Chain-radical fluoroalkylation of thiophenols with freon ClCF2CFCl2 in the presence of sulfur dioxide

Article abstract of DOI:10.1016/j.jfluchem.2008.12.005

A polyfluoroalkylation of thiophenols with CF₂ClCFCl₂ using substituted pyridine-sulfur dioxide system enables to obtain fluoroalkylated thioethers by a S_RN1-type free-radical route.

Full text of DOI:10.1016/j.jfluchem.2008.12.005

Journal of Fluorine Chemistry 130 (2009) 317–320
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Chain-radical fluoroalkylation of thiophenols with
freon ClCF2CFCl2 in the presence of sulfur dioxide
*
Vyacheslav G. Koshechko, Lydiya A. Kiprianova , Ludmyla I. Kalinina
L.V. Pisarzhevsky Institute of Physical Chemistry of the National Academy of Sciences of Ukraine, Pr.Nauky 31, Kiev 03028, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
A polyfluoroalkylation of thiophenols with CF2ClCFCl2 using substituted pyridine–sulfur dioxide system
enables to obtain fluoroalkylated thioethers by a SRN1-type free-radical route.
ß 2008 Elsevier B.V. All rights reserved.
Received 19 May 2008
Received in revised form 10 December 2008
Accepted 12 December 2008
Available online 25 December 2008
Keywords:
Polyfluoroalkylation
Thiophenols
Sulfur dioxide
1. Introduction
the selectivity of the process, but also to produce ArSCFClCF2Cl
instead of ArSCF2CFCl2 [8] according to the following hypothetical
The use of fluorohalocarbons as perfluoroalkyl group synthons
for the synthesis of fluorine containing compounds attracted
considerable interest [1–7]. Unlike iodine- and bromine-contain-
ing fluoroalkanes, chlorofluoroalkanes (CFCs) as the alkylating
agents were explored to a much lesser extent, which is largely
caused by their considerably lower reactivity due to stronger C–Cl
bond compared to C–Br and C–I. At the same time, chlorofluor-
oalkanes usually are cheaper compared to their bromine- and
iodine-containing analogues.
This paper describes a possibility of thiophenols fluoroalkyla-
tion with freon CF2ClCFCl2 (CFC113). Under standard conditions
thiophenols do not react with freons, including CFC113, and
thiophenol potassium salts are employed to activate such process
[8–13]. CF2ClCFCl2–thiophenolates interaction is considered to be
the halophilic process (Scheme 1).
Scheme 2. It would be especially convenient to use thiophenols
themselves, instead of their salts.
Taking this into account the possibility of thiophenols
fluoroalkylation by freon CF2ClCFCl2 by the radical mechanism
was studied.
2. Results and discussion
The CF2ClCFCl2–thiophenols interaction was intended to be
activated in two ways: by increasing the electron-donating ability
of the thiophenols and by introducing an electron transfer
mediator into the system, which facilitates freon reduction and
generation of active radicals.
Our strategy on the one hand was to create such fluoroalkyla-
tion conditions under which the basicity of the nucleophile would
be not sufficient for separation off the bearing partial positive
charge halogen from the freon to rule out the ionic process
(Scheme 1) and, on the other hand, the nucleophile’s electron-
donating ability would be sufficiently high for electron transfer to
the freon to enable the fluoroalkylation process by the radical route
(Scheme 2).
Alternatively, for bromo- and iodofluoroalkanes, in some cases
it is possible to implement thiophenols fluoroalkylation by a chain-
radical route [8,14,15]. Such processes exhibit sufficiently high
selectivity.
If it would be possible to perform thiophenols fluoroalkylation
by CF2ClCFCl2 by a radical route, this will allow not only to improve
We supposed that such substrate activation could be achieved
by addition of organic nitrogen bases into the system, in particular
pyridines, capable to form complexes with thiophenols through
the hydrogen bond. This would contribute to increase of electron-
* Corresponding author. Tel.: +380 44 525 54 14; fax: +380 44 525 62 16.
E-mail address: lkipr@inphyschem-nas.kiev.ua (L.A. Kiprianova).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.12.005

