One-pot α-nucleophilic fluorination of acetophenones in a deep eutectic solvent

Article abstract of DOI:10.1016/j.jfluchem.2009.11.008

Two methods of nucleophilic fluorination to prepare α-fluoroacetophenones from α-bromoacetophenones by using KF with PEG-400 or TBAF with ZnF₂ are described. On the fundamental of nucleophilic fluorination, a novel method of one-pot fluorination to prepare α-fluoroacetophenones directly from acetophenones in DES was developed.

Full text of DOI:10.1016/j.jfluchem.2009.11.008

Journal of Fluorine Chemistry 131 (2010) 340–344
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
One-pot
a
-nucleophilic fluorination of acetophenones in a deep eutectic solvent
*
Zizhan Chen, Wei Zhu, Zubiao Zheng, Xinzhuo Zou
Department of Chemistry, East China Normal University, 3663 Zhongshan Road (N), Shanghai 200062, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Two methods of nucleophilic fluorination to prepare
a-fluoroacetophenones from a-bromoacetophe-
Received 24 October 2009
nones by using KF with PEG-400 or TBAF with ZnF2 are described. On the fundamental of nucleophilic
Received in revised form 12 November 2009
Accepted 12 November 2009
Available online 17 November 2009
fluorination, a novel method of one-pot fluorination to prepare
acetophenones in DES was developed.
a-fluoroacetophenones directly from
ß 2009 Elsevier B.V. All rights reserved.
Keywords:
One-pot
Nucleophilic fluorination
a
-Fluoroacetophenones
Deep eutectic solvents
1. Introduction
more safe and cheaper and are more easily used in the large-scale
fluorination [6].
Fluorinated molecules find innumerable applications in the
industries or daily life and the fluorine atom endows unique
properties such as some characteristic effects on bioactivity to the
molecules that are extremely important in the pharmaceutical and
In order to develop methods for preparing
a-fluoroacetophe-
nones from -bromoacetophenones by nucleophilic strategy, KF or
a
TBAF was respectively used in different conditions and several
substrates were tested. Based on these results, a novel method to
agrochemical industries [1].
contain fluorine atom next to carbonyl group have important usage
in medicinal and biological chemistry and -fluoroacetophenones
that have carbonyl group, -fluorinated carbon and aromatic ring
can be transformed into a large number of interesting molecules
that have potential to constitute an important class of fluorinated
intermediates in the pharmaceutical and agrochemical chemistry
[2].
a
-Fluorocarbonyl compounds that
prepare a-fluoroacetophenones directly from acetophenones in
one pot by nucleophilic strategy was developed in a deep eutectic
solvent. Choline chloride is an important compound in the
chemical and biological technology. Deep eutectic solvents
(DES) prepared from choline chloride are thought to be versatile
alternatives to ionic liquids and have been shown to be good
solvents for many organic reactions [7]. Some good results of
a
a
preparing
a-fluoroacetophenones by nucleophilic strategy were
Generally speaking,
a
-fluoroacetophenones can be prepared
reported [8] and we tried to make the fluorination more safe,
cheaper and easier to handle. In this paper, we wish to report two
nucleophilic processes and a new one-pot method of nucleophilic
from acetophenones through two kinds of strategies that are
electrophilic and nucleophilic fluorination [3]. A wide range of
reagents bearing a R2N-F unit was used in the electrophilic way of
fluorination in a deep eutectic solvent to prepare
phenones (Scheme 1).
