New Electrophilic Trifluoromethylating Agents

Article abstract of DOI:10.1021/jo972213l

Synthetic routes to S-(trifluoromethyl)phenyl-4-fluorophenylsulfonium triflate (8), S-(trifluoromethyl)phenyl-2,4-difluorophenylsulfonium triflate (9), S-(trifluoromethyl)phenyl-3-nitrophenylsulfonium triflate (10), and S-(trifluoromethyl)-4-fluorophenyl-3-nitrophenylsulfonium triflate (11) are described. They are stable molecules and conveniently prepared by treating phenyl trifluoromethyl sulfoxide with benzene and its derivatives. These novel electrophilic trifluoromethylating agents react under mild conditions with a variety of aromatic rings (p-hydroquinone, pyrrole, and aniline) to give trifluoromethylated compounds (2-trifluoromethyl-p-hydroquinone, 2-trifluoromethylpyrrole, 2-trifluoromethylaniline, and 4-trifluoromethylaniline) in moderate to high yields. The electrophilic trifluoromethylating potential can be altered by placing electron-withdrawing substituents on the benzene rings.

Full text of DOI:10.1021/jo972213l

2656
J . Org. Chem. 1998, 63, 2656-2660
New Electr op h ilic Tr iflu or om eth yla tin g Agen ts
J ing-J ing Yang, Robert L. Kirchmeier, and J ean’ne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, Idaho 83844-2343
Received December 5, 1997
Synthetic routes to S-(trifluoromethyl)phenyl-4-fluorophenylsulfonium triflate (8), S-(trifluoro-
methyl)phenyl-2,4-difluorophenylsulfonium triflate (9), S-(trifluoromethyl)phenyl-3-nitrophenyl-
sulfonium triflate (10), and S-(trifluoromethyl)-4-fluorophenyl-3-nitrophenylsulfonium triflate (11)
are described. They are stable molecules and conveniently prepared by treating phenyl trifluo-
romethyl sulfoxide with benzene and its derivatives. These novel electrophilic trifluoromethylating
agents react under mild conditions with a variety of aromatic rings (p-hydroquinone, pyrrole, and
aniline) to give trifluoromethylated compounds (2-trifluoromethyl-p-hydroquinone, 2-trifluoro-
methylpyrrole, 2-trifluoromethylaniline, and 4-trifluoromethylaniline) in moderate to high yields.
The electrophilic trifluoromethylating potential can be altered by placing electron-withdrawing
substituents on the benzene rings.
Ta ble 1. va n d er Wa a ls Ra d iu s a n d Electr on ega tivity of
Differ en t Gr ou p s
In tr od u ction
The trifluoromethyl group (CF3) is an important struc-
tural moiety in diverse classes of bioactive organic
molecules. The CF3 group has a bigger van der Waals
radius than that of a CH3 group and the same electrone-
gativity as oxygen (Table 1).1
van der Waals
radius (Å)
group/atom
group/atom
electronegativity
CF3
CH3
CCl3
F
H
O
2.7
2.0
3.5
1.4
1.2
1.5
CF3
CH3
C
F
H
3.5
2.3
2.5
4.0
2.1
3.5
3.0
The C-F bond in trifluoromethylated compounds
results in added stability and lipophilicity of the molecule.
As a consequence the introduction of a trifluoromethyl
group into organic molecules often changes their physical,
chemical, and physiological properties.2 Compounds
containing the trifluoromethyl group are found in a
variety of commercially important dyes,3,4 polymers,5,6
pharmaceuticals,7 and agrochemicals.8 The dye industry
has found that trifluoromethylated chromophores exhibit
increased light fastness3,4 compared with the nonfluori-
nated compounds. Trifluoromethylated polymers have
high thermal stability and enhanced mechanical and
electrical properties. Many of these polyfluorinated
polymers find application as liquid crystals.5,6 In a wide
variety of agrochemicals and pharmaceuticals, the prop-
erties of the trifluoromethyl group, i.e., to increase
lipophilicity and to act as an inhibitor of enzyme action,
are key reasons for incorporation.7,8 Thus, a variety of
reagents have been developed in order to introduce the
O
Cl
CF3 group into organic molecules.9-11 Currently, there
are three available methods for directly introducing a CF3
group into target compounds: (i) organometallic based
on CF3Cu,9 (ii) nucleophilic based on CF3SiMe3,10 and (iii)
electrophilic based on S-(trifluoromethyl)dibenzothiophe-
nium triflate.11
The introduction of a CF3 group into an electron-rich
environment is becoming more and more important in
organic and bioorganic synthesis. It is not a trivial task,
however. It is extremely difficult to generate the CF3
cation chemically, due to its high electronegativity (3.45).12
In 1984, Yagupol’skii13 reported two trifluoromethyl
sulfonium salts, trifluoromethyl-p-chlorophenyl(2,4-di-
methylphenyl)sulfonium hexafluoroantimonate (1) and
trifluoromethyl-p-chlorophenyl-p-anisylsulfonium hexaflu-
oroantimonate (2), that were capable of acting as tri-
fluoromethylating reagents. Compounds 1 and 2 react
with sodium p-nitrothiophenolate in DMF to give p-
nitrophenyl trifluoromethyl sulfide in high yield. How-
ever, 1 and 2 were synthesized from the extremely
hygroscopic intermediate fluoro(trifluoromethyl)-p-chlo-
(1) McClinton, M. A.; McClinton D. A. Tetrahedron 1992, 48, 6555.
