Synthesis of symmetrical disulfides by reaction of fluorine-containing thiiranes with cyclic amines

Article abstract of DOI:10.1134/S1070428017040030

Regioselective opening of the thiirane ring in fluorine-containing thioglycidyl ethers and [(perfluorobutyl) methyl]thiirane by the action of cyclic amines afforded 1,2-aminothiols which were oxidized in situ to symmetrical disulfides. The rate of formati

Full text of DOI:10.1134/S1070428017040030

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 4, pp. 514–519. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © S.A. Nalet’ko, T.I. Gorbunova, M.G. Pervova, M.I. Kodess, A.Ya. Zapevalov, V.I. Saloutin, 2017, published in Zhurnal
Organicheskoi Khimii, 2017, Vol. 53, No. 4, pp. 507–513.
Synthesis of Symmetrical Disulfides by Reaction
of Fluorine-Containing Thiiranes with Cyclic Amines
S. A. Nalet’ko, T. I. Gorbunova,* M. G. Pervova, M. I. Kodess,
A. Ya. Zapevalov, and V. I. Saloutin
Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
*
e-mail: gorbunova@ios.uran.ru
Received December 21, 2016
Abstract—Regioselective opening of the thiirane ring in fluorine-containing thioglycidyl ethers and [(per-
fluorobutyl)methyl]thiirane by the action of cyclic amines afforded 1,2-aminothiols which were oxidized in situ
to symmetrical disulfides. The rate of formation of the latter depended on the amine basicity. According to the
NMR data, the resulting disulfides were mixtures of erythro and threo diastereoisomers.
DOI: 10.1134/S1070428017040030
Organic disulfides are used in many branches of
industry, as well as in fundamental research. They play
an important role in biochemical processes [1] and are
used as vulcanizing agents [2, 3], extinguisher com-
ponents [4], and convenient precursors of more com-
plex molecules in organic synthesis [5–8]. Sulfur-con-
taining organic compounds are often used as lubricant
additives to improve tribological characteristics [9].
However, all known data refer to hydrocarbyl disul-
fides, whereas only a few published data are available
on fluorinated disulfides.
ed disulfide, N,N,N′,N′-tetramethylcystamine, with
N-(perfluoroethyl)bromoacetamide to form quaternary
ammonium salt (Scheme 1).
The potential of the synthesis of fluorinated sym-
metrical disulfides via opening of the heterocyclic
fragment of fluorine-containing thiiranes by the action
of various nucleophiles, including amines, has not
been exhausted so far. This reaction was used previ-
ously to obtain non-fluorinated analogs [14, 15]. Elec-
tron-withdrawing polyfluoroalkyl substituents enhance
polarization of the thiirane ring and considerably affect
its reactivity, which could lead to the formation of
different products.
There are two synthetic approaches to symmetrical
fluorine-containing disulfides. The first approach
involves formation of a disulfide bond between fluori-
nated molecules, including those containing sulfur
atoms, under basic conditions [10, 11]. For example,
thiouronium salts of the general formula
The goal of the present work was to develop
a procedure for selective synthesis of fluorine-contain-
ing symmetrical disulfides by reaction of polyfluori-
nated thiiranes with cyclic amines.
+
–
[
R (CH ) SC(NH )NH ] X (X = OTs, Br) reacted
F 2 4 2 2
with 10 equiv of sodium hydroxide at 70°C (10 h) to
give symmetrical disulfides R (CH ) SS(CH ) R [11].
The second approach is based on the introduction of
a polyfluoroalkyl substituent into the molecule of
already synthesized symmetrical disulfide. Thebault
et al. [12, 13] reported on the reaction of non-fluorinat-
It is known that opening of the thiirane ring by the
action of nucleophiles yields thiols [16]. These reac-
tions are often accompanied by polymerization or
sulfur extrusion [17, 18]. Examples are reactions of
thiirane with alkali metal alkoxides or sodium phen-
oxide in aprotic solvents, which produced high-molec-
F
2 4
2 4
F
Scheme 1.
Me
N
Br–
H
H
Et O, reflux, 48 h
2
Me
S
N
N
S
+
RF
RF
N
S
Me
Br
N
Me
Me
Me
O
O
2
5
14

SYNTHESIS OF SYMMETRICAL DISULFIDES
515
Scheme 2.
