Synthesis of novel 1, 3-Substituted 1 H-[1, 2, 4]-Triazole-3-Thiol derivatives

Article abstract of DOI:10.1002/hc.20565

By means of regioselective S-alkylation of 1 H-1, 2, 4-triazole-3-thiol (1), a series of S-substituted derivatives 2a-j were synthesized. In certain conditions, the reaction of 2 with arylsul-fochlorides, arylisocyanates, and quaternary ammonium salts of

Full text of DOI:10.1002/hc.20565

Heteroatom Chemistry
Volume 20, Number 7, 2009
Synthesis of Novel 1,3-Substituted
1H-[1,2,4]-Triazole-3-Thiol Derivatives
Karine A. Eliazyan, Lusya V. Shahbazyan, Vergine A. Pivazyan,
Emma A. Ghazaryan, and Aleksandr P. Yengoyan
Laboratory of Pesticide synthesis, State Agrarian University of Armenia, Teryan 74,
Yerevan, 0025, Armenia
Received 2 May 2009
The purpose of the present research was to syn-
ABSTRACT:
By
means
of
regioselective
thesize new 1H-1,2,4-triazole-3-thiol derivatives, by
regioselective substitution in positions 1 and 3 of het-
erocycle and further study of physiological activity
of the obtained substances.
S-alkylation of 1H-1,2,4-triazole-3-thiol (1), a series of
S-substituted derivatives 2a−j were synthesized. In
certain conditions, the reaction of 2 with arylsul-
fochlorides, arylisocyanates, and quaternary ammo-
nium salts of azines corresponding compounds were
obtained 1-arylsulfonyl- (3a−d), 1-arylcarbonamido-
(4a,b), and 1-azinyl-1,2,4- (6a−p) triazoles. Struc-
tures of compounds were confirmed by 1H NMR
RESULTS AND DISCUSSION
Initial 1H-1,2,4-triazole-3-thiol 1 can be obtained
in various tautomeric forms with 3-thiol or 3-thion
groups and depending on localization of hydrogen
atom at three different nitrogen atoms of hetero-
cycle. However, it has been established that un-
der action of halogen derivatives at 20◦C in water
or at short-term heating in acetone proceeds only
3-S-substitution (2a–j, Scheme 1).
ꢀ
C
and elemental analyses.
2010 Wiley Periodicals, Inc.
Heteroatom Chem 20:405–410, 2009; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20565
INTRODUCTION
1
For the benefit of it, the data of H NMR spec-
1,2,4-Triazole derivatives represent one of the most
interesting and important classes of compounds,
possessing a wide spectrum of biological activ-
ity. Thus, some carbonamido(carboxy)methylthio-
4-amino-1,2,4-triazoles and products of their
intramolecular cyclization with antituberculosis ac-
tivity [1], 5-aryl-substituted 1,2,4-triazol-3-thiols,
having anti-inflammatory properties [2], diverse
derivatives having antibacterial, antifungal, hypo-
glycemic, antihypertensive, and analgesic activities
[3–10], and a series of 3,5-substituted 1,2,4-triazoles
with expressed fungicide [11] and herbicide activi-
ties [12–14] are described.
tra are verified. Thus, the chemical shift values
of 5-H singlet (8.10–8.20 ppm) specify that alkyla-
tion proceeds without infringement of heterocycle
aromaticity, and signal of a mobile proton (13,7–
13.8 ppm) corresponds to the NH group. Hence, the
structures with the thion group in the third posi-
tion of triazole are excluded. The chemical shifts of
alkyl groups attached to heteroatom also agree with
S-substitution. These conclusions conform to those
data that were reviewed in [15–18].
Some authors established that N-alkylation of
azoles successfully proceeds in biphase catalytic sys-
tems [19,20]; however, in the case of triazole deriva-
tives, the yields of obtained compounds do not
exceed 43%–68%.
