Effective methods for preparing S-(trifluoromethyl)dibenzothiophenium salts

Article abstract of DOI:10.1016/S0022-1139(99)00087-1

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(99)00087-1

Journal of Fluorine Chemistry 98 (1999) 75±81
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. # 1999 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
1
. Introduction
respectively [12,13]. Tri¯ate 4 was also prepared by treat-
ment of 2-[(tri¯uoromethyl)sul®nyl]biphenyl (1) with tri¯ic
anhydride [12±15] or tri¯uoroacetyl tri¯ate [16]. However,
special technique is required when using potentially danger-
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, con-
siderable attention has been directed to the
tri¯uoromethylation of organic compounds in ®elds of
medicine [4±8], agricultural chemicals [9,10] and new
material science [11].
ous molecular ¯uorine (F ), and tri¯ic anhydride or tri¯uor-
2
oacetyl tri¯ate is expensive and dif®cult to obtain in bulk
quantity. In the case of tri¯ic anhydride, an equimolar
amount of tri¯ic acid is produced as a byproduct. S-(tri-
¯uoromethyl)dibenzothiophenium-3-sulfonate (6) was
synthesized in a stepwise manner by sulfonation of tri¯ate
4 with fuming sulfuric acid [15].
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¯uoromethylation
of enolate anions using a S-(tri¯uoromethyl)dibenzothio-
phenium salt and borane Lewis acid in combination [14].
S-(tri¯uoromethyl)dibenzothiophenium tetra¯uoroborate
1
S-(trifluoromethyl)dibenzothiophenium tetrafluoroborate (3) and tri-
flate (4) were prepared by using CFCl
3 2 2
or CCl FCClF 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 CCl FCClF . The dry and
2
2
alcohol-free chloroform was prepared by distilling commercially available
chloroform on P . In particular, tetrafluoroborate 3 can be prepared in
2 5
O
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,
(
3) and tri¯ate (4) were synthesized by direct ¯uorination of
-[(tri¯uoromethyl)thio]biphenyl (9) in the presence of tet-
ra¯uoroboric acid or boron tri¯uoride and tri¯ic acid,
2
1
:9 (v/v) mixture of F
2
and N
2
gas was introduced at a rate of 200 ml/min
used was
48 mmol. After the atmosphere in the flask was replaced with N gas, the
to the stirred mixture at � 108C. The total amount of F
2
2
2
reaction mixture was warmed to room temperature. 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.
*
Corresponding author. Tel.: +81-298-58-5073; fax: +81-298-58-5082.
$PII of original article S0022-1139(98)00276-0
0022-1139/99/$ ± see front matter # 1999 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 0 8 7 - 1

7
6
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 98 (1999) 75±81
Scheme 1.
This paper describes new effective methods for preparing
and 92% yields, respectively. To trap sulfuric acid liberated
from crystalline 2, powdered sodium hydrogen carbonate
was added in excess to the reaction mixture.
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.
Subsequent to treating sulfoxide 1 with 60% fuming
sulfuric acid (SO 1.8 equiv.) as above, 60% fuming sulfuric
3
acid (SO 3.15 equiv.) was added to the reaction mixture
3
2
. Results and discussion
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
2
.1. Intramolecular cyclization of
2- [(trifluoromethyl)sulfinyl]biphenyl (1) with fuming
sulfuric acid
with excess fuming sulfuric acid (SO 4.95 equiv.) added to
3
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.
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
(
H SO ) and its yield was 79%. This structural formula
2 4
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 HSO in fuming sulfuric acid,
as shown in Scheme 2.
3
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 acet-
onitrile to give tetra¯uoroborate 3 and tri¯ate 4 with 95%
Sul®de 9 was previously prepared by photoreaction of the
sodium salt of 2-mercaptobiphenyl (7) with bromotri¯uor-
omethane 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.
As shown in Route I of Scheme 4, in a method using
dibromodi¯uoromethane (CF Br ) in which CF Br was
Scheme 2.
2
2
2
2
Scheme 3.

