Electrolytic partial fluorination of organic compounds. 64.1 Anodic mono- and difluorination of thiazolyl sulfides

Article abstract of DOI:10.1021/jo020411t

The anodic fluorination of 2-thiazolyl methyl sulfide, 2-thiazolyl propargyl sulfide, and 2-thiazolyl acetonyl sulfide was successfully carried out to provide the corresponding 5-fluorothiazole and 2,5,5-trifluorothiazoline derivatives. The latter products were readily hydrolyzed to give isolable 5,5- difluoro-2-hydroxythiazoline derivatives. On the other hand, anodic fluorination of 2-thiazolyl cyanomethyl sulfide afforded 5-fluorothiazole and α-fluorinated thiazole derivatives. Thus, the product selectivity was found to be greatly changed by the electron-withdrawing ability of substituents at the side chain of the thiazole ring. This is the first report of a successful anodic fluorination of a thiazole ring.

Full text of DOI:10.1021/jo020411t

Electr olytic P a r tia l F lu or in a tion of Or ga n ic Com p ou n d s. 64.1
An od ic Mon o- a n d Diflu or in a tion of Th ia zolyl Su lfid es
Sayed M. Riyadh and Toshio Fuchigami*
Department of Electronic Chemistry, Tokyo Institute of Technology,
Nagatsuta, Midori-ku, Yokohama 226-8502, J apan
fuchi@echem.titech.ac.jp
Received J une 14, 2002
The anodic fluorination of 2-thiazolyl methyl sulfide, 2-thiazolyl propargyl sulfide, and 2-thiazolyl
acetonyl sulfide was successfully carried out to provide the corresponding 5-fluorothiazole and 2,5,5-
trifluorothiazoline derivatives. The latter products were readily hydrolyzed to give isolable 5,5-
difluoro-2-hydroxythiazoline derivatives. On the other hand, anodic fluorination of 2-thiazolyl
cyanomethyl sulfide afforded 5-fluorothiazole and R-fluorinated thiazole derivatives. Thus, the
product selectivity was found to be greatly changed by the electron-withdrawing ability of
substituents at the side chain of the thiazole ring. This is the first report of a successful anodic
fluorination of a thiazole ring.
In tr od u ction
introduction of a difluoromethylene unit into organic
molecules11 can lead to a wide range of biologically
interesting difluoromethylene compounds such as the
anticancer agent gemcitabine,12 HIV-1 protease inhibi-
tors,13 and phosphotyrosine mimetics.14
Thiazole derivatives have attracted a great deal of
interest owing to their antifungal,2 antiinflammatory,3
and antiviral4 activities. They are also useful as anti-
allergic,5 anthelmintic6 agents. The incorporation of a
thiazole ring system into antibacterial agents of the
sulfanilimide series furnishes substances of considerable
clinical value and provides the most familiar example of
the utilization of the thiazole ring in chemotherapeutic
agents.7 In addition to being used in the pharmaceutical
industry, thiazoles also find a wide application in the dye
and photographic industry.8 On the other hand, the
synthesis of heterocyclic compounds containing fluorine
has become an important part of fluoro organic chemis-
try.9 Among nitrogen-containing heterocyclic compounds,
azoles take such a pivotal place due to their biological
activities: the attachment of fluorine-containing substit-
uents to an azole generally considerably increases its
biological activity.10 In addition, it is well-known that
However, the selective direct fluorination of hetero-
cyclic compounds is not straightforward, because con-
ventional direct fluorination usually requires hazardous,
poisonous, or costly fluorinating reagents.15 Moreover, the
chemical direct fluorination of five-membered hetero-
aromatic compounds such as pyrroles and thiophenes
produces extremely low yields (less than 6%) along with
an unsatisfactory level of selectivity.16,17 From this view-
point, electrochemical fluorination is a promising method,
since it can be performed under safe conditions using
fluoride anion as a fluoride source and supporting
electrolyte. Nevertheless, limited examples of anodic
partial fluorination of heterocyclic compounds have been
reported to date and the yields and/or selectivities are
generally quite low.18-23
* Corresponding author. Tel/Fax: 81-45-924-5406.
