Reactions of 1,2,3-triazoles with trifluoromethanesulfonyl chloride and trifluoromethanesulfonic anhydride

Article abstract of DOI:10.1023/B:RUJO.0000010573.40618.c0

Reactions of 4,5-dibromo-1,2,3-triazole, 1H-1,2,3-benzotriazole, and 2-phenyl-2H-1,2,3-triazole-4-carbonyl chloride with trifluoromethanesulfonyl chloride and trifluoromethanesulfonic anhydride were studied. 4,5-Dibromo-1,2,3-triazole sodium salt reacted

Full text of DOI:10.1023/B:RUJO.0000010573.40618.c0

Russian Journal of Organic Chemistry, Vol. 39, No. 10, 2003, pp. 1517 1521. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 10, 2003,
pp. 1583 1587.
Original Russian Text Copyright
2003 by Meshcheryakov, Shainyan, Tolstikova, Albanov.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on the 65th Anniversary of His Birth
Reactions of 1,2,3-Triazoles with Trifluoromethanesulfonyl
Chloride and Trifluoromethanesulfonic Anhydride
V. I. Meshcheryakov, B. A. Shainyan, L. L. Tolstikova, and A. I. Albanov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: bagrat@irioch.irk.ru
Received May 28, 2003
Abstract Reactions of 4,5-dibromo-1,2,3-triazole, 1H-1,2,3-benzotriazole, and 2-phenyl-2H-1,2,3-triazole-
4-carbonyl chloride with trifluoromethanesulfonyl chloride and trifluoromethanesulfonic anhydride were
studied. 4,5-Dibromo-1,2,3-triazole sodium salt reacted with CF3SO2Cl in tetrahydrofuran to give 4,5-di-
bromo-2-(2-tetrahydrofuryl)-2H-1,2,3-triazole rather than expected 4,5-dibromo-2-trifluoromethylsulfonyl-
2H-1,2,3-triazole. The latter was synthesized by treatment of 4,5-dibromo-1,2,3-triazole sodium salt with
trifluoromethanesulfonic anhydride. The reaction of benzotriazole with (CF3SO2)2O afforded 1-trifluoro-
methylsulfonyl-1H-1,2,3-benzotriazole and 1,2,3-benzotriazolium trifluoromethanesulfonate. 2-Phenyl-2H-
1,2,3-triazole-4-carbonyl chloride reacted with trifluoromethanesulfonamide sodium salt in DMF, yielding
N-(dimethylaminomethylene)trifluoromethanesulfonamide. Possible ways for formation of the unexpected
products were proposed.
In continuation of our studies on trifluoromethyl-
sulfonyl derivatives of azoles [1], in the present work
we examined the possibility for introduction of a tri-
fluoromethylsulfonyl group into the heteroring or side
chain of various 1,2,3-triazoles. Preliminary experi-
ments showed that 4-nitro-1,2,3-triazole sodium salt,
whose nucleophilicity is reduced due to the presence
of a nitro group, does not react with trifluoromethane-
sulfonyl chloride. Sodium salt derived from 1,2,3-tri-
azole does react with CF3SO2Cl, but the products thus
formed are unstable, and they undergo spontaneous
thermal decomposition on attempted isolation. Taking
the above into account, as substrates we selected
4,5-dibromo-1,2,3-triazole (I), 1H-1,2,3-benzotriazole
(II), and 2-phenyl-2H-1,2,3-triazole-4-carbonyl
chloride (III). On the one hand, these compounds
should be more reactive toward electrophiles than
4-nitro-1,2,3-triazole, and on the other, the corre-
sponding trifluoromethylsulfonyl derivatives were
expected to be more stable due to the presence of
bulky substituents.
analysis of the 13C NMR spectra recorded in various
solvents at different temperature. The 13C NMR spec-
trum of a solution of I in acetone-d6 contains two
signals: a narrow peak at
124.2 ppm and a broad-
C
ened signal at
1:4. In DMSCO-d6, only one broadened signal is
present at 123.7 ppm with a halfwidth of 37 Hz.
125.3 ppm with an intensity ratio of
C
On heating to 100 C, it becomes narrower (to 8 Hz)
and shifts by 0.9 ppm upfield. The observed pattern
may be interpreted in terms of the equilibrium shown
in Scheme 1. In going from polar acetone to even
more polar DMSO, the equilibrium shifts completely
toward the more polar 1(3)H-tautomer.
