Effective methods for preparing S-(trifluoromethyl)dibenzothiophenium salts

Article abstract of DOI:10.1016/S0022-1139(98)00276-0

New effective methods were developed for the preparation of useful electrophilic trifluoromethylating agents, S-(trifluoromethyl)dibenzothiophenium tetrafluoroborate (3) and triflate (4) and S-(trifluoromethyl)dibenzothiophenium-3-sulfonate (6). Thus, salts 3 and 4 were produced by the intramolecular cyclization of sulfoxide 1 with fuming sulfuric acid, followed by the counteranion replacement reaction of the intermediate (2) with sodium tetrafluoroborate and triflate, and salt 6 was directly produced from 1 by treatment with excess fuming sulfuric acid. Useful preparative methods for 1 were also described.

Full text of DOI:10.1016/S0022-1139(98)00276-0

Journal of Fluorine Chemistry 92 (1998) 181±187
Effective methods for preparing
S-(tri¯uoromethyl)dibenzothiophenium salts
Teruo Umemoto, Sumi Ishihara*
MEC Laboratory, Daikin Industries Ltd., Miyukigaoka 3, Tsukuba, Ibaraki 305-0841, Japan
Received 10 March 1998; received in revised form 12 June 1998; accepted 4 September 1998
Abstract
New effective methods were developed for the preparation of useful electrophilic tri¯uoromethylating agents, S-(tri¯uoromethyl)di-
benzothiophenium tetra¯uoroborate (3) and tri¯ate (4) and S-(tri¯uoromethyl)dibenzothiophenium-3-sulfonate (6). Thus, salts 3 and 4 were
produced by the intramolecular cyclization of sulfoxide 1 with fuming sulfuric acid, followed by the counteranion replacement reaction of
the intermediate (2) with sodium tetra¯uoroborate and tri¯ate, and salt 6 was directly produced from 1 by treatment with excess fuming
sulfuric acid. Useful preparative methods for 1 were also described. # 1998 Elsevier Science S.A. All rights reserved.
Keywords: Electrophilic tri¯uoromethylating agents; S-(tri¯uoromethyl)dibenzothiophenium salts; S-(tri¯uoromethyl)dibenzothiophenium sulfonates;
Tri¯uoromethylation
1. Introduction
respectively [12,13].1 Triflate 4 was also prepared by treat-
ment of 2-[(trifluoromethyl)sulfinyl]biphenyl (1) with triflic
anhydride [12±15] or trifluoroacetyl triflate [16]. However,
special technique is required when using potentially danger-
ous molecular fluorine (F2), and triflic anhydride or trifluoro-
acetyl triflate is expensive and difficult to obtain in bulk
quantity. In the case of triflic anhydride, an equimolar
amount of triflic acid is produced as a byproduct. S-(Tri-
fluoromethyl)dibenzothiophenium-3-sulfonate (6) was syn-
The introduction of a tri¯uoromethyl group into an
organic molecule often greatly changes the original chemi-
cal, biochemical, or physical properties of the molecule,
owing to the high electronegativity, stability and lipophili-
city of the tri¯uoromethyl group [1±3]. Accordingly,
considerable attention has been directed to the tri¯uoro-
methylation of organic compounds in ®elds of medicine [4±
8], agricultural chemicals [9,10] and new material science
[11].
1N-Fluoropyridinium tetrafluoroborate (3) and triflate (4) were prepared
by using CFCl3 or CCl2FCClF2 as a solvent [12,13], which has now been
forbidden to use because it is one of the ozone layer depletion compounds.
They can be prepared by using dry and alcohol-free chloroform instead of
CFCl3 or CCl2FCClF2. The dry and alcohol-free chloroform was prepared
by distilling commercially available chloroform on P2O5. In particular,
tetrafluoroborate 3 can be prepared in high yield by using chloroform
containing a small amount of acetonitrile. This procedure is as follows.