(1) Part 63: Tajima, T.; Ishii, H.; Fuchigami, T. Electrochem.
Commun. 2002, 4, 589.
(2) Usui, Y. Ann. Rep. Takeda Res. Leb. (J pn.) 1968, 27, 144. Chem.
Abstr. 1969, 70, 76696x.
(3) Kuo, S. C.; Huang, L. J .; Nakamura, H. J . Med. Chem. 1984,
27, 539.
(4) (a) Schauer, P.; Lkar, M.; Stanovnik, B.; Fisler, M. Biol. Vestn.
1972, 20, 65. (b) Wei, P. H. L.; Bell, S. C. US patent 3,704,239, 1972
(Chem. Abstr. 1973, 78, 43482m).
(11) Iseki, K.; Kobayashi, Y. Rev. Heteroat. Chem. 1995, 12, 211.
(12) Chou, T. S.; Heath, P. C.; Patterson, L. E.; Poteet, L. M.; Lakin,
R. E.; Hunt, A. H. Synthesis 1992, 565.
(13) Sham, H. L.; Eideburg, N. E.; Spanton, S. G.; Kohlbrenner, D.
W.; Betebenner, D. A.; Kempf, D. J .; Norbeck, D. W.; Plattrer, J . J .;
Erickson, J . W. J . Chem. Soc. Chem. Commun. 1991, 110.
(14) Berkoowitz, D. B.; Sloss, D. G. J . Org. Chem. 1995, 60, 7047.
(15) Welch, J . T., Ed. Selective Fluorination in Organic and Bio-
organic Chemistry; Wiley: New York, 1991.
(5) Musser, J . H.; Brown, R. E.; Love, B.; Kaily, K.; J ones, H.; Kahen,
R.; Huang, F.; Khandwala, A.; Leibowetz, M. J . Med. Chem. 1984, 27,
121.
(6) Brown, H. D. US patent 3,278,547, 1996 (Chem Abstr. 1996, 65,
18593a).
(7) J ones, E. R. H.; Robinson, F. A.; Strachen, M. N. J . Chem. Soc.
1946, 87.
(8) Metzger, J . V. The Chemistry of Heterocyclic Compounds; Inter-
science: New York, 1979; Vol 34, pp 162-169.
(9) Filler, R.; Kobayashi, Y.; Yagupolskii, L. M. Organofluorine
Compounds in Medicinal Chemistry and Biomedical Applications;
Elsevier: Amsterdam, 1993; p 386.
(16) Gozzo, F. C.; Ifa, D. R.; Eberlin, M. M. J . Org. Chem. 2000, 65,
3290.
(17) Cerichelli, G.; Crestono, M. E.; Fornarini, S. Gazz. Chim. Ital.
1999, 120, 749.
(18) Makino, K.; Yoshioka, H. J . Fluorine Chem. 1988, 39, 435.
(19) Ballinger, J . R.; Teare, F. W. Electrochim. Acta 1985, 30, 1075.
(20) Gambaretto, G. P.; Napoli, M.; Franccaro, C.; Conte, L. J .
Fluorine Chem. 1982, 19, 427.
(21) Meurs, J . H. H.; Eilenberg, W. Tetrahedron 1991, 47, 705.
(22) Sono, M.; Morita, N.; Shizuri, Y.; Tori, M. Tetrahedron Lett.
1994, 35, 9237.
(23) Konno, A.; Shimojo, M.; Fuchigami, T. J . Fluorine Chem. 1998,
87, 137.
(10) Ritter, S. K.; Washington, C. Chem. Eng. News 1995, 73, 39.
