One-pot synthesis of disulfide-tethered ionic liquids by the reaction between 4H-1,2,4-triazole-3-thiol and α-iodoketones

Article abstract of DOI:10.1016/j.mencom.2015.09.004

The one-pot reaction of 4H-1,2,4-triazole-3-thiol with 1-iodopropan-2-one or 1,3-diiodopropan-2-one proceeds without solvents and basic media to afford a novel family of ionic liquids containing disulfide bridge.

Full text of DOI:10.1016/j.mencom.2015.09.004

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 334–335
One-pot synthesis of disulfide-tethered ionic liquids by the reaction
between 4H-1,2,4-triazole-3-thiol and a-iodoketones
Lyudmila G. Shagun,* Ivan A. Dorofeev, Larisa V. Zhilitskaya,
Lyudmila I. Larina and Nina O. Yarosh
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
664033 Irkutsk, Russian Federation. Fax: +7 3952 419 346; e-mail: shag@irioch.irk.ru
DOI: 10.1016/j.mencom.2015.09.004
The one-pot reaction of 4H-1,2,4-triazole-3-thiol with 1-iodopropan-2-one or 1,3-diiodopropan-2-one proceeds without solvents and
basic media to afford a novel family of ionic liquids containing disulfide bridge.
Triazole moiety is not uncommon in drugs,1 herbicides, fungi-
cides,2 insecticides and acaricides.3 Triazoles are valuable pre-
cursors for the synthesis of magnetoactive,4 luminescent,5 coor-
dination compounds,6 high-energy compositions,7 ionic liquids,8
and antitumor medicines.9,10
N
N
SH
O
N
N
Me
N
I2
I
+
SH
– HI
– HI
N
O
H
Me
1
2
Classical methods for the S-derivatization of valuable 1,2,4-tri-
azole-3-thiol 1 comprise the use of chloro- or bromomethyl-
substituted aliphatic, aromatic, or heteroaromatic compounds.10,11
For example, S-alkylation with chloromethyl compounds is suc-
cessfully implemented in the presence of anhydrous potassium
carbonate or potassium hydroxide. In the case of bromo
analogues, the reaction requires no basic media. The data on
alkylation of thiol 1 with 1-iodopropan-2-one and 1,3-diiodo-
propan-2-one are lacking in the literature.
A
Me
Me
O
O
N
N
N N
S
S
I–
N
N
N
N
N I3
N
2 (2 equiv.)
N
N
S
S
O O
Me
Me
O
O
Earlier we have found that reactivity of iodo ketones in
comparison with chloro and bromo analogues in alkylation of
azoles is quite specific due to high lability of the C–I bond,
ability of the iodomethyl group to be reduced with hydrogen
iodide released in the course of the alkylation, and formation of
stable triiodide anion or new types of liquid salts.12 With this
assumption, in this work, we have studied the interaction of
1,2,4-triazole-3-thiol 1 with 1-iodopropan-2-one 2 and 1,3-diiodo-
propan-2-one 3.
Thereactionbetween1,2,4-triazole-3-thiol1and1-iodopropan-
2-one 2 proceeds at 45°C in the absence of solvents to deliver
bis-salt 4 (Scheme 1),† in one synthetic operation. The obtained
experimental data allow us to assume that the reaction represents
a domino sequence involving alkylation of triazole 1 with iodo
ketone 2 at the pyrrole ring, partial reduction of iodopropanone 2
to acetone with the released hydrogen iodide, oxidation of the
Me
Me
+
+
HI
I2
2
I–
Me2C=O
I3
+ I2
4
Scheme 1
SH moiety to disulfide by the delivered iodine and quaternization
of the nitrogen pyridine atoms.
It is known that alkylation of benzotriazole and 1,3-bis(benzo-
triazolyl)propan-2-one with 1,3-dihalopropan-2-one occurs with
the participation of two halomethyl groups of ketone that allows
one to synthesize both bis-derivatives and cyclic products with
dimethylenecarbonyl bridges.13,14 However, the interaction between
1,2,4-triazole-3-thiol 1 and 1,3-diiodopropan-2-one 3 is accom-
panied by reduction of the iodomethyl groups with hydrogen
iodide released in the course of alkylation, thus preventing the
reaction involving the second iodomethyl moiety (Scheme 2).†
Therefore, polyiodide 4 becomes the major reaction product.
†
Elemental analysis was performed on an automatic Thermo Scientific
Flash 2000 CHNS-analyzer. UV spectra were recorded on a UV-VIS
Lambda 35 (MeCN) spectrometer. IR spectra were run on a Vertex 70
instrument (film). 1H, 13C, 15N NMR spectra were measured on a Bruker
DPX-400 spectrometer (400.13, 100.61, 40.56 MHz, respectively) in
acetone-d6. Chemical shifts were measured relative to TMS (for 1H and
13C) and nitromethane (for 15N). 2D 1H-15N NMR spectra were recorded
using HMBC-gp 1H-15N technique.
Reaction between mercaptotriazole 1 and a-iodoketones 2, 3 (general
procedure). Mercaptotriazole 1 was added to a-iodoketone 2, 3 under
argon at 45°C. The mixture was stirred for 2 h until disappearance of the
starting ketones 2, 3, diluted with acetone (5 ml) and precipitated with
diethyl ether (30 ml). The red oil formed was re-precipitated 3 times
(acetone:diethyl ether, 1:6) and purified on a chromatographic column
(10×500 mm) filled with silica gel MN Kieselgel 60 (0.063–0.2 mm).
Acetone was used as an eluent.
5,5'-Dithiobis[1,4-bis(2-oxopropyl)-4H-1,2,4-triazol-1-ium] tetraiodide
4. (a) From 1 (0.4 g, 4 mmol) and 2 (1.4 g, 8 mmol), 0.63 g (34%) of
dark-red oil was obtained (Rf = 0.84, acetone). UV (MeCN, lmax/nm):
210 (I–), 293, 361 (I3–). 1H NMR, d: 2.32 (s, 12H, Me), 4.44 (s, 8H,
NCH2), 9.46 (s, 2H, H-5). 13C NMR, d: 27.90 (Me), 42.67 (NCH2), 143.69
(C-5), 153.74 (C-3), 200.05 (C=O). 15N NMR, d: –113.8 (N-1), –146.3
(N-2, 3JNH 8.1 Hz), –187.8 (N-4, 2JNH 9.6 Hz). Found (%): C, 19.97; H,
2.14; I, 54.98; N, 9.51; S, 7.40. Calc. for C16H22I4N6O4S2 (%): C, 20.55;
H, 2.35; I, 54.38; N, 8.99; S, 6.85.
(b) From 1 (0.2 g, 2 mmol) and 3 (1.2 g, 4 mmol), 0.28 g (30%) of dark-
red oil was obtained (Rf = 0.84, acetone). 1H NMR, d: 2.39 (s, 12H, Me),
4.48 (s, 8H, NCH2), 9.50 (s, 2H, H-5). 13C NMR, d: 27.97 (Me), 42.70
(NCH2), 143.72 (C-5), 153.80 (C-3), 200.00 (C=O). Found (%): C, 19.88;
H, 2.00; I, 54.78; N, 8.51; S, 7.10. Calc. for C16H22I4N6O4S2 (%): C, 20.55;
H, 2.35; I, 54.38; N, 8.99; S, 6.85.
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 334 –