Correspondence to: Aleksandr P. Yengoyan; e-mail: ayengoyan@
In our investigation, it was shown that
N-substitution of obtained compounds by action of
405
mail.ru.
c
ꢀ
2010 Wiley Periodicals, Inc.

406 Eliazyan et al.
vents DMSO-d6 and CCl4 (1:3), using tetramethyl-
silane as internal standard. The reaction course con-
trol and individuality of the received substances were
checked by using the TLC method and acetone–
hexane mixture (2:1) as eluent. Melting points are
uncorrected. Initial 1H-[1,2,4]-triazole-3-thiol 1 and
quaternary ammonium salts for synthesis of 6a–p
were prepared as described, respectively, in [21] and
[22].
Ar
H
O
N
N
S
O
N N
SH
SK
N
SR
1
N
l
a
3a–d
H
2
O
S
r
A
H
H
RHal
N N
N
N N
SR
N
2a–j
Synthesis of Compounds 2a−g
(Prepared from 1)
3
3
-
S
O
C N N
General Procedure. To a solution of potassium
salt of 1H-[1,2,4]-triazole-3-thiol (0.01 mol, 1.4 g) in
5 mL water at 0◦C, 0.01 mol alkyl halide was added
dropwise with continuous stirring, and the mixture
was allowed to stand at 20◦C for 24 h. Then the mix-
ture was diluted with water (5 mL), the residue of
a product filtered off, washed with water, and dried
in the air. The resulting compound was purified by
recrystallization from hexane: benzene (1:1).
C
Az
N N
N N
NaS
Ar NH
SR
SR
SR
N
N
N
5
4a,b
6a–p
Az = substituted triazine or pyrimidine
SCHEME 1
arylsulfochlorides easily proceeds in benzene, us-
ing triethylamine as a hydrogen chloride acceptor
(3a–d), and in the presence of catalytic amounts
of pyridine these compounds form with aryliso-
cyanates 1-N-arylcarbonamido derivatives (4a,b).
From compound 2b under action of carbon disul-
fide and in the presence of caustic soda in benzene,
sodium N-dithiocarbamate (5) was formed. Com-
pounds 2a–j in acetone in the presence of caus-
tic potash easily interact with azinyl-2(4)-trimethyl
ammonium chlorides and form corresponding 6a–p
compounds (Scheme 1).
3-Methylsulfanyl-1H-1,2,4-triazol (2a). The co-
mpound was obtained in 74% yield as a white crys-
1
tal; mp 104–106◦C; H NMR δ (ppm): 2.43 (3H, s,
SCH3); 8.15 (1H, w.s, 5-H); 13.70 (1H, w.s, NH); el-
emental anal. (%), Calcd for C3H5N3S: N, 36.52; S,
27.83; Found: N, 36.33; S, 28.09.
(1H-1,2,4-Triazol-3-yl-sulfanyl)-acetic acid meth-
yl ester (2b). The compound was obtained in 81%
1
yield as a white crystal; mp 119–121◦C; H NMR δ
Compounds 2 can exist in three different tau-
tomeric forms, depending on the hydrogen atom at-
tachment. In H NMR spectra of these compounds,
(ppm): 3.70 (3H, s, OCH3); 3.91 (2H, s, SCH2); 8.10
(1H, w.s, CH); 13.80 (1H, w.s, NH); elemental anal.
(%), Calcd for C5H7N3OS: N, 24.28; S, 18.50; Found:
N, 24.04; S, 18.24.
1
signals of NH and 5-H are widened, the spin–spin
interaction between them is invisible, and during
heating the signals are narrowed. This effect can be
explained on the basis of the “fast” (in comparison
with a temporary NMR scale) exchange of a mobile
proton between the nitrogen atoms of heterocycle. At
the same time, the signals of 5-H in 1H NMR spectra
of compounds 3–6 undergo low-field shift at 0.85–
1.0 ppm in comparison with compounds 2, which
agree with 1-N or 4-N-substitution. The last mech-
anism is excluded because the signals of the 5-CH2
(1H-1,2,4-Triazol-3-yl-sulfanyl)-acetic acid ethyl
ester (2c). The compound was obtained in 76%
yield as a white crystal; mp 55–57◦C; 1H NMR δ
(ppm): 1.27 (3H, t, J = 6.9, CH2CH3); 3.93 (2H, s,
SCH2); 4.16 (2H, q, J = 6.9, CH2CH3); 8.14 (1H, w.s,
5-H); 13.70 (1H, w.s, NH); elemental anal. (%), Calcd
for C6H9N3OS: N, 22.46; S, 17.11; Found: N, 22.21;
S, 17.32.
