Selective fluoroalkylation of thiophenols by 1,2-dibromotetrafluoroethane activated by sulfur dioxide

Article abstract of DOI:10.1016/j.jfluchem.2007.06.006

Treatment of 1,2-dibromotetrafluoroethane with thiophenols in DMF in the presence of sulfur dioxide and pyridines having pK_a > 5 gives fluoroalkylated thioethers in high yields under mild conditions. The influence of thiophenol reactant structu

Full text of DOI:10.1016/j.jfluchem.2007.06.006

Journal of Fluorine Chemistry 128 (2007) 1376–1378
www.elsevier.com/locate/fluor
Selective fluoroalkylation of thiophenols by 1,2-dibromotetrafluoroethane
activated by sulfur dioxide
*
Vyacheslav G. Koshechko, Lydiya A. Kiprianova , Ludmyla I. Fileleeva, Ludmyla I. Kalinina
L.V. Pisarzhevsky Institute of Physical Chemistry of the National Academy of Sciences of Ukraine, Pr. Nauky 31, Kiev 01039, Ukraine
Received 4 April 2007; received in revised form 18 June 2007; accepted 20 June 2007
Available online 23 June 2007
Abstract
Treatment of 1,2-dibromotetrafluoroethane with thiophenols in DMF in the presence of sulfur dioxide and pyridines having pKa > 5 gives
fluoroalkylated thioethers in high yields under mild conditions. The influence of thiophenol reactant structure and medium basicity is discussed.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Polyfluoroalkylation; Thiophenols; Sulfur dioxide
1. Introduction
licity [17] and may be considered as potential physiologically
active substances.
Introduction of halocarbon fragments, containing other
halogen atoms besides fluorine, into different organic substrates
allows the synthesis of new polyfluoroalkyl substrates as well as
transformation of fluorine containing substituents to more
complex groups [1–14].
2. Results and discussion
The formation of two types of products in Eq. (1) can be
rationalized by an ionic chain mechanism postulated in
[10–18], including anionic intermediates ArSCF2CF2ꢀ. Reac-
tion with proton donors, including H2O, gives the side product,
ArSCF2CF2H, lowering the yield of the desired ArSCF2CF2Br.
In [11,12] the hypothesis was proposed that one electron
transfer from thiophenolates to perfluorohaloalkanes is
followed by competition between a radical path and release
of a ‘‘positive’’ halogen. In the case of 1,2-dibromotetrafluor-
oethane the thiophenoxides react by a carbanionic process.
We supposed that transformation of the process into a radical
pathway (SRN1 type) seems to increase its selectivity by
excluding the formation of H-substituted products.
The fluoroalkylation of thiophenols, phenols and hetero-
cyclic nitrogen compounds by 1,2-dibromotetrafluoroethane is
usually performed by the interaction of the potassium salts of
these compounds with BrCF2CF2Br [3,10,15–18], as illustrated
(Eq. (1)) for alkylation of thiophenols.
ArSK þ BrCF2CF2Br ! ArSCF2CF2Br þ ArSCF2CF2H
(1)
In addition to the product, ArSCF2CF2Br, this condensation
yields diaryl disulfides and thioethers, containing the –
CF2CF2H group. Electron-withdrawing groups cause an
increase of the yields of H-substituted product and a retardation
of the whole reaction.
As thiophenols, unlike their salts, do not react with
BrCF2CF2Br, it seemed reasonable to stimulate the radical
decay of BrCF2CF2Br using an electron transfer mediator, and
to accelerate the electron transfer by a mediator to increase
the nucleophility of thiopenols. It was demonstrated earlier
[19–23] that sulfur dioxide can serve as an electron transfer
mediator. The second aim was achieved by addition of organic
nitrogen bases (such as pyridines) that increase the thiophenol
nucleophility by complexation.
The aim of our study was to carry out the interaction of
BrCF2CF2Br with thiophenols, but not thiophenolates, as
starting reagents and thereby to increase the selectivity of the
process. Bromoderivatives, ArSCF2CF2Br, have high lipophi-
To verify this assumption we have studied the interaction of
different thiophenols with BrCF2CF2Br in dimethylformamide
* Corresponding author. Fax: +380 44 5256216.
E-mail address: lkipr@inphyschem-nas.kiev.ua (L.A. Kiprianova).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.06.006