a-fluoroaceto-
preparing fluorinated carbonyl compounds and a-fluoroacetophe-
nones were obtained from acetophenones directly by electrophilic
fluorination using Selectfluor or NFSI [4]. But the N-F reagents are
too expensive for large-scale preparation and elemental F, a sort of
hazardous and toxic chemical, is widely used in preparing N-F
reagents and electrophilic fluorination in the plant-scale produc-
tion [5]. Comparing with electrophilic methods, nucleophilic
2. Results and discussion
KF is widely used in the nucleophilic fluorination and
polyethylene glycol (PEG) as a safe and cheap solvent has been
reported to be used in the nucleophilic fluorination with KF to
improve the yields of fluorinated products. Efficient fluorination
was reported using potassium fluoride as a nucleophilic source of
fluorine and PEG-400 as a solvent and the yields of the fluorinated
products were 24–63% [9]. Acetonitrile was used as a solvent and
processes to prepare
a-fluoroacetophenones from a-bromoace-
tophenones by KF or tetrabutylammonium fluoride (TBAF) are
PEG-400 was cosolvent. When
a-bromoacetophenone 2a was
stirred and heated directly with KF and PEG-400 in acetonitrile that
is frequently used as a solvent in nucleophilic fluorination reaction,
* Corresponding author. Tel.: +86 21 62233993; fax: +86 21 62233993.
E-mail address: xzzou@chem.ecnu.edu.cn (X. Zou).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.11.008

Z. Chen et al. / Journal of Fluorine Chemistry 131 (2010) 340–344
341
Scheme 1.
the yield of
a
-fluoroacetophenone was 50% and trans-1,2,3-tri-
at 80 8C and then a solution of substrate (5 mmol) was added into
the reaction mixture. After the reaction completed, the yield of 1a
(benzoyl)cyclopropane that reduced the yield of fluorinated
compound was found among the products. trans-1,2,3-Tri-
was 76%. When DMSO was used as solvent, the yield of a-
(benzoyl)cyclopropane prepared from
has been reported and reducing the concentration of
cetophenone in the solvent is helpful to lower the amount of trans-
1,2,3-tri-(benzoyl)cyclopropane and to offer more fluorinated
a
-bromoacetophenone
fluoroacetophenone 1a declined to 66%. When CaF2 was used
instead of ZnF2, the yield of 1a was 72%; when MgF2 was added
instead of ZnF2, the yield of 1a was 70%. Other substituted
substrates were tested and yields of 1a–1i were 60–90% (Scheme 1,
method II; Table 1). The yields of 1b–1d that have electron-
donating groups were from 82% to 90%, which were better than the
yields of 1e–1i that have deactivating groups (Table 1). Comparing
with method I, the yields of method II were better. In both two
methods, the yields of 1a–1d were higher than the yields of 1e–1i.
Deep eutectic solvents (DES) formed between choline chloride
and acids are thought to be a new kind of solvents that will be
closer to the principles of green chemistry and an efficient method
of chlorination in DES that formed between choline chloride and p-
TsOH has been reported [12]. Based on the nucleophilic fluorina-
tion by TBAF, we tried to combine the chlorination in DES with
nucleophilic fluorination to develop a one-pot fluorination method
a
-bromoa-
products [10]. A diluted solution of
slowly added drop by drop into the mixture of KF, PEG-400 and
acetonitrile at 80 8C and the yield of -fluoroacetophenone
increased to 72%. After that, other substituted -bromoacetophe-
a-bromoacetophenone was
a
a
nones were tested and the yields were from 55% to 74% (Scheme 1,
method I; Table 1). The yields of 1b–1d that have electron-
donating groups were close to 70% (Table 1, entry 2–4) and the
yields of 1e–1g that have weak deactivating groups were lower
than 58% (Table 1, entry 5–7). Only trace amount of 1h or 1i that
has strong electron-withdrawing group was obtained and 3h or 3i
was collected as major product (Table 1, entry 8–9). 85% of 2h was
transformed into 3h and 82% of 2i was transferred into 3i.
Dibromoacetophenone was also used as a tested substrate and
-difluoroacetophenone was not found among the products
a,a-
that
acetophenones. Firstly, acetophenone 3a was selected as the
tested substrate. We thought more -dichloroacetophenone
a-fluoroacetophenones can be prepared directly from
a,a
while 1a and acetophenone were obtained; the yield of 1a was 15%
and the yield of acetophenone was 75%.
a,a
produced in DES would reduce the yield of the fluorinated product
so we tried to control the amount of chlorinating reagent. 1,3-
Dichloro-5,5-dimethylhydantoin (DCDMH) is a bleaching reagent
and it has also been extensively used as a disinfectant for industrial
and domestic water. So DCDMH was selected as the chlorinating
reagent. DES was prepared from choline chloride (1 mmol) and p-
TsOH (1 mmol) and then 3a (2 mmol) was added into the DES.