T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 98 (1999) 75±81
77
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).
photoirradiation. Thus, the CF I method may be considered
3
�
most suitable for industrial application, provided that CF3I
could be supplied in bulk quantity.
However, subsequent to CF Br addition, a vigorous
2
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.
2
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 CF Br dropwise to the solution at � 558C to
2
2
�
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
The chlorination of 10 occurred very rapidly. Chlorina-
tion at 808C caused cleavage of the C±S bond, thus produ-
cing 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
bromodi¯uoromethylation step and so Route I using CF Br2
2
2
would not be appropriate to a large scale preparation.
Aiken et al. [17] have proposed another method for
obtaining 9, in which sodium 2-bromothiophenolate is
allowed to react with CF Br in DMF, followed by treatment
to give 9 in 86% yield. 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
2
with
silver
tetra¯uoroborate.
2-Bromo[(tri¯uoro-
methyl)thio]benzene thus obtained is coupled with phenyl-
boronic acid in the presence of palladium catalyst to give
tri¯uoromethyl sul®de 9 [17]. But this route is not appro-
priate for large scale preparation since only limited overall
yield is possible and the silver salt is quite expensive.
As shown in Route II of Scheme 4, the direct tri¯uor-
omethylation of sodium salt of 7 with iodotri¯uoromethane
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
N,N-dimethylthiocarbamoyl chloride (14) in DMF solvent
at room temperature to 808C (Method A) [19,20,21] or
(
light to give 9 in 76% yield. This method is quite convenient,
CF I) proceeded smoothly around 508C in normal room
3
2
requiring only one-step from sodium salt of 7 and no special
A stainless-steel autoclave used for this reaction was slightly corroded.

7
8
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 98 (1999) 75±81
Scheme 5.
reaction of 13 with 14 in a small amount of dry sulfolane at
00±1508C (Method B). Method B is highly production
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-(tri¯uoromethyl)dibenzothiophenium
hydrogen sulfate exists as adduct with 1/3(H SO ) in the
1
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.
2
4
crystals.
Compound 2. mp 122±1278C (with dec.). 1H NMR
(
(
CD CN) ꢀ: 7.86 (2H, td, Jˆ8, 1 Hz, 3-H, 7-H); 8.07
3
2H, td, Jˆ8, 1 Hz, 2-H, 8-H); 8.35 (2H, dd, Jˆ8, 1 Hz,
1
9
3
. Experimental
1-H, 9-H); 8.44 (2H, d, Jˆ8 Hz, 4-H, 6-H). F NMR
�
3
1
(
CD CN) ꢀ: � 52.8 (s). IR (KBr) (cm ): 3418; 3072;
3
.1. General
2300; 1284; 1208; 1177; 1087; 1078; 1040; 1009; 887;
51; 766; 576. Mass spectrum (FAB) m/z: 253 (M ±HS0 ).
‡
8
4
1
Melting and boiling points were uncorrected. H and
Analysis: Calc. for C H F O S Á1/3(H SO ): C, 40.77; H,
1
3
9
3
4
2
2
4
19F NMR spectra were recorded with 200 and 188 MHz
NMR spectrometers, respectively. 19F NMR chemical shifts
are given in ppm down®eld from CCl F as an internal
standard. Mass spectra were recorded at 70 eV. The struc-
tural assignment of the products was carried out by com-
parison with authentic samples or spectral and elemental
analyses. The data of new compounds are shown below.
2.54; S, 19.53%. Found: C, 40.03; H, 2.87; S, 19.83%.
3.4. Preparation of S-(trifluoromethyl)dibenzothiophenium
tetrafluoroborate and triflate, (3) and (4)
3
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
2 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.
1
3
.3. Preparation of S-(trifluoromethyl)dibenzothiophenium
hydrogen sulfate 1/3(H SO ) (2)
3.5. Preparation of S-
(
2
4
trifluoromethyl)dibenzothiophenium-3-sulfonate (6)
60% fuming sulfuric acid [180 ml (SO : 2.66 mol)] was
3
dropwise added over a period of 35 min to a stirred solution
of 400 g (1.48 mol) of [(tri¯uoromethyl)sul®nyl]biphenyl
A solution of 350 g (1.3 mol) of 2-[(tri¯uoromethyl)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
(
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
[
an ice bath, 434 ml (SO : 6.4 mol) of 60% fuming sulfuric
3
acid was dropwise added over a period of 40 min and the