(2) Banks, R. E.; Smart, B. E.; Tatlow, J . C. Organofluorine
Chemistry, Principles and Commercial Applications; Plenum Press:
New York, 1994.
(3) Banks, R. E. Preparation, Properties and Industrial Applications
of Organofluorine Compound; Ellis Harwood Ltd.: 1982.
(4) Dickey, J . B.; Towne, E. B.; Bloom, M. S.; Taylor, G. J .; Hill, H.
M.; Corbitt, R. A.; McCall, M. A.; Moore, W. H.; Hedberg, D. G. Ind.
Eng. Chem. 1953, 45, 1730-34.
(5) Reynolds, D. W.; Cassidy, P. E.; J ohnson, C. G.; Gameron, M. L.
J . Org. Chem. 1990, 55, 4448-54.
(6) Nohira, H. J . Synth. Org. Chem. J pn. 1991, 49, 467.
(7) Filler, R.; Kobayashi, Y. Biomedicinal Aspects of Fluorine
Chemistry; Kodansha Ltd.: Tokyo, 1982. Kumadaki, I. J . Synth. Org.
Chem. J pn. 1984, 42, 786. Welch, J . T. Tetrahedron 1987, 43, 3123.
Welch, J . T.; Eswarakrishnan, S. Fluorine in Bioorganic Chemistry;
J ohn Wiley & Sons: New York, 1991. Filler, R.; Kobayashi, Y.;
Yagupolskii, L. M. Organofluorine Compounds in Medicinal Chemistry
and Biomedical Applications; Elsevier: Amsterdam, 1993.
(8) Yoshika, H.; Nakayama, C.; Matsuo, N. J . Synth. Org. Chem.
J pn. 1984, 42, 809.
(9) McLoughlin, V. C. R.; Thrower, J . Tetrahedron 1969, 25, 5921.
Kobayashi, Y.; Kumadaki, I.; Sato, S.; Hara, N.; Chikami, E. Chem.
Pharm. Bull. 1970, 18, 2834. Burton, D. J .; Wiemers, D. M. J . Am.
Chem. Soc. 1986, 108, 832.
(10) Ruppert, I.; Schlick, K.; Volbach, W. Tetrahedron Lett. 1984,
25, 2195. Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J . Am. Chem.
Soc. 1989, 111, 393. Bellew, D. R.; Krishnamurti, R.; Prakash, G. K.
S. J . Org. Chem. 1991, 56, 984. Prakash, G. K. S.; Yudin, A. K. Chem.
Rev. 1997, 97, 795-86.
(11) Umemoto, T.; Ishihara, S. Tetrahedron Lett. 1990, 31, 3579.
(12) Huheey, J . E. J . Phys. Chem. 1965, 69, 3284.
(13) Yagupol’skii, L. M.; Kondratenko, N. Y.; Timofeeva, G. N. Zh.
Org. Khim. 1984, 20, 115; Chem. Abstr. 1984, 100, 191494e.
S0022-3263(97)02213-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/28/1998

New Electrophilic Trifluoromethylating Agents
J . Org. Chem., Vol. 63, No. 8, 1998 2657
Sch em e 3
F igu r e 1.
Sch em e 1
Sch em e 2
disulfide in acetonitrile, followed by a metathetical reac-
tion with copper(I) bromide.15 The white solid 3 was
obtained in high yield (98%) and was reacted with
iodobenzene in N-methylpyrrolidone (NMP) to give tri-
fluoromethylthiobenzene (4) in 65% yield.15 When this
reaction was carried out in a different solvent, e.g. in
DMF, the yield was not improved. The product was
purified by column chromatography. The 19F NMR
spectrum of 4 consisted of a single resonance at -43.0
ppm in CDCl3. Phenyl trifluoromethyl sulfoxide (5) was
obtained from the oxidation of trifluoromethylthioben-
zene with m-chloroperbenzoic acid via reaction over-
night at 0 °C in CH2Cl2. This oxidation reaction is very
sensitive to temperature. If the temperature exceeded
0 °C, the yield of sulfone 6 was enhanced. For example,
when the reaction was carried out at room temperature
for 12 h, the ratio of 5:6 was 5:2. On the other hand at
0 °C for 10 h, the ratio of 5:6 was 95:2. Compounds 5
and 6 were separated by column chromatography.