Gaseous boron trifluoride [5.4 l (240 mmol)] was introduced at a rate of
50 ml/min to a stirred solution of 50.9 g (299 mmol) of sulfide 9 in a
mixture of 200 ml of dry and alcohol-free chloroform and 11.5 ml
(220 mmol) of dry acetonitrile at 108C. Then, 1:9 (v/v) mixture of F2 and
N2 gas was introduced at a rate of 200 ml/min to the stirred mixture at
108C. The total amount of F2 used was 248 mmol. After the atmosphere
in the flask was replaced with N2 gas, the reaction mixture was warmed to
room temperatue. Addition of diethyl ether to the reaction mixture resulted
in a precipitate of 3, which was collected by filtration and recrystallized
from acetonitrile±diethyl ether to give 63.4 g (93%) of pure 3.
In the previous studies, we developed a series of S-, Se-,
and Te-(tri¯uoromethyl)dibenzo-thio-, -seleno-, and -tell-
uro-phenium salts and their 3-sulfonates as power-variable
electrophilic tri¯uoromethylating agents [12,13,15]. We
also established a new method for the tri¯uoromethyl-
ation of enolate anions using a S-(tri¯uoromethyl)diben-
zothiophenium salt and borane Lewis acid in combination
[14].
S-(Tri¯uoromethyl)dibenzothiophenium tetra¯uorobo-
rate (3) and tri¯ate (4) were synthesized by direct ¯uorina-
tion of 2-[(tri¯uoromethyl)thio]biphenyl (9) in the presence
of tetra¯uoroboric acid or boron tri¯uoride and tri¯ic acid,
*Corresponding author. Tel.: +81-298-58-5073; fax: +81-298-58-5082.
0022-1139/98/$ ± see front matter # 1998 Elsevier Science S.A. All rights reserved.
P I I : S 0 0 2 2 - 1 1 3 9 ( 9 8 ) 0 0 2 7 6 - 0

182
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
Scheme 1.
thesized in a stepwise manner by sulfonation of triflate 4
with fuming sulfuric acid [15].
This paper describes new effective methods for preparing
useful tri¯uoromethylating agents 3, 4 and 6 via the intra-
molecular cyclization of sulfoxide 1 as a key step, and also
useful preparative methods for the starting material 1.
nitrile to give tetra¯uoroborate 3 and tri¯ate 4 with 95% and
92% yields, respectively. To trap sulfuric acid liberated from
crystalline 2, powdered sodium hydrogen carbonate was
added in excess to the reaction mixture.
Subsequent to treating sulfoxide 1 with 60% fuming
sulfuric acid (SO3 1.8 equiv.) as above, 60% fuming sulfuric
acid (SO3 3.15 equiv.) was added to the reaction mixture
which was then stirred at 428C for 17 h (Scheme 3). This
reaction produced S-(tri¯uoromethyl)dibenzothiophenium-
3-sulfonate (6) in high yield (ca. 80%). It is thus shown
possible to obtain sulfonate 6 in 84% yield by treatment of 1
with excess fuming sulfuric acid (SO3 4.95 equiv.) added to
the reaction system in one portion, as seen in Scheme 3.
Stirring the resulting oily residue in ethanol made it
possible to isolate 6 as a 1:1 crystalline adduct of 6 with
the ethanol molecule in high yield.
As shown in Scheme 4, the starting material sulfoxide 1
was prepared in essentially quantitative yield by the selec-
tive oxidation of sul®de 9 with hydrogen peroxide±acetic
acid. The corresponding sulfone as a byproduct was pro-
duced in only 1±2% yield and thus may be used in sub-
sequent reactions without further puri®cation.
2. Results and discussion
2.1. Intramolecular cyclization of 2-
[(trifluoromethyl)sulfinyl]biphenyl (1) with fuming
sulfuric acid
Sulfoxide 1 dissolved in a small amount of dichloro-
methane was treated with 60% fuming sulfuric acid (SO3 1.8
equiv.) at 08C to room temperature for 1.5 h (Scheme 1).
The recrystallized product was adduct (2) of S-(tri¯uoro-
methyl)dibenzothiophenium hydrogen sulfate with 1/3
(H2SO4) and its yield was 79%. This structural formula
was assigned based on the results of spectral and elemental
analysis. The ready intramolecular cyclization may be
explained as due to the activation of the sul®nyl group
‡
(S=O) with reactive species HSO3 in fuming sulfuric acid,
as shown in Scheme 2.
