A mild hydrodehalogenation of fluoroalkyl halides

Article abstract of DOI:10.1016/j.jfluchem.2009.05.005

A mild hydrodehalogenation reaction of fluoroalkyl halides (R_fCF₂X, X = Br, I) has been developed under weakly basic conditions, giving the corresponding hydrogenolysis products with moderate to high yields.

Full text of DOI:10.1016/j.jfluchem.2009.05.005

Journal of Fluorine Chemistry 130 (2009) 671–673
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A mild hydrodehalogenation of fluoroalkyl halides
a
a
a,
b
Cheng-Pan Zhang , Qing-Yun Chen , Ji-Chang Xiao *, Yu-Cheng Gu
a
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, UK
b
A R T I C L E I N F O
A B S T R A C T
Article history:
A mild hydrodehalogenation reaction of fluoroalkyl halides (R CF X, X = Br, I) has been developed under
f
2
Received 3 April 2009
weakly basic conditions, giving the corresponding hydrogenolysis products with moderate to high
Received in revised form 30 April 2009
Accepted 7 May 2009
yields.
ß 2009 Elsevier B.V. All rights reserved.
Available online 18 May 2009
Keywords:
Hydrodehalogenation
Fluoroalkyl halides
Hydrofluoroalkanes
1
. Introduction
pressure or an excess amount of concentrated strong base were
required for the complete conversion of fluoroalkyl halides [11–
The C–X bonds in fluoroalkyl halides (R
strong and remain intact in many reactions. However, they can be
cleaved under certain conditions. For example, silyl enol ethers of
f
CF
2
X, X = Br, I) are
13]. Once started, the reaction becomes difficult to control, with
the rapid build-up of pressure. This could violently rupture the
reaction vessel, releasing the reaction mixture and causing
personal injury [12].
During the investigation of the reaction of 1,1,2,2-tetrafluoro-2-
(1,1,2,2-tetrafluoro-2-iodoethoxy)ethanesulfonamide (1a) under
basic conditions, we made the unexpected discovery that 1a was
hydrodeiodinated. Further study revealed that the reaction can
take place under mild conditions. Herein, we report the experi-
mental details of this hydrodehalogenation.
ketones reacted with CF
in DME to give -trifluoromethyl ketones in good yields [1].
Perfluoroalkyl anion reagents have been obtained by mixing C
and n-C I with tetrakis(dimethylamino)ethylene [2]. The radical
addition of perfluoroalkyl iodides to ethyl-2-carbethoxy-2-phtha-
limido-pent-4-enoate can be initiated by Et B/O at room
temperature [3]. And reactions between CF X (X = Cl, Br, I) and
tetrafluoroethylene, catalyzed by aluminum chlorofluoride, afford
the corresponding compounds CF CF CF X [4].
3 2 3 3
I and Et Zn in the presence of RhCl(PPh )
a
2 5
F I
4 9
F
3
2
3
3
2
2
2. Results and discussion
Hydrodehalogenation is another important method for break-
ing the C–X bonds of fluoroalkyl halides, and is usually catalyzed by
transition metal. Nevertheless, it is not a synthetically useful
reaction under these conditions [5–10]. For example, hydrodeha-
logenation took place in the reaction of perfluoroalkyl iodides with
cyclohexene or pyrrole in the presence of catalytic amounts of
reductive metals [9,10]. Complete hydrodehalogenation was
achieved for the first time by Durual from the reaction of
perfluoroalkyl iodides in alkaline alcohol solutions [11]. Howell
modified the reaction conditions afterwards and hydrofluoroalk-
anes were obtained in good yields from the reaction of 1-
haloperfluoroalkanes using sodium methoxide as the base [12].
However, drastic conditions such as high temperature and
At first, we found that the hydrodehalogenation of 1a took place
in methanol using sodium hydroxide as the base. After acidifica-
tion, 1,1,2,2-tetrafluoro-2-(1,1,2,2-tetrafluoroethoxy)ethanesulfo-
namide (2a) was obtained in 70% yield (entry 1, Table 1). Then, we
used Cl(CF ) I as a model substrate to explore the applicability of
2
4
this reaction under various conditions.