1
group should be observed in H NMR spectra. For
2-(1H-1,2,4-Triazol-3-yl-sulfanyl)-acetamide (2d).
this reason for compounds 3–6, the structure with
1-N-substitution is attributed.
The compound was obtained in 79% yield as a white
1
crystal; mp 164–166◦C; H NMR δ (ppm): 3.85 (2H,
s, SCH2); 6.95 and 7.37 (2H, w.s, NH2); 8.15 (1H, w.s,
CH); 13.75 (1H, w.s, NH); elemental anal. (%), Calcd
for C4H6N4OS: N, 35.44; S, 20.25; Found: N, 35.18;
S, 19.97.
EXPERIMENTAL
1
The H NMR spectra were determined by Varian
mercury-300 spectrometer, in the mixture of sol-
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Novel 1,3-Substituted 1H-[1,2,4]-Triazole-3-Thiol Derivatives 407
3-(1H-1,2,4-Triazol-3-yl-sulfanyl)-pentane-2,4-di-
3-(2-p-Tolyloxy-ethylsulfanyl)-1H-1,2,4-triazole (2j).
one (2e). The compound was obtained in 65%
The compound was obtained in 86% yield as a white
1
1
yield as a white crystal; mp 114–115◦C; H NMR δ
crystal; mp 104–106◦C; H NMR δ (ppm): 2.26 (3H,
(ppm): 2.35 [6H, s, (CH3)2]; 8.20 (1H, s, 5-H); 13.80
(1H, w.s, NH); 17.10 (1H, s, OH-enol); elemental
anal. (%), Calcd for C7H9N3O2S: N, 21.05; S, 16.08;
Found: N, 20.88; S, 16.37.
s, CH3); 3.50 (2H, t, J = 7.1, SCH2); 4.28 (2H, t,
J = 7.1, OCH2); 6.8–7.03 (4H, m,C6H4), 8.20 (1H,
w.s, 5-H); 13.7 (1H, w.s, NH); elemental anal. (%),
Calcd for C11H13N3OS: N, 17.87; S, 13.62; Found: N,
17.45; S, 13.91.
3-Benzylsulfanyl-1H-1,2,4-triazole (2f). The co-
mpound was obtained in 83% yield as a white crys-
tal; mp 80–82◦C; 1H NMR δ (ppm): 3.83 (2H, s,
SCH2); 7.17–7.45 (5H, m, C6H5); 8.12(1H, w.s, 5-
H); 13.80 (1H, w.s, NH); elemental anal. (%), Calcd
for C9H9N3S: N, 21.99; S, 16.75; Found: N, 22.17; S,
16.48.
Synthesis of Compounds 3a−d
General Procedure. To a solution of 0.01 mol
arylsulfochloride in 10 mL benzene at 7–10◦C, 1.4
mL (0.01 mol) of triethylamine in 10 mL benzene
was added dropwise with continuous stirring, and
1.7 g (0.01 mol) of compound 2b was then added.
The resulting mixture was boiled for 4 h; then was
allowed to cool at room temperature, and triethy-
lamine hydrochloride was filtered off. The filtrate
was evaporated, and the residue was washed with
aqueous sodium hydrocarbonate solution (5%), and
desired compounds 3a–d were filtered off.
3-(4-Chloro-benzylsulfanyl)-1H-1,2,4-triazole (2g).
The compound was obtained in 87% yield as a white
crystal; mp 132–134◦C; 1H NMR δ (ppm): 3.85 (2H, s,
SCH2); 7.32–7.50 (4H, m, C6H4); 8.15 (1H, w.s, 5-H);
13.80 (1H, w.s, NH); elemental anal. (%), Calcd for
C9H8ClN3S: N, 18.63; S, 14.19; Found: N, 18.41; S,
13.88.