2.2. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
Adduct 2 underwent a counteranion replacement reaction
with sodium tetra¯uoroborate and sodium tri¯ate in aceto-
Sul®de 9 was previously prepared by photoreaction of the
sodium salt of 2-mercaptobiphenyl (7) with bromotri¯uoro-
methane in DMF using a high pressure Hg lump. However,
this method was not appropriate to a large scale production
because of relatively low quantum yield for obtaining 9 by
this photoreaction. As shown in Scheme 4, three different
routes I, II, and III for preparing 9 from thiol 7 were
examined.
Scheme 2.
As shown in Route I of Scheme 4, in a method using
dibromodi¯uoromethane (CF2Br2) in which CF2Br2 was
Scheme 3.

T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
183
Scheme 4.
rapidly added to a solution of lithium salt of 7 in DMF at
608C under vigorous stirring, 2-[(tri¯uoromethyl)thio]bi-
phenyl (8) was obtained in high yield (ca. 94% crude).
However, subsequent to CF2Br2 addition, a vigorous
exothermic reaction immediately occurred attended with
a rapid increase in temperature. When conducting this
reaction with the sodium salt of 7 at 208C to 308C,
bis(2-biphenylyl)disul®de and 2-[(di¯uoromethyl)thio]bi-
phenyl were formed in considerable amounts as byproducts.
On adding CF2Br2 dropwise to the solution at 558C to
508C to suppress the vigorous reaction, another byproduct
was formed. The byproduct was not characterized. The
lithium salt of 7 was much better for the reaction than its
sodium salt, the latter being insoluble in DMF at low
temperature. When heating crude 8 with antimony tri¯uor-
ide without solvent as the following step, tri¯uoromethyl
sul®de 9 was produced in an overall 73% yield from 7. It
was dif®cult to suppress the vigorous reaction in the ®rst
bromodi¯uoromethylation step and so Route I using CF2Br2
would not be appropriate to a large scale preparation.
Aiken et al. have proposed another method for obtaining
9, in which sodium 2-bromothiophenolate is allowed to
react with CF2Br2 in DMF, followed by treatment with silver
tetra¯uoroborate. 2-Bromo[(tri¯uoromethyl)thio]benzene
thus obtained is coupled with phenylboronic acid in the
presence of palladium catalyst to give tri¯uoromethyl sul-
®de 9 [17]. But this route is not appropriate for large scale
preparation since only limited overall yield is possible and
the silver salt is quite expensive.
requiring only one-step from sodium salt of 7 and no special
photoirradiation. Thus, the CF3I method may be considered
most suitable for industrial application, provided that CF3I
could be supplied in bulk quantity.
Methylation/chlorination/Cl±F exchange method is
shown as Route III in Scheme 4. 2-(Methylthio)biphenyl
(10) [18] derived by methylation of thiol 7 was chlorinated
by photochlorination with chlorine in a small amount of
carbon tetrachloride or chlorobenzene at room temperature
or under cooling in an ice bath to produce 2-[(trichloro-
methyl)thio]biphenyl (11) in 82% yield. As described in
Section 3.11, 10 could be prepared from 15 via 16 and 7 by a
one-batch method with an overall 74% yield.
The chlorination of 10 occurred very rapidly. Chlorin-
ation at 808C caused cleavage of the C±S bond, thus
producing 2-chlorobiphenyl. The Cl±F exchange of 11
was carried out using triethylamine trihydro¯uoride, an
easy-to-handle compound in contrast to hydrogen ¯uoride.
A mixture of 11 and 3.1 equimolar amount of triethylamine
trihydro¯uoride was heated in an autoclave at 1808C for 9 h
to give 9 in 86% yield.2 Chlorination and Cl±F exchange
(without puri®cation of intermediate 11) in combination
produced 9 as the ®nal product from 10 in 66% yield. This
method is appropriate for large scale production of 9 owing
to its high production ef®ciency per reactor.
2.3. Preparation of 2-mercaptobiphenyl (7)
Thiol 7 was prepared as shown in Scheme 5. Thiocarba-
mate 15 could be obtained by two methods: reaction
of dry sodium salt 12 of 2-hydroxybiphenyl (13) with
As shown in Route II of Scheme 4, the direct tri¯uoro-
methylation of sodium salt of 7 with iodotri¯uoromethane
(CF3I) proceeded smoothly around 508C in normal room
light to give 9 in 76% yield. This method is quite convenient,
2A stainless-steel autoclave used for this reaction was slightly corroded.