318
V.G. Koshechko et al. / Journal of Fluorine Chemistry 130 (2009) 317–320
Table 1
Dependence of peak potentials of p-chlorothiophenol oxidation (Ep) in the mixtures
of acetonitrile and substituted pyridine on pKa of the pyridine. [p-chlorothiophe-
nol] = 0.01 M; [pyridine] = 1.00 M; 0.1 M NaClO4; Ag/AgCl; 25 8C.
Amine
pKa
Ep, V
2-Chloropyridine
2-Bromopyridine
3-Bromopyridine
2,3-Lutidine
0.72
0.90
2.84
6.48
6.82
7.60
1.28
1.13
1.03
0.76
0.71
0.63
Scheme 1.
2,4-Lutidine
g
-Collidine
donating ability of thiophenols due to equilibrium shift to their
anionic forms with lower ionisation potential:
ArSH þ NBB Ð ArSꢀ. . .þHNBB ;
where NBB are the nitrogen bases:
To verify this assumption we studied the effect of various
pyridines on the potentials of electrochemical oxidation of the
thiophenols in acetonitrile, which characterise their electron-
donating properties. It was found that addition of pyridines to
acetonitrile led to a significant increase of the electron-donating
capacity of the thiophenols, as evidenced by decrease of peak
potentials of their electrochemical oxidation, for example, in the
case of p-chlorothiophenol (Table 1).
In the absence of pyridine in acetonitrile solutions the peak
potential (Ep) of p-chlorothiophenol is 1.87 V.
Fig. 1. Peak potentials of p-chlorothiophenol oxidation as a function of pKa of the
pyridines added to the system. [p-ClC6H4SH] = 0.01 M; [pyridine] = 1.0 M; Pt;
NaClO4 0.1 M; Ag/AgCl; 25 8C.
Increase of basicity of the pyridines, which is caused by
hydrogen bond strengthening results in growth of the electron-
donating capacity of p-chlorothiophenol. There is linear relation-
ship between the Ep of the thiophenols and the pKa of the pyridines
(Fig. 1).
However enhancement of the substrate’s electron-donating
capacity alone, caused by the formation of complexes with
pyridines, is an indispensable but insufficient condition for
successful implementation of the process. In the presence of
mediator and of
b-picoline added to enhance electron-donating
capacity of the substrates to be fluoroalkylated. The reaction was
conducted in a sealed ampoules at 35 8C for 5–6 h. It is found that
sulfur dioxide–nitrogen base activation system allows to accom-
plish the thiophenols fluoroalkylation by CF2ClCFCl2 in mild
conditions, and only one product—p-XC6H4SCFClCF2Cl is formed
nitrogen bases only (pyridine,
b-picoline), thiophenols fluoroalk-
ylation with CF2ClCFCl2 in aprotic solvents at room temperature is
not achieved. Donor strength of the complexes appears to be not
enough for the electron transfer to the freon because of too broad
gap between ionisation potentials of the complexes and electron
affinity of the freon, which may be indirectly reflected by the
corresponding electrochemical potentials (reduction potential of
CF2ClCFCl2, Ep = ꢀ2.3 V vs. Ag/AgCl).
In order to activate electron transfer from the substrate–
pyridine complexes to the freon, we used sulfur dioxide that is
highly efficient as electron transfer mediator for the electro-
chemical and chemical processes involving per- and polyfluor-
ohaloalkanes [16–20]. Sulfur dioxide capacity to act as the
mediator of electron transfer to the CFC113 was demonstrated
by catalytic current observed in the cyclic voltammogram of the
sulfur dioxide (Fig. 2), when adding CF2ClCFCl2 to the system,
owing to the SO2 resumption in the near-electrode layer (Scheme
3).
We studied the interaction of different p-substituted thiophe-
nols XC6H4SH (X = H, CH3, Cl, NO2, CF3SO2) with CF2ClCFCl2 in
dimethylformamide in the presence of SO2 as electron transfer
Fig. 2. Cyclic voltammogram of SO2 (–) and SO2 + CF2ClCFCl2 (- - -). [SO2] =
1 ꢁ 10ꢀ2M; [CF2ClCFCl2] = 2 ꢁ 10ꢀ2M; v ¼ 0:2 V=s; Ag/AgCl; 0.1 M Bu4NBF4 in
DMFA.
Scheme 2.