After that, DCDMH (1.1 mmol) was added bit by bit into the
reaction mixture. After the reaction mixture was stirred at room
In order to improve the yields of fluorinated compounds,
tetrabutylammonium fluoride (TBAF) was used as the fluorinating
reagent. Tetrabutylammonium hydrogen bifluoride is a nucleo-
philic fluorine source with good solubility property and tetra-
butylammonium fluoride trihydrate that can generate reactive
fluoride ions in organic solvents has also been reported as a
nucleophilic reagent [11]. Tetrabutylammonium fluoride trihy-
drate is easy to handle and it is cheaper than tetrabutylammonium
hydrogen bifluoride. Some examples using tetrabutylammonium
hydrogen bifluoride were reported and the yields were 20–51%
[2b]. In our research, we tried to improve the yields of the
fluorinated products and tetrabutylammonium fluoride trihydrate
temperature for 1 h, 80% of 3a was transformed into
chloroacetophenone and 12% of 3a was transformed into a,a
a
-
-
dichloroacetophenone. 8% of 3a was also found in the mixture,
which was determined by GC. When the amount of DCDMH
was selected as the fluorinating reagent. When
a
-bromoaceto-
increased to 1.3 or 1.5 mmol, the yield of a-chloroacetophenone
phenone 2a was heated and stirred with TBAFÁ3H2O in acetonitrile,
the isolated yield of 1a was 62%. When TBAFÁ3H2O was replaced by
ZnF2 in this reaction, only trace amount of 1a was obtained. While
2a (5 mmol) was heated with TBAFÁ3H2O (5 mmol) and ZnF2
(5 mmol) in acetonitrile at 80 8C, the yield of 1a was 70%. KF is
cheaper than TBAFÁ3H2O and part of TBAFÁ3H2O used in the
reaction was replaced by KF. A mixture of TBAFÁ3H2O (3.75 mmol),
KF (2.5 mmol), ZnF2 (5 mmol) and acetonitrile (20 ml) was stirred
determined by GC was 86% or 78%. But when 3b was selected as the
tested substrate, the yields of chlorinated products were different.
When the amount of DCDMH was 1.1 mmol, the yield of a-chloro-
4-methylacetophenone determined by GC was 92%. When the
amount increased to 1.3 or 1.5 mmol, the yield declined to 80% or
74%. We thought that 1.1 mmol was a proper amount for 3a and
1.3 mmol was a proper amount for 3b. So both two amounts of
DCDMH (1.1 mmol and 1.3 mmol) were tested when other

342
Z. Chen et al. / Journal of Fluorine Chemistry 131 (2010) 340–344
Table 1
compounds were found in the reaction mixture, which made the
reaction complex.
Nucleophilic fluorination of
a
-bromoacetophenones by KF (I)a or TBAF (II)b.