184
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
Scheme 5.
N,N-dimethylthiocarbamoyl chloride (14) in DMF solvent
at room temperature to 808C (Method A) [19,20,21] or
reaction of 13 with 14 in a small amount of dry sulfolane at
100±1508C (Method B). Method B is highly production
ef®cient per reactor. The recrystallized and dried solid of 15
was heated at 2808C [21] and the rearrangement product 16
thus obtained was hydrolyzed by sodium hydroxide in
methanol under a nitrogen atmosphere [19,20]. Following
neutralization, thiol 7 was obtained in essentially quantita-
tive yield from 15.
ice bath. A vigorous exothermic reaction occurred on mix-
ing. The resulting solid was collected by ®ltration and
puri®ed by recrystallization from methanol±ethyl acetate
to give 448 g (79%) of 2 as crystals. The elemental analysis
indicated that S-[(trichloromethyl)dibenzothiophenium
hydrogen sulfate exists as adduct with 1/3(H2SO4) in the
crystals.
Compound 2. mp 122±1278C (with dec.). 1H NMR
(CD3CN) ꢀ: 7.86 (2H, td, Jˆ8, 1 Hz, 3-H, 7-H); 8.07
(2H, td, Jˆ8, 1 Hz, 2-H, 8-H); 8.35 (2H, dd, Jˆ8, 1 Hz,
1-H, 9-H); 8.44 (2H, d, Jˆ8 Hz, 4-H, 6-H). 19F NMR
(CD3CN) ꢀ: 52.8 (s). IR (KBr) (cm 1): 3418; 3072;
2300; 1284; 1208; 1177; 1087; 1078; 1040; 1009; 887;
3. Experimental
‡
3.1. General
851; 766; 576. Mass spectrum (FAB) m/z: 253 (M ±HSO4).
Analysis: Calc. for C13H9F3O4S2Á1/3(H2SO4): C, 40.77; H,
Melting and boiling points were uncorrected. 1H and 19
F
2.54; S, 19.53%. Found: C, 40.03; H, 2.87; S, 19.83%.
NMR spectra were recorded with 200 and 188 MHz NMR
spectrometers, respectively. 19F NMR chemical shifts are
given in ppm down®eld from CCl3F as an internal standard.
Mass spectra were recorded at 70 eV. The structural assign-
ment of the products was carried out by comparison with
authentic samples or spectral and elemental analyses. The
data of new compounds are shown below.
3.4. Preparation of 2-
[(trichloromethyl)dibenzothiophenium
tetrafluoroborate and triflate, (3) and (4)
Under an argon atmosphere, 600 g (1.57 mol) of 2 was
added by portions to a stirred solution of 176 g (1.57 mol) of
sodium tetra¯uoroborate in 2.5 l of acetonitrile over a period
of 5±10 min at 608C and the mixture was stirred at the
temperature for 1.5 h. After cooling to room temperature,
ca. 600 g of powdered sodium hydrogen carbonate was
added to the mixture. The mixture was stirred at room
temperature for 3 h and insoluble materials were removed
by ®ltration. After evaporation of the solvent from the
®ltrate, the residue was recrystallized from acetonitrile±
diethyl ether to give 508 g (95%) of tetra¯uoroborate 3.
Similarly, tri¯ate 4 was prepared from 2 in 92% yield with
sodium tri¯ate instead of sodium tetra¯uoroborate.
3.2. Materials
Sulfolane was dried by distillation under reduced pres-
sure. Sodium 2-phenylphenolate (12) was dried at 2008C for
12 h under vacuum. 2-Phenylphenol (13) was dried at 508C
for 12 h under vacuum. N,N-Dimethylformamide (DMF)
was dried by distillation on calcium hydride. Other com-
mercially available chemicals were used without further
puri®cation, unless otherwise noted.