V.G. Koshechko et al. / Journal of Fluorine Chemistry 130 (2009) 317–320
319
Scheme 5.
Scheme 3.
the fluoroalkylation product yields (from 52 to 5% for p-
CH3C6H4SCFClCF2Cl) at the presence of radical trap, p-dinitroben-
zene (Table 2).
Table 2
Product yields of thiophenol–CF2ClCFCl2 interaction in the presence of SO2 [p-
With increasing electron-withdrawing capacity of substituent
X the yield of product p-XC6H4SCFClCF2Cl decreases and, in the
case of NO2 and CF3SO2 substituents, fluoroalkylation process fails
to be accomplished under the present conditions. The observed
dependence may be related to the fact that transition from
electron-donating to electron-withdrawing substituents impedes
the electron transfer from the thiophenol to the mediator, sulfur
dioxide, in the first step of the process as well as during its follow-
on development (Scheme 4).
XC6H4SH] = 0.25 M; [CF2ClCFCl2] = 0.65 M, DMFA, 35 8C.
X in p-XC6H4SH
[SO2], M
b-picoline, M
p-XC6H4S–CFClCF2Cl yield, %
CH3
0.65
0.65
0.12
0.25
0.25
0.25
0.25
0.25
2.50
2.50
1.25
1.25
1.25
1.25
1.25
1.25
52
5
a
CH3
CH3
CH3
H
37
56
45
38
–
Cl
NO2
CF3SO2
In some cases we observed 3–4% of CF2 CFCl in the 19F NMR
–
spectrum
along
with
the
polyfluoroalkylarylsulfides
a
p-Dinitrobenzene added.
XC6H4SCFClCF2Cl. This species is seen as an intermediate for the
ionic conversion route. However, we believe that in our case the
formation of such olefin occurs due to further reduction of
fluoroalkyl radical to have been obtained during the second step of
the process (Scheme 5).
in all cases. The yields of polyfluoroalkylarylsulfides are given in
Table 2.
As it can be seen from Table 2, the efficiency of the
thiophenols fluoroalkylation process depends on the concentra-
As it was pointed out above, unlike thiophenols fluoroalkylation
with CF2ClCFCl2, activated using SO2, interaction of thiophenolates
and CF2ClCFCl2 results in a XC6H4SCF2CFCl2 product [8]. It was
rather interesting to elucidate how SO2 electron carrier can impact
on the process with thiophenolates and whether it was possible to
convert the latter from halophilic to free-radical one using SO2. We
found that, in the absence of SO2, interaction of sodium
thiophenolate and CF2ClCFCl2 results in C6H5SCF2CFCl2 (16%)
and C6H5SCF2CFClH (16%) (Table 3). The lower yield compared to
[8] is evidently related to the fact that we had used a sodium
thiophenolate but not more active potassium salt as in [8].
Introduction of sulfur dioxide into the system in quantities
equimolar or near-equimolar to thiophenolate, leads to dramati-
cally changes: there is no hydrothioether, while the resulting
product is C6H5SCFClCF2Cl (38%). A radical trap (p-dinitrobenzene)
decreases this product’s yield tenfold, which may confirm its
radical origin.
tion of the mediator (SO2) and of the base (b-picoline). Only one
single fluoroalkylation product, p-XC6H4SCFClCF2Cl, evidently
points to the fact that fluoroalkylation of thiophenols by
CF2ClCFCl2 in SO2–
b-picoline activated system proceeds by a
S
RN1-type free-radical route. The ionic mechanism (Scheme 1)
would lead to p-XC6H4SCF2CFCl2 [8]. This may be relevant to
diverse species involved in the ionic and free-radical routes:
fluoroalkylation is accomplished with CF2 CFCl olefin for the
former (Scheme 1) and with a ꢂCFClCF2Cl free-radical for the
latter. Assumed mechanism of thiophenols fluoroalkylation with
CF2ClCFCl2 in the presence of SO2 and
represented by the Scheme 4.
b-picoline can be
The first step of the process involves electron transfer from
thiophenol complexes with -picoline, rather than from the ‘‘pure’’
b
thiophenolate anions. Radical mechanism for thiophenols fluor-
oalkylation with CF2ClCFCl2 is evidenced by dramatic decrease in
Scheme 4.
Table 3
Product yields of sodium thiophenolate–CF2ClCFCl2 interaction in the presence of SO2, DMFA, 35 8C.
[C6H5SNa], M
[CF2ClCFCl2] M
[SO2] M
Product yields, %
C6H5S–CF2CFCl2
C6H5S–CF2CFClH
C6H5S–CFClCF2Cl
0.30
1.25
0.50
1.25a
0.30
2.05
1.10
2.05
–
16.0
–
16.0
–
–
38
35
3
0.83
0.35
0.83
–
–
–
–
a
p-Dinitrobenzene added.