RF
X
X
MeCN, reflux
N
RF
[O]
RF
+
N
S
S
HN
X
SH
N
S
X
RF
4a–4c, 5a, 5b
1
a–1c
2a–2c, 3a, 3b
F 2 2 2 2 4 2 4 9
R = H(CF ) CH O (a), H(CF ) CH O (b), n-C F (c); 2, 4, X = O; 3, 5, X = NMe.
ular-weight compounds due to weak nucleophilicity of
alkoxide ion compared to thiolate ion generated in situ
as a result of thiirane ring opening [19]. Non-fluori-
nated thiiranes reacted with amines to give the
corresponding 1,2-aminothiols which can be isolated
and characterized, whereas prolonged reaction time
promoted their dimerization to disulfides [14, 15].
Dimerization of 1,2-aminothiols was accounted for
by their oxidation in situ in the presence of nitrogen
bases [20, 21].
to the corresponding disulfides 4a–4c, 5a, and 5b, the
conversion of 1a–1c being 100%. All our attempts to
isolate pure thiols 2a–2c, 3a, and 3b were unsuccess-
ful, and their formation in the reaction mixtures was
confirmed by GC/MS. We failed to isolate the corre-
sponding disulfide in the reaction of 1c with N-methyl-
piperazine; in this case, resinous unidentifiable prod-
ucts were formed.
Aniline as the weakest base among the examined
amines showed a different reactivity toward thiiranes
1a–1c. The reactions of aniline with thiiranes 1a and
1b gave thiols 6a and 6b which were converted to
disulfides 7a and 7b at a much lower rate (Scheme 3).
When a mixture of 1a or 1b and aniline in acetonitrile
was refluxed for 12 h, only thiols 6a and 6b were
formed, whereas after 24 h the product ratio 6:7 was
In this work we used as starting compounds
fluorine-containing thiiranes 1a–1c prepared as de-
scribed in [18, 22–25] and various moderately basic
cyclic amines, namely aniline (pK 4.58), morpholine
a
(
(
pK 8.70), and N-methylpiperazine (pK 9.62) [26]
Scheme 2). The reactions of 1a–1c with cyclic amines
a
a
1
were carried out in acetonitrile which enhanced the
nucleophilicity of amines. The conversion of the initial
reactants was monitored by GC/MS.
3 :7 according to the H NMR data. No complete
oxidation of 6a and 6b to 7a and 7b was achieved
under the above conditions after heating for 50 h while
bubbling air through the reaction mixture.
More basic aliphatic amines, such as methylamine
(
pK 10.62 [26]), dimethylamine (pK 10.77 [26]),
a
a
We succeeded in accomplishing complete oxidation
of mixtures 6a/7a and 6b/7b only after isolating them
from the reaction mixtures by HPLC and subsequently
heating in boiling acetonitrile in the presence of
N-methylpiperazine. After 5 h, the reaction mixtures
contained only disulfides 7a and 7b. Guseinova et al.
[27] previously synthesized compound 6a by heating
in a sealed ampule without a solvent at 95–100°C for
10 h, but the formation of disulfide 7a was not noted.
Presumably, thiol 6a cannot be oxidized to disulfide 7a
in the absence of air. The conversion of thiirane 1c in
ethylamine (pK 10.63 [26]), and diethylamine
(
mixtures of resinous unidentifiable products. Success-
ful syntheses of disulfides from non-fluorinated
thiiranes and cyclic amines were reported in [14, 15].
a
pK 10.93 [26]) reacted with thiiranes 1a–1c to give
a
According to the GC/MS data, the reactions of
a–1c with N-methylpiperazine and morpholine
1
initially give mixtures of thiols 2a–2c, 3a, and 3b with
disulfides 4a–4c, 5a, and 5b (Scheme 2); after 1.5–
1
2 h, thiols 2a–2c, 3a, and 3b are completely oxidized
Scheme 3.
1
'
3
1
NH2
2
RF
O
N
MeCN, reflux
4 h
H
2
S
1
a, 1b +
+
S
RF
O
N
H
H
N
O
RF
SH
6
a, 6b
7a, 7b
R
F
2 2 2 4
= H(CF ) (a), H(CF ) (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

5
16
NALET’KO et al.
1
2
the reaction with aniline in boiling acetonitrile did not
exceed 2% after 20 h. Further studies are necessary to
rationalize this result.
the H NMR spectrum as two triplets of triplets ( J
=
HF
2
53.2, J = 4.8 Hz) with as small displacement as
HF
1
19
1.9 Hz. In the H–{ F} double resonance spectrum
recorded with broad-band decoupling from fluorine
nuclei, the spectral pattern is considerably simpler, and
two singlets corresponding to two diastereoisomers are
observed.