After that, we tried to combine chlorination with fluorination
to develop a one-pot process. To improve the fluorination in the
DES, the amount of TBAFÁ3H2O used in the reaction was
increased without KF. After 3a was added into the DES and
stirred with DCDMH, ZnF2 and TBAFÁ3H2O were added into the
reaction mixture. After the mixture was heated at 80 8C for 8 h,
the fluorinated product 1a was isolated. When the amount of
DCDMH was 1.1 mmol, the yield of 1a was 60% and the yields of
the other tested substrates were from 32% to 80%. When this
amount was 1.3 mmol, the yields of fluorinated products were
from 35% to 72% (Table 2). When 3c that has a –OCH3 group was
tested as the substrate, 1m, a new compound, that has a –OCH3
group and a chlorine atom on the aromatic ring was obtained as
the major fluorinated product. Maybe 3c was easily transformed
into 3m in the DES (Table 2-entry 3). As to the substrate 3d, only
trace amount of 1d was obtained (Table 2-entry 4). When
1.1 mmol of DCDMH was used, the yields of 1b and 1j were
higher than the yields when 1.3 mmol of DCDMH was used
(Table 2-entry 2, 10). The yields of the other tested products
when 1.1 mmol of DCDMH was used in the reaction were lower
than the yields when 1.3 mmol of DCDMH was used. The
substrates that have –CH3 group like 3b and 3j were perhaps
Entry
Substrate
Product
Yield of I (%)c
Yield of II (%)d
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
1a
1b
1c
1d
1e
1f
72
66
74
70
55
58
58
76
90
84
82
65
70
72
60
66
2g
2h
2i
1g
1h
1i
e
/
f
/
a
Method I: 30 ml of acetonitrile solution of substrate (10 mmol) was added
slowly dropwise into a mixture of KF (50 mmol), PEG-400 (2 ml) and acetonitrile
(50 ml) at 80 8C.
b
Method II: 5 ml of acetonitrile solution of substrate (5 mmol) was added into a
mixture of TBAFÁ3H2O (3.75 mmol), KF (2.5 mmol), ZnF2 (5 mmol) and acetonitrile
(20 ml) at 80 8C.
transformed into more
1.1 mmol of DCDMH was added. These substrates were perhaps
transformed into more -dichloroacetophenones when
a-chloroacetophenones in DES when
c
Isolated yields of method I.
d
a,a
Isolated yields of method II.
e
Only trace amount of 1h was obtained and the yield of the major product 3h
1.3 mmol of DCDMH was added. Comparing with 3b and 3j,
the substrates that have deactivating groups were perhaps
was 85%.
f
Only trace amount of 1i was obtained and the yield of the major product 3i was
transformed into more
a-chloroacetophenones in DES when
82%.
1.3 mmol of DCDMH was added. Additionally, the yields of 3b
and 3j were higher than the yields of the other products.
acetophenones were used as substrates. When DES that was
prepared from ZnCl2 and choline chloride was used, the reaction
mixture was stirred for longer time (3 h) to fully consume starting
material 3a after DCDMH was added. When DBDMH was used
instead of DCDMH, both chlorinated compounds and brominated
3. Conclusion
We tried to prepare a-fluoroacetophenones by three different
methods and nucleophilic fluorination was involved in all these
methods. Method I and method II using KF or TBAFÁ3H2O as
Table 2
fluorinating reagent improved the yields of
a-fluoroacetophe-
One-pot fluorination of acetophenones by TBAFÁ3H2O in DESa.
nones that prepared from
took advantage of chlorination in DES and nucleophilic
fluorination to prepare -fluoroacetophenones directly from
a-bromoacetophenones. Method III
a
acetophenones in one pot and the yields of method III were
higher than some examples of electrophilic fluorination using N-
F reagents [2]. As far as the reactants and products were
concerned, method III completed ‘‘electrophilic’’ fluorination by
nucleophilic strategy.
4. Experimental
Entry
Substrate
Product
Isolated yield (%)b
1
2
3a
3b
3c
3d
3e
3f
1a
1b
1m
1d
1e
1f
60 (72)
80 (66)
33 (38)
4.1. General procedure of method I
3
c
A mixture of KF (50 mmol), PEG-400 (2 ml) and acetonitrile
(50 ml) was stirred and heated at 80 8C for 2 h and then 30 ml of
acetonitrile solution of substrate (10 mmol) was added slowly
dropwise into the reaction mixture. After the addition completed,
the reaction mixture was heated for further 18 h. After the mixture
was filtered, solvent was distilled under reduced pressure. The
crude product was purified by column chromatography on silica
gel using a mixture of petroleum ether and ethyl acetate (10:1) as
eluent to afford the pure product.
