Fluorination of aromatic compounds with xenon difluoride in the presence of boron trifluoride etherate

Article abstract of DOI:10.1007/s11172-015-0974-7

Fluorination of benzene with the XeF₂ - BF₃?Et₂O system in acetonitrile at low temperatures affords fluorobenzene in 18% yield, the conversion of benzene being 92%. The rest products are di-, tri-, tetra-, and polyphenyls with different fluorination pattern. Toluene and chloro- and bromobenzenes are fluorinated predominantly at the ortho and para positions. Fluorination of 4-nitroanisole affords 2-fluoro-4-nitroanisole in 73% yield.

Full text of DOI:10.1007/s11172-015-0974-7

Russian Chemical Bulletin, International Edition, Vol. 64, No. 5, pp. 1049—1052, May, 2015
1049
Fluorination of aromatic compounds with xenon difluoride
in the presence of boron trifluoride etherate*
A. E. Fedorov, A. A. Zubarev, V. Yu. Mortikov, L. A. Rodinovskaya, and A. M. Shestopalov
N. D. Zelinsky Insitute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Eꢀmail: alf@server.ioc.ac.ru
Fluorination of benzene with the XeF2—BF3•Et2O system in acetonitrile at low temperaꢀ
tures affords fluorobenzene in 18% yield, the conversion of benzene being 92%. The rest
products are diꢀ, triꢀ, tetraꢀ, and polyphenyls with different fluorination pattern. Toluene and
chloroꢀ and bromobenzenes are fluorinated predominantly at the ortho and para positions.
Fluorination of 4ꢀnitroanisole affords 2ꢀfluoroꢀ4ꢀnitroanisole in 73% yield.
Key words: xenon difluoride, boron trifluoride etherate, fluorobenzene, fluoroarenes,
organofluorine compounds.
Earlier, xenon difluoride was proposed for fluorination
of organic compounds.1 This reagent offers a number of
advantages over elemental fluorine (solid state, low toxicꢀ
ity). The reaction of XeF2 with aromatic aldehydes and
ketones affords difluoromethyl phenyl ethers,1 while the
use of trifluoroacetic acid as a solvent brings about triꢀ
fluoromethylation products.2
Fluorination of benzene (1) with XeF2 at room and
higher temperatures in tetrachloromethane using HF as
the catalyst affords a mixture of products with a fluoroꢀ
benzene (2) content up to 68%; however, the benzene
conversion is only 12% (per one cycle).3 Fluorination of
other aromatic compounds under similar conditions proꢀ
ceeds with a low selectivity.4—7
Boron trifluoride diethyl etherate (BTFE) is an availꢀ
able Lewis acid used as the catalyst for electrophilic aroꢀ
matic substitution. It has been applied earlier in XeF2
fluorination of perfluoroarenes to perfluorocyclohexane
derivatives,8 as well as in fluorination of fluorene and
benzofuran to the corresponding monofluorinated deꢀ
rivatives.9
The aim of the present work is to study whether it is
possible to raise the selectivity of XeF2 fluorination of
aromatic compounds at low temperature using BTFE as
the catalyst.
MeCN and, on raising the temperature to ~20 C, after
a time the reaction proceeds in a vigorous and unconꢀ
trolled manner to form resinous products.
In the presence of catalytic amounts (1—10 mol.%) of
BTFE using MeCN as the solvent, formation of fluoroꢀ
benzene was observed; however, the conversion was low
and depended only on the amount of BTFE added. Proꢀ
longation of the reaction time and twoꢀfold increase in the
amount of XeF2 did not improve the yield of fluorobenzene
to cause only an increased resinification. We succeeded in
raising the benzene conversion up to 92% to obtain fluoroꢀ
benzene in 18% yield when benzene, BTFE, and XeF2
were used in the molar ratio of 1 : 1.4 : 1.25, respectively.
According to the data from mass spectrometry, the reꢀ