3.3. Preparation of S-(trifluoromethyl)dibenzothiophenium
hydrogen sulfate 1/3(H2SO4) (2)
3.5. Preparation of 2-
[(trichloromethyl)dibenzothiophenium-3-sulfonate (6)
60% fuming sulfuric acid [180 ml (SO3: 2.66 mol)] was
dropwise added over a period of 35 min to a stirred solution
of 400 g (1.48 mol) of [(tri¯uoromethyl)sul®nyl]biphenyl
(1) in 1 l of dichloromethane cooled on an ice bath and the
mixture was stirred at room temperature for 1.5 h. Methanol
[107 ml (2.63 mol)] and diisopropyl ether [ca. 3 l] were
carefully added to the stirred reaction mixture cooled on an
A solution of 350 g (1.3 mol) of 2-[(trichloromethyl)sul-
®nyl]biphenyl (1) in 1 l of dichloromethane was placed in a
¯ask to which a Dimroth condenser with a calcium chloride-
drying tube was attached. To the stirred solution cooled on
an ice bath, 434 ml (SO3: 6.4 mol) of 60% fuming sulfuric
acid was dropwise added over a period of 40 min and the

T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
185
mixture was stirred at 428C for 20 h. Diisopropyl ether (ca.
3.3 l) was carefully added to the stirred reaction mixture
cooled on an ice bath. A vigorous exothermic reaction
occurred on mixing with the ether. The resulting gummy
oil was separated from the solution by decanting and then
washed repeatedly with diisopropyl ether. Ethanol (ca. 1 l)
was then added to the gummy oil and the mixture was stirred
till all of the oil became white powdered crystals; it took ca.
2 h. The crystals were collected by ®ltration, washed with
ethanol (2 times), and dried under vacuum for 6.5 h at 608C
to give 413 g (84%) of 6. 1H NMR indicated that 6 exists as
adduct with one molecule of ethanol in the crystal (6:
C2H5OHˆ1:1).
exothermic reaction ceased, the reaction mixture was stirred
for 10 min on the dry ice±acetone bath cooling and then for
30 min at room temperature, poured into ice-water, and
extracted with ethyl acetate. The extract was washed with
saturated aqueous NaCl solution, dried with MgSO4, and
®ltered. Evaporation of the solvent gave 393 g (ca. 94%) of
crude 8, which was a solid containing a small amount of oil
and could be used for the next halogen exchange reaction
without further puri®cation. Puri®cation of the crude 8 was
carried out by distillation under reduced pressure to give
pure 8 (bp 136±1398C/6 mmHg).
1
Compound 8. mp 45±468C. H NMR (CDCl3) ꢀ: 7.27±
7.59 (8H, m); 7.81 (1H, dm, Jˆ8 Hz, 3-H) ppm. 19F NMR
(CDCl3) ꢀ: 217 (s) ppm. IR (KBr) (cm 1): 1463; 1444;
1082; 1057; 842; 755; 699; 505. Mass spectrum m/z: 314,
Compound 6. mp 142±1478C (with dec.). 1H NMR
(CD3CN) ꢀ: 1.17 (3H, t, Jˆ7 Hz, CH3); 3.60 (2H, q,
Jˆ7 Hz, CH2); 7.92 (1H, td, Jˆ8, 1 Hz, 7-H); 8.10 (1H,
td, Jˆ8, 1 Hz, 8-H); 8.42 (1H, dd, Jˆ8, 1 Hz, 2-H); 8.46±
8.57 (3 H, m, 1-H, 6-H, 9-H); 8.90 (1H, d, Jˆ1 Hz, 4-H). 19F
NMR (CD3CN) ꢀ: 53.9 (s). IR (KBr) (cm 1): 3454; 1229;
1198; 1120; 1082; 1031; 773; 665; 614; 515. Mass spectrum
‡
316 (M ). Analysis: Calc. for C13H9BrF2S: C, 49.54; H,
2.88. Found: C, 49.75; H, 2.67%.
3.8. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
from 8
‡
(FAB) m/z: 333 (M ‡1). Analysis: Calc. for
C13H7F3O3S2ÁC2H6O: C, 47.61; H, 3.46%. Found: C,
Under an argon atmosphere, a mixture of 392 g (ca.
