Reaction of 1-(o-aminophenyl)-1,2,3-triazole-5-thiols with cyclizing reagents

Article abstract of DOI:10.1023/B:RUJO.0000044551.48113.be

Reactions of 1-(o-aminophenyl)-1,2,3-triazole-5-thiols with ring-closing reagents destabilize the triazole ring, promoting the Dimroth rearrangement and subsequent cyclization to 5-(1-benzazolyl)-1,2,3-thiadiazoles.

Full text of DOI:10.1023/B:RUJO.0000044551.48113.be

Russian Journal of Organic Chemistry, Vol. 40, No. 6, 2004, pp. 870–873. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 6, 2004,
pp. 908–911.
Original Russian Text Copyright © 2004 by Tarasov, Volkova, Morzherin, Bakulev.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 70th Anniversary
Reaction of 1-(o-Aminophenyl)-1,2,3-triazole-5-thiols
with Cyclizing Reagents
E. V. Tarasov, N. N. Volkova, Yu. Yu. Morzherin, and V. A. Bakulev
Ural State Technical University, ul. Mira 19, Yekaterinburg, 620002 Russia
e-mail: evt@htf.ustu.ru
Received January 12, 2004
Abstract—Reactions of 1-(o-aminophenyl)-1,2,3-triazole-5-thiols with ring-closing reagents destabilize the
triazole ring, promoting the Dimroth rearrangement and subsequent cyclization to 5-(1-benzazolyl)-1,2,3-
thiadiazoles.
lacked N–H absorption bands at 3430 and 3310 cm–1,
The ability of 1,2,3-thiadiazole and 1,2,3-triazole
which were typical of compound Ia [6]. The mass
spectra of Ia–Ic and IIa–IIc were fully identical, for
the Dimroth rearrangement can occur in the gas phase
while recording the spectra.
rings to undergo rearrangements provides a convenient
tool in the synthesis of new heterocyclic systems [1].
Such rearrangements have been reported for both
single rings and their combinations [2]. Especially
interesting are poorly studied Dimroth rearrangements
which are initiated by modification of side-chain
groups [3]. Dimroth rearrangements in the series of
5-amino-1,2,3-thiadiazoles have been reported [4, 5];
they are induced by heating or variation of the acidity
of the medium [4]. Reverse rearrangements of 1,2,3-
triazole-5-thiols into the corresponding 5-amino-1,2,3-
thiadiazoles have been studied to a considerably lesser
extent. It is known that such processes occur in acid
medium [4]. However, the available information on the
effect of substituent in position 1 of the 1,2,3-triazole
ring is clearly insufficient. In particular, no studies on
the Dimroth rearrangement in the series of 1-aryl-
1,2,3-triazole-5-thiols have been reported.
Theoretically, the presence of two highly reactive
functional groups (SH and NH2) in molecules IIa–IIc
could give rise to ring closure with formation of
a seven-membered ring, e.g., as in structure III.
However, the reactions of 1-(o-aminophenyl)-1,2,3-
triazole-5-thiols IIa–IIc with sodium nitrite in the
presence of hydrochloric acid afforded 5-(1,2,3-benzo-
triazol-1-yl)-1,2,3-thiadiazoles IVa–IVc (Scheme 1).
The structure of products IVa–IVc was proved by
independent synthesis from compounds Ia–Ic. Diazo-
tization of 5-(o-aminophenyl)-1,2,3-thiadiazoles Ia–Ic
gave products which were fully identical to IVa–IVc
in spectral parameters and physical constants. The
1H NMR spectra of IVa–IVc contained signals from
protons in the substituent at C4 and aromatic protons as
several multiplets in the region δ 7.42–8.46 ppm.
Compounds IVb and IVc showed in the mass spectra
the molecular ion peaks (no molecular ion peak was
observed in the mass spectrum of IVa); all compounds
IVa–IVc gave rise to [M – N2]+ ions typical of 1,2,3-
In the present work we examined the Dimroth
rearrangement of 1-(o-aminophenyl)-1,2,3-triazole-5-
thiols IIa–IIc by the action of nitrous acid and triethyl
orthoformate. Initial triazoles IIa–IIc were synthesized
by heating 5-arylamino-1,2,3-thiadiazoles Ia–Ic in
ethanol in the presence of triethylamine, followed by
acidification. Compounds IIa–IIc were characterized
13
thiadiazoles. In the C NMR spectrum of IVa, signals
from the C4 and C5 atoms of the 1,2,3-thiadiazole ring
were located at δC 145.21 and 153.72 ppm, respec-
tively. Their position is characteristic of 1,2,3-thia-
diazoles having an electron-acceptor substituent,
e.g., 1,2,3-triazole ring [2], at C5. In the spectra of
1
1
by IR, H NMR, and mass spectra. In the H NMR
spectra of IIa–IIc, protons of the thiol and amino
groups appeared as broadened singlets which can
readily be distinguished from the NH signal of initial
aminothiadiazoles Ia–Ic [6]. The IR spectrum of IIa
1070-4280/04/4006-0870 © 2004 MAIK “Nauka/Interperiodica”