maining products were diꢀ, triꢀ, tetraꢀ, and polyphenyls
with different fluorination pattern whose formation agrees
with the earlier proposed reaction mechanism10 (Scheme 1).
The necessity for using BTFE in the amount exceeding
the molar ratio is likely caused by its binding to HF evolved
during fluorination to form tetrafluoroboric acid. The atꢀ
tempts to scavenge the released HF using organic (pyriꢀ
dine) and inorganic (K2CO3) bases inhibited the reaction
completely even on boiling.
The reaction pathway also depends significantly on
the reaction temperature. For example, the reaction proꢀ
ceeds very slowly below –38 C and quite vigorously above
–20 C. The optimum conditions were effective cooling
and slow addition of XeF2 to avoid temperature rise above
–25 C.
Results and Discussion
It was found that benzene underwent no fluorination
The optimized procedure was used for fluorination of
other arenes (see Scheme 1). Under these conditions, tolꢀ
uene (3) reacts readily with XeF2 to form (according to
in the absence of catalyst below 10 С in either CH2Cl2 or
* On the occasion of the 100th anniversary of the birth of Acadeꢀ
mician N. K. Kochetkov (1915—2005).
1
the data from GLC and H and 19F NMR spectroscopy)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1049—1052, May, 2015.
1066ꢀ5285/15/6405ꢀ1049 © 2015 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Fedorov et al.
Scheme 1
Compound
R1
H
Me
Cl
R2
H
H
H
H
Compound
R1
NO2
Me
R2
H
NO2
NO2
Compound
9
10
11
R1
Me
Cl
Compound
R1
NO2
Me
1
3
4
5
6
7
8
12
13
14
OMe
Br
OMe
Br
n = 1, 2, 3...
Reagents and conditions: i. 1) XeF2, BF3•Et2O, MeCN, –30 C; 2) NaHCO3, H2O.
a mixture of three isomers 9a—c in the following ratio:
62% of 9a (ortho isomer), 9% of 9b (meta isomer), and
29% of 9c (para isomer) (Table 1). The overall yield of
fluorobenzenes after distillation was 21% at the toluene
conversion of 94%, the distillation residues being highꢀ
molecularꢀweight resinification products.
Chlorobenzene (4) and bromobenzene (5) reacted simꢀ
ilarly (see Table 1). The ratio of isomeric chlorofluoroꢀ
benzenes 10a—c was almost the same as in the case of
toluene fluorination: 63% of 10a, 8% of 10b and 29% of
10c. In the case of bromofluorobenzenes 11a—c, the ratio
of ortho and para isomers changed compared to fluoroꢀ
toluenes to be 29% (11a) and 62% (11c), respectively.
This is likely due to the steric effect of bromine atom
which hinders the ortho position. The yield of meta isomer 11b
is virtually equal to those of fluoro derivatives 9b and 10b.
It should be noted that Ref. 4 gives higher yields of
fluorination products of arenes, but discusses neither conꢀ
version nor amounts of compounds isolated. Our proceꢀ
dure allows less laborous preparation of fluoroarenes in
comparable yields.
Fluorination of nitrobenzene (6) under these conditions
1
proceeds very slowly, according to the H and 19F NMR
spectral data the yield of fluoronitrobenzenes 12a—c was
Table 1. Yields and 19F NMR spectra of compounds 9—14
Comꢀ
pound
Yield Degree of starting
compound conversion
Ratio of
 *
F
o : m : p
isomers
orthoꢀIsomer (a)
metaꢀIsomer (b)
paraꢀIsomer (c)
(%)
9а—с
10а—с
11а—с
12а—с
13
21
42
56
16
10
73
94
99
99
10
13
76
62 : 9 : 29
63 : 8 : 29
29 : 9 : 62
19 : 89 : 2
—
–118.61 (–117.30)11 –114.98 (–113.70)11 –119.27 (–118.00)11
–116.34 (–115.60)11 –111.47 (–110.30)11 –117.15 (–117.38)11
–108.91 (–108.20)11 –111.16 (–110.00)11 –115.86 (–115.47)11
–120.30 (–119.00)11 –110.75 (–109.50)11 –103.61 (–102.40)11
–114.41 (–113.40)12
–132.90 (–131.40)12
—
—
—
—
14
—
* Given in parentheses are literature data.