Scheme 1.
Like other 1,2,3-triazoles having no substituents on
the nitrogen atoms, 4,5-dibromo-1,2,3-triazole (I) can
exist as 1H- and 2H-tautomers, as follows from
Our attempts to replace the bromine atoms in I
by CF3SO2 or CF3SO2NH group via reaction with
sodium trifluoromethanesulfinate or trifluoromethane-
1070-4280/03/3910-1517$25.00 2003 MAIK Nauka/Interperiodica

1518
MESHCHERYAKOV et al.
sulfonamide sodium salt were unsuccessful. Com-
pound I turned out to be inactive toward nucleo-
philic substitution by such weak nucleophiles. The
reaction of triazole I with sodium hydrogen carbonate
gave sodium salt 2Na-I which was then treated with
trifluoromethanesulfonyl chloride in tetrahydrofuran
with a view to obtain 4,5-dibromo-2-trifluoromethyl-
sulfonyl-2H-1,2,3-triazole. Surprisingly, the isolated
product was 4,5-dibromo-2-(2-tetrahydrofuryl)-2H-
1,2,3-triazole (IV) (Scheme 2).
into account that tetrahydrofuran readily undergoes
chlorination at the -position by the action of, e.g.,
sulfuryl chloride [4] and that trifluoromethanesul-
fonyl chloride is capable of acting as chlorinating
agent [5, 6], intermediate formation of 2-chlorotetra-
hydrofuran in the reaction of CF3SO2Cl with THF
could be presumed. In fact, tetrahydrofuran reacts
with CF3SO2Cl, but the reaction is fairly slow and is
accompanied by almost complete tarring. On the other
hand, addition of CF3SO2Cl to a solution of 2Na-I in
THF results in almost instantaneous separation of
a white solid. It is known [7] that 2-chlorotetra-
hydrofuran is also formed by reaction of THF with
N-chlorotriazoles. Therefore, we propose Scheme 3
as a possible way of formation of compound IV.
Scheme 2.
We succeeded in synthesizing the target product,
4,5-dibromo-2-trifluoromethylsulfonyl-2H-1,2,3-tri-
azole (V), by reaction of sodium salt 2Na-I with tri-
fluoromethanesulfonyl chloride in methanol or with
trifluoromethanesulfonic anhydride in methylene
chloride according to the procedure described in [8]
(Scheme 4). In the 13C NMR spectrum of V we
observed only one signal from the triazole carbon
The structure of compound IV was unambiguously
1
proved by the H and 13C (proton-coupled) NMR
spectra, mass spectrum, and elemental analysis. The
symmetric structure of 2-substituted triazole IV fol-
lows from the presence of only one signal from the
triazole ring carbon atoms in the 13C NMR spectrum
atoms (
137 ppm).
C
Scheme 4.
(
125 ppm).
C
Giller et al. reported on the synthesis of N-(2-tetra-
hydrofuryl)-substituted heterocycles exhibiting a high
anticarcinogenic activity [such as Ftorafur, 5-fluoro-1-
(2-tetrahydrofuryl)-1,2,3,4-tetrahydropyrimidine-2,4-
dione] by reaction of N-mercurated [2] or N-silylated
[3] heterocycles with 2-chlorotetrahydrofuran. Taking
X = Cl, CF3SO3.
Due to the presence of fused benzene ring, benzo-
triazole (II) exists exclusively as the 1H-tautomer.
It smoothly reacted with trifluoromethanesulfonic
anhydride under mild conditions, leading to 1-tri-
fluoromethylsulfonyl-1H-1,2,3-benzotriazole (VI) and
1,2,3-benzotriazolium trifluoromethanesulfonate (VII)
(Scheme 5). Compound VI showed in the 13C NMR
spectrum a quartet signal from the CF3 group and six
signals from the benzene ring carbon atoms, while
Scheme 3.
Scheme 5.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

REACTIONS OF 1,2,3-TRIAZOLES WITH TRIFLUOROMETHANESULFONYL
1519
only three aromatic carbon signals were present in the
spectrum of VII. These data indicate asymmetric
structure of N-trifluoromethylsulfonyl derivative VI
and symmetric structure of salt VII.