S-(Trifluoromethyl)diphenylsulfonium triflate and its
derivatives were obtained by an intermolecular conden-
sation reaction of phenyl trifluoromethyl sulfoxide with
benzene, 1-fluorobenzene, or 1,3-difluorobenzene by the
action of trifluoromethanesulfonic anhydride at room
temperature (Scheme 3). The products were easily
purified by column chromatography and recrystallization.
Compound 7 was obtained in a yield of 85%. A parent
ion for 7 appears in the mass spectrum at m/z 255 (FAB-
MS). When 1-fluorobenzene or 1,3-difluorobenzene was
reacted with phenyl trifluoromethyl sulfoxide, we ex-
pected two major products, the ortho- and para-substi-
tuted isomers. In this reaction, however, we obtained
the para-isomer of 8 in a yield of 76% and the para-
isomer of 9 in a yield of 70%. The structure of these
rophenylsulfonium hexafluoroantimonate. Both prod-
ucts, 1 and 2, are also extremely hygroscopic. Further-
more, they are unreactive with the highly activated
aromatic compound N,N-dimethylaniline. In 1990, Ume-
moto reported power-variable electrophilic trifluoro-
methylating agents (Figure 1) that can transfer the CF3
group to different kinds of organic molecules.11,14 They
react readily with strongly activated aromatic systems,
e.g. N,N-dimethylaniline. Although these reagents are
very useful, they are prepared by using multistep,
inconvenient synthetic routes that require gaseous CF3I
or CF3Br for the trifluoromethylation reaction. These
reagents, although available commercially, are expensive.
We have developed a new series of S-(trifluoromethyl)-
diphenylsulfonium triflate derivatives that are easily
prepared from inexpensive reagents. We have explored
their potential to act as practical, useful electrophilic
trifluoromethylating agents, and the results of that
exploration are the focus of this paper.
Resu lts a n d Discu ssion
Based on the literature,11-14 and our unpublished work,
our synthetic targets were derivatized S-(trifluorometh-
yl)diphenylsulfonium triflates (Scheme 1). We have
developed simple, inexpensive routes for their prepara-
tion. Reactivity can be tuned via functionalization of the
aromatic rings.
The precursors to these compounds were synthesized
as described in Scheme 2. Trifluoromethylthiocopper(I)
(3) was prepared by reacting silver(I) fluoride and carbon
1
products was confirmed based on their H and 19F NMR
and mass spectra. The FAB-MS for 8 showed a parent
1
ion at m/z 273. In the H NMR spectrum, H2 and H6
gave peaks that are a doublet of doublets, with coupling
constants of J 23 ) 6.0 Hz and J 2F ) 4.0 Hz. Protons H3
and H5 resonate as another set of doublet of doublets,
J 32 ) 6.0 Hz and J 3F ) 9.0 Hz. These two types of protons
(15) Clark, J . H.; J ones, G. W.; Kybett, A. P.; McClinton, M. A.;
Miller, J . M.; Bishop, D.; Blade, R. J . J . Fluorine Chem. 1990, 48, 249-
53.
(14) Umemoto, T.; Ishihara, S. J . Am. Chem. Soc. 1993, 115, 2156.

2658 J . Org. Chem., Vol. 63, No. 8, 1998
Yang et al.
Sch em e 4
Sch em e 5
at 8.83 ppm as a doublet of doublets with coupling
constants of J 24 ) J 26 ) 2.0 Hz. Proton H4 resonates at
8.75 ppm as a doublet of doublets of doublets, with
coupling constants of J 45 ) 6.0 Hz and J 42 ) J 46 ) 2.0
Hz. Proton H6 is found at 8.42 ppm, as a multiplet, with
one measurable coupling constant of J 65 ) 6.0 Hz. The
other six hydrogenatoms appear as two multiplets at 8.15
and 7.90 ppm. The presence of four different types of
protons and their fine structure in the NMR spectra
confirmed the structure of 10. For compound 11, the
FAB-MS spectrum shows a parent ion at m/z 318. The
1H NMR shows H2′ at 8.81 ppm as a doublet of doublets
with coupling constants of J 2′4′ ) J 2′6′ ) 2.0 Hz. Proton
H4′ is at 8.73 ppm as a doublet of doublets of doublets
confirm that the F group is at the para-position. If the
F atom were located at the ortho-position or the meta-
position, the H NMR would show four types of protons
1
and much more complex fine coupling. For compound
9, the 19F NMR spectrum showed two types of fluorine
atoms on the benzene ring. One gave rise to a resonance
1
at -91.74 ppm and the second at -98.22 ppm. The H
NMR spectrum showed a resonance at 7.90 ppm for H6,
as a broad doublet J 65 ) 7.5 Hz. H5 is at 7.45 ppm as a
doublet of doublets with coupling constants of J 56 ) 8.10
Hz, J 54F ) 7.8 Hz. Proton H3 is at 7.25 ppm and is also
a doublet of doublets with coupling constants of J 32F
)
9.0 Hz, J 34F ) 9.0 Hz. There are three different types of
protons on the fluorinated benzene ring, confirming the
structure of 9 as shown. The FAB-MS shows a parent
ion for 9 at m/z 291. From these results, it is seen that
steric factors are important with respect to the isomer
formed. When either the group on the ring or the
attacking group is large, steric hindrance inhibits the
formation of the ortho-product, and the amount of para-
isomer obtained is increased.