REACTION OF 1-(o-AMINOPHENYL)-1,2,3-TRIAZOLE-5-THIOLS
871
Scheme 1.
R
R
N2
S
S1
N
N
N
N
3 N
NaNO2/HCl
or HC(OEt)3
5
S
N
H+
N
SH
X
4
N
N
NH
N
X
2'
1'
7a'
N
OH–
3'
R
R
N
NH2
NH2
7'
6'
3a'
4'
5'
III
IIa–IIc
Ia–Ic
IVa–IVc, Va–Vc
NaNO2/HCl or HC(OEt)3
IIa–IIc
IVa–IVc, Va–Vc
I, II, IV, V, R = COOEt (a), CONHMe (b), CONH2 (c); IV, X = N; V, X = CH.
5-sulfanyl-1,2,3-triazoles, the corresponding carbon
signals appear at δC 138–145 (C4) and 128–132 ppm
(C5) [2, 6].
the molecular ion peaks and strong peaks of the
[M – N2 – CO2Et]+ ions. The 13C NMR spectrum of
Va is analogous to that obtained for compound IVa;
the spectral data are consistent with the presence of
a 1,2,3-thiadiazole ring with an electron-acceptor sub-
stituent at C5. All compounds Va–Vc were also syn-
thesized independently, by heating 1,2,3-thiadiazoles
Ia–Ic with triethyl orthoformate.
An additional support to the assumed structure of
15
compounds IVa–IVc was obtained from the N NMR
spectrum of IVa, which was recorded in DMSO-d6
using ammonia as external reference. The following
signals were observed, δN, ppm: 411.21 (N2), 444.46
(N3), 211.76 (N1'), 380.04 (N2'), 352.50 (N3'). These
The cyclization with triethyl orthoformate occurs in
neutral medium. Therefore, effect of acid which is
necessarily present in the diazotization process (and is
capable of initiating the Dimroth rearrangement) may
be ruled out. The Dimroth rearrangement in the reac-
tion with triethyl orthoformate could be promoted by
heating. However, 1,2,3-thiadiazoles Ia–Ic were not
formed when compounds IIa–IIc were heated in DMF
at 140°C. Therefore, just the reaction at the aromatic
amino group induces the Dimroth rearrangement.
15
values are very consistent with the N NMR data for
1,2,3-thiadiazole and 1,2,3-triazole derivatives [7].
Triazole IIa having an ester group in position 4
turned out to be unstable in acid medium (pH < 1).
1
According to the H NMR data, it underwent partial
rearrangement into the corresponding 1,2,3-thiadiazole
Ia. By contrast, carboxamides IIb and IIc are stable
even in strongly acidic medium: no respective thiadi-
azole I was detected on prolonged storage of com-
pounds IIb and IIc in 10% hydrochloric acid at room
temperature. Therefore, we believe that the Dimroth
rearrangement is promoted by diazotization of the
amino group rather than by change of pH. An ana-
logous rearrangement was induced by diazotization of
5-amino-1-(o-aminophenyl)-1,2,3-triazoles [8].
EXPERIMENTAL
The NMR spectra were recorded on Bruker WM-
250 (250 MHz) and AMX 400 (400.14 MHz) spec-
trometers from solutions in DMSO-d6 containing TMS
as internal reference. The IR spectra were obtained
on a UR-20 spectrometer from samples pelleted with
KBr. The mass spectra (electron impact) were run
on a Varian MAT-311 instrument. The progress of
reactions was monitored, and the purity of products
was checked, by TLC on DC-Plastikfolen Kieselgel
60 F 254 plates using chloroform–ethanol (9:1) as
eluent. The melting points were not corrected.
Similar results were obtained when triethyl ortho-
formate was used as ring-closing agent. By heating
1,2,3-triazole-5-thiols IIa–IIc in triethyl orthoformate
we obtained compounds Va–Vc (Scheme 1). The
1H NMR spectra of Va–Vc contained signals from the
substituent in position 4 of the 1,2,3-thiadiazole ring,
signals from protons in the aromatic ring (a two-proton
multiplet at δ 7.13–7.43 ppm and two one-proton
multiplets at δ 7.42–7.63 and 7.71–7.94 ppm),
and signal of the CH proton in the imidazole ring at
δ 8.50 ppm. In the mass spectra of Va–Vc we observed
Compounds Ia–Ic were synthesized by the proce-
dure reported in [6].
1-(o-Aminophenyl)-1,2,3-triazol-5-thiols IIa–IIc
(general procedure). A mixture of 5 mmol of 5-o-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