Thus the trifluoromethylsulfonylation of 1,2,3-tri-
azoles and their sodium salts can occur in both usual
way, leading to the corresponding N-trifluoromethyl-
sulfonyl derivatives (compounds V and VI), and
anomalous mode, leading to oxidative coupling prod-
uct IV with reduction of sulfonate moiety to sulfinate.
Taking into account that amide IX does not react with
methanol, the reaction is likely to follow a nucleo-
philic catalysis pattern with formation of intermediate
having a highly nucleofugal CF3SO2NH group, which
then undergoes methanolysis (Scheme 7).
Scheme 7.
We also tried to synthesize a mixed imide, N-tri-
fluoromethylsulfonyl-2-phenyl-2H-1,2,3-triazole-4-
carboxamide (which was expected to be a very strong
NH acid), by reaction of 2-phenyl-2H-1,2,3-triazole-
4-carbonyl chloride (III) with trifluoromethanesulfon-
amide sodium salt in dimethylformamide. However,
the products were N-(dimethylaminomethylene)tri-
fluoromethanesulfonamide (VIII) and 2-phenyl-2H-
1,2,3-triazole-4-carboxylic acid (Scheme 6).
Scheme 6.
EXPERIMENTAL
The IR spectra were recorded on an IKS-29 spec-
trometer from samples prepared as KBr pellets or
dispersed in mineral oil. The NMR spectra were ob-
tained on a Bruker DPX-400 instrument at 400 MHz
1
for H, 100 MHz for 13C, and 376 MHz for 19F; the
chemical shifts were measured relative to TMS
(1H and 13C; HMDS was used as internal reference)
and CCl3F (19F). The mass spectra (70 eV) were run
on a Hewlett Packard HP 5971A mass-selective
detector coupled with an HP 5890 gas chromatograph
(Ultra-2 column, 5% of phenylmethylsilicone; injector
temperature 250 C; oven temperature programming
from 70 to 280 C at 20 deg/min). The progress of
reactions was monitored by thin-layer chromatography
using Silufol UV-254 plates.
Reaction of 4-nitro-2H-1,2,3-triazole sodium salt
with trifluoromethanesulfonyl chloride. To a solu-
tion of 4-nitro-2H-1,2,3-triazole sodium salt in acetone
we added dropwise under stirring and cooling
an equimolar amount of trifluoromethanesulfonyl
chloride in dioxane. The mixture was stirred for 1 h
and was then heated for 2 h under reflux. After ap-
propriate treatment, initial 4-nitro-2H-1,2,3-triazole
was isolated.
The synthesis N-perfluoroalkylsulfonylamidines of
the general formula RFSO2N C(R)NR1R2 was de-
scribed in [9 11]. These compounds are obtained by
reaction of N-trimethylsilylamide C4F9SO2NHSiMe3
with dimethylformamide in the presence of CsF [9],
by reaction of sodium salt C4F9SO2NHNa with the
Vilsmeier reagent (POCl3 + DMF) [10], and by reac-
tion of perfluoroalkanesulfonyl azides with ketones
and secondary amines [11]. Obviously, in our case,
acyl chloride III initially reatcs with DMF to give
an adduct analogous to the Vilsmeier reagent. Its sub-
sequent reaction with trifluoromethanesulfonamide
sodium salt yields formamidine VIII and triazole-
carboxylic acid.
Reaction of 1,2,3-triazole sodium salt with tri-
fluoromethanesulfonyl chloride. To a solution of
1,2,3-triazole sodium salt in tetrahydrofuran we added
dropwise under stirring and cooling an equimolar
amount of trifluoromethanesulfonyl chloride in THF.
An alternative route is the reaction of 2-phenyl-2H-
1,2,3-triazole-4-carboxamide (IX) with CF3SO2Cl in
methanol. However, it afforded methyl 2-phenyl-2H-
1,2,3-triazole-4-carboxylate (X) and trifluoromethane-
sulfonamide instead of the desired mixed imide.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

1520
MESHCHERYAKOV et al.
The mixture was stirred for 1 h, heated for 2 h under
reflux, and cooled. The precipitate was filtered off,
and the filtrate was evaporated. The viscous semicrys-
talline residue underwent spontaneous decomposition
with strong heat evolution and tarring on exposure
to air (in an attempt to dry the product).
b. 4,5-Dibromo-2H-1,2,3-triazole sodium salt,
1.5 g (0.006 mol), was added in portions to a solution
of 0.93 g (0.0033 mol) of trifluoromethanesulfonic
anhydride in 30 ml of methylene chloride, cooled to
78 C, the mixture was stirred for 30 min at that
temperature, the cooling bath was removed, and the
mixture was stirred for 1 h at room temperature.