(1-Benzenesulfonyl-1H-1,2,4-triazol-3-ylsulfanyl)-
acetic acid methyl ester (3a). The compound was
obtained in 90% yield as a white crystal; mp 79–
Synthesis of Compounds 2h−j
(Prepared from I)
1
81◦C; H NMR δ (ppm): 3.58 (3H, s, OCH3); 4.04
(2H, s, SCH2); 7.80 and 8.10 (4H, m,C6H4); 9.37 (1H,
s, 5-H); elemental anal. (%), Calcd for C11H11N3O4S2:
N, 13.42; S, 20.45; Found: N, 13.18; S, 20.66.
General Procedure. To a suspension of potas-
sium salt of 1H-[1,2,4]-triazole-3-thiol (0.01 mol,
1.4 g) in 10 mL acetone, 0.01 mol aryloxyethyl bro-
mide was added dropwise with continuous stirring,
and the resulting mixture was allowed to stand at 50–
60◦C for 3 h. The potassium bromide was filtered off,
and after evaporation and processing with water the
residue was filtered off. The resulting compounds
were purified by recrystallization from hexane:
benzene (1:1).
[1-(4-Chloro-benzenesulfonyl)-1H-1,2,4-triazol-3-
ylsulfanyl]-acetic acid methyl ester (3b). The com-
pound was obtained in 91% yield as a white crystal;
mp 126–128◦C; 1H NMR δ (ppm): 3.63 (3H, s,
OCH3); 3.90 (2H, s, SCH2); 7.50–8.05 (4H, m,C6H4);
9.05 (1H, s, 5-H); elemental anal. (%), Calcd for
C11H10ClN3O4S2: N, 12.09; S, 18.42; Found: N, 12.30;
S, 18.18.
3-(2-Phenoxy-ethyl-sulfanyl)-1H-1,2,4-triazole (2h).
The compound was obtained in 88% yield as a white
[1-(Toluene-4-sulfonyl)-1H-1,2,4-triazol-3-ylsul-
fanyl]-acetic acid methyl ester (3c). The compound
was obtained in 72% yield as a white crystal; mp
1
crystal; mp 87–89◦C; H NMR δ (ppm): 3.55 (2H, t,
J = 7.1, SCH2); 4.25 (2H, t, J = 7.1, OCH2); 6.70–
7.00 (5H, m, C6H5); 8.10 (1H, s, 5-H), 13.75 (1H, w.s,
NH); elemental anal. (%), Calcd for C10H11N3OS: N,
19.00; S, 14.48; Found: N, 19.21; S, 14.11.
1
90–91◦C; H NMR δ (ppm): 2.48 (3H, s, CH3); 3.65
(3H, s, OCH3); 3.92 (2H, s, SCH2); 7.45–7.93 (4H,
m,C6H4); 9.0 (1H, s, 5-H); elemental anal. (%), Calcd
for C12H13N3O4S2: N, 12.84; S, 19.57; Found: N,
13.11; S, 19.81.
3-(2-o-Tolyloxy-ethylsulfanyl)-1H-1,2,4-triazole (2i).
The compound was obtained in 93% yield as a white
1
crystal; mp 86–88◦C; H NMR δ (ppm): 2.20 (3H, s,
[1-(2,5-Dimethyl-benzenesulfonyl)-1H-1,2,4-tri-
azol-3-ylsulfanyl]-acetic acid methyl ester (3d). The
compound was obtained in 90% yield as a white
CH3); 3.52 (2H, t, J = 7.1, SCH2); 4.25 (2H, t, J =
7.1, OCH2); 6.75–7.05 (4H, m, C6H4), 8.16 (1H, w.s,
5-H); 13.7(1H, w.s, NH); elemental anal. (%), Calcd
for C11H13N3OS: N, 17.87; S, 13.62; Found: N, 17.60;
S, 14.00.
