Electrolytic Partial Fluorination of Organics
J . Org. Chem., Vol. 62, No. 26, 1997 9175
Sch em e 5
dinium triflates resulted in no formation of the desired
product. Therefore, the electrochemical fluorination is
more advantageous than the conventional chemical
methods for such heterocyclic sulfides: successful fluo-
rination can be achieved in one step under mild condi-
tions.
In summary, we successfully carried out anodic mono-
fluorination of 2-benzothiazolyl and 5-chloro-2-benzothia-
zolyl sulfides and have found that this fluorination is
greatly affected by the supporting fluoride salts as well
as the electrolytic solvents. These findings could be of
importance for future selective anodic fluorination of
organic molecules.
Exp er im en ta l Section
Ca u tion . Me4NF‚3HF, Et3N‚3HF, and Et3N‚5HF are toxic
and if in contact with skin causes serious burn, so proper safety
precautions should be taken all the time. It is therefore
recommended to protect hands with rubber gloves.
1H NMR and 19F NMR spectra were recorded at 270 MHz
using CDCl3 as a solvent. The chemical shifts for 1H and 19F
NMR are given in δ ppm downfield from TMS and TFA,
respectively. Analytical instruments are described in our
previous paper.16b
Sch em e 6
P r ep a r a tion of 2-Ben zoth ia zolyl Su lfid es 1a -c a n d
5-Ch lor o-2-ben zoth ia zolyl Su lfid es 1d -f. To a solution of
2-mercaptobenzothiazole or 5-chloro-2-mercaptobenzothiazole
(0.02 mol) in 40 mL of THF containing 3 g (0.024 mol) of K2CO3
was added R-halogeno compound (0.02 mol). The reaction
mixture was heated under reflux for 1 h. The product was
purified by column chromatography on silica gel (hexane:
AcOEt ) 5:1) to provide the desired product 1.
the fluorosulfonium ion for this reaction as shown in
Scheme 5.9e,f Considering failure of anodic fluorination
of 2-(methylthio)benzothiazole (3), the regioselectivity can
be explained in terms of facilitated deprotonation of A.
Due to the effect of the electron-withdrawing group,
deprotonation of A derived from 1 should occur more
easily as compared to A derived from 3; therefore, high
regioselectivity observed in these anodic fluorinations is
reasonable.
Anodic fluorination of simple benzothiazole 5 was also
attempted (Scheme 6). The formation of 5- and 6-fluo-
robenzothiazoles 6a and 6b was detected by MS [m/z 153
(M+), 134 (M+ - F), 126 (M+ - HCN)] and 19F NMR
spectra [δ -34.53 (dd, J ) 5.6, 9.3 Hz) and -45.37 (dd,
J ) 4.5, 10.1 Hz)]. However, compound 6 could not be
isolated because of extremely low yields. In this case,
the thiazolyl ring was not fluorinated at all as shown by
the 19F NMR spectra mentioned above. This result is
quite similar to the cases of the anodic fluorination of
oxindole in Me4NF‚4HF16 and isoquinoline in Et4NF‚4HF/
MeCN.17 In those cases, polyfluorination took place at
the benzene ring predominately and the heterocyclic
moiety was not fluorinated at all. The reason is not clear
at the present stage.
2-Ben zoth ia zolyl cya n om eth yl su lfid e (1a ):19a 1H NMR
δ 4.19 (s, 2H), 7.36 (td, J ) 7.4, 1.3 Hz, 1H), 7.47 (td, J ) 7.3,
1.3 Hz, 1H), 7.78 (d, J ) 8.3 Hz, 1H), 7.93 (d, J ) 7.6 Hz, 1H);
MS m/z 206 (M+), 166 (M+ - CH2CN). Anal. Calcd for
C9H6N2S2: C, 52.40; H, 2.93; N, 13.58. Found: C, 52.30; H,
2.74; N, 13.57.
2-Ben zot h ia zolyl (m et h oxyca r b on yl)m et h yl su lfid e
(1b):19a 1H NMR δ 3.79 (s, 3H), 4.20 (s, 2H), 7.30 (td, J ) 7.3,
1.3 Hz, 1H), 7.42 (td, J ) 7.3, 1.3 Hz, 1H), 7.75 (d, J ) 7.8 Hz,
1H), 7.86 (d, J ) 8.9 Hz, 1H); MS m/z 239 (M+), 180 (M+
-
CH3CO2). Anal. Calcd for C10H9NO2S2: C, 50.19; H, 3.79; N,
5.85. Found: C, 50.09; H, 3.43; N, 5.78.
2-Aceton yl ben zoth ia zolyl su lfid e (1c):19b 1H NMR δ
2.40 (s, 3H), 4.24 (s, 2H), 7.30 (td, J ) 7.9, 1.3 Hz, 1H), 7.42
(td, J ) 7.3, 1.3 Hz, 1H), 7.75 (d, J ) 7.9 Hz, 1H), 7.83 (d, J )
7.3 Hz, 1H); MS m/z 223 (M+), 208 (M+ - CH3), 180 (M+
-
CH3CO). Anal. Calcd for C10H9NOS2: C, 53.79; H, 4.06; N,
6.27. Found: C, 53.70; H, 3.85; N, 6.22.
2-(5-Ch lor ob en zot h ia zolyl)
cya n om et h yl
su lfid e
(1d ):19c 1H NMR δ 4.19 (s, 2H), 7.34 (dd, J ) 8.6, 2.0 Hz, 1H),
7.71 (d, J ) 8.6 Hz, 1H), 7.94 (d, J ) 2.0 Hz, 1H); MS m/z 240
(M+), 200 (M+ - CH2CN). Anal. Calcd for C9H5ClN2S2: C,
44.91; H, 2.09; N, 11.64. Found: C, 44.94; H, 1.83; N, 11.69.
2-(5-Ch lor oben zoth ia zolyl) (m eth oxyca r bon yl)m eth yl
su lfid e (1e):19a 1H NMR δ 3.79 (s, 3H), 4.18 (s, 2H), 7.28 (dd,
J ) 8.6, 2.0 Hz, 1H), 7.67 (d, J ) 8.4 Hz, 1H), 7.84 (d, J ) 2.2
Hz, 1H); MS m/z 273 (M+), 214 (M+ - CH3CO2) Anal. Calcd
for C10H8ClNO2S2: C, 43.88; H, 2.95; N, 5.12. Found: C, 44.22;
H, 2.73; N, 5.13.
It is well-known that fluorinated sulfides could be
prepared from the corresponding sulfides using XeF2 or
DAST; however, the former reagent is costly and the
latter one requires the corresponding sulfoxides as the
starting material. Recently, N-fluoropyridinium triflates
and tetrafluoroborates have been shown to be alternative
fluorination reagents.18 However, fluorination of 1e as
a model compound with various types of N-fluoropyri-
Aceton yl 2-(5-ch lor oben zoth ia zolyl) su lfid e (1f): solid;
1H NMR δ 2.40 (s, 3H), 4.24 (s, 2H), 7.28 (dd, J ) 8.6, 2.0 Hz,
1H), 7.65 (d, J ) 8.6 Hz, 1H), 7.82 (d, J ) 2.0 Hz, 1H); MS m/z
257 (M+), 242 (M+ - CH3), 214 (M+ - CH3CO). Anal. Calcd
for C10H8ClNOS2: C, 46.60; H, 3.13; N, 5.43. Found: C, 46.67;
H, 3.16; N, 5.36.
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