V.G. Koshechko et al. / Journal of Fluorine Chemistry 128 (2007) 1376–1378
1377
Table 1
Condensation of BrCF2CF2Br (0.024 mol Lꢀ1) with thiophenols p-XC6H4SH
(0.020 mol Lꢀ1) in the presence of sulfur dioxide and b-picoline
Table 2
Condensation of BrCF2CF2Br (0.024 mol Lꢀ1) with thiophenols p-XC6H4SH
(0.020 mol Lꢀ1) in the presence of sulfur dioxide (0.020 mol Lꢀ1) and b-
picoline (0.10 mol Lꢀ1
)
X
b-Picoline
(mol Lꢀ1
SO2
(mol Lꢀ1
Yielda of
)
)
p-XC6H4SCF2CF2Br (%)
X in p-XC6H4SH
CH3
H
Cl
NO2
H
0.02
0.01
0.02
0.04
0.10
0.10
0.10
0.20
0.20
–
–
s
ꢀ0.17
0
+0.23
42.5
+0.78
21.9
H
0.02
0.02
0.02
0.02
0.02
0.06
0.06
0.10
21.6
63.5
82.4
88.1
12.0
78.8
82.7
76.4
Yieldsa (%) p-XC6H4SCF2CF2Br
88.0
61.7
H
19F NMR yields.
a
CH3
CH3
CH3
CH3
CH3
CH3
b
We studied the influence of electronic reactant structure on the
interaction of thiophenols with 1,2-dibromotetrafluoroethane
(Table 2).
In all cases only thioethers p-XC6H4SCF2CF2Br were
obtained. Electron-donating groups promoted the reaction, but
electron-withdrawing ones caused a decrease in the yield of
thioethers; dependence on s-constants of Hammett of
thiophenol substituents was observed.
a
19F NMR yields.
b
p-Dinitrobenzene was added.
(DMF) in the presence of sulfur dioxide as mediator and b-
picoline as a base (Table 1).
The yields’ decrease is probably due to the retarding of
electron transfer from thiophenols to SO2 at the first, fourth and
fifth stages of the scheme (2).
In contrast to interaction of potassium salts of thiophenols
with BrCF2CF2Br only one product ArSCF2CF2Br was formed
(Table 1); hydrogenated by-product, ArSCF2CF2H, was absent.
In the absence of sulfur dioxide and picoline, condensation of
BrCF2CF2Br with thiophenols did not occur. An excess of
picoline strongly increases the yields of the desired product.
Low yields of thioethers were obtained when b-picoline
concentration was 0.01 mol Lꢀ1, however the yield increased to
63.5% at equimolecular ratio of sulfur dioxide: b-picoline.
Thiocresole demonstrates similar behavior. The yield of 76% of
p-CH3C6H4SCF2CF2Br at twofold excess of picoline increases
to 88% at a fivefold excess.
Fluoroalkylation of thiophenols by BrCF2CF2Br yielding p-
XC6H4SCF2CF2Br may be performed also in DMSO; accord-
ing to [24] this solvent stimulates the fragmentation of the
anion-radical.
Addition of organic bases has an effect in fluoroalkylation of
thiophenols by BrCF2CF2Br. These investigations were carried
out using thiocresol as an example (Table 3).
The above results demonstrate that in the presence of rather
weak bases as 2-chloropyridine and p-acetylpyridine there was
no fluoroalkylation reaction. In contrast stronger bases
efficiently stimulate thiocresol polyfluoroalkylation, producing
p-CH3C6H4SCF2CF2Br. The increase of pKa of bases used
resulted in higher yields of p-CH3C6H4SCF2CF2Br; in the case