1
crystal; mp 100–102◦C; H NMR δ (ppm): 2.40 and
2.47 [6H, s,s, 2- and 5-CH3); 3.62 (3H, s, OCH3); 3.90
(2H, s, SCH2); 7.38–7.85 (3H, m,C6H3); 9.02 (1H, s,
Heteroatom Chemistry DOI 10.1002/hc

408 Eliazyan et al.
5-H); elemental anal. (%), Calcd for C13H15N3O4S2:
N, 12.32; S, 18.77; Found: N, 12.08; S, 19.09.
was evaporated. The resulting suspension was
evaporated; the residue washed with water and
filtered off. The desired compounds 6a–p were
recrystallized from toluene or /hexane: benzene
(1:2).
Synthesis of Compounds 4a,b
General Procedure. A mixture of compound 2b
(0.01 mol, 1.7 g) and arylisocyanate (0.01 mol) in
benzene (20 ml) in the presence of catalytic amounts
of pyridine was boiled for 3 h. The resulting mix-
ture was filtered, and the filtrate was evaporated.
The residues of compounds 4a,b were recrystallized
from ethanol (50%).
2,4-Bis-dimethylamino-6-(3-methylsulfanyly-1H-
1,2,4-triazol-1-yl)-1,3,5-triazine (6a). The com-
pound was obtained as a white crystal; prepared
from 2a; yield: 89%, mp 138–140◦C; 1H NMR δ
(ppm): 2.62 (3H, s, SCH3); 3.18 and 3.22 [6H, s,s,
N(CH3)4]; 9.08 (1H, s, 5-H)∗; elemental anal. (%),
Calcd for C10H16N8S: N, 40.00; S, 11.43; Found: N,
39.75; S, 11.10.
(1-Phenylcarbamoyl-1H-1,2,4-triazol-3-ylsulfanyl)-
acetic acid methyl ester (4a). The compound was
obtained in 69% yield as a white crystal; mp 95–
2,4-Diethylamino-4-methylamino-6-(3-methylsu-
lfanyl-1H-1,2,4-triazol-1-yl)-1,3,5-triazine (6b). The
compound was obtained as a white crystal; pre-
1
97◦C; H NMR δ (ppm): 3.70 (3H, s, OCH3); 4.07
(2H, s, SCH2); 7.10–7.72 (5H, m, C6H5); 9.02 (1H,
s, 5-H); 10.23 (1H, w.s, NH); elemental anal. (%),
Calcd for C12H12N4O3S: N, 19.18; S, 10.96; Found:
N, 19.38; S, 10.69.
1
pared from 2a; yield: 90%, mp 134–136◦C; H NMR
δ (ppm): 1.20 (3H, t, J = 7.0, CH3CH2); 2.60 and 2.65
(5:1) (2H, s,s, SCH3); 2.88 and 2.95 (5:1) (3H, d.d,
J = 5.6, NCH3); 3.63 (2H, m, CH3CH2); 7.05 and
7.68 (5:1) (1H, w.q, J = 5.6, NH); 9.03 and 9.07
(5:1) (1H, s,s, 5-H)∗; elemental anal. (%), Calcd for
C11H18N8S: N, 38.49; S, 11.00; Found: N, 38.12; S,
11.39.
[1-(4-Chloro-phenylcarbamoyl)-1H-1,2,4-triazol-
3-ylsulfanyl]-acetic acid methyl ester (4b). The
compound was obtained in 81% yield as a white
crystal; mp 123–124◦C; 1H NMR δ (ppm): 3.73 (3H, s,
OCH3); 4.10 (2H, s, SCH2); 7.48–8.03 (4H, m, C6H4);
9.05 (1H, s, 5-H); 10.23 (1H, w.s, NH); elemental
anal. (%), Calcd for C12H11ClN4O3S: N, 17.15; S,
9.80; Found: N, 17.43; S, 10.09.