with coupling constants of J 4′5′ ) 6.0 Hz, J 4′2′ ) J 4′6′
)
2.0 Hz. Proton H5′ is found at 8.10 ppm as a doublet of
doublets with coupling constants of J 5′4′ ) J 5′6′ ) 8.0 Hz,
while a complex multiplet at 8.42 ppm was assigned to
H6′. One measurable coupling constant is J 6′5′ ) 8.0 Hz.
For H2 and H6 at 8.24 ppm, a doublet of doublets
resonance is seen and the coupling constants are J 23
)
8.0 Hz and J 2F ) 8.0 Hz. H3 and H5 are at 7.67 ppm
also as a doublet of doublets with coupling constants of
J 32 ) 8.0 Hz, J 3F ) 8.1 Hz. These data are consistent
with the presence of a single NO2 group on the nonflu-
orinated benzene ring. Only two types of protons are
present on the benzene ring that contains a fluorine
atom. The other four types of protons and their coupling
constants confirm the fact that the NO2 group is at the
meta-position of the nonfluorinated benzene ring. When
8 was nitrated, the nitro group was not incorporated into
the fluorobenzene ring under the reaction conditions
used. Only the nonfluorinated benzene ring could be
nitrated. The electrophilic nitration reaction becomes
more difficult when more fluoro groups are on the
benzene ring. For example, the compound S-(trifluoro-
methyl)phenyl-2,4-difluorophenylsulfonium triflate was
examined, and no nitration reaction occurred under any
of the reaction conditions employed.
When 1,2,4-trifluorobenzene or pentafluorobenzene
was the substrate in this intermolecular condensation
reaction, mixtures of products were obtained because of
interfering nucleophilic reactions. The CF3SO3- nucleo-
phile attacked the fluorobenzene ring and replaced
fluorine atoms. No reaction occurred when the substrate
used was nitrobenzene or trifluoromethylbenzene. Not
surprisingly the reactivity toward electrophiles of the
benzene ring substituted with electron-withdrawing groups
(NO2, CF3) was greatly reduced.
The intermolecular condensation reaction of phenyl
trifluoromethyl sulfoxide (5) with benzene induced by
Tf2O apparently proceeds via intermediate A (Scheme 4).
This is also consistent with the fact that electron-
withdrawing groups on the benzene-ring reduced its
reactivity with the sulfoxide.
The reactivity of the S-(trifluoromethyl)diphenylsul-
fonium triflate salt can be modified by the introduction
of different substituents into the ring. Mononitrated
thiophenium salts were prepared from the reaction of 7
or 8 with a mixture of fuming HNO3 and concentrated
H2SO4 at 80 °C (Scheme 5). Products 10 and 11 were
purified by recrystallization. When 7 and 8 were ni-
trated, the meta-substituted products were expected since
CF3S+ is a meta-directing group. Compounds 10 and 11
were obtained in yields of 75% and 70%, respectively. The
structures of 10 and 11 were elucidated by NMR and MS
spectral analysis. For compound 10, FAB-MS shows a
Tables 2-4 compare the reactivities of a series of S-
(trifluoromethyl)diphenylsulfonium triflates and deriva-
tives with respect to their ability to transfer CF3 to
different substrates. Relative amounts of products formed
were determined based on 19F NMR spectral analysis.