1.24 mol) of crude 8 and 81.4 g (0.45 mol) of antimony
tri¯uoride was heated gradually to 1508C and maintained at
150±1608C for ca. 2 h under stirring. After cooling, hexane
was added to the reaction mixture and insoluble materials
were removed by ®ltering through celite. The ®ltrate was
washed twice with 2±3 N aqueous HCl solution and then
twice with saturated aqueous NaCl solution, dried with
MgSO4, and ®ltered. Evaporation of the solvent gave
280 g of an oil, which was puri®ed by distillation under
reduced pressure to give 245 g (overall 73% from 7) of 9 (bp
109±1118C/6 mmHg).
46.77; H, 3.46%.
3.6. Preparation of 2-[(trichloromethyl)sulfinyl]biphenyl
(1)
31% hydrogen peroxide [132 g (1.20 mol)] was added
dropwise to a stirred solution of 245 g (0.96 mol) of 2-
[(trichloromethyl)thio]biphenyl (9) in 1250 ml of acetic
acid over a period of 40 min at 70±848C. After the addition,
the mixture was stirred at 80±888C for 3 h, cooled and
poured into ca. 3 l of ice-water. The resulting precipitate was
collected by ®ltration, washed with water, and dissolved in
diethyl ether. The ether layer was washed with water (2
times), aqueous sodium carbonate (2 times), water and
saturated aqueous NaCl solution, dried with MgSO4, and
®ltered. Evaporation of the solvent gave 256 g (98%) of 1.
19F NMR indicated that the product was contaminated with
ca. 2% of the corresponding sulfone.
3.9. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
from 7 and iodotrifluoromethane
Under nitrogen atmosphere, 5.59 g (30 mmol) of 2-mer-
captobiphenyl (7) in 30 ml of dry DMF was placed in a
100 ml reaction ¯ask. Into it, 1.21 g (32 mmol) of NaH
(60% in oil) was added under stirring and cooling on an ice
bath. The reaction mixture was stirred at the temperature for
10 min and then at room temperature for 20 min. The
pressure in the reaction ¯ask was reduced by vacuum pump
and then the atmosphere in the ¯ask was ®lled with ca.
37 mmol (7.3 g) of gaseous iodotri¯uoromethane by con-
necting a balloon containing the amount of iodotri¯uoro-
methane and additionally with N2 till the pressure became
atmospheric pressure. An exothermic reaction occurred
soon. After the exothermic reaction ceased, the reaction
mixture was stirred at 508C for 3 h, poured into water and
extracted with hexane. The extract was washed with water
and saturated aqueous NaCl solution, dried with MgSO4,
and ®ltered. After evaporation of the solvent, the residue
was column chromatographed on silica gel using hexane as
an eluent to give 5.8 g (76%) of 9.
3.7. Preparation of 2-[(bromodifluoromethyl)thio]
biphenyl (8)
Under an argon atmosphere, a solution of 246 g
(1.32 mol) of 2-mercaptobiphenyl (7) in 350 ml of dry
DMF was added dropwise to a stirred suspension of
10.6 g (1.33 mol) of lithium hydride in 1.15 l of dry
DMF cooled on an ice bath. After an exothermic reaction
ceased, the mixture was stirred at room temperature for
20 min and cooled to 608C (the reaction solution's tem-
perature) on a dry ice±acetone bath. Dibromodi¯uoro-
methane [145 ml (1.58 mol)] was rapidly added to the
stirred solution; it took ca. 1±2 min. At this time, a vigorous
exothermic reaction immediately occurred and the reaction
mixture's temperature rose up to nearly 58C. After the

186
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
3.10. Preparation of 2-(methylthio)biphenyl (10) from 7
Jˆ8, 1 Hz, 5-H); 8.05 (1H, dd, Jˆ8, 1 Hz, 3-H). IR (KBr)
(cm 1): 1463; 1447; 788; 759; 747; 733; 722; 500. Mass
‡
Into a solution of 36.0 g (0.86 mol) of sodium hydroxide
in 150 ml of water 140.0 g (0.75 mol) of 2-mercaptobiphe-
nyl (7) was added. Into the solution stirred and cooled on an
ice bath, 78.3 ml (0.83 mol) of dimethyl sulfate was drop-
wise added over a period of 25 min, and the reaction mixture
was heated at 1108C for 140 min. After cooling, the reaction
mixture was extracted with diethyl ether. The organic layer
was washed with water and then saturated aqueous NaCl
solution, dried with MgSO4, and ®ltered. Evaporation of the
solvent gave 150.5 g of oil, which was then distilled under
reduced pressure to give 138 g (92%) of 10 (bp 135±1378C/
4 mmHg).
spectrum m/z: 302, 304, 306 (M ). Analysis: Calc. for
C13H9Cl3S: C, 51.42; H, 2.99%. Found: C, 51.37; H, 2.88%.