10.1021/jo020411t CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/28/2002
J . Org. Chem. 2002, 67, 9379-9383
9379

Riyadh and Fuchigami
TABLE 2. An od ic F lu or in a tion of 2-(4-P h en ylth ia zolyl)
P r op a r gyl Su lfid e u n d er Differ en t Electr olytic
Con d ition s
SCHEME 1
ox
TABLE 1. Oxid a tion P oten tia ls (p ea k p oten tia ls, Ep
)
% yielda
of Th ia zolyl Su lfid es a n d th e Cor r esp on d in g Mon oflu or o
Der iva tives
supporting
electrolyte
charge passed,
F/mol
run
2a
2b
1b
2
3
4
5
Et4NF‚4HF
Et4NF‚4HF
Et4NF‚5HF
Et3N‚5HF
Et4NF‚4HF
Et4NF‚5HF
Et3N‚5HF
3
3
3
3
6
6
6
10
20
18
25 (20)
10
7
5
15
32
28
28
40
37
50
6
7
ox
ox
Ep
(V vs SCE)a no.
Ep
no.
X
Z
X
Z
(V vs SCE)a
a
Determined by 19F NMR, and the isolated yield is shown in
1
2
3
4
H
H
H
H
H
1.47
1.57
1.61
1.72
1a
2a
3a
4a
F
F
F
F
H
1.37
1.57
1.52
1.71
b
parentheses. Under constant current.
CtCH
COCH3
CN
CtCH
COCH3
CN
methyl thiazolyl sulfide, while other R-electron-with-
drawing groups such as acetylenyl and acetyl groups
cause a slight increase of the oxidation potentials, ca. 0.1
and 0.14 V, respectively.
a
Substrate (0.01 M) in 0.1 M Bu4N‚BF4/MeCN; Sweep rate 100
mV/s.
An od ic F lu or in a tion of Th ia zolyl Su lfid es 1-3.
Anodic fluorination of 2-(4-phenylthiazolyl) propargyl
sulfide (2) was carried out mainly at constant potential
(1.6 V vs SCE) in DME containing various fluoride salts,
and the results are summarized in Table 2.
Regardless of the electrolytic conditions, monofluori-
nated thiazole derivative 2a and trifluorinated thiazoline
derivative 2b were always formed. Although constant
current electrolysis provided both products in low yields
due to the formation of a considerable amount of un-
identified fluorinated products (run 1), constant potential
electrolysis afforded them in moderate total yield. Elec-
trolysis in Et3N‚5HF/DME at 3 F/mol gave the highest
yield (25%) of 2a (run 4), while similar electrolysis at 6
F/ mol afforded the highest yield (50%) of 2b (run 7).
Thus, Et3N‚5HF was found to be the most suitable for
the formation of both 2a and 2b.
As mentioned above, monofluoro 2a and trifluoro 2b
were always formed, regardless of supporting fluoride
salts. This is quite different from our previous finding:
anodic fluorination of N-methylpyrrole provided mono-
fluoro and/or trifluoro products, depending on the fluoride
salts and solvent used.26 In all cases, the side chain was
not fluorinated at all. This is in sharp contrast to the
anodic fluorination of 2-propargylthiobenzothiazole, which
provided the corresponding R-fluorinated product.27
The relationships between the yields of fluorinated
products 2a and 2b and the charge passed were inves-
tigated.
With these facts in mind, the anodic fluorination of
thiazolyl sulfides has been attempted. The reactions give
the corresponding 5-fluorothiazole derivatives in addition
to 5,5-difluoro-2-hydroxythiazoline or R-fluorinated sul-
fides, depending on the nature of the side chain on the
thiazole ring. This paper presents the first example of
the direct electrochemical fluorination of a thiazole ring.
Resu lts a n d Discu ssion
P r ep a r a tion of Th ia zolyl Su lfid es 1-4. Methyl
2-thiazolyl sulfide 124 and cyanomethyl 2-thiazolyl sulfide
425 were prepared according to literature procedures.
Propargyl 2-thiazolyl sulfide 2 was prepared by refluxing
the corresponding 2-mercaptothiazole with propargyl
bromide in boiling EtOH. On the other hand, acetonyl
2-thiazolyl sulfide 3 was prepared in good yield by the
reaction of 2-mercaptothiazole with chloroacetone in
boiling THF in the presence of K2CO3, as shown in
Scheme 1.