4
/
5
45 (50)
50 (50)
60 (60)
32 (35)
35 (40)
75 (62)
50 (55)
40 (46)
6
7
3g
3h
3i
1g
1h
1i
8
9
10
11
12
3j
1j
3k
3l
1k
1l
a
Substrate (2 mmol) was stirred with DCDMH (1.1 mmol or 1.3 mmol) in DES
(1 mmol choline chloride and 1 mmol p-TsOH) at room temperature for 1 h. After
that, ZnF2 (5 mmol) and TBAFÁ3H2O (6 mmol) were added and the reaction mixture
was heated at 80 8C for 8 h.
4.2. General procedure of method II
b
When the amount of DCDMH was 1.1 mmol, the yields was written out of the
A mixture of TBAFÁ3H2O (3.75 mmol), ZnF2 (5 mmol), KF
bracket; when the amount was 1.3 mmol, the yields was in the bracket.
c
Only trace amount of 1d was obtained.
(2.5 mmol) and acetonitrile (20 ml) was stirred and heated at

Z. Chen et al. / Journal of Fluorine Chemistry 131 (2010) 340–344
343
80 8C for 1 h and then 5 ml of acetonitrile solution of substrate
(5 mmol) was added into the reaction mixture. After the reaction
mixture was heated for further 10 h at 80 8C, the mixture was
filtered and acetonitrile was distilled under reduced pressure.
Water (40 ml) was added to the residue and ether (4Â 40 ml) was
used to extract the water layer. The combined ether layer was
washed by dilute hydrochloric acid (2Â 40 ml, 0.5 M) and by brine
(3Â 40 ml) and dried on magnesium sulfate. After that, the organic
layer was filtered and solvent was removed under reduced
pressure. The crude product was purified by column chromato-
graphy on silica gel using a mixture of petroleum ether and ethyl
acetate (10:1) as eluent to afford the pure product.
found: C, 43.4%; H, 3.6%. Calculated for C10H10BrFO3 (277.08): C,
43.3%; H, 3.6%.
4.8. 1-(4-Chlorophenyl)-2-fluoroethanone (1e) [14]
White solid. m.p.: 51–52 8C (lit: 52–53 8C). 1H NMR (CDCl3,
500 MHz) d: 5.48 (d, J = 47 Hz, 2H, CH2F), 7.45–7.47 (m, 2H, ArH),
7.83–7.85 (m, 2H, ArH). Ms: 173, 155, 140, 126, 112, 100, 86, 76,
61, 50.
4.9. 1-(4-Bromophenyl)-2-fluoroethanone (1f) [15]
White solid. m.p.: 69–70 8C (lit: 71–72 8C). 1H NMR (CDCl3,
4.3. General procedure of method III
500 MHz) d: 5.47 (d, J = 47 Hz, 2H, CH2F), 7.64–7.66 (m, 2H, ArH),
7.77–7.79 (m, 2H, ArH).
A mixture of choline chloride (1 mmol) and TsOH (1 mmol)
was added into a flask with a magnetic stirring bar under N2
atmosphere. The flask was heated in an oil bath at 100 8C
for 40 min and then was cooled to room temperature slowly.
After cooling down, the colorless DES was prepared in the
flask. Substrate (2 mmol) and acetonitrile (3 ml) were added into
DES and DCDMH (1.1 mmol or 1.3 mmol) was added bit by bit
into the reaction mixture. After addition, the mixture was stirred
at room temperature for 1 h and then ZnF2 (5 mmol) and
TBAFÁ3H2O (6 mmol) were added into the mixture. After
the reaction mixture was heated at 80 8C for 8 h, the mixture
was filtered and acetonitrile was distilled under reduced
pressure. Dilute hydrochloric acid (20 ml, 0.5 M) was added
to the residue and dichloromethane (2Â 20 ml) was used to
extract the water layer. The combined organic layer was
washed by saturated aqueous sodium bicarbonate solution
(2Â 20 ml) and water (2Â 20 ml) and dried on magnesium
sulfate. The organic layer was filtered and solvent was removed
under reduced pressure. The crude product was purified by
4.10. 1-(3-Bromophenyl)-2-fluoroethanone (1g)
Clear oil. 1H NMR (CDCl3, 500 MHz)
CH2F), 7.37–7.40 (m, 1H, ArH), 7.75–7.77 (m, 1H, ArH), 7.82–7.83
(m, 1H, ArH), 8.04–8.05 (m, 1H, ArH). 13C NMR (CDCl3, 125 MHz)
d: 5.47 (d, J = 47 Hz, 2H,
d
:
83.4 (CH2F), 123.2 (ArC), 126.3 (ArCH), 130.4 (ArCH), 130.9 (ArCH),
135.3 (ArCH), 136.9 (ArC), 192.2 (CO). IR (KBr, cmÀ1): 2933, 1716,
1568, 1424, 1227, 1095, 990, 786, 701 and 680. Ms: 217, 183, 155,
104, 76, 61, 50.
