Fluoride-assisted trifluoromethylation of aromatic thiones with (trifluoromethyl)trimethylsilane

Article abstract of DOI:10.1016/S0022-1139(03)00203-3

In the presence of a stoichiometric amount of Bu₄NF·3H₂O, (trifluoromethyl)trimethylsilane reacts with aromatic thiones in both thiophilic and carbophilic ways to deliver, in medium yield, a mixture of (trifluoromethylthio)diarylmethane and 1,1-diaryl-2,2,2-trifluoroethanethiol, the former product being the major one.

Full text of DOI:10.1016/S0022-1139(03)00203-3

Journal of Fluorine Chemistry 124 (2003) 147–149
Fluoride-assisted trifluoromethylation of aromatic thiones
with (trifluoromethyl)trimethylsilane
Sylvie Large-Radix, Thierry Billard, Bernard R. Langlois*
´
Laboratoire SERCOF (UMR 5622), Universite Claude Bernard-Lyon I, 43, Bd du 11 Novembre 1918,
F-69622 Villeurbanne Cedex 69622, France
Received 12 May 2003; received in revised form 23 July 2003; accepted 23 July 2003
Abstract
In the presence of a stoichiometric amount of Bu4NFꢀ3H2O, (trifluoromethyl)trimethylsilane reacts with aromatic thiones in both thiophilic
and carbophilic ways to deliver, in medium yield, a mixture of (trifluoromethylthio)diarylmethane and 1,1-diaryl-2,2,2-trifluoroethanethiol,
the former product being the major one.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Trifluoromethylation; (Trifluoromethyl)trimethylsilane; Trifluoromethyl sulfides; a-(Trifluoromethyl)thiols
1. Introduction
proposed to issue from reactions consecutive to the thio-
philic process.
(Trifluoromethyl)trimethylsilane constitutes an ubiqui-
tous and powerful tool for the introduction of a trifluoro-
methyl moiety on organic substrates [1]. Nevertheless,
though this reagent has been extensively added to carbonyl
functions, little work has been focused on its reaction with
sulfur-containing compounds, despite the economic inter-
est of trifluoromethyl sulfides, especially in the agrochem-
ical field [2]. From the few papers that exist, it appears that,
under fluoride catalysis, the Ruppert–Prakash reagent
allows the preparation of trifluoromethyl sulfides from
disulfides [3] or thiocyanates [4]. Recently, Mloston et al.
[5] described the reaction, under moisture free conditions,
of (trifluoromethyl)trimethylsilane with thiones, especially
diaryl thiones, in the presence of a catalytic amount of
thoroughly dried tetrabutylammonium fluoride (TBAF)
(Scheme 1).
These interesting results, which were previously pre-
sented in a symposium in 1998 [6], prompt us to report
briefly on similar work we simultaneously and indepen-
dently carried out and that we mentioned in a poster session
during the same meeting.
2. Results and discussion
For our part, we also trifluoromethylated thiones 1a
and 1b with CF3TMS but under different conditions than
CF3TMS (1.25 eq)
TBAF (2.5 % mol)
Ar
Ar
Ar
Ar
Ar
Ar
Ar
F
SCF3
H
S
+
THF/r.t./3-4 h
Ar
1a
1b
F
2
3
Ar = C6H5
As proposed by the authors, product 2 arose from a
thiophilic attack of a formal trifluoromethyl anion upon
the thione but, surprisingly, the a-(trifluoromethyl)thiol
resulting from a carbophilic attack was not observed,
since it was probably consumed to deliver product 3.
As far as products 4 and 5 were concerned, they were
Ar
Ar
Ar
Ar
Ar
Ar = 4-MeO-C6H4
+
+
Ar
S
4
5
a)
a)
a)
a)
2
3
4
5
30 % (22 %) 8 % (6 %) (45 %) (3 %)
from 1a
from 1b
b)
b)
29 % (21 %) 7 % (5 %)
a)
b)
Crude yield. In parentheses : isolated yield.
Not determined
* Corresponding author. Tel.: þ33-4-72-44-81-63;
fax: þ33-4-72-43-13-23.
Scheme 1. Fluoride-catalyzed reaction of CF3SiMe3 on aromatic
thiones.
E-mail address: bernard.langlois@univ-lyon1.fr (B.R. Langlois).
0022-1139/$ – see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00203-3