Oxid a tion P oten tia ls of Th ia zolyl Su lfid es 1-4.
The anodic peak potentials of thiazolyl sulfides having
an electron-withdrawing group (2-4) and methyl thi-
azolyl sulfide 1 were measured by cyclic voltammetry
using a platinum anode in an anhydrous acetonitrile
solution containing Bu4N‚BF4 (0.1 M) using SCE as a
reference electrode. These sulfides showed irreversible
ox
anodic waves. The first peak potentials Ep are sum-
marized in Table 1.
A strong electron-withdrawing cyano group at the
position R to the sulfur atom greatly increases the
As shown in Figure 1, the yield of 2a increased to 25%
with an increase of electricity up to 3 F/mol, and then
the yield decreased. On the other hand, trifluorinated
ox
oxidation potential Ep (ca. 0.3 V) when compared to
(24) Gaston, V.; Chhan, S.; J acques, H. J . Heterocycl. Chem. 1978,
15, 1361.
(25) Ahluwalia, V. K.; Mallika, N.; Singh, R. P.; Khanduri, C. H.
Indian J . Chem., Sect. B 1990, 29B, 667.
(26) Tajima, T.; Ishii, H.; Fuchigami, T. Tetrahedron lett. 2001, 42,
4857.
(27) Riyadh, S. M.; Ishii, H.; Fuchigami, T. Tetrahedron 2001, 57,
8817.
9380 J . Org. Chem., Vol. 67, No. 26, 2002

Electrolytic Fluorination of Organic Compounds
SCHEME 2
SCHEME 3
F IGURE 1. Relationships between the yields of the fluori-
nated products 2a and 2b and the electricity passed.
TABLE 3. An od ic F lu or in a tion of 2-(4-p h en ylth ia zolyl)
Su lfid es 1 a n d 3
SCHEME 4
charge
passed,
F/mol
anodic
potential
(V vs SSCE)
% yielda
run
no.
R
a
b
1
2
3
4
1
1
3
3
H
H
3
6
3
6
1.5
1.5
1.65
1.65
25 (20)
10
20 (18)
8
28
55
23
50
COCH3
COCH3
same (2a , 4a ) or slightly less positive (1a , 3a ) compared
with the corresponding nonfluorinated starting sulfides
1-4, although a fluorine atom has an electron-withdraw-
ing effect. Next, we carried out the electrolysis of 2a at
constant potential (1.6 V vs SCE) in Et3N‚5HF/DME as
an electrolytic solution and found that 2b was formed
selectively in good yield as shown in Scheme 3.
As mentioned, the trifluorinated thiazoline derivative
2b was too unstable to be isolated by preparative thin-
layer chromatography. Therefore, immediately after the
electrolysis of 2 in Et3N‚5HF/DME, an excess of water
was added to the electrolytic solution in the presence of
SiO2, and then the reaction mixture was stirred at room
temperature to hydrolyze 2b, which resulted in the
formation of the isolable difluorinated product 2c in
reasonable yield, as shown in Scheme 4.
These results indicate that monofluorinated thiazole
derivatives 1a -3a were found to be the precursors of
trifluorinated thiazoline derivatives 1b-3b. On the other
hand, trifluorothiazolines 1b-3b were the precursors of
difluorinated thiazoline derivatives 1c-3c.
An od ic F lu or in a tion of Cya n om eth yl 2-Th ia zolyl
Su lfid e 4. In contrast to the cases of 1-3, anodic
fluorination of cyanomethyl 2-thiazolyl sulfide 4 gave
R-fluorocyanomethyl 2-thiazolyl sulfide 4c in addition to
5-fluorothiazolyl sulfide 4a . The results are summarized
in Table 4.
a
Determined by 19F NMR; the isolated yields are shown in
parentheses.
product 2b was formed even at the early stage of the
electrolysis and the yield of 2b increased linearly with
amount of electricity and 50% yield was obtained at 6
F/mol. However, after 6 F/ mol, the yield decreased. At 8
F/mol, 2b was obtained exclusively. These facts suggest
that 2a is easily oxidized to give 2b immediately after
2a is formed during the electrolysis.