TARASOV et al.
872
aminophenyl-1,2,3-thiadiazole Ia–Ic and 30 ml of
triethylamine was heated for 1 h under reflux. The
mixture was evaporated, the residue was dissolved in
50 ml of water, and an equivalent amount of 10%
hydrochloric acid was added to the solution. The
precipitate was filtered off, washed with cold water,
and dried. The yields were nearly quantitative.
mp 116°C. IR spectrum, ν, cm–1: 2960 (CH), 1700
1
(C=O), 1520, 1400, 1300, 1280, 1210, 1020. H NMR
spectrum, δ, ppm: 1.00 t (3H, CH3), 4.25 q (2H,
OCH2), 7.42–7.55 m (1H, Harom), 7.63–7.72 m (2H,
Harom), 8.12–8.21 m (1H, Harom). 13C NMR spectrum,
δC, ppm: 13.31 (CH3), 61.95 (CH2), 111.82 (C7'),
119.85 (C4'), 129.56 (C5'), 133.48 (C6'), 133.48 (C7a'),
145.17 (C3a'), 145.21 (C4) 153.72 (C5), 158.29 (CO).
Mass spectrum, m/z (Irel, %): 247(20.5), [M – N2]+, 147
(100). Found, %: C 47.85; H 3.28; N 25.36; S 11.35.
C11H9N5O2S. Calculated, %: C 47.99; H 3.30; N 25.44;
S 11.65.
Ethyl 1-(o-aminophenyl)-5-sulfanyl-1,2,3-tri-
azole-4-carboxylate (IIa). Yield 99%, mp 144°C.
IR spectrum, ν, cm–1: 2780 (CH), 1700 (C=O), 1450,
1
1320, 1205. H NMR spectrum, δ, ppm: 1.41 t (3H,
CH3), 4.52 q (2H, OCH2), 7.21–7.45 m (2H, Harom),
7.51–7.62 m (2H, Harom), 9.32 br.s. (2H, NH2),
9.64 br.s (1H, SH). Found, %: C 50.14; H 4.67;
N 21.34; S 12.21. C11H12N4O2S. Calculated, %:
C 49.99; H 4.58; N 21.20; S 12.13.
N-Methyl-5-(1,2,3-benzotriazol-1-yl)-1,2,3-thia-
diazole-4-carboxamide (IVb). Yield 85% (a), 80%
(b); mp 188–189°C. IR spectrum, ν, cm–1: 3340 (NH),
2940 (CH), 1670 (C=O), 1560, 1520, 1510, 1470,
1
1410. H NMR spectrum, δ, ppm: 2.83 d (3H,
N-Methyl-1-(o-aminophenyl)-5-sulfanyl-1,2,3-
triazole-4-carboxamide (IIb). Yield 99%, mp 189–
191°C (decomp.). IR spectrum, ν, cm–1: 3330 (NH),
2780 (CH), 1680 (C=O), 1580, 1470, 1310, 1225.
1H NMR spectrum, δ, ppm: 2.82 d (3H, NHCH3),
7.22–7.71 m (4H, CHarom), 9.21 q (1H, NH), 10.22 br.s
(3H, NH2, SH). Found, %: C 48.66; H 4.58; N 27.97;
S 12.65. C10H11N5OS. Calculated, %: C 48.48; H 4.45;
N 28.09; S 12.86.
NHCH3), 7.51–7.84 m (3H, Harom), 8.13–8.22 m (1H,
H
arom), 9.22 q (1H, NH). Mass spectrum, m/z (Irel, %):
260 (8.2) [M]+, 232 (17.3) [M – N2]+, 135 (100).
Found, %: C 46.07; H 3.06; N 32.19; S 12.24.
C10H8N6OS. Calculated, %: C 46.15; H 3.10; N 32.29;
S 12.32.
5-(1,2,3-Benzotriazol-1-yl)-1,2,3-thiadiazole-4-
carboxamide (IVc). Yield 74% (a), 85% (b); mp 185–
187°C. IR spectrum, ν, cm–1: 3460 (NH), 3350 (NH),
1670 (C=O), 1570, 1540, 1510, 1430, 1400, 1270,
1210, 1000. 1H NMR spectrum, δ, ppm: 27.51–7.73 m
(3H, Harom), 8.00 br.s (1H, NH), 8.21–8.24 m (1H,
1-(o-Aminophenyl)-5-sulfanyl-1,2,3-triazole-4-
carboxamide (IIc). Yield 99%, mp 195–200°C
(decomp.). IR spectrum, ν, cm–1: 3320 (NH), 1680
1
(CO), 1575, 1460, 1310, 1215. H NMR spectrum, δ,
ppm: 7.13–7.22 m (2H, Harom), 7.43–7.61 m (2H,
Harom), 10.00 br.s (3H, NH2, SH). Found, %: C 46.15;
H 3.76; N 28.58; S 13.49. C9H9N5OS. Calculated, %:
C 45.95; H 3.86; N 28.77; S 13.63.
Harom), 8.46 br.s (1H, NH). Mass spectrum, m/z
(Irel, %): 246 (7.7) [M]+, 218 (14.5) [M – N2]+, 135
(100). Found, %: C 43.97; H 2.55; N 34.24; S 13.19.
C9H6N6OS. Calculated, %: C 43.90; H 2.46; N 34.13;
S 13.02.
5-(1,2,3-Benzotriazol-1-yl)-1,2,3-thiadiazoles
IVa–IVc (general procedure). a. 5-Sulfanyl-1,2,3-tri-
azole IIa–IIc, 3 mmol, was dispersed in 20 ml of 10%
hydrochloric acid, and an equivalent amount of sodium
nitrite dissolved in a minimal volume of water was
added dropwise on cooling. The mixture was stirred
for 1 h, and the precipitate was filtered off, washed
with water, dried, and recrystallized from ethanol.
5-(1-Benzimidazolyl)-1,2,3-thiadiazoles Va–Vc
(general procedure). a. A mixture of 3 mmol of
5-sulfanyl-1,2,3-triazole IIa–IIc and 20 ml of triethyl
orthoformate was stirred for 3 h at 140°C. The mix-
ture was cooled, and the precipitate was filtered off,
washed with diethyl ether, and recrystallized from
ethanol.
b. 5-o-Aminophenyl-1,2,3-thiadiazole Ia–Ic, 3 mmol,
was dispersed in 20 ml of 10% hydrochloric acid, and
an equivalent amount of sodium nitrite dissolved in
a minimal volume of water was added dropwise on
cooling. The mixture was stirred for 1 h, and the
precipitate was filtered off, washed with water, dried,
and recrystallized from ethanol.
b. A mixture of 3 mmol of 5-o-aminophenyl-1,2,3-
thiadiazole Ia–Ic and 20 ml of triethyl orthoformate
was stirred for 3 h at 140°C. The mixture was cooled,
and the precipitate was filtered off, washed with
diethyl ether, and recrystallized from ethanol.
Ethyl 5-(1-benzimidazolyl)-1,2,3-thiadiazole-4-
carboxylate (Va). Yield 65% (a), 68% (b); mp 115–
117°C. IR spectrum, ν, cm–1: 2940 (CH), 1700 (C=O),
Ethyl 5-(1,2,3-benzotriazol-1-yl)-1,2,3-thiadi-
azole-4-carboxylate (IVa). Yield 94% (a), 87% (b);
1
1570, 1430, 1340, 1290. H NMR spectrum, δ, ppm:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