Because of the electron-withdrawing properties of the
nitro group on the benzene ring, compounds 10 and 11
are more effective transfer reagents than 7 and 8. When
there are two fluorine atoms on the benzene ring, the
electrophilic trifluoromethylating ability of the sulfonium
1
parent ion at m/z 300. The H NMR spectrum shows H2

New Electrophilic Trifluoromethylating Agents
J . Org. Chem., Vol. 63, No. 8, 1998 2659
Ta ble 2. Tr iflu or om eth yla tion of p-Hyd r oqu in on e by
Ta ble 4. Tr iflu or om eth yla tion of An ilin e by Va r iou s
Tr iflu or om eth yla tin g Agen ts
Va r iou s Tr iflu or om eth yla tin g Agen ts
X
molar ratioa
condition
yield, %b
7
10
8
11
9
9
2:1
2:1
2:1
2:1
2:1
2:1
rt, 5 h
rt, 5 h
rt, 5 h
rt, 5 h
rt, 5 h
reflux, 10 h
5
40
6
40
10
85
X
molar ratioa
condition
yield (12:13), %
7
10
8
11
9
1:2
1:2
1:2
1:2
1:2
reflux, 10 h
reflux, 10 h
reflux, 10 h
reflux, 10 h
reflux, 10 h
trace, trace
70, 18
trace, trace
66, 17
33, 31
a
+ b
Molar ratio ) substrate:CF3
NMR spectra. Reference 16.
.
Yields determined from 19F
a
+ b
Molar ratio ) substrate:CF3
.
Yields determined from 19F
NMR spectra. Reference 18.
Ta ble 3. Tr iflu or om eth yla tion of P yr r ole by Va r iou s
Tr iflu or om eth yla tin g Agen ts
Table 4 shows the results of the trifluoromethylation
of aniline and the two products identified when treating
aniline with reagents 7-11 in THF at reflux. When the
reactions were carried out at room temperature, only
starting materials were obtained.
X
molar ratioa
condition
yield, %b
Con clu sion
7
10
8
11
9
9
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
reflux, 2 h
reflux, 2 h
reflux, 2 h
reflux, 2 h
reflux, 2 h
reflux, 10 h
6
80
10
85
50
87
We have demonstrated that aromatic ring substituted
S-(trifluoromethyl)diphenylsulfonium triflates react with
aromatic ring substrates to give aromatic compounds
containing the trifluoromethyl group. The electrophilic
trifluoromethylating reagents that we have described are
stable molecules and are inexpensive and convenient to
prepare. Their electrophilic trifluoromethylating poten-
tial can be altered by changing the substitutents on the
benzene rings. When electron-withdrawing groups (NO2,
F) were present on the benzene ring, transfer of the CF3
group to electron-rich substrates was enhanced.
Molar ratio ) substrate:CF3+. Yields determined from 19F
NMR spectra. Reference 17.
a
triflate is enhanced. Thus 9 is also more reactive than
either 7 or 8.
p-Hydroquinone was trifluoromethylated with reagents
7-11 in the presence of pyridine as a base (Table 2), and
the yields of 2-trifluoromethyl-p-hydroquinone obtained
were determined by 19F NMR and 1H NMR spectral
analysis. At rt, the abilities of 10 and 11 to transfer CF3
appeared about equal. At higher temperatures, 9 func-
tioned very effectively as an electrophilic trifluoromethy-
lating reagent, but increase in temperature did not
impact the ability of the other four reagents to transfer
CF3.
Exp er im en ta l Section
19F, 1H, and 13C NMR spectra were obtained with a 200 MHz
NMR spectrometer using CDCl3 as solvent unless otherwise
indicated. Chemical shifts are reported with respect to (CH3)4-
Si or CFCl3. Products were separated by column chromatog-
raphy with 70-230 mesh silica gel.
P r ep a r a tion of P h en yl Tr iflu or om eth yl Su lfoxid e (5)
a n d P h en yl Tr iflu or om eth yl Su lfon e (6). To a stirred
solution of phenyl trifluoromethyl sulfide (1.0 g, 5.6 mmol) in
dry CH2Cl2 (40 mL) at 0 °C under N2 was added m-chlorop-
erbenzoic acid (1.46 g, 7.3 mmol) in small portions. After the
reaction mixture was stirred for 10 h at 0 °C, and then rt for
1 h, the solution was filtered and evaporated. The residue was
subjected to silica gel column chromatography using a mixture
of ethyl acetate and hexanes (30:1) as eluent to give product
519 (0.981 g, 90%). IR (film): 3067 (w), 2359 (w), 1448 (m),
2-Trifluoromethylpyrrole was the product of trifluo-
romethylation of pyrrole under reflux conditions (Table
3). No products containing more than one CF3 group
were isolated. When the reactions were carried out at
room temperature, the yields were poor, e.g., for com-
pounds 7 and 8, only starting material was recovered,
and for compounds 9, 10, and 11, the yields were less
than 10%. However, at reflux, 9, 10, and 11 gave yields
of 2-trifluoromethylpyrrole of 80% or better. With 9 a
longer reflux time was required.