Next, the anodic fluorination of other thiazolyl sulfides
1 and 3 was carried out similarly in Et3N‚5HF/DME.
As shown in Table 3, regardless of substituent groups
(R), fluorination took place smoothly to provide 5-fluoro-
thiazoles 1a and 3a together with 2,5,5-trifluorothiazo-
lines 1b and 3b. The product ratio depended on the
electricity passed. The monofluorinated products 1a -3a
were easily isolated by column chromatography, while
trifluorinated products 1b-3b were too unstable to be
isolated by preparative thin-layer chromatography. In-
stead of 1b-3b, the hydrolyzed 5,5-difluoro-2-hydroxy-
thiazoline derivatives 1c-3c were obtained following
chromarography, as shown in Scheme 2.To clarify the
reason for the lower yields of monofluorothiazole 1a -3a
compared with those of trifluorinated products 1b-3b,
the oxidation potentials of monofluorinated products 1a -
4a were measured.
As shown in Table 1, it was found that the oxidation
potentials of monofluorinated thiazoles were almost the
Although constant potential electrolysis gave low yields
of both 4a and 4c, constant current electrolysis provided
J . Org. Chem, Vol. 67, No. 26, 2002 9381

Riyadh and Fuchigami
TABLE 4. An od ic F lu or in a tion of Cya n om eth yl
2-(4-P h en ylth ia zolyl) Su lfid e 4
SCHEME 6
From these results, a possible reaction mechanism was
proposed, as shown in Scheme 5.
% yielda
supporting
This reaction can be explained by a conventional ECEC
process: One-electron oxidation of starting sulfides 1-4
generates radical cation A, which reacts with a fluoride
ion to give the corresponding radical B, and further
oxidation of the radical B followed by deprotonation
affords monofluorothiazole derivatives 1a -4a . Since 1a -
3a are more easily oxidized than 1-3, trifluorinated
products 1b-3b are preferentially formed by further
electrochemical oxidative fluorination. Moreover, hy-
drolysis of 1b-3b produces difluorinated compounds 1c-
3c. On the other hand, the formation of R-monofluoro-
cyanomethyl 2-thiazolyl sulfide 4c can be explained as
follows. The deprotonation from the R-position of the
radical cation C is facilitated by the strongly electron-
withdrawing cyano group to generate the R-radical
intermediate, followed by further oxidation and fluoride
ion attack.
run
electrolyte
4a
10
20 (18)
15
4c
20
65 (60)
60
1b
2
3
Et4NF‚4HF
Et4NF‚4HF
Et4NF‚5HF
Et3N‚5HF
4
15
58
Determined by 19F NMR; the isolated yields are shown in
parentheses. Under constant potential (1.75 V vs SCE).
a
b
SCHEME 5
To disclose the role of a thioalkyl group, anodic
fluorination of 4-methyl thiazole was attempted. How-
ever, no fluorinated products were formed, as shown in
Scheme 6. Therefore, the presence of thioalkyl group is
essential for this regioselective anodic fluorination.
Con clu sion
In conclusion, we have successfully carried out for the
first time the anodic fluorination of thiazolyl sulfides. The
products 1b-3b and 1c-3c have a biologically interest-
ing gem-difluoromethylene unit in the heterocyclic thi-
azoline ring and the products 1a -4a have a fluorine atom
on the aromatic thiazole ring. Therefore, 1a -4a , 1b -
3b, and 1c-3c seem to be useful fluorinated building
blocks.