Our data suggest that opening of the thiirane ring in
1
a–1c by the action of amines and subsequent oxida-
tion of thiols 2a–2c, 3a, 3b, 6a, and 6b to symmetrical
disulfides 4a–4c, 5a, 5b, 7a, and 7b with atmospheric
oxygen are sensitive to the amine nature. Increased
basicity of the amine favors formation of thiolate ion
which then reacts with atmospheric oxygen according
to single-electron transfer mechanism, and dimeriza-
tion of the sulfanyl radicals thus formed yields the cor-
responding disulfides [28].
1
3
On the other hand, the C NMR spectra of all
disulfides 4a–4c, 5a, 5b, 7a, and 7b displayed different
signals from almost all carbon atoms in the vicinity of
the chiral centers. The diastereoisomer ratio for disul-
fides 4a, 4b, 5a, 5b, 7a, and 7b was about 1:1, while
the isomer ratio for compound 4c was 2.3:1.
1
The molecular ion peaks of 1,2-aminothiols 2a–2c,
The H NMR spectral data given in [27] for
3
a, and 3b had a relative intensity of lower than 0.1%,
and the intensity of the molecular ion peaks of 6a and
b did not exceed 10%. The characteristic peaks were
compound 6a included only the range δ 2.85–3.45 ppm
for the CH CH(SH)CH NH protons, whereas no
2
2
1
6
H(CF ) CH signals were given. The H NMR spec-
2 2 2
+
those belonging to the [M – HS] ions with relative
intensities of 0.1–10%, and the [CH R] ions (R =
morpholin-4-yl, 4-methylpiperazin-1-yl, anilino) had
the maximum intensity. Compounds 4a–4c, 5a, 5b,
trum of mixture 6a/7a recorded by us under analogous
conditions contained a doublet at δ ~1.7 ppm with
a coupling constant of ~9 Hz due to the SH proton.
Thus, we have refined chemical shifts of protons in
some functional groups of fluorine-containing thiols
and disulfides.
+
2
7
a, and 7b displayed no molecular ion peak in
the mass spectra, while the heaviest ion was
+
[R CH CH(SS)CH R] with a relative intensity of up
F 2 2
It is known that non-fluorinated disulfides are used
as lubricant additives [9]. There are no data on similar
application of fluorine-containing analogs, though
fluorine atoms, as well as sulfur atoms, are active
species capable of forming monomolecular layers on
the surface of metal friction pair, which improves
tribological characteristics of lubricant oils. Com-
pounds 4a, 4b, and 5b are sparingly soluble in I-20A
industrial oil; however, ultrasonic dispersion method
made it possible to obtain 2% emulsions of 4a, 4b, and
5b in I-20A, which were stable over 1–1.5 h. The
friction coefficients of the obtained compositions were
compared with that of the unmodified oil (see table). In
all cases, the friction coefficients of I-20A modified
with disulfides 4a, 4b, and 5b were lower than that of
the initial oil. The best effect was attained at small
loads (10 and 20 N), whereas raising the load to 30 and
to 2%. This ion decomposed via successive elimination
+
of two sulfur atoms, and the [CH R] ion was the most
2
abundant.
As shown in [29], bis(3-chloro-1,1,1-trifluoro-
propan-2-yl) disulfide obtained by reaction of 3,3,3-tri-
fluoroprop-1-ene with sulfur monochloride at 115–
1
20°C exists as a mixture of erythro and threo dia-
stereoisomers; however, the isomer ratio was not
given. Molecules of disulfides 4a–4c, 5a, 5b, 7a, and
7
b possess two asymmetric carbon atoms, so that they
also can exist as mixtures of threo and erythro isomers.
The diastereoisomers showed insignificant differences
1
in the H NMR chemical shifts, and signal doubling
was observed only for a few protons of compounds 4a
and 5a with a relatively short fluoroalkyl radical. For
example, the terminal HCF proton of 4a resonated in
2
6
0 N reduced the effect.
Friction coefficients for 2% emulsions of compounds 4a, 4b,
and 5b in I-20A commercial oil
In summary, we have proposed a convenient
synthetic approach to symmetrical fluorine-containing
disulfides, which is based on the reaction of thiiranes
containing polyfluorinated substituents with cyclic
amines in a polar aprotic solvent. The rate of formation
of the target disulfides depends on the amine basicity:
more basic amines ensure higher reaction rate. The
resulting fluorine-containing disulfides attract interest
as lubricant additives.
Load, N
I-20A
I-20A/4a I-20A/4b I-20A/5b
1
2
3
6
0
0
0
0
0.099
0.101
0.107
0.116
0.046
0.061
0.071
0.091
0.016
0.051
0.066
0.096
0.055
0.054
0.072
0.093
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

SYNTHESIS OF SYMMETRICAL DISULFIDES
517
EXPERIMENTAL
Intermediate 1,2-aminothiols 2a–2c, 3a, 3b, 6a, and
b were characterized only by mass spectral data.
