Synthesis of azoles from 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides

Article abstract of DOI:10.1007/s10593-007-0176-9

Condensation of 3-[(3-hydrazino-3-oxopropyl)anilino]-and 3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides with 2,4-pentanedione, phenyl isocyanate or phenyl isothiocyanate (with subsequent work up of the semicarbazides obtained by base), and carbon disulfide gave respectively: 1-(3,5-dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl) -3-oxopropylanilino]-1-propanone, 3-(2-{[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4- triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-5-one and its thio analog, and 5-(2-{[2-(2-thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl) ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-oxadiazole-2(3H)-thione plus their methyl derivatives.

Full text of DOI:10.1007/s10593-007-0176-9

Chemistry of Heterocyclic Compounds, Vol. 43, No. 9, 2007
SYNTHESIS OF AZOLES FROM 3-[(3-HYDRAZINO-
3-OXOPROPYL)ANILINO]- AND 3-[(3-HYDRAZINO-
3-OXOPROPYL)-4-METHYLANILINO]PROPANE
HYDRAZIDES
I. Tumosiene and Z. I. Beresnevicius
Condensation of 3-[(3-hydrazino-3-oxopropyl)anilino]- and 3-[(3-hydrazino-3-oxopropyl)-4-methyl-
anilino]propane hydrazides with 2,4-pentanedione, phenyl isocyanate or phenyl isothiocyanate (with
subsequent work up of the semicarbazides obtained by base), and carbon disulfide gave respectively:
1-(3,5-dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl)-3-oxopropylanilino]-1-propanone,
3-(2-{[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-
1H-1,2,4-triazol-5-one and its thio analog, and 5-(2-{[2-(2-thioxo-2,3-dihydro-1,3,4-oxadiazol-
5-yl)ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-oxadiazole-2(3H)-thione plus their methyl derivatives.
Keywords: hydrazides, 1,3,4-oxadiazoles, pyrazoles, 1,2,4-triazoles, cyclization.
1,2,3-Triazoles, oxa- and thiadiazoles have a broad spectrum of biological activity. A widely known
method for the synthesis of diazoles is the cyclization of hydrazine derivatives with the dicarbonyl compounds
acetylacetone or acetoacetic ester. In a series of studies carboxylic acid hydrazides have been used as the azo
component [1-3].
The aim of this work was a study of the possible reaction of 3-[(3-hydrazino-3-oxopropyl)anilino]- and
3-[(3-hydrazino-3-oxopropyl)-4-methylanilino]propane hydrazides to give compounds with two pyrazole,
oxadiazole, or triazine rings in their structure.
Refluxing the dihydrazides 1 with 2,4-pentanedione causes condensation to 1-(3,5-dimethyl-1H-
1-pyrazolyl)-3-[3-[3,5-dimethyl-1H-1-pyrazolyl]-3-oxopropylanilino]-1-propanone (2a) or its 4-methyl analog
2b. Formation of the pyrazole rings was confirmed by the presence of two methyl group singlets at 2.17 and 2.47
1
or 2.14 and 2.19 ppm and a methine singlet at 6.18 and 5.75 ppm in their H NMR spectra. The carbon atom
signals for the pyrazole rings were fully in agreement with analogous signals given for substituted
pyrazoles [4-6]. Reaction of the dihydrazides 1 with phenyl isocyanate or phenyl isothiocyanate in methanol
gave the hydrazinocarboxamide 3 and hydrazinocarbothioamide 4 derivatives, cyclization of which in basic
medium gave 3-(2-{[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-
3H-1,2,4-triazol-5-one (5a) or its methyl derivative 5b and the thio analogs 6. In the reaction of dihydrazides 1
with phenyl isocyanate, crystals of the semicarbazides 3 began to appear after 15 min heating while phenyl
isothiocyanate required more prolonged heating. The 1H NMR spectra of the semicarbazides 3 and
__________________________________________________________________________________________
Kaunas University of Technology, Kaunas LT-50254, Lithuania; e-mail: zigmuntas.beresnevicius@ktu.lt.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1353-1358, September, 2007. Original
article submitted January 19, 2007.
1148
0009-3122/07/4309-1148©2007 Springer Science+Business Media, Inc.