Exp er im en ta l Section
CAUTION. Et4NF‚4HF and Et3N‚5HF are toxic and contact
with skin causes serious burns, so proper safety precautions
should be taken all the time. It is therefore recommended to
protect hands with rubber gloves.28
4a and 4c in reasonable and moderate yields, respectively
(runs 2-4). Among the supporting fluoride salts used,
the use of Et4NF‚4HF was the most suitable for the
monofluorination of 4. As compared with other thiazolyl
sulfides 1-3, cyanomethyl 2-thiazolyl sulfide 4 has the
highest oxidation potential (Table 1); therefore, its cor-
responding 5-fluorothiazole 4a should be the most dif-
ficult to oxidize. In fact, 4a was found to have the highest
oxidation potential, as shown in Table 1. This seems to
be one of the main reasons why 4a was not susceptible
to further oxidation, leading to the 2,5,5-trifluoro thi-
azoline derivative. Meanwhile, a strongly electron-
withdrawing cyano group was responsible for the exclu-
sive anodic fluorination at the R-position toward the
sulfur atom, leading to R-monofluorinated sulfide 4c in
rather good yield, particularly when Et4NF‚4HF/DME
was used as the electrolytic solution (Table 4 run 2).
Ma ter ia ls. Methyl 2-thiazolyl sulfide 124 and cyanomethyl
2-thiazolyl sulfide 425 were prepared according to the literature
methods. Et4NF‚4HF and Et3N‚5HF were obtained from
Morita Chemical Industries Co. Ltd. (J apan).
P r ep a r a tion of 2-(4-P h en ylth ia zolyl) P r op a r gyl Su l-
fid e 2. To a stirred solution of 4-phenyl-2-mercaptothiazole
(10 mmol) in ethanol (50 mL) was added propargyl bromide
(10 mmol) dropwise. The mixture was refluxed for 5 h. After
evaporation of the solvent and pouring the residue onto
crushed ice, the precipitated solid was filtered and purified
by column chromatography on silica gel using hexane/AcOEt
(5:1) as an eluent to give the pure product 2: 1H NMR δ 2.32
(t, 1 H, J ) 2.6 Hz), 4.07 (d, 2 H, J ) 2.6 Hz), 7.25-7.45 (m,
4 H), 7.93 (d, 2 H, J ) 8 Hz); MS m/z 231 (M+), 230 (M+ - H).
Anal. Calcd for C12H9NS2: C, 62.30; H, 3.92; N, 6.05; S, 27.72.
Found: C, 62.54; H, 4.07; N, 6.29; S, 27.58.
(28) Peter, D.; Mietchen, R. J . Fluorine Chem. 1996, 79, 161.
9382 J . Org. Chem., Vol. 67, No. 26, 2002

Electrolytic Fluorination of Organic Compounds
P r ep a r a tion of Aceton yl 2-(4-P h en ylth ia zolyl) Su lfid e
3. To a stirred solution of 4-phenyl-2-mercaptothiazole (10
mmol) in THF (50 mL) in the presence of anhydrous K2CO3
(15 mmol), was added R-chloroacetone (10 mmol). The reaction
mixture was refluxed for 2 h and then left to cool to room
temperature. The inorganic salts were filtered off, and the
filtrate was evaporated under vacuum. The obtained product
was purified by column chromatography on silica gel using
benzene as an eluent to give the pure product 3: 1H NMR δ
2.27 (s, 3 H), 4.02 (s, 2 H), 7.25-7.34 (m, 4 H), 7.93 (d, 2 H, J
) 8 Hz); MS m/z 249 (M+), 206 (M+ - COCH3). Anal. Calcd
for C12H11NOS2: C, 57.80; H, 4.45; N, 5.62; S, 25.72. Found:
C, 57.83; H, 4.54; N, 5.81; S, 25.62.
7.35-7.59 (m, 5 H). 19F NMR δ -22.3 (d, J ) 200 Hz), 3.25 (d,
J ) 200 Hz); MS m/z 261 (M+), 244 (M+ - OH). Anal. Calcd
for C10H9F2NOS2: C, 45.96; H, 3.47; N, 5.36; S, 24.54. Found:
C, 45.89; H, 3.21; N, 5.28; S, 24.33.