6
The NMR spectra were recorded on Bruker DRX-
00 and Avance 500 spectrometers (400 and 500 MHz,
1
-(Morpholin-4-yl)-3-(2,2,3,3-tetrafluoropropyl-
4
oxy)propane-2-thiol (2a). Mass spectrum, m/z (I ,
rel
1
19
respectively, for H; 376 and 470 MHz for F;
+
+
%
): 291 (0.2) [M] , 258 (0.3) [M – HS] , 171 (1.0),
1
3
1
26 MHz for C); the chemical shifts were measured
1
45 (2.7), 100 (100), 70 (8.5), 56 (16.1), 42 (12.2).
1-(Morpholin-4-yl)-3-(2,2,3,3,4,4,5,5-octafluoro-
1
relative to tetramethylsilane ( H), hexafluorobenzene
1
9
13
(
F), or solvent signal ( C). Signals in the NMR
pentyloxy)propane-2-thiol (2b). Mass spectrum, m/z
1
13
spectra of 4a were assigned using 2D H– C HSQC
+
+
(
(
(
I , %): 391 (0.01) [M] , 358 (0.05) [M – HS] , 271
–
1
rel
technique. The IR spectra (400–4000 cm ) were
recorded on a Perkin Elmer Spectrum One spectrom-
eter equipped with an ATR accessory. The elemental
analyses were obtained with a Perkin Elmer 2400
automated CHN analyzer. Gas chromatographic/mass
spectrometric analysis was performed with a Trace GC
Ultra DSQ II chromatograph coupled with a mass-
selective detector [Thermo TR-5ms capillary column,
0.2), 245 (0.7), 145 (0.9), 100 (100), 70 (14.1), 56
28.2), 42 (20.3).
1
-(Morpholin-4-yl)-4,4,5,5,6,6,7,7,7-nonafluoro-
heptane-2-thiol (2c). Mass spectrum, m/z (I , %): 379
rel
+
+
+
(
2
(
0.05) [M] , 360 (0.1) [M – F] , 346 (0.6) [M – HS] ,
92 (0.4), 146 (0.8), 126 (2.2), 100 (100), 70 (5.1), 56
8.3), 42 (5.0).
-(1-Methylpiperazin-4-yl)-3-(2,2,3,3-tetra-
fluoropropyloxy)propane-2-thiol (3a). Mass spec-
1
3
0 m×0.25 mm, film thickness 0.25 μm (polydi-
methylsiloxane containing 5% of phenyl groups); oven
temperature programming from 40°C (3 min) to 280°C
at a rate of 10 deg/min; injector temperature 250°C,
detector temperature 200°C, interface temperature
50°C; carrier gas helium, split ratio 1:50, flow rate
.0 mL/min; total ion current monitoring, a.m.u. range
0–1000; electron impact, 70 eV]. Preparative HPLC
+
+
trum, m/z (I , %): 304 (0.05) [M] , 302 (1.0) [M – 2] ,
rel
+
2
71 (9.2) [M – HS] , 113 (100), 70 (60.2), 42 (40.7).
1-(1-Methylpiperazin-4-yl)-3-(2,2,3,3,4,4,5,5-
2
1
2
octafluoropentyloxy)propane-2-thiol (3b). Mass
+
spectrum, m/z (Irel, %): 404 (0.02) [M] , 402 (1.0)
+
+
[M – 2] , 371 (8.4) [M – HS] , 113 (100), 70 (71.8),
was done with an Agilent 1200 semipreparative liquid
chromatograph equipped with an autosampler
42 (39.7).
1-Anilino-3-(2,2,3,3-tetrafluoropropyloxy)]-
(
900 μL), diode array detector (λ 200 nm), and fraction
propane-2-thiol (6a). Mass spectrum, m/z (I , %):
297 (9.7) [M] , 264 (1.1) [M – HS] , 106 (100), 77
(28.8), 51 (24.9).
rel
+
+
collector; ZORBAX Eclipse XDB-C18 semiprepara-
tive column, 9.4 mm×250 mm, grain size 5 μm; room
temperature; eluent acetonitrile–water (75 :25 by
volume), flow rate 4 mL/min, isocratic elution. The
friction coefficients were measured with a CSM
Instruments tribometer using a ball/disk friction pair
1
-Anilino-3-(2,2,3,3,4,4,5,5-octafluoropentyloxy)-
propane-2-thiol (6b). Mass spectrum, m/z (I , %):
rel
+
+
3
97 (1.2) [M] , 364 (0.3) [M – HS] , 106 (100), 77
(
27.9), 51 (27.1).