4.11. 2-Fluoro-1-(4-nitrophenyl)ethanone (1h) [15]
White solid. m.p.: 90–92 8C (lit: 96–97 8C). 1H NMR (CDCl3,
500 MHz) d: 5.52 (d, J = 47 Hz, 2H, CH2F), 8.08–8.11 (m, 2H, ArH),
8.35–8.37 (m, 2H, ArH).
4.12. 2-Fluoro-1-(4-nitrophenyl)ethanone (1i)
White solid. m.p.: 92–93 8C. 1H NMR (CDCl3, 500 MHz)
d: 5.54
column chromatography on silica gel using
a
mixture of
petroleum ether and ethyl acetate (10:1) as eluent to afford
the pure product.
(d, J = 47 Hz, 2H, CH2F), 7.73–7.76 (m, 1H, ArH), 8.26–8.28 (m, 1H,
ArH), 8.47–8.49 (m, 1H, ArH), 8.73–8.74 (m, 1H, ArH). 13C NMR
(CDCl3, 125 MHz) d: 83.8 (CH2F), 123.1 (ArCH), 128.3 (ArCH), 130.3
4.4. 2-Fluoro-1-phenylethanone (1a) [8a]
(ArCH), 133.7 (ArCH), 135.0 (ArC), 148.3 (ArC), 191.9 (CO). IR (KBr,
cmÀ1): 2939, 1704, 1609, 1535, 1352, 1230, 1074, 974, 826, 739
and 670. Ms: 183, 167, 150, 134, 122, 104, 92, 76, 63, 50. Element
Analysis: found: C, 52.6%; H, 3.3%. Calculated for C8H6FNO3
(183.03): C, 52.5%; H, 3.3%.
Clear oil. 1H NMR (CDCl3, 500 MHz)
d: 5.52 (d, J = 47 Hz, 2H,
CH2F), 7.47–7.50 (m, 2H, ArH), 7.60–7.62 (m, 1H, ArH), 7.87–7.88
(m, 2H, ArH).
4.5. 2-Fluoro-1-(4-methylphenyl)ethanone (1b) [2d]
4.13. 2-Fluoro-1-(3-methylphenyl)ethanone (1j) [16]
Clear oil. 1H NMR (CDCl3, 500 MHz)
d
: 2.41 (s, 3H, CH3), 5.50 (d,
Clear oil. 1H NMR (CDCl3, 500 MHz)
d: 2.41 (s, 3H, CH3), 5.52 (d,
J = 47 Hz, 2H, CH2F), 7.26–7.29 (m, 2H, ArH), 7.77–7.79 (m, 2H,
J = 47 Hz, 2H, CH2F), 7.36–7.39 (m, 1H, ArH), 7.42–7.44 (m, 1H,
ArH).
ArH), 7.66–7.67 (m, 1H, ArH), 7.70 (m, 1H, ArH).