148
S. Large-Radix et al. / Journal of Fluorine Chemistry 124 (2003) 147–149
CF3TMS (2 eq)
TBAF.3 H2O (2 eq)
might occur in our experiments, the disulfide formed
Ar
Ar
Ar
Ar
Ar
Ar
SCF3
H
CF3
SH
should be readily transformed into the trifluoromethyl
sulfide 2, since the conditions we used are those we
reported to be efficient for the trifluoromethylation of
disulfides [3b].
+
S
THF
0 ˚C then r.t.
2
6
a)
a)
Ar = C6H5
1a
1b
37 % (30 %) 14 % (10 %)
a)
a)
Ar = 4-MeO-C6H4
35 % (35 %) 13 %
a)
Crude yield. In parentheses : isolated yield.
3. Conclusion
Scheme 2. Reaction of CF3TMS upon thiones with stoichiometric
TBAFꢀ3 H2O.
In conclusion, our work complements that of Mloston
et al. These two studies demonstrate that tetrabutylammo-
nium fluorotrimethyl(trifluoromethyl)silicate, which is
probably the real trifluoromethylating agent generated from
CF3TMS, is a nucleophile which stands at the border
between soft and hard. However, since thiophilic attack
of thiones was more important than carbophilic, its soft
character predominates.
Mloston et al., since we applied the conditions we used for
the trifluoromethylation of disulfides [3b], that is, 1 eq. of
thione, 2 eq. of CF3TMS and 2 eq. of Bu4NFꢀ3H2O (1 M in
THF), introduced at 0 8C by means of a syringe-pump,
before warming up to room temperature. Consequently,
our results were different from those of Mloston, since,
along with the major trifluoromethyl sulfide 2, the trifluor-
omethylated thiol 6 was formed and isolated (Scheme 2).
Product 3, also claimed to result from a carbophilic attack,
was not detected by 19F NMR. Moreover, the reaction was
faster and the global yield of fluorinated species was higher
than under Mloston’s conditions. By-products such as 4 and
5 may have been formed but we did not succeed in isolating
them after chromatography.
Such a difference in the results can be easily rationa-
lized from the reaction mechanisms proposed by Mloston
et al. (Scheme 3) and was due mainly to the fact that we
used commercial TBAFꢀ3H2O in excess; that means that
an abundant source of protons was present to quench
rapidly the intermediate anions 7 and 9 before they
reversibly collapse (for 7) or enter further reactions
(for 9).
4. Experimental
Prior to use, THF was distilled over sodium-benzophe-
˚
none then stored over 3 A molecular sieves under N2.
Diphenylthione 1a was prepared according to [7]. bis-
(4-Methoxyphenyl)thione was obtained from Prof. Alois
Fu¨rstner. Other reagents were used as received. TLC
analyses were carried out on silica gel (Kieselgel 60F
254) deposited on aluminum plates, detection being by
UV (254 nm). Flash-chromatographies were performed on
silica gel Geduran SI 60. Unless stated otherwise, NMR
spectra were recorded in CDCl3. 1H NMR were recorded at
200 MHz or 300 MHz and 13C NMR spectra at 50 MHz or
75 MHz. The substitution pattern of the different carbons
were determined by a ‘‘DEPT 135’’ sequence. 19F NMR
spectra were recorded at 188 MHz. Chemical shifts (d) are
given in ppm versus TMS (1H, 13C) or CFCl3 (19F) used as
internal references. Coupling constants are given in hertz.
Crude yields were determined by 19F NMR versus PhOCF3
(dF ¼ ꢁ58:3 ppm) used as standard. GC was carried out on
an apparatus fitted with a semi-capillary column (length:
15 m, diameter: 0.53 mm, film thickness (DB1): 1 mm) and
a catharometric detector. Mass spectrometry, coupled with
gas chromatography, was carried out under electron impact
at 70 eV.
Moreover, Mloston et al. demonstrated in the same
paper that fluoride anions, thoroughly dried over molecular
sieves, are able to catalyze the transformation of diphe-
nylthione into benzhydryl disulfide. If such a reaction
Ar
Ar
Ar
Ar
CF3
S
Ar
Ar
CF3
SH
H2O
+
S
CF3
6
7
9
- F
1
Ar
Ar
Ar
Ar
SCF3
H
H2O
:CF2
SCF3
4.1. Trifluoromethylation of thiones with
(trifluoromethyl)trimethylsilane
2
S
Ar
Ar
F
Ar
Ar
Ar
Ar
Ar2C=S
F
Ar
8
4.1.1. General procedure
Ar
Ar
CF3S 10
Ar
5
- S
(Trifluoromethyl)trimethylsilane (300 ml, 2 mmol) was
added at 0 8C, under nitrogen, to a solution of thione
(1 mmol) in THF (1 ml). At the same temperature,
Bu4NFꢀ3H2O (2 ml of a 1 M solution in THF, 2 mmol)
was slowly dropped with a syringe pump (1 ml minꢁ1).
Then the reaction mixture was warmed up to room tem-
perature and stirred for 2 h. After evaporation of the solvent,
S
- S
Ar
Ar
F
F
Ar
Ar
Ar
Ar
- CF3S
3
S
4
Scheme 3. Reaction mechanisms (according to [5]).