5,5-Diflu or o-2-h yd r oxy-4-p h en yl-2-p r op a r gylth io-2,5-
d ih yd r oth ia zole (2c): 1H NMR δ 2.32 (t, 1 H, J ) 2.6 Hz),
3.44 (s, 1 H), 4.11 (d, 2 H, J ) 2.6 Hz), 7.35-7.61 (m, 5 H); 19
F
NMR δ -22.7 (d, J ) 200 Hz), 3.66 (d, J ) 200 Hz); MS m/ z
285 (M+), 284 (M+ - H); HRMS m/z calcd for C12H9F2NOS2
285.0144, found 285.0145. Anal. Calcd for C12H9F2NOS2: C,
50.51; H, 3.18; N, 4.91; S, 22.48. Found: C, 50.28; H, 3.11; N,
4.77; S, 22.31.
2-Aceton ylth io-5,5-d iflu or o-2-h yd r oxy-4-p h en yl-2,5-d i-
h yd r oth ia zole (3c): 1H NMR δ 2.35 (s, 3 H), 3.66 (s, 1 H),
4.10 (s, 2 H), 7.35-7.63 (m, 5 H). 19F NMR δ -22.5 (d, J )
An od ic F lu or in a tion of Th ia zolyl Su lfid es 1-3. The
electrolyses were carried out with platinum plate electrodes
(3 × 3 cm2) in 0.37 M Et3N‚5HF/DME (30 mL) containing a
sulfide (1-3, 1 mmol) using a divided cell under nitrogen
atmosphere at room temperature. Constant potential was
applied until the starting material was consumed (checked by
TLC). After the electrolysis, the electrolytic solution was
passed through a short column filled with silica gel using
AcOEt as an eluent to remove fluoride salts. The eluent was
evaporated under reduced pressure. The yields of the fluori-
nated products were estimated by means of 19F NMR by using
a known amount of monofluorobenzene as an internal stand-
ard: The yields were calculated on the basis of the integral
ratios between the monofluorobenzene and the fluorinated
products. The residue was further purified by column chro-
matography on silica gel using hexane/AcOEt (1:10) as an
eluent.
200 Hz), 3.62 (d, J ) 200 Hz); MS m/z 303 (M+), 286 (M+
-
OH); HRMS m/z calcd for C12H11F2NO2S2 303.0199, found
303.0216. Anal. Calcd for C12H11F2NO2S2: C, 47.51; H, 3.65;
N, 4.62; S, 21.14. Found: C, 47.38; H, 3.41; N, 4.47; S, 21.02.
An od ic F lu or in a tion of Cya n om eth yl 2-(4-P h en ylth i-
a zolyl) Su lfid e 4. The electrolysis were carried out with
platinum plate electrodes (3 × 3 cm2) in 0.37 M Et4NF‚4HF/
DME (30 mL) containing a sulfide 4 (1 mmol) using a divided
cell under nitrogen atmosphere at room temperature. Constant
current (5 mA/cm2) was passed until the starting material 4
was consumed (checked by TLC).
r-[2-(5-F lu or o-4-p h en ylth ia zolyl)th io]a ceton itr ile (4a ):
1H NMR δ 3.99 (s, 2 H), 7.35-7.90 (m, 5 H); 19F NMR δ -68.5
(s); MS m/z 250 (M+), 210 (M+ - CH2CN). Anal. Calcd for
C11H7FN2S2: C, 52.78; H, 2.82; N, 11.19; S, 25.62. Found: C,
52.56; H, 3.07; N, 11.12; S, 25.48.
r-F lu or o-r-[2-(4-P h en ylth ia zolyl)th io]a ceton itr ile (4c):
1H NMR δ 6.22 (d, 1 H, J ) 58.6 Hz), 7.35-7.55 (m, 4 H), 7.64
(d, 2 H, J ) 8 Hz); 19F NMR δ -72.28 (d, J ) 58.6 Hz); MS
m/z 250 (M+); HRMS m/z calcd for C11H7FN2S2 250.0035, found
250.0015. Anal. Calcd for C11H7FN2S2: C, 52.78; H, 2.82; N,
11.19; S, 25.62. Found: C, 52.62; H, 2.71; N, 11.05; S, 25.49.