of 2,5-lutidine and g-collidine almost quantitative yields were
attained.
A sole product leads to the assumption that this conversion
follows a radical pathway. It was demonstrated also by the
absence of hydrogenated thioethers in the presence of water.
The addition of free radical traps such as p-dinitrobenzene to
the reaction mixture leads to inhibition of the process, lowering
the yield from 88% to 12% (Table 1, entry 6) supporting the
hypothesis of a radical pathway. We suppose that SRN1 type
mechanism (scheme (2)) is involved in the formation of aryl
polyfluoroalkyl sulfides.
It should be noted that fluoroalkylation process in the
presence of g-collidine occurred with simultaneous formation
of precipitate due to the interaction of SO2 with amine, however
the yield of desired thioether was almost quantitative, probably
the polyfluoroalkylation had enough time to be completed.
Hence polyfluoroalkylation of thiophenols by BrCF2CF2Br
may be efficiently performed in mild conditions in the presence
At the first step a single electron transfer takes place from the
complexes of thiophenol with picoline. The ability of sulfur
dioxide to induce some electrochemical and chemical
processes of halofluorocarbon activation was demonstrated
earlier [19–22]. In a few cases the presence of small amounts
(1.5–4%) of tetrafluoroethylene was detected. Formation of this
by-product can be explained by reduction of the radical
ꢁCF2CF2Br.
Table 3
Condensation of BrCF2CF2Br (0.04 mol Lꢀ1) with thiocresol (0.02 mol Lꢀ1) in
the presence of sulfur dioxide (0.03 mol Lꢀ1) and substituted pyridines
(0.10 mol Lꢀ1
)
Pyridines
pKa
Yieldsa of
p-CH3C6H4SCF2CF2Br (%)
ꢀ
1: XC6H4Sꢀ þ SO2 ! XC6H4Sꢁ þ SOꢁ
2
ꢀ
ꢀ
2: SOꢁ þ BrCF2CF2Br ! SO2 þ ½BrCF2CF2Brꢂꢁ
2-Chloropyridine
p-Acetylpyridine
Pyridine
0.72
3.18
5.23
6.25
7.60
5.23
7.60
–
–
2
! ꢁCF2CF2Br þ Brꢀ
ꢀ
78
98
99
28
46
3: XC6H4Sꢀ þ ꢁCF2CF2Br ! ½XC6H4SCF2CF2Brꢂꢁ
2,5-Lutidine
g-Collidine
Pyridineb
ꢀ
ꢀ
4: ½XC6H4SCF2CF2Brꢂꢁ þ SO2! XC6H4SCF2CF2BrþSOꢁ
2
5: ½XC6H4SCF2CF2Brꢂꢁꢀ þ BrCF2CF2Br
ꢀ
! XC6H4SCF2CF2Br þ ½BrCF2CF2Brꢂꢁ
g-Collidine
ꢀ
6: SOꢁ þ ꢁCF2CF2Br ! SO2 þ Brꢀ þ CF2 ¼ CF2
a
19F NMR yields.
2
b
(2)
p-Dinitrobenzene was added.

1378
V.G. Koshechko et al. / Journal of Fluorine Chemistry 128 (2007) 1376–1378
of strong nitrogen bases mediating the process by sulfur
dioxide.
3.3. Interaction of BrCF2CF2Br with thiophenols in the
presence of SO2 and substituted pyridines
The interaction of reagents, further treatment of reaction
mixture and determination of products were carried out
similarly to 3.1, but instead of b-picoline other pyridines
(Table 3) were added.
3. Experimental
1H NMR and 19F NMR spectra were recorded using a Bruker
CXP-90 (90 MHz) instrument. 1H and 19F chemical shifts were
recorded in d(ppm) values relatively to hexamethyl disiloxane
(1H) and CCl3F (19F) as internal standard.
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