(
6-mm ball and 35-mm disk made of steel 3 with
Bis[6,6,7,7-tetrafluoro-1-(morpholin-4-yl)-4-oxa-
a Rockwell hardness of 60–63 (C scale); loads 10, 20,
3
1
heptan-2-yl] disulfide (4a, erythro–threo ~1:1). Yield
0, and 60 N, number of cycles 10000; lubricant dose
00 μL; all tests were carried out in quadruplicate; the
–1
7
2
7%, dark yellow viscous oil. IR spectrum, ν, cm :
1
858, 2812 (C–H), 1099 (C–F, C–O–C). H NMR
measurement error did not exceed 0.002.
spectrum (500 MHz, CDCl ), δ, ppm: 2.46 m [4H,
3
General procedure for the reaction of thiiranes
a–1c with amines. A round-bottom flask equipped
N(CH ) ], 2.52–2.60 m (2H, 1-H), 3.07 t.t and 3.09 t.t
2
2
1
(1H each, 2-H, J = 7.3, 5.4 Hz), 3.69 m [4H, O(CH ) ],
2 2
with a reflux condenser and a magnetic stirrer was
charged with 20 mL of acetonitrile, 10 mmol of
thiirane 1a–1c, and 20 mmol of the corresponding
amine. The mixture was heated to the boiling point and
kept for 12–24 h under reflux. It was then cooled and
washed with 30 mL of water, the organic layer was
separated, and the aqueous layer was extracted with
chloroform (2×5 mL). The combined extracts were
3.76–3.90 m (4H, 3-H, 1′-H), 5.93 t.t (1H, 3′-H, J =
1
3
53.2, 4.8 Hz). C NMR spectrum (126 MHz, CDCl ),
3
2
δ , ppm: 49.29 and 49.35 (C ), 53.89 [N(CH ) ], 59.35
and 59.39 (C ), 66.86 [O(CH ) ], 68.14 t and 68.17 t
(C , J = 28.1 Hz), 72.51 (C ), 109.20 t.t (C , J = 249.5,
34.8 Hz), 114.95 t.t (C , J = 250.2, 26.9 Hz). F NMR
spectrum (470 MHz, CDCl ), δ , ppm: 22.33 d.m (2F,
C
2 2
1
2
2
1
′
3
3′
2
′
19
3
F
3′-F, J = 53.0 Hz), 36.93 m (2F, 2′-F). Found, %:
C 41.13; H 5.54; F 26.80; N 4.74; S 10.87.
C H F N O S . Calculated, %: C 41.37; H 5.56;
dried over MgSO , the solvent was distilled off, and
4
the product was purified by preparative HPLC or flash
chromatography using methylene chloride as eluent.
2
0
32
8
2
4 2
F 26.18; N 4.82; S 11.04.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

5
18
NALET’KO et al.
Bis[6,6,7,7,8,8,9,9-octafluoro-1-(morpholin-4-yl)-
spectrum (376 MHz, CDCl ), δ , ppm: 22.03 d.m
3
F
4
-oxanonan-2-yl] disulfide (4b, erythro–threo ~1:1).
(2F, 3′-F, J = 53.0 Hz), 36.72 m (2F, 2′-F). Found, %:
C 43.34; H 6.66; F 24.84; N 9.16; S 10.33.
C H F N O S . Calculated, %: C 43.56; H 6.31;
Yield 69%, dark yellow viscous oil. IR spectrum, ν,
–
1
cm : 2920, 2857 (C–H), 1166 (C–F), 1114 (C–O–C).
2
2
38
8
4
2 2
1
H NMR spectrum (500 MHz, CDCl ), δ, ppm: 2.44 m
F 25.05; N 9.24; S 10.57.