3.13. Preparation of 2-[(trichloromethyl)thio]biphenyl (9)
from 11
A mixture of 3.0 g (9.9 mmol) of 11 and 5.0 ml
(30.7 mmol) of triethylamine trihydro¯uoride was placed
in an autoclave (inside this was a container made of poly-
tetra¯uoroethylene) and heated at 1808C for 9 h. After
cooling, the reaction mixture was poured into water and
extracted with hexane. The extract was washed with water
(2 times) and saturated aqueous NaCl solution, dried with
MgSO4, and ®ltered. After evaporation of the solvent, the
residue was column chromatographed on silica gel using
hexane as an eluent to give 2.2 g (86%) of 9.
3.11. Preparation of 2-(methylthio)biphenyl (10) from 15
Under an argon atmosphere, 329 g (1.28 mol) of O-(2-
biphenylyl)-N,N-dimethylthiocarbamate (15) was heated to
2808C and maintained at the temperature for 1 h under
stirring. After cooling, the reaction mixture was dissolved
in 880 ml of methanol which was degassed (O2) with argon.
Sodium hydroxide [107 g (2.56 mol)] was added to the
solution, and the solution was again degassed (O2) with
argon and heated under re¯ux for 18 h. Then, dimethyl
sulfate [134 ml (1.41 mol)] was dropwise added over a
period of 45 min to the reaction mixture stirred and cooled
on an ice bath. The mixture was stirred for 2 h at room
temperature, heated under re¯ux for 1 h, cooled, poured into
water and extracted with hexane (3 times). The extract was
washed with water (2 times) and saturated aqueous NaCl
solution, dried with MgSO4, and ®ltered. Evaporation of the
solvent gave an oil, which was then distilled under reduced
pressure to obtain 190 g (74%) of 10 (bp 154±1608C)/
8 mmHg).
3.14. Preparation of 2-[(trichloromethyl)thio]biphenyl (9)
from 10
Cl2 [104 l (4.6 mol)] was introduced over a period of
3.5 h to a stirred solution of 301 g (1.5 mol) of 2-
(methylthio)biphenyl (10) in 250 ml of chlorobenzene in
a photoreaction vessel which was irradiated with a high-
pressure Hg lamp (450 W) under cooling on an ice bath. The
¯ow rate of Cl2 was controlled so that Cl2 was absorbed
completely. After removing chlorobenzene by distillation
under reduced pressure, 808 ml (4.96 mol) of triethylamine
trihydro¯uoride was added to the residue. This mixture was
placed in a stainless steel autoclave (cf. 2), heated at 1808C
for 12 h, cooled, and poured into ice-water. Then, ca. 1 l of
hexane and 744 g (7.43 mol) of calcium carbonate were
added to the mixture. After ®ltration, the ®ltrate was
extracted with hexane. The hexane layer was washed with
water (3 times), dried with MgSO4, and ®ltered. After
evaporation of the solvent, the residue was distilled under
reduced pressure to give 253 g (66%) of 9 (bp 109±1148C/
5±6 mmHg).
3.12. Preparation of 2-[(trichloromethyl)thio]biphenyl
(11) from 10
A solution of 80.0 g (0.40 mol) of 10 in 140 ml of carbon
tetrachloride was placed in a ¯ask and the atmosphere in the
¯ask was replaced with chlorine (Cl2). The reaction mixture
was irradiated with a high-pressure Hg lamp (450 W) during
introduction of Cl2 for 105 min while cooling on an ice bath.
The ¯ow rate of Cl2 was controlled so that Cl2 was almost
completely absorbed into the reaction solution. After
absorption of Cl2 ceased, excess Cl2 in the reaction vessel
was removed by ¯owing N2. The reaction mixture was then
washed with aqueous sodium thiosulfate solution. The
organic layer was separated, washed with water and satu-
rated aqueous NaCl solution, dried with MgSO4, and ®l-
tered. Evaporation of the solvent gave 100 g (82%) of 11.