REACTION OF 1-(o-AMINOPHENYL)-1,2,3-TRIAZOLE-5-THIOLS
873
[M – N2 – CO2Et]+, 129 (48.2). Found, %: C 48.89;
H 2.89; N 28.36; S 13.18. C10H7N5OS. Calculated, %:
C 48.97; H 2.88; N 28.55; S 13.07.
1.22 t (3H, CH3), 4.31 q (2H, OCH2), 7.21–7.41 m
(2H, Harom), 7.45–7.57 m (1H, Harom), 7.82–7.94 m
13
(1H, Harom), 8.50 s (1H, 2'-H). C NMR spectrum, δC,
ppm: 13.55 (CH3), 61.74 (CH2), 110.70 (C7'), 120.04
(C4'), 123.71 (C5'), 124.4 (C6'), 134.26 (C7a'), 143.29
(C4), 144.61 (C2), 145.21 (C4) 145.41 (C5), 158.64
(CO). Mass spectrum, m/z (Irel, %): 274 (47.4) [M]+,
174 (100) [M – N2 – CO2Et]+, 129 (48.8). Found, %:
C 52.58; H 3.69; N 20.38; S 11.38. C12H10N4O2S.
Calculated, %: C 52.55; H 3.67; N 20.43; S 11.69.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 01-03-32609) and by the CRDF (grant no. RC1-
2393-EK-02).
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1
2990 (CH), 1640 (C=O), 1520, 1480, 1440. H NMR
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5-(1-Benzimidazolyl)-1,2,3-thiadiazole-4-carbox-
amide (Vc). Yield 74% (a), 81% (b), mp 229–231°C.
IR spectrum, ν, cm–1: 3450 (NH), 3350 (NH), 2990
1
(CH), 1640 (C=O), 1570, 1520, 1410, 1400. H NMR
spectrum, δ, ppm: 7.21–7.43 m (2H, Harom), 7.51–
7.63 m (1H, Harom), 7.71–7.85 m (1H, Harom), 7.94 br.s
(1H, NH), 8.32 br.s (1H, NH), 8.50 s (1H, 2'-H). Mass
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004