1370 (m), 1191 (s), 1141 (s), 1089 (s), 688 (m), 606 (m) cm-1
;
1H NMR (CDCl3): 7.54-8.06 (m, 5H); 19F NMR (CDCl3): -74.9
(s); 13C NMR (CDCl3): 134, 131, 130, 126, 121 (q, J ) 260 Hz)
ppm; EI-MS [m/e (species, intensity)]: 194 (M+, 4.8), 141 (M+
- C4H5, 13), 125 (M+ - CF3, 100), 109 (M+ - CF3 - O, 8), 77
(C6H5, 65), 69 (CF3, 7.2). Phenyl trifluoromethyl sulfone (6)20
(30.1 mg, 3%). IR (film): 3070 (w), 1585 (w), 1451 (m), 1370
(s), 1221 (s), 1143 (s), 1075 (m), 605 (m), 576 (m) cm-1; 1H NMR
(CDCl3): 8.04 (bd, J 23 ) 11.2 Hz, 2H), 7.84 (dt, J 43 ) 8.0 Hz,
p-Hydroquinone is more electron-rich than pyrrole, and
consequently its reactivity is higher as demonstrated by
the fact that transfer of CF3 takes place readily at room
temperature.
J 42 ) 2.0 Hz, 1H), 7.63 (dt, J 32 ) 8.0 Hz, J 34 ) 8.0 Hz, 2H); 19
F
(16) Feiring, A. E.; Sheppard, W. A. J . Org. Chem. 1975, 40, 2543.
Naumann, D.; Kischkewitz, J . J . Fluorine Chem. 1990, 46, 265.
(17) Tordeux, M.; Langlois, B.; Wakselman, C. J . Chem. Soc., Perkin
Trans. 1 1990, 2293.
NMR (CDCl3): -78.8 (s, 3F); 13C NMR (CDCl3): 137, 131, 130,
(19) Yagupol’skii, L. M.; Marenets, M. S.; Kondratenko, N. V. Zh.
Obsch. Khim. 1965, 35, 377.
(20) Kolmoeitsev, A. A.; Movchum, V. N.; Kondratenko, N. V.;
Yagupol’skii, Yu. L. Synthesis 1990, 1151.
(18) The Aldrich Library of 13C and 1H FT NMR Spectra, 1st ed.;
Pouchert, C. J ., Behnke, J ., Eds.; Aldrich Chemical Co., Inc.: Milwau-
kee, 1993; Vol. 2, pp 461 and 480.

2660 J . Org. Chem., Vol. 63, No. 8, 1998
Yang et al.
129, 124 (q, J ) 261 Hz) ppm; EI-MS [m/e (species, intensity)]:
210 (M+, 2.7), 141 (M+ - CF3, 44.8), 125 (M+ - CF3 - O, 2.9),
77 (C6H5+, 100), 69 (CF3+, 2.9). These compounds were
previously synthesized but characterized based on 19F NMR
spectral data and boiling points only.
262), 123 (q, J ) 262 Hz), 120, 117, 115, 108 ppm; FAB+-MS
[m/e (species, intensity)]: 291 ((C13H8F5S)+, 100), 222
((C13H8F5S)+ - CF3, 80.6), 145 ((C13H8F5S)+ - C6H5 - CF3,
15.0)). Anal. Calcd for C14H8F8O3S2: C, 38.18; H, 1.83; F,
34.52. Found: C, 37.97; H, 1.88; F, 34.90.
P r ep a r a tion of S-(Tr iflu or om eth yl)d ip h en ylsu lfon iu m
Tr ifla te (7). To a solution of phenyl trifluoromethyl sulfoxide
(194.17 mg, 1.0 mmol) in dry benzene (2.6 mL, 30 mmol) was
added (CF3SO2)2O (0.84 mL, 5.0 mmol) at 0 °C. The resulting
solution was stirred for 1 h at 0 °C and then rt for another 24
h. The solvent was evaporated, and the residue was purified
by column chromatography on silica gel with CH3CN-CH2-
Cl2 (1:4) as eluent. The product was obtained as a white
crystal (343.4 mg, 85%), mp 84-5 °C (recrystallized from ethyl
acetate/hexanes). IR (Nujol): 3115 (w), 1263 (s), 1224 (s), 1146
(s), 1083 (s), 513 (s) cm-1; 1H NMR (CDCl3): 8.15 (d, J 23 ) 7.6
Hz, 4H), 7.82 (m, 6H); 19F NMR (CDCl3): -49.6 (s, 3F), -78.6
(s, 3F); 13C NMR (CDCl3): 137, 133, 132, 127 (q, J ) 252 Hz),
122 (q, J ) 253 Hz), 117 ppm; FAB+-MS [m/e (species,
intensity)]: 255 ((C13H10F3S)+, 100), 186 ((C13H10F3S)+ - CF3,
81.2), 178 ((C13H10F3S)+ - C6H5, 2.1), 109 ((C13H10F3S)+ - C6F5
- CF3, 14.6). Anal. Calcd for C14H10F6O3S2: C, 41.58; H, 2.49;
F, 28.22. Found: C, 41.62; H, 2.57; F, 28.60.