For further puri®cation, distillation under reduced pressure
was carried out (bp 173±1758C/5±6 mmHg).
3.15. Preparation of O-(2-(biphenylyl)-N,N-
dimethylthiocarbamate (15)
Method A. Under an argon atmosphere, 714.5 g
(5.61 mol) of N,N-dimethylthiocarbamoyl chloride (14)
was added to a solution of 1025 g (5.34 mol) of dry sodium
2-phenylphenolate (12)3 in 3.5 l of dry DMF at 5±128C. The
mixture was stirred at room temperature and an exothermic
reaction occurred. If needed, the reaction mixture was
3As an alternative method, sodium 2-phenylphenolate (12) was in situ
prepared by reacting dry 2-hydroxybiphenyl (13) with sodium hydride
(60% in oil) as follows: a solution of 13 in DMF was dropwise added into
an equimolar amount of sodium hydride in DMF under stirring and
cooling on an ice bath.
Compound 11. mp 59±608C. 1H NMR (CDCl3) ꢀ: 7.32±
7.42 (5H, m); 7.45±7.51 (2H, m, 4-H, 6-H); 7.59 (1H, td,

T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 92 (1998) 181±187
187
cooled on a water bath. After the exothermic reaction
ceased, the reaction mixture was heated at 808C for
45 min. The reaction mixture was concentrated by distillat-
ing DMF under reduced pressure at 70±858C and the
concentrated reaction mixture was poured into water. The
resulting precipitate was collected by ®ltration and recrys-
tallized from ethanol (500 g/1 l ethanol). Materials insolu-
ble in hot ethanol were removed by ready ®ltration. The
crystals obtained by the recrystallization were washed with
a 3:1 mixture of hexane and ethanol to give 1029 g (75%) of
15. In s similar experiment using 34.6 g (0.178 mol) of 12,
25.1 g (0.197 mol) of 14, and 120 ml of DMF, 39.1 g (86%)
of 15 was obtained.
Method B. Under an argon atmosphere, a solution of
70.0 g (0.55 mol) of 14 in 60 ml of dry sulfolane was
dropwise added over a period of 25 min to 85.1 g
(0.5 mol) of dry 2-phenylphenol (13) which was heated
and stirred at 85±908C. Hydrogen chloride was evolved.
After the addition of 14, the mixture was heated gradually to
1508C in a period of 2.5 h, cooled, and poured into ca.
600 ml of water. The resulting precipitate was collected by
®ltration and puri®ed by recrystallization from ethanol to
obtain 100.9 g (79%) of 15.
benzothiophenium tetra¯uoroborate (3) and tri¯ate (4),
and S-(tri¯uoromethyl)dibenzothiophenium-3-sulfonate
(6). These methods have an advantage that the potentially
dangerous molecular ¯uorine is not used. Methods for
effectively obtaining sulfoxide 1, sul®de 9, and thiol 7 have
also been established. Thus, complete methods starting from
2-hydroxybiphenyl have been developed for the production
of 3, 4, and 6.
Acknowledgements
The authors thank M.Sc. Kenji Adachi and M.Eng.
Masayuki Harada for their partial technical contribution.
References
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3.16. Preparation of 2-mercaptobiphenyl (7) from 15
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Under a nitrogen atmosphere, 1166 g (4.54 mol) of 15
was heated to 2808C and maintained at 264±2828C for
35 min under stirring. After cooling, the reaction mixture
was dissolved in 4 l of methanol which was degassed (O2)
with argon. Sodium hydroxide [363 g (9.08 mol)] was
added to the reaction mixture and the mixture was again
degassed with argon and heated under re¯ux for 12 h. After
cooling, the mixture was poured into cold and dilute HCl
solution (HCl; ca. 14 mol). The resulting precipitate was
collected by ®ltration and dissolved in dichloromethane.
The organic layer was dried with MgSO4, and ®ltered.
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4. Conclusion
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Effective methods using the intramolecular cyclization of
sulfoxide 1 with cheap fuming sulfuric acid as a key step
have been developed for the production of useful electro-
philic tri¯uoromethylating agents, S-(tri¯uoromethyl)di-
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