2-Methoxy-4-methyl-6-(3-methylsulfanyl-1H-1,2,
4-triazol-1-yl)-pyrimidine (6c). The compound was
obtained as a white crystal; prepared from 2a; yield:
1
72%, mp 132–134◦C; H NMR δ (ppm): 2.50 (3H, s,
CH3); 2.64 (2H, s, SCH3); 4.06 (3H, s, OCH3); 6.62
(1H, s, CH-pyrim.); 9.13 (1H, s, 5-H); elemental
anal. (%), Calcd for C9H11N5OS: N, 29.54; S, 13.50;
Found: N, 29.33; S, 13.21.
Synthesis of Compound 5
Sodium salt of 3-methylsulfanyl-1,2,4-triazole-1-
carbodithioic acid (5). To a suspension of NaOH
(0.011 mol, 0.44 g) in absolute benzene (10 mL), car-
bon bisulfide (0.011 mol, 0.66 g) was added dropwise
followed by the slow addition of compound 2a (0.01
mol, 1.15 g). The mixture was vigorously stirred at
20◦C and was allowed to stand overnight. Benzene
was decanted, the reaction mass was rubbed with
hexane, and the desired compound 5 was filtered
off and washed with ether. The compound was ob-
tained in 78% yield as a white crystal; mp 72–74◦C;
1H NMR δ (ppm): 2.43 (3H, s, SCH3); 7.60 (1H, s,
CH); elemental anal. (%), Calcd for C4H9N3S3Na: N,
19.72; S, 45.07; Found: N, 19.44; S, 44.68.
[1-(2,4-Bis-dimethylamino-1,3,5-triazine-6-yl)-1H-
1,2,4-triazol-3-ylsulfanyl]-acetic acid methyl ester
(6d). The compound was obtained as a white crys-
tal; prepared from 2b, yield: 82%, mp 147–148◦C;
1H NMR δ (ppm): 3.18 and 3.23 [6H, ss, N(CH3)4];
3.73 (3H, s, OCH3); 4.00 (2H, s, SCH2); 9.10 (1H, s,
5-H)∗; elemental anal. (%), Calcd for C12H18N8O2S:
N, 33.14; S, 9.48; Found: N, 32.89; S, 9.71.
[1-(2-Dimethylamino-4-pyrrolidin-1-yl-1,3,5-tri-
azine-6-yl)-1H-1,2,4-triazol-3-ylsulfanyl]-acetic acid
methyl ester (6e). The compound was obtained as
a white crystal; prepared from 2b, yield: 82%, mp
131–133◦C; 1H NMR δ (ppm): 1.85 (4H, m, CH2CH2);
3.15 and 3.20 [6H, s,s N(CH3)2]; 3.55–3.65 [4H, m,
N(CH2)2]; 3.73 (3H, s, OCH3); 4.00 (2H, s, SCH2);
Synthesis of Compounds 6a−p
General Procedure. To
a
suspension of
N-potassium salt of
2
(0.01 mol), azinyl-2-
∗
trimethylammonium chloride (0.01 mol) was
added with continuous stirring at 20◦C for 1 h, then
at 45–50◦C for 3–4 h, until all the trimethylamine
9.08 (1H, s, 5-H) ; elemental anal. (%), Calcd for
C14H20N8O2S: N, 30.77; S, 8.79; Found: N, 31.09; S,
9.10.
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of Novel 1,3-Substituted 1H-[1,2,4]-Triazole-3-Thiol Derivatives 409
[1-(4-Methyl-6-pyrrolidin-1-yl-pyrimidin-2-yl)-1H-
(6k). The compound was obtained as a white crys-
tal; prepared from 2d, yield: 85%, mp 245–247◦C;
1H NMR δ (ppm): 1.55–1.73 [6H, m, (CH2)3]; 2.87
and 2.95 (5:1) (6H, d, J = 5.8); 3.80 (2H, s, SCH2);
3.75–3.86 [4H, m, N(CH2)2]; 6.98 and 7.36 (2H, w.s,
NH2); 7.10 and 7.78 (1:5) (1H, q, J = 5.8, NH);
9.10 (1H, s, 5-H)∗; elemental anal. (%), Calcd for
C13H19N9OS: N, 36.10; S, 9.17; Found: N, 36.35; S,
9.40.