5-F lu or o-2-m eth ylth io-4-p h en ylth ia zole (1a ): 1H NMR
δ 2.72 (s, 3 H), 7.35-7.93 (m, 5 H); 19F NMR δ -63.8 (s); MS
m/z 225 (M+), 210 (M+ - CH3). Anal. Calcd for C10H8FNS2: C,
53.31; H, 3.58; N, 6.22; S, 28.46. Found: C, 53.04; H, 3.33; N,
6.35; S, 28.33.
5-F lu or o-4-p h en yl-2-p r op a r gylt h iot h ia zole (2a ): 1H
NMR δ 2.32 (t, 1 H, J ) 2.6 Hz), 4.07 (d, 2 H, J ) 2.6 Hz),
7.35-7.91 (m, 5 H); 19F NMR δ -64.2 (s). MS m/ z 249 (M+),
248 (M+ - H); HRMS m/z calcd for C12H8FNS2 249.0082, found
249.0076. Anal. Calcd for C12H8FNS2: C, 57.81; H, 3.23; N,
5.62; S, 25.72. Found: C, 57.68; H, 3.13; N, 5.45; S, 25.53.
2-Aceton ylth io-5-flu or o-4-p h en ylth ia zole (3a ): 1H NMR
δ 2.33 (s, 3 H), 4.06 (s, 2 H), 7.35-7.93 (m, 5 H); 19F NMR δ
-67.33 (s). MS m/z 267 (M+), 224 (M+ - COCH3); HRMS m/z
calcd for C12H10FNOS2 267.0188, found 267.0190. Anal. Calcd
for C12H10FNOS2: C, 53.91; H, 3.77; N, 5.24; S, 23.99. Found:
C, 53.77; H, 3.53; N, 5.05; S, 23.78.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research on Priority Areas
(A) “Exploitation of Multi-Element Cyclic Molecules”
from the ministry of Education, Culture, Sports, Science
and Technology, J apan. We also thank Dr. H. Ishii for
recording the HRMS.
2-Met h ylt h io-4-p h en yl-2,5,5-t r iflu or o-2,5-d ih yd r ot h i-
Note Ad d ed a fter ASAP . The version posted ASAP
on November 28, 2002, had the following errors: the
supporting electrolyte in runs 4 and 7 of Table 2 and run
4 of Table 4; the products listed in columns 3 and 4 of
Table 4 and the Supporting Information paragraph. The
corrected version was posted December 4, 2002.
1
a zole (1b): H NMR δ 2.72 (s, 3 H), 7.35-7.88 (m, 5 H); 19F
NMR δ 3.23 (dd, J ) 200, 5 Hz), -22.98 (dd, J ) 205, 3 Hz),
-43.50 (t, J ) 3 Hz); MS m/z 263 (M+), 248 (M+ - CH3); HRMS
m/ z calcd for C10H8F3NS2 263.0188, found 263.0190.
4-P h en yl-2-pr opar gylth io-2,5,5-tr iflu or o-2,5-dih ydr oth i-
a zole (2b): 19F NMR δ 4.63 (dd, J ) 205, 3 Hz), -21.61 (dd,
J ) 205, 3 Hz), -42.75 (t, J ) 3 Hz).
2-Aceton ylth io-4-p h en yl-2,5,5-tr iflu or o-2,5-d ih yd r oth i-
a zole (3b): 19F NMR δ 4.72 (dd, J ) 205, 3 Hz), -20.66 (dd,
J ) 205, 3 Hz), -43.67 (t, J ) 3 Hz).
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 19F
NMR of 1b. This material is available free of charge via
Internet at http://pubs.acs.org.
5,5-Diflu or o-2-h yd r oxy-2-m et h ylt h io-4-p h en yl-2,5-d i-
h yd r oth ia zole (1c): 1H NMR δ 2.65 (s, 3 H), 3.62 (s, 1 H),
J O020411T
J . Org. Chem, Vol. 67, No. 26, 2002 9383