Fluorination of arenes
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1051
~6% at the total nitrobenzene conversion of 10%. It should
be noted that, although metaꢀfluoronitrobenzene (12b)
accounts for 90% of fluoronitrobenzenes, the ratio of ortho/
para isomers (12a/c) was 5 : 1, which is quite unusual.
Fluorination of 1ꢀmethylꢀ4ꢀnitrobenzene (7) also resultꢀ
ed in a low yield (~10%) of 2ꢀfluoroꢀ1ꢀmethylꢀ4ꢀnitroꢀ
benzene (13) at the total degree of conversion of the startꢀ
ing compound of 13%. At the same time, fluorination of
the more reactive 1ꢀmethoxyꢀ4ꢀnitrobenzene (8) afforded
2ꢀfluoroꢀ1ꢀmethoxyꢀ4ꢀnitrobenzene (14) in 73% yield and
the total conversion of compound 8 was 76%, which was
likely caused by the activating effect of methoxy group.
It should be noted that the formation of polyphenyls in
such processes took place only in the case of benzene (1).
Iodobenzene (15) reacted in a unique manner under
optimized conditions (Scheme 2). The analysis of reaction
products of iodobenzene with XeF2 in the presence of comꢀ
pound 2 showed that the resulted mixture of products conꢀ
sists of 76% of iodobenzene (16) and 24% of (4ꢀiodoꢀ
phenyl)(phenyl)iodonium tetrafluoroborate (17). It is
known that the related (4ꢀiodophenyl)(phenyl)iodonium
triflate (18) is obtained by the exposure of benzene, iodine,
and iodobenzene to oxidizing agents13,14 or by the direct
reaction between iodobenzene and iodosobenzene15 or diꢀ
acetoxyiodosobenzene in the presence of trifluoromethꢀ
anesulfonic acid.16 Tetrafluoroborate 17 has been prepared
earlier by the reaction between phenylboronic acid, iodoꢀ
benzene, and MCPBA in the presence of BTFE (see Ref. 11).
Thus, the reaction of aromatic compounds with
XeF2—BTFE system requires a great excess of BTFE. Even
at low temperatures the reaction proceeds unselectively
and, as judged by the ratio of isomers, complies with the
rules of electrophilic aromatic substitution in monoꢀ
substituted benzenes. However, one should note some deꢀ
viations from the rule in the case bromobenzene, which is
likely due to steric factors. The nitro group significantly
retards fluorination and the activating effect of such elecꢀ
tronꢀdonating group as the methyl one is insufficient for
complete overcoming the deactivation. However, introꢀ
duction of the methoxy group already allows overcoming
the effect of highly ringꢀdeactivating groups. Selection of
the corresponding disposition of different substituents in
the molecule can allow achieving high yields and selectivꢀ
ities upon fluorination of aromatic compounds with XeF2.
Experimental
Commercially available reagents were used for syntheses.
The commercially available MeCN was kept for 1 day over phosꢀ
phorus pentoxide (20 g per 1 L of MeCN), additional portion of
the pentoxide (20 g) was added, and the mixture was refluxed for
1 h and distilled. The resulted distillate was fractionated over
calcined K2CO3. The reaction product composition was conꢀ
trolled by GLC on a LKhMꢀ8D chromatograph equipped with
a catharometer (stainless steel column 5000×3 mm, the stationary
phase was 8.5% diethylene glycol succinate on Chromaton,
80—100 mesh, the carrier gas was helium, the detector temperaꢀ
ture was 250 C, and the injector temperature was 300 C). The
column temperature was varied to be on average the half of the
boiling point of starting aromatic compound. 1H and 19F NMR
spectra were recorded on a Bruker Avance 11 300 spectrometer
(300 and 282 MHz, respectively) in DMSOꢀd6.
Scheme 2
General procedure for fluorination. A threeꢀnecked flask
equipped with an argon inlet and thermometer was loaded with
arene 1 or 3—8 (10 mmol) in dry MeCN (15 mL). Then, BTFE
(2.0 g, 14 mmol) was added. The mixture was cooled in the
argon stream down to –35 C and XeF2 (2.05 g, 12.5 mmol) was
added in small portions. The mixture was warmed to –25 C,
stirred for 30 min at this temperature, then heated to 20 C for
1 h, and stirred for additional 1 h (GLC control). A saturated
solution of sodium bicarbonate was added to the reaction mass
until termination of gas evolution. The resulted mixture was
extracted with diethyl ether (3×20 mL). The extract was washed
with water and dried with sodium sulfate.
In the case of benzene (1), toluene (3), and chlorobenzene
(4), the diethyl ether extracts were subjected to molecular distilꢀ
lation and fractionated, each fraction was analyzed by GLC and
NMR spectroscopy. In the case of bromobenzene (5), nitrobenꢀ
zene (6), pꢀnitrotoluene (7), and pꢀnitroanisole (8), the ethereal
extracts were evaporated in vacuo at the temperature below 25 С,
the residue was dissolved in chloroform and subjected to flash
chromatography (the eluent was hexane—chloroform, 3 : 1). The
eluent was concentrated under normal pressure and the residue
was analyzed by NMR spectroscopy.
X = BF4 (17), CF3SO3 (18)
Reagents and conditions: i. 1) XeF2, BF3•Et2O, MeCN, –30 C;
2) NaHCO3, H2O.
Probably, on contact with XeF2, iodobenzene underꢀ
goes double fluorination at the iodine atom and, then, the
resulted compound 19 reacts with excessive iodobenzene
to form product 17. The formation of iodosobenzene 16 is
likely caused by the hydrolysis of compound 19 under the
action of aqueous NaHCO3 (see Scheme 2).
In the case of iodobenzene (15), a precipitate formed upon
neutralization with a solution of sodium bicarbonate was filꢀ
tered, washed with water, sequentially with MeCN (5 mL) and

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Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Fedorov et al.
Et2O (5 mL) preserving the filtrate, and dried in air to yield a
solid residue (1.1 g), which according to the NMR spectral data
was a mixture consisting of (based on the weight percentages)
76% of iodosobenzene (16) and 24% of (4ꢀiodophenyl)phenylꢀ
iodonium tetrafluoroborate (17). Evaporation of the organic filꢀ
trate followed by the treatment of the residue with CHCl3 affords
100 mg of compound 18 with m.p. 149 C (cf. Ref. 17:
147—149 C). 1H NMR (DMSOꢀd6), : 7.59 (m, 3 H); 7.91
(d, 2 H, J = 7.3 Hz); 8.02 (d, 2 H, J = 7.3 Hz); 8.23 (d, 2 H,
J = 7.1 Hz). 19F NMR, : –149.05 (BF4)–.
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This work was financially supported by the Russian
Foundation for Basic Research (Project No. 12ꢀ03ꢀ00429a).
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Received March 5, 2015;
in revised form March 23, 2015