R
N
R
N
7
8
N
S
N
S
N
O
N
O
9
HN
NH
HN
NH
N
N
N
N
10
Ph
Ph
Ph
Ph
R
N
R
5a,b
6a,b
N
7
8
O
O
O
O
9
NH
NH
O
NH
O
NH
S
HN
HN
10
HN
HN
S
HN
HN
HN
HN
11
12
13
14
4a,b
3a,b
10
4
R
R 11
3
2
1
15
R
N
N
7
4
N
3
2
O
8
O
7
9
8
1
NH
HN
N
N
S
9
NH2
H2N
HN
NH
O
O
7
8
1a,b
10
O
N
O
N
S
9
7a,b
11
R
Me
Me
N
N
13
12
10
Me
Me
2a,b
14
N
N
N
S
HN
NH
N
N
NH2 H2N
S
8a,b
1–8 a R = H, b R = Me
1149

thiosemicarbazides 4 showed a set of signals for the protons of the phenyl radical and the absence of the signals
for primary amino group protons present in the hydrazide 1. The triazole ring proved to have a marked
deshielding effect on the hydrogen atoms of the neighboring methylene group as a result of which the signals in
1
the H NMR spectra of compounds 5, 6 are found 0.19 and 0.31 ppm to lower field than the corresponding
signals in the starting dihydrazides 1 [7]. The 1,3,4-oxadiazole-2(3H)-thiones 7 were prepared [3] by refluxing
the hydrazides 1 with carbon disulfide in basic alcoholic medium and subsequent cyclization of the potassium
salts of the hydrazinocarbodithioates formed using hydrochloric acid (without their isolation). The oxadiazole-
2(3)-thiones 7 were separated from the reaction mixture as a difficult to crystallize mass. Methanol, ethanol, and
butanol were used as solvent in this reaction, the best yield being obtained with ethanol. It is known [8, 9] that
the nitrogen atom in 1,3,4-oxadiazole-2(3H)-thiones can be exchanged for an alkylamino group using aliphatic
amines. Refluxing the oxadiazolethiones 7 with aniline in dioxane for 16 h did not give the phenyl derivative 6.
Treatment of the 1,3,4-oxadiazole-2(3H)-thiones 7 with hydrazine in refluxing dioxane caused exchange of the
oxygen atom for a nitrogen and gave 4-amino-3-{2-[4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-ylethyl-
1
anilino]ethyl}-4,5-dihydro-1H-1,2,4-triazol-5-thione (8a) and its methyl derivative 8b. The H NMR spectra of
compound 8 shows singlet signals for the amino groups at 5.67 and 5.63 ppm respectively and NH signals at
13.56 ppm typical of 1,3,4-oxadiazole-2-thiones.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Varian 300 instrument (300 and 75 MHz respectively)
using TMS as internal standard and DMSO-d6 as solvent. IR spectra were taken on a Perkin-Elmer Spectrum Bx
FT-IR spectrometer for KBr tablets. Mass spectra were recorded on a Waters Micromass ZQ 2000 instrument
using chemical ionization. Monitoring of the reaction course and purity of the compounds prepared was carried
out using TLC on Silufol 254 and Silufol UV-254 plates.
1-(3,5-Dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl)-3-oxopropylanilino]-1-propa-
none (2a). A mixture of the dihydrazide 1a (1.325 g, 5 mmol), methanol (50 ml), 2,4-pentanedione (2 ml, 2.0 g,
20 mmol), and HCl (2M, 1 ml) was refluxed for 4 h, cooled, and water (50 ml) was added. The oily layer
produced was separated and crystallized from methanol to give compound 2a (1.32 g, 42%) with mp 112-113ºC.