3
[
2
(
5
4H, N(CH ) ], 2.51–2.63 m (2H, 1-H), 3.09 m (1H,
-H), 3.68 m [4H, O(CH ) ], 3.84 m (2H, 3-H), 3.98 t
2 2
2 2
Bis[6,6,7,7,8,8,9,9-octafluoro-1-(4-methylpipera-
zin-1-yl)-4-oxanonan-2-yl] disulfide (5b, erythro–
threo ~1:1). Yield 77%, dark yellow viscous oil. IR
2H, 1′-H, J = 13.9 Hz), 6.06 t.t (1H, 3′-H, J = 52.0,
1
3
–
1
.5 Hz). C NMR spectrum (126 MHz, CDCl ), δ ,
3 C
spectrum, ν, cm : 2940, 2800 (C–H), 1163 (C–F),
2
1
ppm: 49.27 and 49.42 (C ), 53.85 [N(CH ) ], 59.33
and 59.34 (C ), 66.86 [O(CH ) ], 67.95 t (C , J =
2
2
2
Hz), 115.40 t.t (C , J = 256.8, 30.7 Hz). F NMR
spectrum (470 MHz, CDCl ), δ , ppm: 24.47 d.m (2F,
5
3
F 38.89; N 3.59; S 8.04. C H F N O . Calculated,
%
2
2
1121 (C–O–C). H NMR spectrum (400 MHz, CDCl ),
3
1
1′
2
3
2
δ, ppm: 2.28 s (3H, CH ), 2.32–2.64 m [10H, 1-H,
3
5′
5.5 Hz), 72.93 and 72.94 (C ), 107.62 t.t (C , J =
54.1, 30.8 Hz), 110.07 t.t.t (C or C , J = 264.5, 29.7,
6.9 Hz), 110.87 t.t.t (C or C , J = 265.1, 33.6, 31.3
N(CH ) ], 3.09 m (1H, 2-H), 3.83 (2H, 3-H), 3.98 t
2
2
3
′
4′
(
5
2H, 1′-H, J = 14.0 Hz), 6.06 t.t (1H, 3′-H, J = 52.0,
4
′
3′
1
3
.4 Hz). C NMR spectrum (126 MHz, CDCl ), δ ,
3 C
2
′
19
2
ppm: 45.94 and 45.96 (NCH ), 49.49 and 49.58 (C ),
53.34 and 55.03 [N(CH ) ], 58.74 and 58.78 (C ),
67.97 t (C , J = 25.4 Hz), 73.04 and 73.08 (C ),
107.61 t.t (C , J = 253.8, 30.5 Hz), 110.06 t.t.t (C or
C , J = 263.8, 31.0, 26.6 Hz), 110.86 t.t.t (C or C ,
J = 264.6, 32.9, 31.1 Hz), 115.41 t.t (C , J = 256.6,
3
3
1
3
C
2 2
1
′
3
′-F, J = 52.0 Hz), 31.53 m (2F, 4′-F), 36.16 m (2F,
′-F), 41.97 m (2F, 2′-F). Found, %: C 36.52; H 4.13;
5′
3′
4
′
4′
3′
2
4
32 16
2
4
2
′
: C 36.93; H 4.13; F 38.94; N 3.59; S 8.21.
19
0.6 Hz). F NMR spectrum (376 MHz, CDCl ), δ ,
Bis[3,3,4,4,5,5,6,6,6-nonafluoro-1-(morpholin-4-
3 F
ppm: 24.45 d.m (2F, 5′-F, J = 52.0 Hz), 31.45 m (2F,
′-F), 36.12 m (2F, 3′-F), 41.97 m (2F, 2′-F). Found, %:
C 38. 81; H 4. 85; F 37. 54; N 6. 93; S 8. 09.
C H F N O S . Calculated, %: C 38.71; H 4.75;
yl)hexan-2-yl] disulfide (4c, erythro–threo ~2.3:1).
4
Yield 75%, amorphous solid, mp 54–59°C. IR spec-
–
1
trum, ν, cm : 2815 (C–H), 1216 (C–N), 1131 (C–F),
1
1
117 (C–O–C). H NMR spectrum (400 MHz, CDCl ),
26 38 16
4
2 2
3
F 37.68; N 6.94; S 7.95.
δ, ppm: 2.31–2.85 m [8H, N(CH ) , 1-H, 3-H], 3.21 m
2
2
1
3
(
1H, 2-H), 3.63–3.73 m [4H, O(CH ) ]. C NMR
Disulfides 7a and 7b (general procedure). Mix-
tures 6a/7a and 6b/7b were obtained according to the
general procedure for the reaction of thiiranes 1a and
1b with amines. Acetonitrile, 10 mL, and N-methyl-
piperazine, 5 mmol (0.5 g), were added to 1 g of mix-
ture 6a/7a or 6b/7b, and the mixture was refluxed for
5 h. The mixture was washed with 30 mL of water, the
organic layer was separated, and the aqueous layer was
extracted with chloroform (2×5 mL). The extracts
were combined with the organic phase and dried over
2
2
spectrum (126 MHz, CDCl ), δ , ppm: 32.42 t and
3
C
3
2
3
[
[
1
(
2.81 t (C , J = 21.1 Hz), 40.71 and 40.82 (C ), 53.57
N(CH ) ], 62.58 and 62.71 (C ), 66.79 and 66.81
O(CH ) ], 108.72 t.q.m (C , J = 266.7, 38.7 Hz),
10.33 t.t.t (C , J = 265.7, 33.6, 32.3 Hz), 117.35 q.t
C , J = 288.1, 33.3 Hz), 118.05 t.t (C , J = 255.9,
1.3 Hz). F NMR spectrum (376 MHz, CDCl ), δ ,
1
2 2
6
2
2
5
7
4
1
9
3
3 F
ppm: 35.80 m (2F, 6-F), 37.36 m (2F, 5-F), 49.92 m
2F, 4-F), 80.68 m (2F, 7-F). Found, %: C 34.69;
H 3.36; F 46.21; N 3.64; S 8.62. C H F N O S . Cal-
(
22
26 18
2
2
2
MgSO , the solvent was distilled off, and the product
4
culated, %: C 34.92; H 3.46; F 45.20; N 3.70; S 8.48.