320
V.G. Koshechko et al. / Journal of Fluorine Chemistry 130 (2009) 317–320
3. Conclusion
129.0 (1C), 129.4 (2C), 138,2 (1C), 138.6 (1C); Anal. Calcd for
C8H4Cl3F3S: C, 32.51; H, 1.36; found: C, 32.00; H, 1.24.
Thus
a
possibility of fluoroalkylating thiophenols with
X = H; b.p.101 8C/13 mm Hg; 19F NMR (84.79 MHz, Me2SO-d6):
CF2ClCFCl2, using nitrogen base–sulfur dioxide system is shown,
that enables not only to activate such process, setting it by free-
radical route, but also to obtain fluoroalkylated products whose
structure drastically differs from those which form in the course of
fluoroalkylation of thiophenolates: p-XC6H4SCFClCF2Cl for the
substituted pyridine-SO2 system and p-XC6H4SCF2CFCl2 in the case
of fluoroalkylation of alkaline salts of thiophenols.
d
89.9 (tr, 1F, J = 14.3 Hz, SCFCl), 62.6 (d, 2F, J = 14.3 Hz, CF2Cl); 13
C
2
NMR (100.61 MHz, CDCl3):
d
117.7; 120.7 (1C, dt, JCF = 295.3 Hz,
1JCF = 33.5 Hz, CFCl), 126.4; 129.3; 132.3 (1C, td, JCF = 301.3 Hz,
2JCF = 35.9 Hz, CF2Cl); 130.2 (1C), 133.3 (2C), 135.1 (2C), 141.3 (1C);
Anal. Calcd for C8H5Cl2F3S: C, 36.80; H, 1.93; F, 21.83. Found: C,
36.79; H, 2.05; F, 21.80.
1
4.2. Interaction of sodium thiophenolate with CF2ClCFCl2
4. Experimental
1,1,2-Trichlorotrifluoroethane CF2ClCFCl2 (0.08 ml, 0.6 ꢁ
10ꢀ3 M) was added to
a solution of sodium thiophenolate
Melting points were uncorrected. The dimethylformamide was
distilled and stored over A4 sieves. 1,1,2-trichlorotrifluoroethane
was distilled prior to use. Sodium thiophenoxide was prepared via
sodium methylate–thiophenol interaction in methanol. The 19F
(0.079 g, 0.6 ꢁ 10ꢀ3 M) in 2 ml of DMFA under argon atmosphere.
The sealed ampoule was kept at 35 8C for 5–6 h. The yield of
polyfluoroalkylated product was calculated from 19F NMR spectra.
Further treatment of reaction products and their determination
were carried out similarly to the above mentioned. The isolated
products were found to be [(2,2-dichloro-1,1,2-trifluor-
oethyl)thio]benzene C6H5SCF2CFCl2 and C6H5SCF2CFClH [2].
NMR spectra were recorded in
d (ppm) using Bruker-CXP-90 NMR
spectrometer (DMSO-d6, vs. CCl3F), the 13C NMR spectra using a
Bruker AVANCE 400 (CDCl3, vs. TMS). Cyclic voltammetry
experiments were carried out in the undivided three electrode
analytical cell; working electrode – disk cathode of platinum;
auxiliary electrode – platinum wire; reference electrode – Ag/AgCl.
The solvent of analytical grade (10 ml) contained supporting salt
(0.1 M Bu4NBF4). The cell was purged for 15 min with nitrogen. The
study was carried out using EP 20A potentiostate- and PC-based
computerized electrochemical facilities.
4.3. Interaction of sodium thiophenolate with CF2ClCFCl2 in the
presence of sulfur dioxide
CF2ClCFCl2 (0.47 ml, 4.1 ꢁ 10ꢀ3 M) and a sulfur dioxide (0.54 ml
of sulfur dioxide solution in DMFA, 1.65 ꢁ 10ꢀ3M SO2) were added
to a solution of sodium thiophenolate (0.33 g, 2.5 ꢁ 10ꢀ3M) in 2 ml
of DMFA under argon atmosphere. The sealed ampoule was kept at
35 8C for 5–6 h. The yield of polyfluoroalkylated product was
calculated from 19F NMR spectra. The subsequent treatment was
carried out as specified above. The isolated product was found to be
[(1,2-dichloro-1,2,2-trifluoroethyl)thio]benzene C6H5SCFClCF2Cl
described in 3.1. The reaction was inhibited by addition
0.8 ꢁ 10ꢀ3 M of p-dinitrobenzene.
4.1. General procedure for the interaction of thiophenol with
CF2ClCFCl2 in the presence of sulfur dioxide
1,1,2-TrichlorotrifluoroethaneCF2ClCFCl2 (0.15 ml,13 ꢁ 10ꢀ4 M)
andsulfurdioxide(0.17 mlofSO2 solutioninDMFA, 5 ꢁ 10ꢀ4 MSO2)
were added to a solution of thiophenol (0.055 g, 5 ꢁ 10ꢀ4 M) in a
mixture of DMFA (1.5 ml) with
b
-picoline (0.25 ml, 2.5 ꢁ 10ꢀ3 M)
underargonatmosphere.Thesealedampoulewaskeptat35 8Cfor4–
5 h. The yield ofpolyfluoroalkylatedproduct was calculated from 19
F
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procedures were carried out for other p-XC6H4SH–CF2ClCFCl2
interactions. The corresponding physical and spectral data of p-
XC6H4SCFClCF2Cl are given below (X, b.p., 19F NMR, 13C NMR, the
elemental analysis):
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