Mendeleev Commun., 2015, 25, 334–335
I
In conclusion, we have discovered a new and convenient access
to novel type of ionic liquids possessing two disulfide-tethered
azolium moieties. The key steps of the reaction mechanism
involve oxidation of the mercapto group and alkylation of the
azole nitrogen atoms. The synthesis can be accomplished in one
synthetic operation without solvents and basic media.
O
I–
N
N
N
N
I2
2 I
I
+
SH
4
SH
N
– HI
O
N
H
1
3
This work was supported by the President of the Russian
Federation (program for the support of leading scientific schools,
grant no. NSh-3649.2014.3). The main results were obtained
using the equipment of Baikal Analytical Center of Collective
Users SB RAS.
O
I
B
4
I–
Me2C=O
I3
+ 2 I2
+
+
2 HI
I2
References
Scheme 2
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To verify the results obtained, we have carried out a counter
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disulfide 5 and 1-iodopropan-2-one 2 (Scheme 3).‡ In this case,
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N
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H
H
Me
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O
O
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N I–
N
I–
N
2 (2 equiv.)
N
N
4
S
S
N
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Scheme 3
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13 A. R. Katritzky and J. Wu, Synthesis, 1994, 597.
The structure of salt 4 was proved by elemental analysis,
IR, UV, H, 13C and 15N NMR techniques. In the H and 13C
NMR spectra, signals of the CH2 groups are observed at 4.4 and
42.7 ppm, respectively. The 2D 15N HMBC 1H-15N NMR spectra
of the salt show cross-peaks of N-1, N-2, N-4 nitrogen atoms with
protons of both the triazole ring and the methylene fragments. In
the IR spectra, the carbonyl groups are present in the region of
1737 cm–1. The UV spectra of salt 4 contain absorption bands,
which are typical of iodide (210 nm) and triiodide (287 and
362 nm) anions.15
1
1
‡
Reaction between 3,3'-dithiobis-4H-1,2,4-triazole 5 and 1-iodopropan-
2-one 2. Disulfide 5 (0.2 g, 1 mmol) was added to ketone 2 (0.74 g,
4 mmol) under argon at 45°C. The reaction mixture was stirred for 2 h at
62°C until disappearance of compound 2. Salt 4 was isolated and purified
by general procedure to give 0.33 g (32%) of dark-red oil (Rf = 0.84,
acetone). 1H NMR, d: 2.34 (s, 12H, Me), 4.40 (s, 8H, NCH2), 9.41 (s, 2H,
H-5). 13C NMR, d: 28.05 (Me), 42.77 (CH2), 143.90 (C-5), 153.95 (C-3),
199.85 (C=O). 15N NMR, d: –113.8 (N-1), –146.3 (N-2, 3JNH 8.1 Hz), –187.8
(N-4, 2JNH 9.6 Hz). Found (%): C, 20.15; H, 2.12; I, 54.10; N, 8.45; S, 6.55.
Calc. for C16H22I4N6O4S2 (%): C, 20.55; H, 2.35; I, 54.38; N, 8.99; S, 6.85.
Compound 5 was synthesized according to the published protocol16
by mixing the ethanol solution of 1,2,4-triazole-3-thiol 1 (1 g, 10 mmol)
and I2 (5 g, 20 mmol). The reaction course and compounds purity were
monitored by TLC using Silufol UV-254 plates (acetone as eluent).
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16 M. S. Chernovyants, N. V. Aleshina, I. N. Shcherbakov, Z. A. Starikova,
Russ. J. Gen. Chem., 2013, 83, 986 (Zh. Obshch. Khim., 2013, 83, 852).
Received: 11th February 2015; Com. 15/4561
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