1,2,4-triazol-3-ylsulfanyl]-acetic acid methyl ester
(6f). The compound was obtained as a white crys-
tal; prepared from 2b, yield: 80%, mp 132–134◦C; 1H
NMR δ (ppm): 2.00 (4H, w.m, CH2CH2); 2.38 (3H,
s, CH3); 3.38–3.65 [4H, w.m, N(CH2)2]; 3.75 (3H, s,
OCH3); 4.02 (2H, s, SCH2); 6.20 (1H, s, CH-pyrim);
∗
9.03 (1H, s, 5-H) ; elemental anal. (%), Calcd for
C14H18N6O2S: N, 25.15; S, 9.58; Found: N, 24.87; S,
9.22.
1-(2,4-Bis-dimethylamino-1,3,5-triazine-6-yl)-3-
benzylsulfanyl-1H-1,2,4-triazol (6l). The compound
was obtained as a white crystal; prepared from 2f,
[1-(2-Amino-4-methyl-pyrimidin-6-yl)-1H-1,2,4-
triazol-3-ylsulfanyl]-acetic acid ethyl ester (6g). The
compound was obtained as a white crystal; pre-
1
yield: 90%, mp 125–127◦C; H NMR δ (ppm): 3.20
1
pared from 2c, yield: 78%, mp 133–135◦C; H NMR
and 3.28 [6H, s,s, N(CH3)4]; 4.40 (2H, s, SCH2);
7.15–7.45 (5H, m, C6H5); 9.10 (1H, s, 5-H)∗; elemen-
tal anal. (%), Calcd for C16H19N8S: N, 31.55; S, 9.01;
Found: N, 31.71; S, 8.78.
δ (ppm): 1.28 (3H, t, J = 7.1, CH2CH3); 2.35 (3H,
s, CH3-cycL.); 3.98 (2H, s, SCH2); 4.15 (2H, q, J
= 7.1, CH2CH3); 6.08 (2H, w.s, NH2); 6.79 (1H, s,
CH-pyrim.); 9.05 (1H, s, 5-H); elemental anal. (%),
Calcd for C11H14N6O2S: N, 28.57; S, 10.88; Found:
N, 28.81; S, 11.19.
1-(2-Methylamino-4-dimethylamino-1,3,5-tria-
zine-6-yl)-3-benzylsulfanyl-1H-1,2,4-triazol
(6m).
The compound was obtained as a white crystal;
prepared from 2f, yield: 91%, mp 194–196◦C; 1H
NMR δ (ppm): 2.90 and 2.95 (5:1) (6H, d.d, J = 5.9,
NCH3); 3.22 [6H, w.s, N(CH3)2]; 4.40 and 4.42 (2H,
s, SCH2); 7.10 and 7.65 (1:5) (1H, q, J = 5.9, NH);
7.18–7.43 (5H, m, C6H5); 9.08 and 9.10 (5:1) (1H,
s,s, 5-H)∗; elemental anal. (%), Calcd for C15H18N8S:
N, 32.75; S, 9.36; Found: N, 32.54; S, 9.69.
[1-(4-Methyl-6-phenoxy-pyrimidin-2-yl)-1H-1,2,
4-triazol-3-ylsulfanyl]-acetic acid ethyl ester (6h).
The compound was obtained as a white crystal;
prepared from 2c, yield: 63%, mp 108–110◦C; 1H
NMR δ (ppm): 1.27 (3H, t, J = 7.1, CH2CH3); 2.55
(3H, s, CH3-cycL.); 3.98 (2H, s, SCH2); 4.15 (2H, q,
J = 7.1, CH2CH3); 6.76 (1H, s, CH-pyrim.); 7.20–7.55
(5H, m, C6H5); 8.85 (1H, s, 5-H); elemental anal. (%),
Calcd for C17H17N5O3S: N, 18.87; S, 8.63; Found: N,
18.65; S, 8.36.