1
IR spectrum, ν, cm-1: 1722 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.17, 2.47 (12H, 2s, CH3); 3.29 (4H, t,
J = 7.05, COCH2); 3.75 (4H, t, J = 7.05, NCH2); 6.18 (2H, s, CH=); 6.65 (1H, t, J = 7.2, H-4 Ar); 6.82 (2H, d,
J = 7.9, H-2,6 Ar); 7.19 (2H, t, J = 7.9, H-3,5 Ar). 13C NMR spectrum, δ, ppm: 171.96 (C-9); 151.36 (C-11);
146.71 (C-1); 143.07 (C-12), 129.14 (C-3); 115.97 (C-4); 112.04 (C-2); 111.08 (C-10); 45.99 (C-7); 33.13
(C-8); 14.39 (C-14); 13.97 (C-13). Mass spectrum (20 eV), m/z (Irel, %): 394 [M+H]+ (50). Found, %: C 67.36;
H 6.87; N 17.65. C22H27N5O2. Calculated, %: C 67.15; H 6.92; N 17.80.
1-(3,5-Dimethyl-1H-1-pyrazolyl)-3-[3-(3,5-dimethyl-1H-1-pyrazolyl)-4-methylanilino-3-oxopropyl]-
1-propanone (2b) was prepared similarly to compound 2a from the dihydrazide 1b (1.395 g, 5 mmol). Yield
0.75 g (36%); mp 117-118ºC. IR spectrum, ν, cm-1: 1728 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.14 (3H, s,
4-CH3); 2.19, 2.22 (12H, 2s, CH3); 3.54 (4H, t, J = 7.0, COCH2); 3.61 (4H, t, J = 7.0, NCH2); 5.75 (2H, s, CH=);
6.64 (2H, d, J = 8.5, H-2,6 Ar); 7.02 (2H, t, J = 8.5, H-3,5 Ar). 13C NMR spectrum, δ, ppm: 172.04 (C-9); 151.93
(C-11); 144.49 (C-1); 142.64 (C-12); 129.62 (C-3); 124.89 (C-4); 112.58 (C-2); 103.09 (C-10); 51.27 (C-7);
46.30 (C-8); 31.58 (C-15); 19.78 (C-14); 11.83 (C-13). Mass spectrum (30 eV), m/z (Irel, %): 408 [M+H]+ (40).
Found, %: C 67.52; H 6.95; N 17.01. C23H29N5O2. Calculated, %: C 67.79; H 7.17; N 17.19.
N-Phenyl-2-[3-({3-[2-(anilinocarbonyl)hydrazino]-3-oxopropyl}anilino)propanoyl]-1-hydrazino-
carboxamide (3a). Phenyl isocyanate (1.19 ml, 10 mmol) was added to a hot solution of dihydrazide 1a
(1.325 g, 5 mmol) in methanol (50 ml). The mixture was refluxed until a precipitate appeared, cooled, the
crystals filtered off, washed with methanol, and recrystallized from methanol. Yield 1.5 g (59%);
1150

1
mp 203-204ºC. IR spectrum, ν, cm-1: 1717 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.35 (4H, t, J = 7.2,
CH2CO); 3.61 (4H, t, J = 7.2, CH2N); 6.66 (1H, t, J = 7.2, H-4 Ar); 6.78 (2H, d, J = 8.1, H-2,6 Ar); 6.99 (2H, t,
J = 8.1, H-3,5 Ar); 7.19-7.30 (10H, m, H Ar); 8.07 (2H, s, NHNHCO); 8.75 (2H, s, NHNHCO); 9.78 (2H, s,
NH Ar). 13C NMR spectrum, δ, ppm: 170.58 (C-9); 155.22 (C-10); 146.81 (C-1); 139.51 (C-11); 129.20 (C-3);
128.58 (C-13); 121.82 (C-14); 118.41 (C-4); 115.76 (C-12); 111.78 (C-2); 46.40 (C-7); 31.22 (C-8). Mass
spectrum (35 eV), m/z (Irel, %): 504 [M+H]+ (40). Found, %: C 61.83; H 5.67; N 19.50. C26H29N7O4. Calculated,
%: C 62.02; H 5.80; N 19.47.