was purified by flash chromatography using methylene
chloride as eluent.
Bis[6,6,7,7-tetrafluoro-1-(4-methylpiperazin-
1
~
-yl)-4-oxaheptan-2-yl] disulfide (5a, erythro–threo
1:1). Yield 77%, dark yellow viscous oil. IR spec-
Bis(1-anilino-6,6,7,7-tetrafluoro-4-oxaheptan-
2-yl) disulfide (7a, erythro–threo ~1:1). Yield 80%,
–
1
–1
trum, ν, cm : 2815 (C–H), 1216 (C–F), 1131 (C–N),
dark yellow viscous oil. IR spectrum, ν, cm : 3411
1
1117 (C–O–C). H NMR spectrum (400 MHz, CDCl ),
(N–H), 2923 (C–H), 1602, 1505 (C–N), 1199 (C–F,
3
1
δ, ppm: 2.28 s (3H, CH ), 2.32–2.64 m [10H, 1-H,
C–O–C). H NMR spectrum (500 MHz, CDCl ), δ,
3
3
N(CH ) ], 3.06 m (1H, 2-H), 3.73–3.93 m (4H, 3-H,
ppm: 3.11 m (1H, 2-H), 3.27 m (1H, 1-H), 3.47 m
(1H, 1-H), 3.55–4.07 m (5H, 3-H, 1′-H, NH), 5.86 t
(1H, 3′-H, J = 53.2 Hz), 6.59 m (2H, m-H), 6.73 m
2
2
1
3
1
′-H), 5.94 t.t (1H, 3′-H, J = 53.2, 4.9 Hz). C NMR
spectrum (126 MHz, CDCl ), δ , ppm: 45.91 and
3
C
2
13
4
5.92 (NCH ), 49.50 and 49.51 (C ), 53.33 and 55.00
(1H, p-H), 7.16 m (2H, o-H). C NMR spectrum
3
1
1
[N(CH ) ], 58.71 and 58.81 (C ), 68.18 t and 68.21 t
(126 MHz, CDCl ), δ , ppm: 44.17 and 44.28 (C ),
2
2
3
C
1
′
3
3′
2
1′
(
C , J = 28.3 Hz), 72.57 (C ), 109.14 t.t (C , J = 249.5,
51.00 and 51.49 (C ), 67.91 t and 67.94 t (C , J =
28.1 Hz), 72.56 and 72.58 (C ), 109.18 t.t (C , J =
2
′
19
3
3′
3
4.4 Hz), 114.95 t.t (C , J = 250.1, 26.6 Hz). F NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017

SYNTHESIS OF SYMMETRICAL DISULFIDES
519
o
2
1
(
49.7, 35.1 Hz), 112.91 and 112.94 (C ), 114.81 t.t and
10. Naud, C., Calas, P., Blancou, H., and Commeyras, A.,
2′
J. Fluorine Chem., 2000, vol. 104, p. 173.
11. Mureau, N., Guittard, F., and Géribaldi, S., Tetrahedron
Lett., 2000, vol. 41, p. 2885.
14.82 t.t (C , J = 250.0, 26.7 Hz), 118.04 and 118.06
C ), 129.41 (C ), 147.12 and 147.13 (C ). F NMR
spectrum (470 MHz, CDCl ), δ , ppm: 22.81 d.m and
2.86 d.m (2F, 3′-F, J = 53.0 Hz), 37.17 m (2F, 2′-F).
Found, %: C 47.46; H 4.82; F 25.60; N 4.41; S 10.77.
C H F N O S . Calculated, %: C 48.64; H 4.76;
p
m
i
19
3
F
1
2. Thebault, P., Taffin de Givenchy, E., Guittard, F.,
Guimon, C., and Géribaldi, S., Thin Solid Films, 2008,
vol. 516, p. 1765.
2
2
4
28
8
2
2 2
1
3. Thebault, P., Taffin de Givenchy, E., Géribaldi, S.,
Levy, R., Vandenberghe, Y., and Guittard, F., J. Fluorine
Chem., 2010, vol. 131, p. 592.