The precipitate of sodium trifluoromethanesulfonate
was filtered off and washed with methylene chloride,
the filtrate was combined with the washings, and
the solvent was distilled off to obtain 1.54 g (71%)
of compound V as an orange viscous material. The
13C and 19F NMR spectra of the product coincided
with those of a sample prepared as described in a.
4,5-Dibromo-2-(2-tetrahydrofuryl)-2H-1,2,3-tri-
azole (IV). A solution of 1.5 g (0.006 mol) of 4,5-di-
bromo-2H-1,2,3-triazole sodium salt (4,5-dibromo-
2H-1,2,3-triazole was synthesized by the procedure
described in [12]) in 20 ml of tetrahydrofuran was
cooled to 10 15 C, and a solution of 1 g (0.006 mol)
of trifluoromethanesulfonyl chloride in 5 ml of THF
was added dropwise. The mixture slightly warmed up,
and a colorless solid precipitated. When the addition
was complete, the mixture was stirred for 2 h at room
temperature and for 1 h at 60 C, cooled, poured into
ice water, and extracted with two portions of diethyl
ether. The combined ether extracts were washed with
a solution of sodium carbonate and with water, dried
over MgSO4, and evaporated to isolate 1.68 g (94%)
of crude product IV which was purified by recon-
Reaction of 1H-1,2,3-benzotriazole (II) with tri-
fluoromethanesulfonic anhydride. To a solution of
0.6 g (5 mmol) of 1H-1,2,3-benzotriazole in 8 ml
of methylene chloride we added dropwise under stir-
ring at room temperature 0.71 g (2.5 mmol) of tri-
fluoromethanesulfonic anhydride, and the mixture was
stirred for 1 h and was left to stand for 24 h. The
precipitate was filtered off, washed with anhydrous
diethyl ether, and dried. The product was 1,2,3-benzo-
triazolium trifluoromethanesulfonate (VII), yield
0.77 g (100%), colorless crystals with mp 144 C. IR
1
densation under reduced pressure. H NMR spectrum
(CDCl3), , ppm: 2.03 m (1H, NCCHB), 2.34 m (2H,
OCCH2), 2.54 m (1H, NCCHA), 4.00 d.t (1H, OCHB,
J = 6.8, 7.6 Hz), 4.11 d.t (1H, OCHA, J = 6.4, 7.6 Hz),
6.16 d.d (1H, CH, J = 2.4, 6.4 Hz). 13C NMR spec-
1
spectrum, , cm : 3100 2700, 1620, 1430, 1290
1
1130, 1030, 1010, 900, 780, 760, 640, 510. H NMR
spectrum (acetone-d6), , ppm: 7.99 m (2H, 5-H,
6-H), 8.32 m (2H, 4-H, 7-H), 13.0 15.5 br.s (2H,
NH). 13C NMR spectrum (acetone-d6), C, ppm:
trum (CDCl3), C, ppm: 23.95 t (OCH2CH2, JCH
131.9 Hz), 31.10 t (NCC, JCH = 133.2 Hz), 69.76 t
(OCH2, JCH = 149.4 Hz), 93.57 d (NCO, JCH
169.4 Hz), 125.02 (C N). Mass spectrum, m/z
(Irel, %): 295 (2) [M]+, 117 (4) [C2NBr]+, 79 (4) [Br]+,
71 (100) [C4H7O]+, 43 (20) [C2H3O]+. Found, %:
C 23.76; H 2.31; N 14.10. C6H7Br2N3O. Calculated,
%: C 24.27; H 2.38; N 14.15.
=
=
115.07 (C4, C7), 131.85 (C5, C6), 135.02 (C8, C9),
1
121.78 q (CF3, JCF = 319.30 Hz). 19F NMR spectrum
(acetone-d6):
79.09 ppm. Found, %: C 31.71;
F
H 2.23; F 19.89; N 15.74; S 11.80. C7H6F3N3O3S.
Calculated, %: C 31.23; H 2.25; F 21.17; N 15.61;
S 11.91.