As indicated in Table 1, the reaction was performed in different
alkaline solvents. Temperature played an important role in this
reaction. High temperatures led to a high yield of 1-chloro-
1,1,2,2,3,3,4,4-octafluorobutane (2b) regardless of the solvent and
base used (entries 2 and 3, entries 5 and 6, entries 12 and 13). For
example, at 80 8C, 2b was formed in quantitative yield in methanol
and 80% yield in DMF (entries 3 and 6). Methanol was a good
solvent for the deiodination of perfluoroalkyl iodides (entries 3, 4, 6
and 14). Considering the high volatility of methanol and its similar
boiling point to those of the hydrodehalogenated products,
*
Corresponding author. Fax: +86 21 64166128.
E-mail address: jchxiao@mail.sioc.ac.cn (J.-C. Xiao).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.05.005

6
72
C.-P. Zhang et al. / Journal of Fluorine Chemistry 130 (2009) 671–673
Table 1
f 2
The reaction of R CF X with base.
.
a
b
Entry
R
f
X
R
f
CF
2
X
Base (B)
Solvent
R
f 2
CF X:B
Temperature (T/8C)
Time (h)
Yield (%)
1
2
3
4
5
6
H
2
NSO
2
C
2
F
4
OCF
2
I
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1a
1c
1d
1e
1f
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
CH
CH
CH
3
3
3
OH
OH
OH
1:3
1:3
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:1
1:1
1:2
1:3
1:2
Reflux
r.t.
80
80
r.t.
80
80
80
80
80
80
r.t.
80
80
80
80
80
80
80
80
80
r.t.
r.t.
3
70 (2a)
55 (2b)
100 (2b)
2 (2b)
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
Cl(CF
2
2
2
2
2
2
2
2
2
2
2
2
2
)
3
3
3
3
3
3
3
3
3
3
3
3
3
I
28
10
12
24
25
22
22
22
20
18
20
16
16
17
38
15
90
77
23
21
21
21
)
)
)
)
)
)
)
)
)
)
)
)
I
I
2
H O
I
DMF
18 (2b)
80 (2b)
100 (2b)
100 (2b)
52 (2b)
95 (2b)
0 (2b)
I
DMF
c
7
I
DMF/H
DMF/H
DMF/H
DMF/H
DMF/H
DMF
2
O
2
O
2
O
2
O
2
O
d
8
I
d
9
I
Na
NEt
2
CO
3
d
1
0
1
I
3
d
1
I
DMAP
1
1
1
1
1
1
1
1
2
2
3
4
5
6
7
8
9
I
K
K
K
K
K
K
K
K
K
K
3
PO
3
PO
3
PO
3
PO
3
PO
3
PO
3
PO
3
PO
3
PO
3
PO
4
4
4
4
4
4
4
4
4
4
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
Á3H
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
O
0 (2b)
I
DMF
65 (2b)
100 (2b)
100 (2a)
11 (2c)
100 (2d)
9 (2e)
I
DMF
H
2
NSO
ClCF
CF (CF
C
2 2
F
4
OCF
2
I
DMF
2
I
DMF
3
2
)
4
I
DMF
1:1.6
1:2
1:2
1:2
1:2
1:1
1:1
C
C
6
H
N
5
OCF
CF
2
Br
Br
Br
I
DMF
e
2
3
2
H
3
DMF
30 (2f)
90 (2b)
23 (2b)
45 (2b)
0 (2b)
0
f
Cl(CF
Cl(CF
Cl(CF
Cl(CF
2
2
2
2
)
3
1g
1b
1b
1b
DMF
2
1
)
)
)
3
3
3
DMF
2
2
I
NaOH
NaOH
CH
CH
3
OH
OH
c
2
3
I
3
a
b
c
d
e
f
Molar ratio.
Determined by F NMR.
DMF:H O = 10:1 (volume ratio), H
DMF:H O = 100:1 (volume ratio), H
-(2-Bromo-1,1,2,2-tetrafluoroethyl)-1H-imidazole.
p-Dinitrobenzene was added and the molar ratio of p-dinitrobenzene to 1b was 1:5.
19
2
2
O:NaOH = 28:1 (molar ratio).
O:NaOH = 3:1 (molar ratio).
2
2
1
solvents with higher boiling points were chosen as the substitutes
entries 4 and 6). In water, almost no 2b was generated at 80 8C
used (entry 13). Increasing the ratio of K
3
PO
4
Á3H
2
O to 1b resulted
(
in complete conversion (entry 14). It should be noted that all the
reactions proceeded very well under these mild conditions,
without any incidents in which the reaction flask was ruptured.