T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 98 (1999) 75±81
79
mixture was stirred at 428C for 20 h. Diisopropyl ether (ca.
.3 l) was carefully added to the stirred reaction mixture
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
3
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.
saturated aqueous NaCl solution, dried with MgSO , and
4
®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
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. H NMR indicated that 6 exists as
1
pure 8 (bp l36±l398C/6 mm Hg).
1
adduct with one molecule of ethanol in the crystal (6:
C H OHˆ1:1).
Compound 8. mp 45±468C. H NMR (CDCI ) ꢀ: 7.27±
3
1
9
7.59 (8 H,m); 7.81 (IH, din, Jˆ8 Hz, 3-H) ppm. F NMR
2
5
Compound 6. mp 142±1478C (with dec.). 1H NMR
CD CN) ꢀ: 1.17 (3H, t, Jˆ7 Hz, CH ); 3.60 (2H, q,
(CDCl ) d: � 21.7 (s) ppm. IR (KBr) (cm ): 1463; 1444;
� 1
3
(
1082; 1057; 842; 755; 699; 505. Mass spectrum m/z: 314,
316 (M ). Analysis: Calc. for C H BrF S: C, 49.54; H,
2.88. Found: C, 49.75; H, 2.67%.
3
3
‡
Jˆ7 Hz, CH ); 7.92 (1H, td, Jˆ8, 1 Hz, 7-H); 8.10 (1H,
2
13
9
2
td, Jˆ8, 1 Hz, 8-H); 8.42 (1H, dd, Jˆ8, 1 Hz, 2-H); 8.46±
8
.57 (3H, m, 1-H, 6-H, 9-H); 8.90 (lH, d, Jˆ1 Hz, 4-H).
19
� 1
F NMR (CD CN) ꢀ: � 53.9 (s). IR (KBr) (cm ): 3454;
3.8. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
from 8
3
1
229; 1198; 1120; 1082; 1031; 773; 665; 614; 515. Mass
‡
spectrum (FAB) m/z: 333 (M ‡1). Analysis: Calc. for
C H F O S ÁC H O: 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
1
3
7
3
3
2
2 6
4
6.77; H, 3.46%.
3
.6. Preparation of 2-[(trifluoromethyl)sulfinyl]biphenyl
1)
(
3
1% hydrogen peroxide [132 g (1.20 mol)] was added
dropwise to a stirred solution of 245 g (0.96 mol) of 2-
(tri¯uoromethyl)thio]biphenyl (9) in 1250 ml of acetic acid
[
MgSO , and ®ltered. Evaporation of the solvent gave
4
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
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 mm Hg).
3.9. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
from 7 and iodotrifluoromethane
saturated aqueous NaCl solution, dried with MgSO , and
4
®
ltered. Evaporation of the solvent gave 256 g (98%) of 1.
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
1
9F NMR indicated that the product was contaminated with
ca. 2% of the corresponding sulfone.
(
60% in oil) was added under stirring and cooling on an ice
3
.7. Preparation of 2-
(bromodifluoromethyl)thio]biphenyl (8)
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-
[
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
0.6 g (1.33 mol) of lithium hydride in 1.15 l of dry
(
1
methane and additionally with N till the pressure became
2
DMF cooled on an ice bath. After an exothermic reaction
ceased, the mixture was stirred at room temperature for
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.
2
0 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 mm. At this time, a vigorous
exothermic reaction immediately occurred and the reaction
mixture's temperature rose up to nearly � 58C. After the