4.6. 2-Fluoro-1-(4-methoxyphenyl)ethanone (1c) [13]
4.14. 2-Fluoro-1-(4-fluorophenyl)ethanone (1k) [17]
White solid. m.p.: 78–79 8C (lit: 78–79 8C). 1H NMR (CDCl3,
White solid. m.p.: 47–49 8C (lit: 49–51 8C). 1H NMR (CDCl3,
500 MHz)
d
: 3.88 (s, 3H, OCH3), 5.47 (d, J = 47 Hz, 2H, CH2F), 6.95–
500 MHz) d: 5.47 (d, J = 47 Hz, 2H, CH2F), 7.15–7.18 (m, 2H, ArH),
6.97 (m, 2H, ArH), 7.89–7.90 (m, 2H, ArH).
7.94–7.96 (m, 2H, ArH).
4.7. 1-(2-Bromo-4,5-dimethoxyphenyl)-2-fluoroethanone (1d)
4.15. 1-(3,4-Dichlorophenyl)-2-fluoroethanone (1l)
White solid. m.p.: 52–54 8C. 1H NMR (CDCl3, 500 MHz)
d: 5.45
White solid. m.p.: 86–87 8C. 1H NMR (CDCl3, 500 MHz)
(s, 3H, OCH3), 3.93 (s, 3H, OCH3), 5.50 (d, J = 47 Hz, 2H, CH2F), 7.06
(s, 1H, ArH), 7.23 (s, 1H, ArH). 13C NMR (CDCl3, 125 MHz)
: 56.2
d
: 3.91
(d, J = 47 Hz, 2H, CH2F), 7.58–7.60 (m, 1H, ArH), 7.73–7.75 (m, 1H,
ArH), 8.00–8.01 (m, 1H, ArH). 13C NMR (CDCl3, 125 MHz)
: 83.6
d
d
(OCH3), 56.4 (OCH3), 84.5 (CH2F), 112.3 (ArCBr), 113.1 (ArCH),
116.4 (ArCH), 129.1 (ArC), 148.5 (ArC), 152.6 (ArC), 195.0 (CO). IR
(KBr, cmÀ1): 2940, 1676, 1592, 1509, 1392, 1262, 1219, 1172, 1043,
880, 833, 765 and 632. Ms: 278, 267, 256, 245, 232, 216, 200, 186,
170, 158, 142, 132, 122, 109, 94, 78, 61, 50. Element Analysis:
(CH2F), 127.1 (ArCH), 130.1 (ArCH), 131.1 (ArCH), 133.2 (ArC),
133.8 (ArC), 138.9 (ArC), 191.7 (CO). IR (KBr, cmÀ1): 2926, 1704,
1587, 1383, 1230, 1087, 1030, 983 and 835. Ms: 207, 173, 145, 109,
74, 61, 50. Element Analysis: found: C, 46.8%; H, 2.3%. Calculated
for C8H5Cl2FO (205.97): C, 46.4%; H, 2.4%.

344
Z. Chen et al. / Journal of Fluorine Chemistry 131 (2010) 340–344
(d) S.C. Yoon, J. Cho, K. Kim, J. Chem. Soc. Perkin Trans. 1 (1998) 109–116;
(e) G.K.S. Prakash, J. Hu, G.A. Olah, J. Fluorine Chem. 112 (2001) 357–362.
[3] (a) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley–VCH, Weinheim, Germany,
2004;
4.16. 1-(3-Chloro-4-methoxyphenyl)-2-fluoroethanone (1m)
White solid. m.p.: 73–74 8C. 1H NMR (CDCl3, 500 MHz)
d
: 3.96
(b) K. Uneyama, Organofluorine Chemistry, Blackwell Publishing, UK, 2006;
(c) F. Qing, X. Qiu, Organofluorine Chemistry, Science Publishing, China, 2007.
[4] G. Stavber, M. Zupan, S. Stavber, Tetrahedron Lett. 48 (2007) 2671–2673.
[5] K. Mu¨ller, C. Faeh, F. Diederich, Science 317 (2007) 1881–1886.
[6] D.W. Kim, C.E. Song, D.Y. Chi, J. Am. Chem. Soc. 124 (2002) 10278–10279.
[7] A.P. Abbott, D. Boothby, G. Capper, D.L. Davies, R.K. Rasheed, J. Am. Chem. Soc. 126
(2004) 9142–9147, and references therein.