4,5-Dibromo-2-trifluoromethylsulfonyl-2H-1,2,3-
triazole (V). a. A solution of 2.5 g (0.01 mol) of
4,5-dibromo-2H-1,2,3-triazole sodium salt in 5 ml of
methanol was added dropwise over a period of 30 min
to a solution of 2.54 g (0.015 mol) of trifluoro-
methanesulfonyl chloride in 10 ml of methanol,
cooled to 3 5 C. A white solid gradually precipitated
during the addition. The mixture was stirred for 2 3 h
at room temperature, the progress of the reaction
being monitored by TLC. The precipitate was filtered
off and washed with cold methanol, and the solvent
was distilled off from the filtrate to isolate 3.42 g
(95%) of compound V as slightly yellowish crystals.
Evaporation of the filtrate gave 0.56 g (89%) of
1-trifluoromethylsulfonyl-1H-1,2,3-benzotriazole (VI)
as brownish crystals with mp 35 C. IR spectrum, ,
1
cm : 1600, 1490, 1440, 1280 1110, 1060, 900, 780,
1
750, 680, 610, 580, 550, 520. H NMR spectrum
(acetone-d6), , ppm: 7.77 d.d.d (1H, 6-H, J4, 6 = 1.3,
J5, 6 = 7.0, J6, 7 = 8.3 Hz), 7.97 d.d.d (1H, 5-H, J4, 5
8.3, J5, 7 = 1.1 Hz), 8.01 d.d.d (1H, 4-H, J4, 7
=
=
0.9 Hz), 8.34 d.d.d (1H, 7-H). 13C NMR spectrum
(acetone-d6), C, ppm: 112.66 (C4), 120.11 q (CF3,
1JCF = 322.8 Hz), 122.51 (C7), 128.49 (C6), 133.08
(C8), 133.59 (C5), 145.60 (C9). 19F NMR spectrum
13C NMR spectrum (acetone-d6), C, ppm: 119.47 q
(CF3, JCF = 324.0 Hz), 136.83 (X N). 19F NMR
(acetone-d6):
76.09 ppm. Found, %: C 33.65;
F
H 1.65; F 22.06; N 16.40; S 13.67. C7H4F3N3O2S.
Calculated, %: C 33.47; H 1.61; F 22.69; N 16.73;
S 12.76.
spectrum:
73.58 ppm. Found, %: C 10.67;
H 11.56. C3FBr2F3N3O2S. Calculated, %: C 10.04;
H 11.71.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

REACTIONS OF 1,2,3-TRIAZOLES WITH TRIFLUOROMETHANESULFONYL
N-(Dimethylaminomethylene)trifluoromethane- REFERENCES
1521
sulfonamide (VIII). A solution of 1.63 g (9.5 mmol)
of trifluoromethanesulfonamide sodium salt in 10 ml
of DMF was added dropwise to a mixture of 1.95 g
(9.5 mmol) of 2-phenyl-2H-1,2,3-triazole-4-carbonyl
chloride (III) (prepared by treatment of 2-phenyl-2H-
1,2,3-triazole-4-carboxylic acid [13] with SOCl2) and
20 ml of DMF, cooled to 10 15 C. The mixture was
stirred for 2 h at room temperature, the solvent was
removed on a rotary evaporator, the residue was
treated with an alcohol hexane mixture, and the pre-
cipitate of 2-phenyl-2H-1,2,3-triazole-4-carboxylic
acid, 1.07 g (60%), was filtered off, washed, and dried
in air. The mother liquor was concentrated to isolate
formamidine VIII which was purified by recrystalliza-
tion from diethyl ether hexane. Yield 1.83 g (94%),
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=
139.8 Hz), 119.56 q (CF3, JCF = 320.5 Hz),
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methanesulfonyl chloride in 5 ml of methanol was
added dropwise at room temperature to a mixture of
0.5 g (2.7 mmol) of 2-phenyl-2H-1,2,3-triazole-4-car-
boxamide (IX) [14] and 0.56 g (4 mmol) of K2CO3
in 10 ml of methanol. The mixture was stirred for 2 h
and poured into ice water, and the precipitate was
filtered off and dried in air. Yield 0.52 g (95%),
mp 84 85 C; published data [13]: mp 85 86 C.
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The authors thank Yu.A. Chuvashev for recording
the mass spectrum of compound IV.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003