N-Phenyl-2-[3-({3-[2-(anilinocarbonyl)hydrazino]-3-oxopropyl}-4-methylanilino)propanoyl]-1-hydra-
zinocarboxamide (3b) was prepared similarly to compound 3a from dihydrazide 1b (2.79 g, 10 mmol) and
phenylisocyanate (2.38 g, 20 mmol). Yield 4.0 g (77%); mp 201-202ºC. IR spectrum, ν, cm-1: 1670 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 2.18 (3H, s, 4-CH3); 2.38 (4H, t, J = 7.2, CH2CO); 3.58 (4H, t, J = 7.2,
CH2N); 7.19 (2H, d, J = 8.5, H-3,5 Ar); 6.63 (2H, d, J = 8.5, H-2,6 Ar); 6.86-7.11 (10H, m, H Ar); 7.98 (2H, s,
NHNHCO); 8.73 (2H, s, NHNHCO); 9.74 (2H, s, NH Ar). 13C NMR spectrum, δ, ppm: 170.06 (C-9); 155.37
(C-10); 144.94 (C-1); 139.68 (C-11); 129.63 (C-3); 128.60 (C-13); 124.26 (C-4); 121.80 (C-14); 115.75 (C-12);
112.49 (C-2); 46.51 (C-7); 31.22 (C-8); 31.58 (C-15). Mass spectrum (15 eV), m/z (Irel, %): 518 [M+H]+ (100).
Found, %: C 63.07; H 5.59; N 18.70. C27H31N7O4. Calculated, %: C 62.65; H 6.04; N 18.94.
N-Phenyl-2-[3-({3-[2-(anilinothiocarbonyl)hydrazino]-3-oxopropyl}anilino)propanoyl]-1-hydrazino-
carbothioamide (4a). A mixture of 1a (1.325 g, 5 mmol), methanol (50 ml), and phenyl isothiocyanate
(1.32 ml, 1.49 g, 11 mmol) was refluxed for 4 h, a solution of KOH (20%, 20 ml) was added, and the product
was refluxed for a further 20 min. It was cooled and the crystals produced were filtered off, washed with ether,
and crystallized from a mixture of DMF and water. Yield 1.93 g (67%); mp 160-161ºC. IR spectrum, ν, cm-1:
1
3199 (NH), 1680 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.27 (4H, t, J = 7.05, COCH2); 3.64 (4H, t,
J = 7.05, CH2N); 6.67 (1H, t, J = 7.05, H-4 Ar); 6.81 (2H, d, J = 8.2, H-2,6 Ar); 7.17 (2H, t, J = 8.2, H-3,5 Ar);
7.18-7.26 (10H, m, H Ar); 9.62 (4H, s, NHNHCO); 10.04 (2H, br. s, NH Ar). 13C NMR spectrum, δ, ppm:
180.96 (C-10); 170.62 (C-9); 146.85 (C-1); 139.04 (C-11); 129.24 (C-3); 128.07 (C-13); 125.19 (C-14); 118.65
(C-4); 115.87 (C-12); 111.94 (C-2); 46.19 (C-7); 31.25 (C-8). Mass spectrum (30 eV), m/z (Irel, %): 536 [M+H]+
(100). Found, %: C 57.93; H 5.75; N 17.96. C26H29N7O2S2. Calculated, %: C 58.29; H 5.46; N 18.30.
N-Phenyl-2-[3-({3-[2-(anilinothiocarbonyl)hydrazino]-3-oxopropyl}4-methylanilino)propanoyl]-
1-hydrazinocarbothioamide (4b) was prepared similarly to compound 4a from dihydrazide 1b (1.395 g,
5 mmole) and phenylisothiocyanate (1.32 ml, 1.49 g, 11 mmol). Yield 1.1 g (41%), mp 168-169ºC. IR spectrum,
ν, cm-1: 3162 (NH), 1702 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.16 (3H, s, 4-CH3); 2.35 (4H, t, J = 7.05,
COCH2); 3.58 (4H, t, J = 7.05, CH2N); 6.96 (2H, d, J = 8.1, H-2,6 Ar); 7.05 (2H, dd, J = 7.3, J = 8.1, H-3,5 Ar);
7.25-7.34 (10H, m, H Ar); 9.59, 9.54 (4H, s, NHNHCO); 10.00 (2H, s, NH Ar). 13C NMR spectrum, δ, ppm:
181.96 (C-10); 170.59 (C-9); 144.83 (C-1); 139.69 (C-11); 130.47 (C-14); 128.04 (C-13); 127.78 (C-12); 125.75
(C-4); 124.64 (C-3); 112.47 (C-2); 50.43 (C-7); 31.25, 30.89 (C-8); 20.64 (C-15). Mass spectrum (45 eV), m/z
(Irel, %): 550 [M+H]+ (60). Found, %: C 58.96; H 6.09; N 17.57. C27H31N7O2S2. Calculated, %: C 58.99; H 5.68;
N 17.83.