[8] (a) M. Makosza, R. Bujok, J. Fluorine Chem. 126 (2005) 209–216;
(b) M. Makosza, R. Bujok, Tetrahedron Lett. 45 (2004) 1385–1386;
(c) K. Moughamir, A. Atmani, H. Mestdagh, C. Rolando, C. Francesch, Tetrahedron
Lett. 39 (1998) 7305–7306;
(s, 3H, OCH3), 5.43 (d, J = 47 Hz, 2H, CH2F), 6.96–6.98 (m, 1H, ArH),
7.81–7.83 (m, 1H, ArH), 7.93–7.94 (m, 1H, ArH). 13C NMR (CDCl3,
125 MHz) d: 56.4 (OCH3), 83.5 (CH2F), 111.5 (ArCH), 123.3 (ArC),
125.5 (ArCH), 128.5 (ArCH), 130.2 (ArC), 159.5 (ArC), 191.2 (CO). IR
(KBr, cmÀ1): 2926, 1691, 1596, 1508, 1396, 1274, 1096, 1061, 1009,
861, 704 and 617. Ms: 202, 189, 169, 154, 141, 126, 111, 97, 85, 71,
57. Element Analysis: found: C, 53.3%; H, 4.0%. Calculated for
C9H8ClFO2 (202.02): C, 53.4%; H, 4.0%.
(d) J. Cousseau, P. Albert, J. Org. Chem. 54 (1989) 5380–5383;
(e) P.J. Wagner, M.J. Thomas, A.E. Puchalski, J. Am. Chem. Soc. 108 (1986) 7739–
7744;
Acknowledgements
(f) J. Leroy, J. Org. Chem. 46 (1981) 206–209;
(g) G.A. Olah, J.T. Welch, Y.D. Vankar, M. Nojima, I. Kerekes, J.A. Olah, J. Org. Chem.
44 (1979) 3872–3881.
The authors thank Shanghai Foundation of Science and
Technology for financial support (No. 073919106).
[9] J.A. Wilkinson, Chem. Rev. 92 (1992) 505–519.
[10] A. Saba, Gazz. Chim. Ital. 121 (1991) 55–56.
References
[11] A. Koschella, T. Heinze, Macromol. Symp. 197 (2003) 243–254.
[12] Z. Chen, B. Zhou, H. Cai, W. Zhu, X. Zou, Green Chem. 11 (2009) 275–278.
[13] B. Barkakaty, Y. Takaguchi, S. Tsuboi, Tetrahedron 63 (2006) 970–976.
[14] R. Katoch-Rouse, O.A. Pavlova, T. Caulder, A.F. Hoffman, A.G. Mukhin, A.G. Horti, J.
Med. Chem. 46 (2003) 642–645.
[15] C.F. Bridge, D. O’ Hagan, J. Fluorine Chem. 82 (1997) 21–24.
[16] E.D. Bergmann, S. Cohen, E. Hoffman, Z. Rand-Meir, J. Chem. Soc. (1961) 3452–
3457.
[1] (a) R.N. Perutz, Science 321 (2008) 1168–1169;
(b) B.E. Smart, J. Fluorine Chem. 109 (2001) 3–11;
(c) Q. Chen, X. Qiu, F. Qing, J. Org. Chem. 71 (2006) 3762–3767;
(d) J. Qian, W. Cao, H. Zhang, J. Chen, S. Zhu, J. Fluorine Chem. 128 (2007) 207–210.
[2] (a) G.K.S. Prakash, P. Beier, Angew. Chem. Int. Ed. 45 (2006) 2172–2174;
(b) E. Fuglseth, T.H.K. Thvedt, M.F. Moll, B.H. Hoff, Tetrahedron 64 (2008) 7318–
7323;
[17] W.J. Middleton, E.M. Bingham, J. Am. Chem. Soc. 102 (1980) 4845–4846.
(c) M.R. Heinrich, Tetrahedron Lett. 48 (2007) 3895–3900;