, Abdelwareth, A.O., ElSherif, Hassan, A.H., Mah-
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Compounds VII, VIII. Into a flask equipped with
a stirrer and a thermometer to a solution of 10 mmol of
compound I or II in 50 mL of water was added 30 mmol
of NaOH. The reaction mixture wasboiled till a forma-
tion of a transparent solution (30 min or 3 h respectively,
the mixture was cooled, HCl was added to рН 4–5, the
separated precipitate was filtered off, washed with water
on the filter, and dried.
{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}acetic acid (VII). Yield 2.46 g (95%), mp
149.5–150.5°C. IR spectrum, ν, cm–1: 3174 (NH), 1682
1
(C=O). Н NMR spectrum, δ, ppm: 2.38 s (3H, CH3),
3.94 s (2H, СH2), 7.28 d (2Н, H3'',5'', J 7.8 Hz), 7.83 d
(2Н, H2'',6'', J 7.8 Hz), 12.81 br.s (1H, СООH), 14.24 br.s
(1H, NH). Mass spectrum, m/z (Irel, %): 241 [M]+ (1),
249 (2), 205 (28), 172 (7), 118 (17), 117 (19), 116 (10),
91 (6), 43 (100). Found, %: C 52.57; H 4.57; N 16.73.
C11H11N3O2S. Calculated, %: C 53.00; H 4.45; N 16.86.
M 249.29.
2-{[5-(4-Methylphenyl)-1H-1,2,4-triazol-3-yl]
sulfanyl}-3-phenylprop-2-enoic acid (VIII). Yield
2.83 g (84%), mp 224–226°C. IR spectrum, ν, cm–1: 3262
1
(NH), 1681 (C=О). Н NMR spectrum, δ, ppm: 2.38 s
(3H, CH3), 7.32 br.d (1Н, H3''',5''', J 8.0 Hz), 7.43 t (1Н, H4',
12. Rzhevskii, A.A., Gerasimova, N.P., Alov, E.M., Ko-
zlova, O.S., Danilova, A.S., Khapova, S.A., Suponitskii,
K.Yu. Izv. Akad. Nauk, Ser. Khim., 2012, p. 2116.
13. Minkin, V.I., Garnovskii,A.D., Elguero, J., Katritzky,A.R.,
and Denisko, O.V., Adv. Heterocyclic, Chem., 2000, vol. 76,
p. 157.
14. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc., Perkin Trans.
II, 1987, p. 1.
J 7.0 Hz), 7.47 t (2Н, H3',5', J 7.0 Hz), 7.79 d (2Н, H2',6'
,
J 7.0 Hz), 7.82 d (2Н, H2''',6''', J 8.0 Hz), 8.09 s (1H, СH),
12.80 s (1H, СООH), 14.39 s (1H, NH). Mass spectrum,
m/z (Irel, %): 337 [M]+ (2), 292 (10), 191 (100), 134 (56),
118 (37), 117 (21), 91 (35). Found, %: C 63.96; H 4.39;
N 12.41. C18H15N3O2S. Calculated, %: C 64.08; H 4.48;
N 12.45. M 337.40.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013