3-(2-{[2-(5-Oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-4,5-dihydro-
1H-1,2,4-triazol-5-one (5a). A solution of hydrazinocarboxamide 3a (1.3 g, 2.6 mmol) in KOH solution (20%,
20 ml) was refluxed for 1 h. The reaction mixture was cooled, conc. HCl was added to pH 4, and the precipitated
crystals were filtered, washed with water, and recrystallized from a mixture of DMF and water. Yield 1.0 g
(80%); mp 190-191ºC. IR spectrum, ν, cm-1: 3166 (NH), 1707 (C=O). 1H NMR spectrum, δ, ppm (J, Hz): 2.46 (4H,
t, J = 7.2, CH2CN); 3.25 (4H, t, J = 7.2, CH2N); 6.56 (1H, t, J = 7.2, H-4 Ar); 6.71 (2H, d, J = 7.2, H-2,6 Ar); 6.99
(2H, t, J = 7.2, H-3,5 Ar); 7.28-7.57 (10H, m, H Ar); 11.74 (2H, s, NNH). 13C NMR spectrum, δ, ppm: 154.28
(C-10); 145.99 (C-1); 144.97 (C-9); 132.73 (C-3); 129.44 (C-11); 129.09 (C-14); 128.66 (C-13); 127.50 (C-12);
115.78 (C-4); 110.93 (C-2); 46.63 (C-7); 23.57 (C-8). Mass spectrum (30 eV), m/z (Irel, %): 468 [M+H]+ (40).
Found, %: C 67.10; H 5.40; N 20.64. C26H25N7O2. Calculated, %: C 66.79; H 5.39; N 20.97.
1151

3-(2-{4-Methyl[2-(5-oxo-4-phenyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-
4,5-dihydro-1H-1,2,4-triazol-5-one (5b) was prepared similarly to compound 5a from hydrazinocarboxamide
3b (0.63 g, 1.3 mmol). Yield 0.48 g (83%); mp 246-247ºC. IR spectrum, ν, cm-1: 3156 (NH), 1722 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 2.19 (3H, s, 4-CH3); 2.48 (4H, t, J = 7.2, CH2CN); 3.59 (4H, t, J = 7.2,
CH2N); 6.75 (2H, d, J = 8.5, H-3,5 Ar); 6.95 (2H, d, J = 8.5, H-2,6 Ar); 7.24-7.51 (10H, m, H Ar); 11.84 (2H, s,
NNH). 13C NMR spectrum, δ, ppm: 154.15 (C-10); 144.09 (C-1); 143.62 (C-9); 132.50 (C-3); 129.95 (C-11);
129.41 (C-14); 128.65 (C-13); 127.32 (C-12); 125.23 (C-4); 109.96 (C-2); 59.53 (C-7); 43.89 (C-8); 20.06
(C-15). Mass spectrum (20 eV), m/z (Irel, %): 482 [M+H]+ (60). Found, %: C 67.21; H 5.38; N 20.34.
C27H27N7O2. Calculated, %: C 67.34; H 5.65; N 20.36.