1-(2-Amino-4-methyl-pyrimidin-6-yl)-3-benzylsul-
fanyl-1H-1,2,4-triazol (6n). The compound was
obtained as a white crystal; prepared from 2f, yield:
1
89%, mp 222–224◦C; H NMR δ (ppm): 2.37 (3H,
2-[1-(2,4-Bis-dimethylamino-1,3,5-triazine-6-yl)-
1H-1,2,4-triazol-3-ylsulfanyl]-acetamide (6i). The
compound was obtained as a white crystal; pre-
pared from 2d, yield: 93%, mp 180–182◦C; 1H NMR
δ (ppm): 3.18 and 3.21 [6H, s,s, N(CH3)4]; 3.80 (2H,
s, SCH2); 6.95 and 7.35 (2H, w,s, NH2); 9.13 (1H, s,
5-H)∗; elemental anal. (%), Calcd for C11H17N9OS:
N, 39.01; S, 9.91; Found: N, 39.30; S, 10.22.
s, CH3); 4.40 (2H, s, SCH2); 6.42 (2H, w.s, NH2);
6.80 (1H, s, CH-pyrim); 7.18–7.45 (5H, m, C6H5);
9.05 (1H, s, 5-H); elemental anal. (%), Calcd for
C14H14N6S: N, 28.19; S, 10.74; Found: N, 27.89; S,
10.36.
1-(2,4-Bis-dimethylamino-1,3,5-triazine-6-yl)-2-
p-tolyloxy-ethylsulfanyl-1H-1,2,4-triazol (6o). The
compound was obtained as a white crystal; pre-
1
pared from 2j, yield: 90%, mp 134–136◦C; H NMR
2-[1-(2-Dimethylamino-4-methoxy-1,3,5-triazine-
6-yl)-1H-1,2,4-triazol-3-ylsulfanyl]-acetamide
(6j).
δ (ppm): 2.26 (3H, s, CH3); 3.18 and 3.24 [6H, s,s
N(CH3)4]; 3.50 (2H, t, J = 7.1, SCH2); 4.28 (2H, t,
J = 7.1, OCH2); 6.80–7.05 (4H, m, C6H4); 9.10 (1H,
s, 5-H)∗; elemental anal. (%), Calcd for C18H24N8OS:
N, 28.00; S, 8.00; Found: N, 28.27; S, 8.32.
The compound was obtained as a white crystal;
1
prepared from 2d, yield: 80%, mp 185–186◦C; H
NMR δ (ppm): 3.22 and 3.30 [6H, s,s, N(CH3)4]; 3.85
(2H, s, SCH2); 4.00 (3H, s, OCH3); 6.95 and 7.38 (2H,
w.s, NH2); 9.20 (1H, s, 5-H)∗; elemental anal. (%),
Calcd for C10H14N8O2S: N, 36.13; S, 10.32; Found:
N, 36.34; S, 10.59.
1-(2,4-di-Pyrrolidin-1-yl-1,3,5-triazine-6-yl)-2-p-
tolyloxy-ethylsulfanyl-1H-1,2,4-triazol
(6p). The
compound was obtained as a white crystal; pre-
1
2-[1-(2-Methylamino-4-piperidine-1-yl-1,3,5-tri-
azine-6-yl)-1H-1,2,4-triazol-3-ylsulfanyl]-acetamide
pared from 2j, yield: 87%, mp 135–137◦C; H NMR
δ (ppm): 1.95 [8H, m, (CH2)4]; 2.25 (3H, s, CH3);
Heteroatom Chemistry DOI 10.1002/hc

410 Eliazyan et al.
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3.46–3.70 [8H, m, N(CH2)4]; 3.50 (2H, t, J = 7.1,
SCH2); 4.28 (2H, t, J = 7.1, OCH2); 6.78–7.03 (4H,
m, C6H4); 9.07 (1H, s, 5-H)∗; elemental anal. (%),
Calcd for C22H28N8OS: N, 24.78; S, 7.08; Found: N,
25.10; S, 7.41.
Note: Two groups of signals in H NMR spec-
tra are caused by the presence of conformational
isomers as a result of internal rotation of N-alkyl
groups around the N-C bond [23].
∗
1
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