Compared with the previous reports, these could be considered to
be much milder reaction conditions in view of the weak basicity of
after 12 h (entry 4). When the reactions were conducted in DMF,
hydrodehalogenation was found to proceed smoothly (entries 6–8
and 14), indicating that DMF is a good substitute for methanol. In
addition, the reaction was improved when carried out in a mixture
of DMF and water (entries 6–8). Compound 1b was completely
converted into the dehalogenated product in the presence of a
small amount of water (entries 7 and 8).
The hydrodehalogenation was also influenced by the base used.
Using NaOH as the base, 2b could be formed in quantitative yield in
DMF (entries 7 and 8). Similar results were achieved when NaOH
K
3
PO
4
and the effectiveness of the hydrodehalogenation [11,12].
PO O as the base and DMF
Having found that the use of K
3
4
Á3H
2
as solvent was optimal for the substrate 1b, the scope of the
reaction was then studied with other fluoroalkyl halides. As shown
in Table 1, the hydrodeiodination of 1a proceeded very well in the
K
3
PO
4
Á3H
2
O/DMF system. Compound 2a was formed in a
was replaced by NEt
3
(entry 10). When Na
2
CO
3
was selected, only a
satisfactory yield when the reaction was run at 80 8C for 17 h
(entry 15). In the case of 1d, the hydrodehalogenation product of
1H-perfluorohexane (2d) was formed in quantitative yield even
5
2% yield of 2b was obtained (entry 9). These results indicated that
increasing the strength of the base used in the reaction would
improve the rate of the hydrodeiodination of perfluoroalkyl
iodides. However, when DMAP was employed as the base and
the reaction mixture was heated at 80 8C for 18 h, none of the
product 2b was formed (entry 11), suggesting that DMAP is not a
good reagent for the reduction of perfluoroalkyl iodides. Although
the deiodination of 1b worked well in DMF in the presence of
NaOH, there is the possibility that DMF might be hydrolyzed under
these strongly basic conditions [14]. If this is the case, it would
make it difficult to separate the reaction products from the
when a lower molar ratio of K
3
PO
4
Á3H
2
O and a shorter reaction
time was used (entry 17). However, the reaction of 1c led to the
formation of 1-chloro-1,1,2,2-tetrafluoroethane (2c) in a yield of
only 11% even when the reaction was run at 80 8C for 38 h (entry
16). These results suggest that fluoroalkyl iodides with long alkyl
chains are easier to reduce under these reaction conditions. This
method was also effective for the hydrodehalogenation of
fluoroalkyl bromides. Thus, similar results were obtained for the
hydrodebromination of 1e–g (entries 18–20), in which fluoroalkyl
bromides with longer alkyl chains again underwent more rapid
debromination.
hydrolyzed products of DMF. Therefore, K
as a substitute for NaOH. It was found that 2b was obtained in
3
PO
4
Á3H
2
O was selected
quantitative yield when the reaction was carried out in DMF at
To understand the mechanism of this hydrodehalogenation,
various inhibition experiments were carried out. Addition of
20 mol% of the electron transfer scavenger p-dinitrobenzene to the
8
0 8C for 16 h while using K
amount of K PO O used also had some influence on the
Á3H
reaction. Compound 2b was formed only in 65% yield under these
conditions when equimolar amount of 1b and K PO O were
Á3H
3
PO
4
Á3H
2
O as the base (entry 14). The
3
4
2
reaction of 1b in the K
3
PO
4
2
Á3H O/DMF system decreased the yield
3
4
2
of 2b from 100% (entry 14) to 23% (entry 21). Furthermore, reaction

C.-P. Zhang et al. / Journal of Fluorine Chemistry 130 (2009) 671–673
673
of 1b in the NaOH/CH
dinitrobenzene (entries 22 and 23). On the basis of these
experiments, it appears that the radical R
in these reactions, indicating a single electron transfer mechanism
for this hydrodehalogenation initiated by base [12,15,16].
3
OH system was completely inhibited by p-
4.3.2. 1-Chloro-1,1,2,2-tetrafluoroethane (2c)
1
19
H NMR
d
5.86 (tt, J = 54 Hz, J = 2.3 Hz, 1H), F NMR
d
d
À72.4 (t,
Á
f
CF
2
might be involved
J = 7.2 Hz, 2F), À131.8 (dt, J = 53.6 Hz, J = 7.2 Hz, 2F).