F 25.65; N 4.73; S 10.82.
Bis(1-anilino-6,6,7,7,8,8,9,9-octafluoro-4-oxa-
nonan-2-yl) disulfide (7b, erythro–threo ~1:1). Yield
0%, dark yellow viscous oil. IR spectrum, ν, cm :
410 (N–H), 2917 (C–H), 1602, 1506 (C–N), 1167
C–F), 1120 (C–O–C). H NMR spectrum (500 MHz,
CDCl ), δ, ppm: 3.14 m (1H, 2-H), 3.29 m (1H, 1-H),
.54 m (1H, 1-H), 3.70 m (1H, 3-H), 3.75–3.91 m (3H,
-H, 1′-H), 3.97 br.s (1H, NH), 6.03 t.t (1H, 5′-H, J =
2.0, 5.3 Hz), 6.61 d (2H, m-H, J = 7.1 Hz), 6.73 m
1H, p-H), 7.17 m (2H, o-H). C NMR spectrum
126 MHz, CDCl ), δ , ppm: 44.27 and 44.39 (C ),
1.16 and 51.63 (C ), 67.89 t (C , J = 25.6 Hz), 73.11
and 73.13 (C ), 107.62 t.t (C , J = 254.3, 30.9 Hz),
10.11 t.t.t (C or C , J = 263.8, 30.1, 27.1 Hz), 110.90
t.t.t (C or C , J = 265.4, 33.2, 31.9 Hz), 113.01 and
13.03 (C ), 115.32 t.t (C , J = 257.5, 30.6 Hz), 118.07
and 118.09 (C ), 129.42 (C ), 147.19 (C ). F NMR
14. Birk, C. and Voss, J., Tetrahedron, 1996, vol. 52,
–
1
8
3
(
p. 12745.
1
5. Dwivedi, A.K., Sharma, V.L., Kumaria, N.,
Kumar, S.T.V.S.K., Srivastava, P.K., Ansari, A.H.,
Maikhuri, J.P., Gupta, G., Dhar, J.D., Roy, R.,
Joshi, B.S., Shukla, P.K., Kumar, M., and Singh, S.,
Bioorg. Med. Chem., 2007, vol. 15, p. 6642.
1
3
3
3
5
(
(
1
6. Fokin, A.V., Allakhverdiev, M.A., and Kolomiets, A.F.,
1
3
Russ. Chem. Rev., 1990, vol. 59, p. 405.
17. Fokin, A.V. and Kolomiets, A.F., Khimiya tiiranov
1
3 C
2
1′
5
(Chemistry of Thiiranes), Moscow: Nauka, 1978.
3
5′
1
8. Nalet’ko, S.A., Pervova, M.G., Gorbunova, T.I., Zape-
valov, A.Ya., Toporova, M.S., and Saloutin, V.I., Russ. J.
Gen. Chem., 2014, vol. 84, p. 2120.
3
′
4′
1
4
′
3′
o
2′
1
19. Fokin, A.V., Kolomiets, A.F., and Rudnitskaya, L.S.,
Bull. Acad. Sci. USSR, Div. Chem. Sci., 1974, vol. 23,
p. 2744.
p
m
i
19
spectrum (470 MHz, CDCl ), δ , ppm: 24.51 d.m (2F,
3
F
5
3
′-F, J = 52.0 Hz), 31.54 m (2F, 4′-F), 36.37 m (2F,
′-F), 42.06 m (2F, 2′-F). Found, %: C 42.39; H 3.51;
20. Christoforou, A., Nicolaou, G., and Elemes, Y.,
Tetrahedron Lett., 2006, vol. 47, p. 9211.
F 37.97; N 3.56; S 8.13. C H F N O S . Calculated,
21. Ruano, J.L.G., Parra, A., and Alemán, J., Green Chem.,
2
8
28 16
2
2 2
2
008, vol. 10, p. 706.
%: C 42.43; H 3.56; F 38.35; N 3.53; S 8.09.
2
2
2
2. Malinovskii, M.S., Okisi olefinov i ikh proizvodnye
(Olefin Oxides and Their Derivatives), Moscow:
Goskhimizdat, 1961.
3. Solov’ev, D.V., Kolomenskaya, L.V., Rodin, A.A.,
Zenkevich, I.G., and Lavrent’ev, A.N., Zh. Obshch.
Khim., 1991, vol. 61, p. 673.
4. Bazhin, D.N., Gorbunova, T.I., Zapevalov, A.Ya.,
Kirichenko, V.E., and Saloutin, V.I., Russ. J. Org.
Chem., 2007, vol. 43, p. 656.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 4 2017