P r ep a r a tion of S-(Tr iflu or om eth yl)p h en yl-3-n itr op h e-
n ylsu lfon iu m Tr ifla te (10). To fuming nitric acid (0.12 mL,
2.5 mmol, 90%, d ) 1.5) was added concentrated H2SO4 (0.35
mL, d ) 1.98). After the mixture was stirred for 0.5 h,
S-(trifluoromethyl)diphenylsulfonium triflate (1.0 g, 2.5 mmol)
was added. The reaction mixture was stirred for 5 h at 100
°C, and then diethyl ether was slowly added to the mixture.
The resulting pale yellow crystal was collected by filtration
and recrystallized with CH3CN-CH2Cl2 to give 833 mg (75%)
of 10, mp 87-9 °C. IR (Nujol): 1450 (s), 1225 (s), 1589 (m),
1031 (s), 639 (s), 585 (s) cm-1; 1H NMR (CDCl3): 8.83 (dd, J 24
) J 26 ) 2.0 Hz, 1H), 8.75 (ddd, J 45 ) 6.0 Hz, J 42 ) J 46 ) 2.0
Hz, 1H), 8.42 (dm, J 65 ) 6.0 Hz, 1H), 8.15 (m, 4H), 7.90 (m,
2H); 19F NMR (CDCl3): -48.1 (s, 3F), -78.3 (s, 3F); 13C NMR
(CDCl3): 139, 138, 137, 136, 135, 134, 133, 132, 129, 123 (q, J
) 264 Hz), 122 (q, J ) 263 Hz), 117 ppm; FAB+-MS [m/e
(species, intensity)]: 300 ((C13H9F3NO2S)+, 100)). Anal. Calcd
for C14H9F6NO5S2: C, 37.42; H, 2.02; N, 3.12. Found: C, 37.32;
H, 1.98; N, 2.90.
P r epar ation of S-(Tr iflu or om eth yl)ph en yl-4-flu or oph e-
n ylsu lfon iu m Tr ifla te (8). To a solution of phenyl trifluo-
romethyl sulfoxide (582 mg, 3.0 mmol) in dry 1-fluorobenzene
(8.4 mL, 30 mmol) was added (CF3SO2)2O (2.5 mL, 15 mmol)
at 0 °C. The reaction mixture was stirred for 10 h at 0 °C and
then at rt for another 2 h. Removal of the solvent left a crude
residue that was subjected to column chromatography on silica
gel using CH3CN-CH2Cl2 (1:4) as eluent to give the product
as a white crystal (886 mg, 70%), mp 80-1 °C (recrystallized
from ethyl acetate/hexanes). IR (Nujol): 3108 (m), 1719 (w),
P r ep a r a tion of S-(Tr iflu or om eth yl)-4-flu or op h en yl-3-
n itr op h en ylsu lfon iu m Tr ifla te (11). To fuming nitric acid
(0.60 mL, 14.2 mmol, 90%, d ) 1.5) was added concentrated
H2SO4 (2.0 mL, d ) 1.98). After the mixture was stirred for
0.5 h, S-(trifluoromethyl)phenyl-4-fluorophenylsulfonium tri-
flate (2.0 g, 4.7 mmol) was added to the solution. The reaction
mixture was stirred for 20 h at 100 °C. Diethyl ether was
slowly added to the mixture. The resulting pale yellow crystal
was collected by filtration and then was recrystallized with
CH3CN-CH2Cl2 to give 1.5 g of 11 (70%), mp 87-8 °C. IR
1
1589 (m), 1494 (m), 1255 (s), 1171 (s), 640 (s) cm-1; H NMR
(CDCl3): 8.35 (dd, J 23 ) 6.0 Hz, J 2F ) 4.0 Hz, 2H), 8.19 (bd,
(Nujol): 3105 (m), 1588 (s), 1494 (m), 1450 (s), 1087 (s) cm-1
1H NMR (CDCl3): 8.81 (dd, J 2′4′ ) J 2′6′ ) 2.0 Hz, 1H), 8.73
(ddd, J 4′5′ ) 6.0 Hz, J 4′2′ ) J 4′6′ ) 2.0 Hz, 1H), 8.42 (dm, J 6′5′
;
J 2′3′ ) 6.0 Hz, 2H), 7.83 (m, 3H), 7.51 (dd, J 32 ) 6.0 Hz, J 3F
)
9.0 Hz, 2H); 19F NMR (CDCl3): -50.7 (s, 3F), -78.7 (s, 3F),
-95.5 (s, 1F); 13C NMR (CDCl3): 170 (d, J ) 261 Hz), 139,
137, 135, 135, 127 (q, J ) 265 Hz), 126 (q, J ) 263 Hz), 121,
116 ppm; FAB+-MS [m/e (species, intensity)]: 273 ((C13H9F4S)+,
100), 272 ((C13H8F4S)+, 14.2), 254 ((C13H9F3S)+, 5.9), 204
((C13H9F4S)+ - CF3, 98.0), 196 ((C13H9F4S)+ - C6H5, 5.3), 178
((C13H9F4S)+ - C6H4F, 3.4), 127 ((C6H4FS)+, 13.0), 109 ((C6H5S)+,
20.1)). Anal. Calcd for C14H9F7O3S2: C, 39.81; H, 2.15.