8
0
T. Umemoto, S. Ishihara / Journal of Fluorine Chemistry 98 (1999) 75±81
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)
�
1
cm ): 1463; 1447; 788; 759; 747; 733; 722; 500. Mass
(
spectrum m/z: 302, 304, 306 (M ). Analysis: Calc. for
‡
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
C H Cl S: C, 51.42; H, 2.99%. Found: C, 51.37; H, 2.88%.
9
13
3
3.13. Preparation of 2-[(trifluoromethyl)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
solution, dried with MgSO , and ®ltered. Evaporation of the
4
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
mm Hg).
(
MgSO , 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.
2 times) and saturated aqueous NaCl solution, dried with
3
.11. Preparation of 2-(methylthio)biphenyl (10) from 15
Under an argon atmosphere, 329 g (1.28 mol of O-(2-
4
biphenylyl)-N,N-dimethylthiocarbamate (15) was heated to
808C and maintained at the temperature for 1 h under
stirring. After cooling, the reaction mixture was dissolved
2
3.14. Preparation of 2-[(trifluoromethyl)thio]biphenyl (9)
from 10
in 880 ml of methanol which was degassed (O ) with argon.
2
Sodium hydroxide [107 g (2.56 mol)] was added to the
solution, and the solution was again degassed (O ) with
Cl [104 l (4.6 mol)] was introduced over a period of
2
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 Cl was controlled so that Cl was absorbed
2
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
2
2
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
2
solution, dried with MgSO , and ®ltered. Evaporation of the
4
placed in a stainless steel autoclave (cf. ) heated at 1808 C
solvent gave an oil, which was then distilled under reduced
pressure to obtain 190 g (74%) of 10 (bp 154±1608C)/
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
8
mm Hg).
3
.12. Preparation of 2-[(trichloromethyl)thio]biphenyl
water (3 times), dried with MgSO , and ®ltered. After
4
(
11) from 10
evaporation of the solvent, the residue was distilled under
reduced pressure to give 253 g (66%) of 9 (bp 109±1148C/
5±6 mm Hg).
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 (Cl ). The reaction mixture
was irradiated with a high-pressure Hg lamp (450 W) during
introduction of Cl for 105 min while cooling on an ice bath.
¯
3.15. Preparation of O-(2-(biphenylyl)-N,N-
dimethylthiocarbamate (15)
2
2
The ¯ow rate of Cl was controlled so that Cl was almost
2
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) 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
2
completely absorbed into the reaction solution. After
absorption of Cl ceased, excess Cl in the reaction vessel
was removed by ¯owing N . The reaction mixture was then
2
2
3
2
washed with aqueous sodium thiosulfate solution. The
organic layer was separated, washed with water and satu-
rated aqueous NaCl solution, dried with MgSO , and ®l-
4
tered. Evaporation of the solvent gave 100 g (82%) of 11.
For further puri®cation, distillation under reduced pressure
3
As an alternative method, sodium 2-phenylphenolate (12) was in situ
prepared by reacting dry 2-hydroxybiphenyl (13) with sodium hydride
was carried out (bp 173±1758C/5±6 mm Hg).
(
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.
1
Compound 11. mp 59±608C. H NMR (CDCl ) ꢀ: 7.32±
3
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 98 (1999) 75±81
81
cooled on a water bath. After the exothermic reaction
ceased, the reaction mixture was heated at 808C for
benzothiophenium tetra¯uoroborate (3) and tri¯ate (4),
and S-(tri¯uoromethyl)dibenzothiophenium-3-sulfonate
4
5 min. The reaction mixture was concentrated by distillat-
(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.
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
1
2
5. In s similar experiment using 34.6 g (0.178 mol) of 12,
5.1 g (0.197 mol) of 14, and 120 ml of DMF, 39.1 g (86%)
of 15 was obtained.
Acknowledgements
The authors thank M.Sc. Kenji Adachi and M.Eng.
Masayuki Harada for their partial technical contribution.
Method B. Under an argon atmosphere, a solution of
7
0.0 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
(
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After the addition of 14, the mixture was heated gradually to
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1
6
508C in a period of 2.5 h, cooled, and poured into ca.
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[
[
[
2] R.D. Chambers, Fluorine in Organic Chemistry, Wiley, New York,
973.
1
®ltration and puri®ed by recrystallization from ethanol to
obtain 100.9 g (79%) of 15.
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3
.16. Preparation of 2-mercaptobiphenyl (7) from 15
Under a nitrogen atmosphere, 1166 g (4.54 mol) of 15
[
[
[
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3
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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
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[
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(
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[
[
[
[
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The organic layer was dried with MgSO , and ®ltered.
4
Evaporation of the solvent gave 834 g (99%) of 7 (bp
1
21.5±1228C/4 mm Hg).
[
[
[
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4
. Conclusion
Effective methods using the intramolecular cyclization of
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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-
[
[
20] M.S. Newman, H.A. Karnes, J. Org. Chem. 31 (1966) 3980.
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