4-Phenyl-3-(2-{[2-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4,5-di-
hydro-1H-1,2,4-triazol-5-thione (6a). Compound 4a (0.54 g, 1 mmol) and KOH solution (20%, 20 ml) were
refluxed for 5 h. After cooling to room temperature, conc. HCl was added to pH 4 and the precipitated crystals
were filtered off, washed with water, and recrystallized from a mixture of DMF and water. Yield 0.4 g (89%);
1
mp 228-229ºC. IR spectrum, ν, cm-1: 3296 (NH), 1670 (C=O), 1540, 1468 (C=S). H NMR spectrum, δ, ppm
(J, Hz): 2.45 (4H, t, J = 7.05, CH2CN); 3.54 (4H, t, J = 7.05, CH2N); 6.68 (1H, t, J = 8.3, H-4 Ar); 6.79 (2H, d,
J = 8.3, H-2,6 Ar); 7.12 (2H, t, J = 8.3, H-3,5 Ar); 7.28-7.47 (10H, m, H Ar); 13.71 (2H, s, NNHC=S). 13C NMR
spectrum, δ, ppm: 167.61 (C-10); 146.91 (C-1); 133.52 (C-9); 129.35 (C-3); 129.68 (C-11); 129.63 (C-13);
128.31 (C-14); 122.99 (C-12); 118.78 (C-4); 112.01 (C-2); 46.86 (C-7); 44.89 (C-8). Mass spectrum (20 eV),
m/z (Irel, %): 500 [M+H]+ (100). Found, %: C 62.35; H 4.91; N 19.43. C26H25N7S2. Calculated, %: C 62.50;
H 5.04; N 19.62.
3-(2-{4-Methyl[2-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4-phenyl-
4,5-dihydro-1H-1,2,4-triazole-3-thione (6b). The hydrazinocarbothioamide 4b (0.625 g, 1.3 mmol) was
refluxed for 1 h with KOH solution (20%, 20 ml). After cooling to room temperature conc. HCl was added to pH
4 and the precipitated crystals were filtered off, washed with water, and crystallized from methanol. Yield 0.48 g
(82%); mp 262-263ºC. IR spectrum, ν, cm-1: 1500, 1452 (C=S). 1H NMR spectrum, δ, ppm (J, Hz): 2.09 (3H, s,
4-CH3); 2.49 (4H, t, J = 7.05, CH2CN); 3.39 (4H, t, J = 7.05, CH2N); 5.92 (2H, d, J = 8.5, H-2,6 Ar); 6.73 (2H,
13
d, J = 8.5, H-3,5 Ar); 7.37-7.56 (10H, m, H Ar); 13.77 (2H, s, NNHC=S). C NMR spectrum, δ, ppm: 167.55
(C-10); 143.60 (C-1); 133.47 (C-9); 129.52 (C-3); 129.46 (C-11); 129.41 (C-13); 128.29 (C-14); 124.54 (C-4);
122.97 (C-12); 111.28 (C-2); 46.95 (C-7); 44.91 (C-8); 20.60 (C-15). Mass spectrum (70 eV), m/z (Irel, %): 514
[M+H]+ (40). Found, %: C 62.99; H 5.25; N 18.85. C27H27N7S2. Calculated, %: C 63.13; H 5.30; N 19.09.
5-(2-{[2-(2-Thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl)ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-oxadiazole-
2-thione (7a). CS2 (5.7 g, 4.5 ml, 75 mmol) was added dropwise with stirring to a solution of KOH (2.8 g,
50 mmol) in ethanol (75 ml) and stirred for 15 min at 20ºC. Dihydrazide 1a (13.25 g, 50 mmol) in ethanol
(50 ml) was added to the solution obtained and the product was stirred at reflux for 24 h. The liquid fraction was
distilled off, the residue was dissolved in water (150 ml), HCl added to pH 3-4, and the mass produced was
separated, and was washed with and crystallized from methanol. Yield 11.8 g (69%); mp 167-168ºC. IR
1
spectrum, ν, cm-1: 3179 (NH), 1505 (C=S). H NMR spectrum, δ, ppm (J, Hz): 2.43 (4H, t, J = 7.1, CH2CN);
13
3.01 (4H, t, J = 7.1, CH2N); 6.64-6.91 (5H, m, H Ar); 9.97, 10.12 (2H, 2s, NN H). C NMR spectrum, δ, ppm:
177.69 (C-10); 162.44 (C-9), 146.18 (C-1); 129.32 (C-3); 116.13 (C-4); 112.02 (C-2); 46.89 (C-7); 32.20 (C-8).
Mass spectrum (20 eV), m/z (Irel, %): 350 [M+H]+ (30). Found, %: C 47.75; H 3.90; N 19.86. C14H15N5O2S2.
Calculated, %: C 48.14; H 4.30; N 20.06.