4.3.3. 1,1,1,2,2,3,3,4,4,5,5,6,6-Tridecafluorohexane (2d)
1
19
H NMR
d
6.05 (tt, J = 52 Hz, J = 5.0 Hz, 1H), F NMR
À80.2 (t,
J = 9.2 Hz, 3F), À122.3 (m, 2F), À122.9 (s, 2F), À125.6 (m, 2F),
3
. Conclusion
À128.6 (m, 2F), À136.4 (dm, J = 52 Hz, 2F).
In summary, we have shown that the hydrodehalogenation of
4
.4. Typical procedure for the preparation of 2e and 2f
perfluoroalkyl halides proceeds smoothly in DMF in the presence
of K PO O. This offers a simple and efficient method for the
3
4
Á3H
2
1
f (0.498 g, 2.01 mmol) and K PO O (1.059 g, 3.98 mmol)
3
4
Á3H
2
conversion of perfluoroalkyl halides into the corresponding
hydrogenolysis compounds. When bases are used in the reactions
of fluoroalkyl bromides or iodides, the potential hydrodehalogena-
tion reactions should be considered.
were placed in a sealed tube equipped with a magnetic stir bar.
DMF (15 ml) was added and the mixture was heated to 80 8C for
7
7 h, then cooled, extracted with ethyl ether (60 ml), washed with
water (3Â 20 ml) and dried over anhydrous Na SO . The crude
product was purified by column chromatography to give pure 2f in
1% yield.
2
4
4
. Experimental
2
4
.1. General
4
.4.1. 1-(1,1,2,2-Tetrafluoroethyl)-1H-imidazole (2f)
1
H NMR
H), F NMR
d
7.81 (s, 1H), 7.20 (s, 1H), 7.18 (s, 1H), 6.06 (t, J = 54 Hz,
NMR spectra were recorded in dueterated chloroform, unless
19
1
d
À96.1 (s, 2F), À135.1 (d, J = 54 Hz, 2F).
1
otherwise stated, on Mercury 300 at 300 MHz ( H NMR) and
2
to TMS and CFCl
standards.
19
82 MHz ( F NMR). Chemical shifts were reported in ppm relative
4
.4.2. 1-(1,1,2,2-Tetrafluoroethoxy)benzene (2e)
1
3
(positive for downfield shifts) as external
H NMR
d
5.91 (tt, J = 53 Hz, J = 2.8 Hz 1H), 7.25 (m, 3H), 7.38 (m,
19
2
H), F NMR
d
À88.1 (t, J = 6.2 Hz, 2F), À136.7 (dt, J = 53 Hz,
J = 6.2 Hz, 2F).
4
.2. Preparation of 1,1,2,2-tetrafluoro-2-(1,1,2,2-
tetrafluoroethoxy)ethanesulfonamide (2a)
Acknowledgements
1
a (1.01 g, 2.38 mmol) and K
3
PO
4
Á3H
2
O (1.88 g, 6.58 mmol)
This project was financially supported by the Chinese Academy
of Sciences (Hundreds of Talents Program), the National Science
Foundation (20772147) and the Syngenta PhD studentship
awarded to Cheng-Pan Zhang. We thank Dr John Clough of
Syngenta at Jealott’s Hill International Research Centre for
proofreading of the manuscript.
were placed in a 25 ml round-bottomed flask equipped with a
magnetic stirrer. DMF (10 ml) was added. The mixture was heated
to 80 8C for 17 h, then cooled and poured into 50% sulfuric acid
solution for acidification till pH < 1. The acidified mixture was
extracted with ethyl ether (80 ml), washed with water (3Â 30 ml)
2 4
and dried over anhydrous Na SO . The crude product was purified
1
by column chromatography to give 0.580 g of pure 2a (82%).
NMR (CD COCD 6.60 (tt, J = 52 Hz, J = 3.2 Hz, 1H), 8.07 (s, 2H),
F NMR (CD COCD
À76.8 (m, 2F), À84.1 (m, 2F), À112.9 (s, 2F),
À134.3 (dt, J = 52 Hz, J = 4.2 Hz, 2F).
H
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3
3
) d
1
9
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.3. Typical procedures for the preparation of 2b–d
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2
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(
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[
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20.
4
.3.1. 1-Chloro-1,1,2,2,3,3,4,4-octafluorobutane (2b)
1
19
H NMR
J = 11.9 Hz, 2F), À121.0 (t, J = 7.2 Hz, 2F), À128.0 (m, 2F), À136.3
dt, J = 52 Hz, J = 6.2 Hz, 2F).
d
6.04 (tt, J = 52 Hz, J = 5.0 Hz, 1H), F NMR
d
À67.6 (t,
[
[
(