S. Large-Radix et al. / Journal of Fluorine Chemistry 124 (2003) 147–149
149
the crude residue was deposited at the top of a chromato-
graphic column and eluted.
3.72 (s, 6H), 7.00–7.80 (M, 10H). 19F NMR (188 MHz):
d ꢁ73.90 (s).
4.1.1.1. (Trifluoromethylthio)diphenylmethane 2a. Elution
with pure petroleum ether (PE): 77 mg (30%) of a colorless
oil. 1H, 13C and 19F NMR spectra, as well as mass spectrum,
are in accordance with the literature [5].
Acknowledgements
Prof. Alois Fu
¨rstner is very much acknowledged for a
generous grant of bis-(4-methoxyphenyl)thione.
4.1.1.2. 1,1-Diphenyl-2,2,2-trifluoroethanethiol 6a. Elution
with pure petroleum ether: 27 mg (10%) of a colorless oil. 1H
NMR and IR spectra were in accordance with [8], in which 6a
was prepared through an independent way from 1,1-diphenyl-
2,2,2-trifluoroethanol. 19F NMR (188 MHz): d ꢁ73.92 (s).
References
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4.1.1.3. (Trifluoromethylthio)-bis-(4-methoxyphenyl)-
methane 2b. Elution with petroleum ether/acetone (7:1):
77 mg (30%) of a colorless oil (according to [5], 2b is a
low-melting solid mp ¼ 36ꢁ38 8C). 13C NMR spectrum is
in accordance with the literature [5]. 1H NMR (300 MHz): d
3.78 (s, 6H), 5.65 (s, 1H), 6.86 (d, J ¼ 8:0, 4H), 7.31 (d,
J ¼ 8:0, 4H). 13C NMR (75 MHz): d 52.60 (q, J ¼ 1:9),
55.26, 114.09, 129.33, 130.03 (q, J ¼ 308), 131.47, 159.17.
19F NMR (188 MHz): d ꢁ41.34 (s). MS: m/z 227 (100,
Mꢂþ–SCF3), 212, 196, 113.
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4.1.1.4. 1,1-bis-(4-Methoxyphenyl)-2,2,2-trifluoroe-
1
thanethiol 6b. H NMR (200 MHz): d 2.95 (broad s, 1H),