5-(2-{4-Methyl[2-(2-thioxo-2,3-dihydro-1,3,4-oxadiazol-5-yl)ethyl]anilino}ethyl)-2,3-dihydro-1,3,4-
oxadiazole-2-thione (7b) was prepared similarly to compound 7a from KOH solution (1.4 g, 25 mmol) in
ethanol (50 ml), CS2 (3.8 gm, 3 ml, 50 mmol), and the dihydrazide 1b (6.97 g, 25 mmol) in ethanol (50 ml).
Yield 1.4 g (11%), mp 166-167ºC. IR spectrum, ν, cm-1: 3175 (NH), 1507 (C=S). 1H NMR spectrum, δ, ppm (J,
Hz): 2.20 (3H, s, 4-CH3); 2.54 (4H, t, J = 7.1, CH2CN); 3.48 (4H, t, J = 7.1, CH2N); 6.63-7.04 (5H, m, H Ar);
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10.02, 10.18 (2H, 2s, NNH). 13C NMR spectrum, δ, ppm: 177.73 (C-10); 162.69 (C-9), 144.96 (C-1); 129.47
(C-3); 124.27 (C-4); 111.81 (C-2); 47.01 (C-7); 32.48 (C-8); 19.85 (C-11). Mass spectrum (20 eV), m/z (Irel, %):
364 [M+H]+ (30). Found, %: C 49.25; H 4.98; N 18.93. C15H17N5O2S2. Calculated, %: C 49.57; H 4.71; N 19.27.
4-Amino-3-{2-[4-amino-(5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethylanilino]ethyl}-4,5-dihydro-
1H-1,2,4-triazole-5-thione (8a). A mixture of the oxadiazolethione 7a (3.49 g, 10 mmol), NH2NH2 (1.5 g,
30 mmol), and dioxane (20 ml) was refluxed for 10 h and a solution of KOH (10%) was added to pH 10. The
basic solution was filtered and the filtrate was acidified with HCl to pH 3. The precipitate was filtered off,
washed with cold water to neutral reaction, and crystallized from ethanol. Yield 2.5 g (66%); mp 200-201ºC. IR
1
spectrum, ν, cm-1: 1722 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.24 (4H, t, J = 7.3, CH2CN); 3.53 (4H, t,
13
J = 7.3, CH2N); 6.64-6.97 (5H, m, H Ar); 5.67 (4H, s, 2NH2); 13.56 (2H, s, 2NH). C NMR spectrum, δ, ppm:
165.87 (C-10); 146.73 (C-1); 143.59 (C-9); 129.26 (C-3); 115.92 (C-4); 111.75 (C-2); 47.75 (C-7); 22.53 (C-8).
Mass spectrum (20 eV), m/z (Irel, %): 378 [M+H]+ (40). Found, %: C 44.89; H 5.48; N 32.95. C14H19N9S2.
.Calculated, %: C 44.54; H 5.07; N 33.39.
4-Amino-3-{2-[4-amino-(5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl-4-methylanilino]ethyl}-
4,5-dihydro-1H-1,2,4-triazole-5-thione (8b) was prepared similarly to compound 8a from the oxadiazolethione
7b (1.82 g, 5 mmol), NH2NH2 (0.76 g, 15 mmol), and dioxane (20 ml). Yield 2.5 g (66%); mp 165-166ºC. IR
1
spectrum, ν, cm-1: 1722 (C=O). H NMR spectrum, δ, ppm (J, Hz): 2.20 (3H, s, 4-CH3); 2.91 (4H, t, J = 7.2,
CH2CN); 3.66 (4H, t, J = 7.2, CH2N); 6.78-7.03 (4H, m, H Ar); 5.63 (4H, s, 2NH2); 13.56 (2H, s, 2NH). 13C
NMR spectrum, δ, ppm: 165.91 (C-10); 144.48 (C-1); 143.61 (C-9); 129.76 (C-3); 124.36 (C-4); 112.14 (C-2);
48.00 (C-7); 22.55 (C-8); 19.88 (C-11). Mass spectrum (20 eV), m/z (Irel, %): 392 [M+H]+ (60). Found, %: С
44.89; Н 5.48; N 32.95. C15H21N9S2. Calculated, %: С 44.54; Н 5.07 N 33.39.
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