Found: C, 39.45; H, 2.17.
)
8.0 Hz, 1H), 8.24 (dd, J 23 ) 8.0 Hz, J 2F ) 8.0 Hz, 2H), 8.10
(dd, J 5′4′ ) J 5′6′ ) 8.0 Hz, 1H), 7.67 (dd, J 32 ) 8.0 Hz, J 3F ) 8.1
Hz, 2H); 19F NMR (CDCl3): -48.3 (s, 3F), -78.3 (s, 3F), -95.3
(s, 1F); 13C NMR (CDCl3): 170 (d, J ) 260 Hz), 152, 138, 137,
135, 132, 129, 127 (q, J ) 262 Hz), 121, 121, 120 (q, J ) 262
Hz), 116 ppm; FAB+-MS [m/e (species, intensity)]: 318 ((C13H8F4-
NO2S)+, 100), 300 ((C13H8F4NO2S)+ - F + H, 61.2), 272
((C13H8F4NO2S)+ - NO2, 3.6), 250 ((C13H8F4NO2S)+ - CF3
+
P r ep a r a tion of S-(Tr iflu or om eth yl)p h en yl-2,4-d iflu o-
r op h en ylsu lfon iu m Tr ifla te (9). To a solution of phenyl
trifluoromethyl sulfoxide (485 mg, 2.5 mmol) in dry 1,3-
difluorobenzene (7.4 mL, 75 mmol) was added (CF3SO2)2O
(2.10 mL, 12.5 mmol) at 0 °C. The reaction mixture was
stirred for 2 h at 0 °C and then at rt for another 20 h. The
solvent was evaporated under reduced pressure, and the
residue was purified by column chromatography on silica gel
using CH3CN-CH2Cl2 (1:4) as eluent. The product was
obtained as a white crystal (770 mg, 70%), mp 78-9 °C
(recrystallized from ethyl acetate/hexanes). IR (Nujol): 3099
(s), 1600 (s), 1479 (s), 1450 (s), 1200 (s) (cm-1); 1H NMR
(CDCl3): 8.26 (d, J 2′3′ ) 8.1 Hz, J 4′3′ ) 8.1 Hz, 3H), 7.90 (bd,
J 65 ) 7.5 Hz, 1H), 7.75 (dd, J 3′2′ ) 7.8 Hz, J 3′4′ ) 7.8 Hz, 2H),
7.45 (dd, J 56 ) 8.1 Hz, J 54F ) 7.8 Hz, 1H), 7.25 (dd, J 32F ) 9.0
Hz, J 34F ) 9.0 Hz, 1H); 19F NMR (CDCl3): -47.6 (s, 3F), -78.3
(s, 3F), -91.7 (s, 1F), -98.2 (s, 1F); 13C NMR (CDCl3): 168 (d,
J ) 261 Hz), 163 (d, J ) 262), 138, 137, 133, 132, 126 (q, J )
H, 2.9)). Anal. Calcd for C14H8F7NO5S2: C, 35.98; H, 1.73;
N, 3.00. Found: C, 35.74; H, 1.67; N, 2.92.
Gen er a l Meth od for th e Tr iflu or om eth yla tion Rea c-
tion s. To a stirred solution of 0.9-2.5 mmol of substrate in
10 mL of dry THF under N2 was added 1 mmol of a
trifluoromethyl onium salt. Detailed conditions are shown in
Tables 2-4. After the reaction was complete, the reaction
mixture was studied by 1H and 19F NMR. In 19F NMR, the
triflate anion of the trifluoromethyl onium triflate was used
as an internal standard to determine the yield of product.
Ack n ow led gm en t. This research was made possible
by NSF-Idaho EPSCoR Program (EPS - 9350539) and
British Nuclear Fuels plc. The authors express their
gratitude to Dr. Gary Knerr for recording mass spectra.
J O972213L